More than 5.4 million adults in the U.S. have autism. That’s about the populations of Los Angeles and Phoenix combined. Autism, or autism spectrum disorder (ASD), is a developmental disability that affects how a person experiences the world around them. If this definition sounds broad, there’s a reason for that. Autism manifests in many different ways.

“ASD is characterized by deficits in reciprocal social interactions, restricted interest, and repetitive behaviors,â€� says Â鶹´«Ã½Ó³»­ (CSHL) Professor Ivan Iossifov. “It’s a very prevalent disorder, with one in a hundred girls and even more boys diagnosed.â€�

Despite its prevalence, there’s still a lot we don’t know about autism. Research has shown that early diagnosis, therapy, and treatment of co-occurring conditions can improve quality of life for people with autism. But without understanding its cause, many people aren’t diagnosed until later in life—if ever at all.

At CSHL, scientists research autism with a common goal in mind. They aim to help improve the lives of people with autism and their families.

A recent episode of Â鶹´«Ã½Ó³»­â€™s At the Lab podcast breaks down decades of autism research in less than three minutes.

Looking in the right places

Professor Iossifov has been working on the genetics side of autism research for years. His most recent innovation, a tool called (GPF), may one day enable researchers to make new discoveries about the disorder’s roots.

As a young scientist, however, Iossifov started his career with a very different subject in mind. “In high school and college, I was interested in computers,� he says. “Biology was completely foreign to me.�

After earning his master’s degree in computer science, Iossifov was introduced to computational biology. He enrolled in a Ph.D. program at Columbia University and began developing software that could extract information about molecular interactions from large chunks of text in scientific research journals.

“I started working on autism with the hope that the functional knowledge we’d extracted from articles could help us make progress with autism genetics,� he says. “Not only autism genetics— related disorders, too—but that’s where I started.�

Autism is a tricky disorder to research, in part because it’s so diverse. As hinted earlier, ASD can manifest with a wide range of symptoms and severities. Some people with the disorder face significant day-to-day challenges, including learning disabilities. They may be unable to speak, live on their own, or complete basic tasks without help. Others have little or no difficulty communicating, do extremely well in school, and have no problem living by themselves. Yet, despite the broad spectrum, some traits are common among people with autism, including sensitivity to stimuli, anxiety, difficulty in social situations, and special interests.

While at Columbia, Iossifov began collaborating with CSHL Professor Michael Wigler, a molecular biologist researching how spontaneous changes in DNA could lead to autism. Wigler and his team would make a big breakthrough in autism research in the 2000s. Using a new method of genomic analysis on a small collection of data, they discovered that spontaneous, or de novo, genetic mutations were a higher risk factor for autism than previously thought.

CSHL Professor Michael Wigler outlines his “hypotheses of maximum hope.�

When Iossifov graduated, Wigler recruited him to join CSHL as a fellow. Around that time, Wigler’s colleagues were spearheading an effort to build a bigger dataset for continued research of de novo mutations in families that had only one child with autism. By 2011, this dataset, called the (SSC) from the (SFARI), would include genetic information on 2,659 volunteer families.

Iossifov began putting together projects using data collected from the SSC and a new technique called next-generation sequencing. “Everybody was crazy about next-generation sequencing at the time,â€� he says. “W±ð successfully executed a large-scale project generating and analyzing whole-exome sequences for all 9,000 individuals from the SSC.â€� (The exome is the part of the genome thought to hold the key to most genetic disorders.) This effort would set the stage for more groundbreaking projects to come.

In 2016, SFARI launched , the largest study of autism ever, with over 275,000 participants. Using SFARI family datasets, Wigler and Iossifov have made a series of important discoveries. In 2021, they found that even more in children whose siblings do not also have the condition. In 2023, they found that siblings with autism share more of their father’s genome than previously thought.

Today, Iossifov’s powerful new tool, ​​GPF, helps researchers organize and analyze large-scale family datasets like SPARK and the SSC. It allows them to explore genetic variants more easily and upload their data securely to share it with the wider scientific community.

Using GPF, a scientist investigating a specific gene could look for it with the tool’s search function and see all variants in that gene across numerous autism genetics datasets. They could see how many families have variants in that gene, how many people have autism in each family, and how it manifests. A researcher could also search for specific variants across all genes in all datasets.

It took decades of research to identify the first genetic markers of autism. This platform could help researchers find new markers much faster. And that could make earlier diagnoses a reality for many families unknowingly living with autism.

How is autism passed down in families? It’s complicated. This video offers a few possible clues using easy-to-follow infographics.

From awareness to acceptance and support

“The science part of my mind wonders how amazing it would be if they could track down the genetic markers of autism,� tells Marina Sarris of the Simons Foundation. Juricich is a SPARK participant who wasn’t formally diagnosed with autism until she was 58. “If they could test infants, and give them the support they need immediately, how amazing it would be for that person. They wouldn’t have to suffer from not knowing that they have autism.�

Rates of autism diagnoses in children are rising, according to the Centers for Disease Control and Prevention. In 2020, about one in every 36 children was diagnosed by age 8—up from one in 44 in 2018. The trend is likely due in part to increases in awareness and testing.

At the same time, acceptance of autism is also increasing. “In my view, autism doesn’t have to be a strength or a deficit,� SPARK participant tells Sarris. “It’s just a thing I have, a natural variation.�

The term ‘neurodiversity’ was coined in the 1990s by a sociologist living with autism. Neurodiverse individuals, especially those with autism, may struggle to act in a way that suppresses or “masks� behaviors that come naturally to them but fall outside social norms. Masking can be uncomfortable, stressful, and exhausting. It often happens subconsciously, especially among those who are unaware they have autism.

Wigler and Iossifov’s work is made possible by thousands of volunteer families who support autism genetics research through the Simons Foundation. Video: SPARK

Research has shown that autism may be severely underdiagnosed in adults. ASD wasn’t even listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM) psychiatric handbook until 1980. Women and people of color tend to be diagnosed later than white males, giving them fewer opportunities for intervention and therapy. A study from 2022 suggests that nearly .

CSHL research stands to bring that percentage down. Iossifov and Wigler’s work in identifying and categorizing genetic markers of autism has already allowed for more precise diagnoses. Today, they continue to build upon science and society’s growing knowledge of autism. In effect, they’re teaching us not only about the condition—but also about ourselves.

“I think about how much of my life was wasted on masking and not being who I am, and not really knowing who I am,� Juricich says. “If I had known and I had gotten support when I was younger, things would have been so much easier.�

In time, Wigler and Iossifov’s efforts should help more people with autism get the support they may need when they need it most.

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It is with great sadness that we share with the Â鶹´«Ã½Ó³»­ (CSHL) community the passing of Jim Simons, an Honorary Trustee and one of the most significant supporters of and donors to this institution. Jim was an award-winning mathematician, a legend in quantitative investing, and an inspired and generous philanthropist.

Jim chaired the math department at nearby Stony Brook University in New York, and the mathematical breakthroughs he made during his time there are now instrumental to fields such as string theory, topology, and condensed matter physics.

In 1978, Jim founded what would become , a hedge fund that pioneered quantitative trading and became one of the most profitable investment firms in history. With his wife, Marilyn, Chair of the CSHL Board of Trustees, he then turned his focus to making a difference in the world through the , , , and other philanthropic efforts. Their support of CSHL has been unparalleled, transforming both our research and education programs. They provided a founding gift for our Simons Center for Quantitative Biology and sponsored research on autism and cancer. Their lead gifts to our endowment and research infrastructure have transformed this institution.

Jim was genuinely interested in research; he was insightful and had a quick wit. He will be missed by all. On behalf of the Board of Trustees, the faculty, and our staff, I send our deepest condolences to Marilyn and the entire Simons family.

— Bruce Stillman, Ph.D., President

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This year, more than 66,000 people in the U.S. will be diagnosed with pancreatic cancer. That includes about 3,600 New Yorkers. Here on Long Island, Â鶹´«Ã½Ó³»­ (CSHL) has already made great progress in the fight against this deadly disease. But with more than 51,000 people expected to die from pancreatic cancer this year (2,800 in New York), the need for new diagnostic and therapeutic approaches remains urgent.

To help address this need, New York State has announced $15 million in funding for a new Pancreatic Cancer Center of Excellence at CSHL. The Center is part of CSHL’s Foundations for the Future expansion project.

“New York State is leading on innovation in the healthcare space, and this funding will advance research to better understand pancreatic cancer—one of the most devastating forms of cancer,� said . The governor recently visited CSHL for a closer look at our ongoing expansion. Here, she met with CSHL President & CEO Bruce Stillman and CSHL Chair Marilyn Simons.

Take an aerial tour of the construction site at the heart of CSHL’s Foundations for the Future expansion. Hear more from Governor Hochul as she meets with CSHL President & CEO Bruce Stillman to discuss the project.

“New York State’s commitment offers a catalyst to mobilize further private investment in pancreatic cancer research at CSHL,� said Simons. “On a personal note, my father was diagnosed with pancreatic cancer when he was 75. He went to the doctor, asked for an exploratory operation, and lived another 14 years. But few people are so lucky. Our wonderful scientists at Cold Spring Harbor are working with Northwell Health and the Feinstein Institutes to help more people get access to the latest biomedical advances. On behalf of the CSHL Board of Trustees, I thank the governor for her support of this exciting initiative.�

In related news, CSHL recently extended its affiliation with Northwell Health, the largest healthcare provider in the state. One of the greatest success stories of this collaboration has been the development of pancreatic cancer organoids—living 3D tissue models that allow for disease analysis and drug testing. CSHL Cancer Center Director David Tuveson is leading this critical effort.

Of course, like other deadly diseases, pancreatic cancer knows no state lines or national borders. And Foundations for the Future isn’t just about cutting-edge research happening here in New York. It also aims to enhance CSHL’s capabilities as a hub for science education and international collaboration. The expansion includes a new Conference Center and Collaborative Research Center with more than 100 rooms for visiting scientists. This will allow for more long-term collaborations of the kind that helped put CSHL on the map.

Check out the video above for a bird’s eye view of our massive expansion project.

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On May 5, the Â鶹´«Ã½Ó³»­ (CSHL) School of Biological Sciences (SBS) celebrated its 21st commencement ceremony. The SBS conferred Doctor of Philosophy degrees on 11 graduates. The School also awarded neurobiologist Cori Bargmann, Ph.D. an honorary Doctor of Science degree.

“For over 130 years, CSHL has remained true to its mission of educating at all levels,� says Director of Graduate Studies Zachary Lippman. “The many experiences these 11 individuals have had here, within and beyond science, will give them comfort and confidence to rise to the level of their greatest potential.�

Honorary degree recipient Cori Bargmann’s research focuses on the roundworm C. elegans. Her work explores C. elegans genetics and the neural pathways controlling behavior. She is the Torsten N. Wiesel Professor and Vice President for Academic Affairs at Rockefeller University and a recipient of the Kavli Prize in Neuroscience and the Breakthrough Prize in Life Sciences. From 2013-14, Bargmann co-chaired the advisory group to the NIH Director for President Obama’s BRAIN Initiative.

This year’s Winship Herr Award for Excellence in Teaching went to Â鶹´«Ã½Ó³»­ Assistant Professor and 2016 SBS alum Arkarup Banerjee. The annual award is named for the graduate school’s founding dean. Its recipient is chosen by first-year students.

This year marks the School of Biological Sciences’ 25th anniversary. Since its founding in 1999, the SBS has enrolled 206 students and conferred 156 doctoral degrees. The Class of 2024 joins a distinguished group of alumni. Their achievements include many prestigious fellowships and awards as well as over 500 publications. To date, 48 SBS graduates have secured faculty positions at leading academic institutions around the world. Graduates have also moved on to influential roles across the private sector.

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DNA is the great uniter. It’s in all of us. Because genetics is so fundamental to our lives, genetics education should be available to everyone. That’s the founding principle of Â鶹´«Ã½Ó³»­â€™s (CSHL’s) .

On April 25, DNA Day, community leaders from across New York came together in Brooklyn at . There, they celebrated the great strides CSHL has made in advancing science, technology, engineering, and mathematics (STEM) education and career opportunities.

DNA Learning Center NYC occupies a renovated 17,500-square-foot space at the CUNY City Tech campus in Downtown Brooklyn. The Center has six teaching labs with state-of-the-art equipment, two bioinformatics computer labs, a lunchroom, and exhibit space.

One notable Brooklyn native in attendance was U.S. Senator Chuck Schumer. “To take the world-class expertise that exists at the lab and then share it with the next generation of young STEM students who want to learn more about how the world works at a basic molecular level—that’s noble and that’s applauding,� said Sen. Schumer. “And that’s what you’re doing here.�

The DNA Learning Center is renowned for its hands-on teaching method, which helps make genetics accessible for all. CSHL Board of Trustees Vice Chair Casey Cogut echoed that point in kicking off the evening’s ceremony. “W±ð’re here to celebrate the DNA Learning Center’s ongoing commitment to delivering an exceptional scientific learning experience to every visitor—especially those students who may not otherwise have access,â€� said Cogut.

Check out the video above to join in on the celebration and get an inside look at DNA Learning Center NYC.

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The Â鶹´«Ã½Ó³»­ (CSHL) School of Biological Sciences has awarded an honorary Doctor of Science degree to neuroscientist and geneticist Cori Bargmann, Ph.D. She was honored for her work in C. elegans genetics and the neural pathways controlling behavior, including pathogen response and odor recognition, and for her commitment to education. Bargmann is currently the Torsten N. Wiesel Professor and Vice President for Academic Affairs at Rockefeller University.

Bargmann graduated from the University of Georgia and received her Ph.D. from MIT, where she studied the neu/HER2 oncogene with Bob Weinberg. Her work on the neurobiology and genetics of behavior began during a postdoctoral fellowship with Bob Horvitz at MIT. She was a faculty member at the University of California, San Francisco (1991-2004) and has been the Torsten N. Wiesel Professor at Rockefeller University since 2004. Her work has addressed the relationships between genes, circuits, and behaviors in C. elegans, including the basis of odor recognition and odor preference, the circuits and neuromodulatory systems that regulate innate behaviors, the genetics of natural behavioral variation, and behavioral responses to pathogens.

Among other honors, she is a member of the National Academy of Sciences and the National Academy of Medicine and has received the Kavli Prize in Neuroscience and the Breakthrough Prize in Life Sciences. In 2013-2014, she and Bill Newsome co-chaired the advisory group to the NIH Director for President Obama’s BRAIN Initiative. In 2016, she became the first Head of Science at a new philanthropy, the Chan Zuckerberg Initiative, a position she held until 2022.

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The Â鶹´«Ã½Ó³»­ (CSHL) School of Biological Sciences (SBS) takes an innovative approach to advanced science education. Graduates of the doctoral program go on to pursue diverse careers. This year, the SBS awarded 11 Ph.D. degrees. Here, members of the class of 2024 reflect on their time and experiences at CSHL.

Salomé Carcy

Paris Descartes University
École normale supérieure
Annette Kade Fellow
Entering Class of 2020
Thesis: “How human and murine T cells meet their fate: cross-species comparison of conventional and innate T cells�

A scientific journey is often filled with serendipity. The beauty of science is, for many of us, to end up in unforeseen places, may it be in our careers or scientific projects.Halfway through medical school training in France, I came to CSHL as a visiting student in Prof. Fearon’s laboratory. I was charmed by this small community where scientists felt unusually approachable, students and investigators alike. As a matter of fact, interacting with clinician-scientists Prof. Fearon and Dr. Janowitz inspired me to do a Ph.D. In addition, CSHL has a unique community where scientists and non-scientists get together, may it be for a little Sunday bike ride, or weekly frisbee games, creating an enjoyable working place. Hence, I later joined Dr. Hannah Meyer’s laboratory during my graduate studies to investigate the regulation of T cell development in the human thymus, a project that couldn’t align better to my scientific interests. Under her guidance, I acquired both wet and dry lab skills, extended my immunology knowledge, trained my critical thinking, and presented at international conferences. There is still much I have yet to learn, but I believe my experience in the Meyer lab and at CSHL taught me different aspects of how to be a scientist, from generating hypotheses to designing robust experiments and sharing your observations with the scientific community. Overall, my serendipitous passage through CSHL was an invaluable opportunity to meet inspiring scientists, from lab technicians to investigators, from whom I learned tremendously.

In retrospect, the most important lesson I will remember from Â鶹´«Ã½Ó³»­ is that “true science teaches, above all, to doubt and to be ignorantâ€� (Miguel de Unamuno).

King Hei (Teri) Cheng

University of Edinburgh
Robert and Teresa Lindsay Fellow
Entering Class of 2018
Thesis: “Transcription-replication conflict resolution by nuclear RNAi�

I learned about Â鶹´«Ã½Ó³»­ and its contributions to molecular biology during my studies in Edinburgh. Upon arriving at Grace Auditorium on the eve of beginning my Ph.D. program, I was struck with awe by the DNA helix model illuminating from inside, a feeling that I can still recall vividly to this day. Though I was determined to pursue a Ph.D., I couldn’t have fathomed the profound impact CSHL would have on both my personal and scientific development. The unique environment of CSHL aside, it’s the brilliant scientists that I get to work and become friends with that I treasure the most.

I would like to thank my mentor, Rob Martienssen, for providing not only advice and support, but also the freedom to explore challenging scientific inquiries. Working with the wonderful people in the Martienssen lab has been a privilege beyond measure. The countless insightful scientific exchanges and casual conversations have enriched my academic pursuits and shaped my intellectual growth. I must also thank my family and friends who have been supportive throughout. I am grateful to CSHL for providing this experience, and as I transition to the next phase of my career, I will treasure the fond memories created during my time here.

Danielle Hunter Ciren

Queen’s University
Robert and Teresa Lindsay Fellow
NSERC Scholar
Entering Class of 2018
Thesis: “Decoding cis-regulatory control and evolution of conserved and divergent phenotypes in plants�

I am grateful for the past five years of my life spent in New York. While Ph.D. research can be stressful at times, it is definitely never boring at Cold Spring Harbor. I had the opportunity to explore many different fields of biology, including those outside of my comfort zone, and grew as a scientist. I am very grateful to my thesis advisor, Zach Lippman, for his reliable mentorship and guidance, especially during the pandemic. I am grateful to the class of 2018, as well as past and present Lippman lab members, who made the lab a fun place to learn and work, and who I know will be good friends for the rest of my life. I will look back fondly on many experiences, including volleyball games, raft races, lab symposiums, conferences, and all of the time spent exploring New York with friends. I am excited to apply everything I’ve learned at Â鶹´«Ã½Ó³»­ in my future career as a biologist.

Marie Dussauze

University of Versailles Saint Quentin-en-Yvelines
École normale supérieure Paris-Saclay
Florence Gould Fellow
Annette Kade Fellow
Entering Class of 2018
Thesis: “Sensorimotor neural representations in the olfactory cortex�

My passion for science was the driving force behind my decision to join the Â鶹´«Ã½Ó³»­ graduate program. I could think of no better way to satisfy my scientific curiosity than to join a community devoted to science that prides itself on its collaborative and multidisciplinary identity. Like many starting graduate students, I had a limited view of what my time at CSHL would bring. Above learning what it means to be an accomplished scientist, I have developed my own independent and inquisitive mind. More importantly, I have had the chance to be part of a cohort full of bright and colorful characters whom I am proud to call my friends. It comes as no surprise when I say that my Ph.D. experience was not “a long and quiet river.â€� There was some turbulence along the way, often coming at the least expected of times. My thesis work focused on how expectations shape one’s reality and how violating these expectations creates opportunities for flexible responses and learning. This principle could be equally well applied to my experience as a trainee.

I am grateful for all the scientific and personal support I have received throughout my Ph.D. I would like to thank my lab mentors, Florin Albeanu and Priyanka Gupta, for allowing me to work on a challenging project and for our many discussions over the years. I also want to thank my colleagues for sharing their knowledge and dedication. Finally, I want to thank my family and friends (“my family away from home�) for their steady support and encouragement throughout this journey.

Yuzhao Hu

Tsinghua University
George A. and Marjorie H. Anderson Fellow
Entering Class of 2017
Thesis: “Role of cryptochromes in chromatin remodeling and DNA damage repair�

I would like to express my heartfelt gratitude to the Â鶹´«Ã½Ó³»­ School of Biological Sciences for granting me the invaluable opportunity to pursue my Ph.D. degree. Over the span of six enriching years at CSHL, I have not only expanded my academic knowledge, but also matured significantly in my personal and professional life. Foremost, I am immensely grateful for the profound lessons I have learned in scientific research during my graduate studies. These transformative years have empowered me to evolve from a novice daunted by experimental setbacks to a confident scientist capable of overcoming any scientific challenges in pursuit of answers. I extend my deepest appreciation to my Ph.D. mentor, Professor Ullas Pedmale, whose unwavering guidance and unwavering support have been instrumental in shaping my research journey. Additionally, I am indebted to the vibrant CSHL community, particularly my colleagues at the Delbruck building, whose camaraderie and generosity have been a constant source of encouragement.

As I reflect on my time at CSHL, I am filled with gratitude for the indelible impact it has had on my life. The memories forged and the experiences gained will forever hold a special place in my heart. I am deeply thankful for the opportunity to be a part of this esteemed institution and for the lifelong friendships and mentorships that have enriched my journey.

Dennis Mann Singh Maharjan

Caldwell University
Brandeis University
John and Amy Phelan Scholar
Entering Class of 2017
Thesis: “Cell-type specific regulation of auditory decision-making�

Pursuing my graduate education at the School of Biological Sciences was motivated by my eagerness to be part of a vibrant community filled with talented and inspiring individuals. My experience at CSHL has indeed exceeded my expectations. I have had the privilege of interacting with remarkable scholars from various fields, creating lifelong friendships that have greatly enriched my journey here.

I was fortunate to conduct my Ph.D. research in the lab of Tony Zador, investigating the role of striatal neurons in auditory decision-making behavior. I am profoundly grateful for his mentorship and the autonomy he granted me in shaping my experiments. In his lab, and throughout the Marks building, I encountered exceptionally bright and generous scientists who have expanded my intellectual perspectives and significantly influenced my career trajectory. Tony’s open approach to science, along with the school’s supportive and flexible framework, have empowered me to carve out my own scientific path. This experience has instilled in me the values of creativity, thoroughness, and perseverance in scientific inquiry, contributing immensely to my development as a scientist and academic.

Outside of academia, I have felt embraced by the warm and welcoming CSHL community and the broader Huntington community. As I near the completion of my time at this institution, I look back with deep appreciation and fond memories of playing beach volleyball in the pouring rain, enjoying jam sessions in Blackford Bar, assembling microscopes in the middle of the night, and so much more. To everyone I have crossed paths with during my time at CSHL, I extend my heartfelt gratitude.

Ziyi Mo

New York University Abu Dhabi
Gladys and Roland Harriman Foundation Fellow
Entering Class of 2018
Thesis: “Scalable and robust deep-learning methods power evolutionary-genetic studies of biobank-scale population genomic data�

At the outset of my Ph.D. at CSHL, I had a broad interest in computational research in the biomedical sciences. The graduate program provided ample opportunities and great support for me to explore a wide range of topics. Reflecting on my time at CSHL, I’m grateful for the professional growth it has fostered. I have been fortunate to collaborate with brilliant minds from across and beyond the Lab. I would like to thank my advisor Adam Siepel, my mentors, and colleagues for their guidance and support, as well as my family and friends for their unwavering encouragement.

Ziqi Amber Tang

University of North Carolina at Chapel Hill
Elisabeth Sloan Livingston Fellow
Entering Class of 2019
Thesis: “Exploring the representational power of genomic deep learning models�

When I first arrived at Cold Spring Harbor, I had many uncertainties about the path ahead, from research topics to life as a graduate student. However, my time at CSHL has been most valuable. The graduate program’s unique opportunities allowed me to delve into a research area I had not previously explored. Through all the conferences and courses on campus, I met friends and collaborators who enriched my scientific perspective. And among people in my lab, I made friends that shared countless joyful moments with me. It’s all these experiences combined that provided me with a Ph.D. journey that benefits me beyond research and into all aspects of life.

I would like to thank my mentor, Peter Koo, for not just the scientific mentorship, but also the consistent support throughout my graduate study. He has inspired me to grow as a scientist, as well as a person. My thanks also to the faculty and staff members of the School of Biological Sciences, for always caring and helping when I needed it most. To the great people that I met here, for making my experience special. And lastly, special thanks to my friends and family for always being by my side, offering support and advice.

Shushan Toneyan

University of Oxford
Robert and Teresa Lindsay Fellow
Crick-Clay Fellow
Entering Class of 2019
Thesis: “Evaluating and interpreting genomic insights from sequence-based deep learning for regulatory genomics�

I would like to thank my classmates and friends at CSHL for saving me from failing the program countless times, listening to all of my rants about life, the universe, and everything, and never letting me walk for longer than 2 minutes (at least not without a fight). I would also like to thank my Ph.D. advisor for being one of those friends, in addition to being an amazing mentor and sharing his well measured excitement about deep learning and its applications in genomics.One of the reasons why I chose to join the graduate program at CSHL was the warmth and genuine dedication to seeing students succeed that I felt at the dean’s office (despite Alex Gann’s strange way about expressing it). I believe this is a unique place to do science for many reasons, including the personal touch that the smaller community of students gets from the school, so I would also like to extend my sincere gratitude to the School for giving me the chance to join the program.

I would like to thank my family for encouraging me to travel great distances for better education while making it their absolute priority to get me to travel home as soon and for as long as possible. Finally, I would like to thank my Cedric for being my anchor, traveling across the ocean many times to see me and supporting me through the pain (sometimes through shipments of chocolate), and sharing the happy moments throughout this degree.

Jonathan M. Werner

University of Maryland Baltimore County
NSF Graduate Research Fellow
Entering Class of 2018
Thesis: “Transcriptomic approaches for investigating developmental lineage�

It is an immense privilege to have been given the opportunity for graduate study at CSHL; one that I do not take lightly and view as arising largely from the efforts of those who, for whichever reason, decided I was worth a moment of their time and invested into my future. I stand where I am today due to the actions of a large collection of friends, family, and colleagues, to all of whom I sincerely say thank you.I would like to thank my research advisor, Jesse Gillis, for his time and thoughts over the years; one of the most rewarding aspects of my time at CSHL has been the continual intellectual challenges I’ve faced working in your lab, not just in my own research, but in thinking about many areas of science. My experience in the Gillis lab was greatly enhanced thanks to my fellow lab members, whom I thank for all the conversations over the years. I’d particularly like to acknowledge Sara Ballouz, Maggie Crow, and Stephan Fischer for their patience in being bothered with questions and their willingness to help me get started in the lab.

To the staff of the CSHL School of Biological Sciences, the support we receive from the School is unparalleled in my opinion, and I am very grateful to have benefited from the care and dedication you all bring to CSHL. And to the Class of 2018, you inspire me as friends and colleagues, and I look forward to seeing all of your future successes.

Cole Gregory Wunderlich

Purdue University
National Institutes of Health Trainee
Entering Class of 2017
Thesis: “Quantifying transposable element expression in single-cell RNA sequencing data�

It has truly been a privilege to study at Â鶹´«Ã½Ó³»­. A particular highlight of my time here was the free access to CSHL’s Meetings & Courses. Having unfettered access to a revolving door of the world’s top scientists was an incredible learning experience not to be found anywhere else. I will miss the beautiful campus, the intellectually stimulating environment, its collaborative and interdisciplinary spirit, and, above all else, the people.

I would like to thank my advisor, Molly Gale Hammell, for her tireless support and the opportunity to work in her lab. I would also like to thank Adam Siepel, Saket Navlakha, and Dan Levy for the additional support and guidance they provided.

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Women’s health is often talked about in terms of major, life-altering events like pregnancy and menopause. A new study from Â鶹´«Ã½Ó³»­ (CSHL) underscores the importance of considering everyday occurrences’ impact on women’s well-being.

CSHL researchers have made a surprising discovery involving urinary tract infections (UTIs). The scientists found that UTIs in mice can provoke a bodily response that results in structural changes in breast tissue. Remarkably, these changes are reversible once the infections are resolved.

The study was led by Â鶹´«Ã½Ó³»­ Associate Professor Camila dos Santos, graduate students Samantha Henry and Steven Lewis, and former postdoc Samantha Cyrill. Their findings show how disturbances far across the body can influence breast health.

More than half of all women will experience at least one UTI in their lifetime. So, the potential ramifications here are substantial. “Recurrent and hard-to-treat UTIs could provide opportunities for abnormal breast cell growth,� dos Santos says.

Cyrill notes that the breast changes that the team observed in mice with UTIs “were not directly caused by the infection itself. Rather, they were caused by the body’s responses.� The responses were mainly driven by a molecule called TIMP1. “This molecule mediated increased collagen deposits and milk duct enlargement in breast tissue,� Henry explains. Such changes are also observed during pregnancy.

Hormonal changes during pregnancy and menopause are known factors that can influence breast cancer risk. This new research suggests doctors and scientists need to think even more broadly about breast health. “It opened up a new research program in our lab,� dos Santos says. They’re now looking at how other changes women go through in their lifetimes might unexpectedly influence breast tissue.

“More research is needed to determine if the tissue changes we observed contribute to tumor growth and metastasis,� Lewis notes. It’s also not yet clear if UTIs and other infections could be associated with breast cancer risk in humans. Clarifying these relationships would help doctors provide more precise recommendations related to breast cancer risk, screening, and prevention. Moreover, it would empower women to become stronger advocates for their own health.

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The historic agreement aims to translate basic bioscience into a clinical setting, providing cancer patients with greater access to personalized healthcare.

NEW YORK, NY — Leaders from two of New York’s preeminent bioscience and healthcare institutions came together at Carnegie Hall to acknowledge the signing of an update to their affiliation agreement initiated in 2015. The Â鶹´«Ã½Ó³»­-Northwell Health affiliation aims to bring cutting-edge biology research to the bedside of tens of thousands of cancer patients in diverse communities across the state. The agreement ensures continued collaboration and support for ongoing clinical trials, among other advanced biotechnology initiatives.

“The alliance between Â鶹´«Ã½Ó³»­ (CSHL) and Northwell Health brings transformative bioscience research into the clinic,â€� says CSHL President & CEO Bruce Stillman. “As New York’s largest healthcare provider, the Northwell Health system serves a remarkably diverse patient population. This agreement will provide patient communities with greater access to cutting-edge biomedical technology, allowing for more precise diagnoses and treatments, and ultimately facilitating new breakthroughs in cancer care.â€�

“Reaffirming our exclusive strategic affiliation with Â鶹´«Ã½Ó³»­ and Northwell Health’s 400 physician-researchers marks a pivotal moment in accelerating our efforts to advance cancer research and revolutionize treatment in the fight against cancer,â€� said , president and CEO of Northwell Health. “W±ð are building on nearly 10 years of shared vision and collaboration, merging cutting-edge discovery science with novel clinical trials to drive therapeutic applications for the patients we serve across the New York metropolitan area and beyond.â€�

The CSHL-Northwell Health affiliation aims to enhance biology and cancer research at CSHL’s NCI-designated Cancer Center and more than 60 research labs, as well as the , the home of research at Northwell Health with 50 research labs and 5,000 researchers and staff systemwide. The affiliation also seeks to translate basic research into clinical applications, provide access to diverse patient populations, and train the next generation of scientist-clinicians. Over the past ten years, the affiliation has funded 82 research projects, resulting in more than 100 peer-reviewed publications. Through this integration, CSHL appointed 13 adjunct professors and trained 24 medical students and 27 residents and fellows. Together, they’ve initiated three clinical trials in various stages.

One of the affiliation’s greatest collaborations to date has been the development of more than 200 cancer organoid models through its organoid facility on Long Island. These living three-dimensional tissue models are derived from patient tumor cells and cultivated outside the body, in a clinical laboratory, for disease analysis and drug testing. This revolutionary technology in Phase-II clinical trials enables clinicians to predict favorable patient responses to new drug combinations. The CSHL-Northwell Health affiliation has also led to significant discoveries in pancreatic cancer, leukemia, glioblastoma, and COVID-19 research.

Northwell Health and the , with its 400 physicians and researchers, have significantly expanded their oncology footprint since the initial CSHL affiliation was announced in 2015. Over the past three years, the Northwell Health Cancer Institute has invested nearly $550 million to open and expand cancer treatment centers throughout Long Island and the boroughs. Major initiatives include the $32 million, 70,000-square-foot outpatient Northwell Cancer Institute at Rego Park, Queens, which serves one of the most diverse communities in the country; and the $43 million, 40,000-square-foot Florina Cancer Center in Staten Island, which provides adult and pediatric care. In addition, the health system is building a new 200,000-square-foot medical pavilion adjacent to Northwell Lenox Hill Hospital in Manhattan, which will be anchored by an innovative cancer center. Northwell Health treats more than 19,000 people with cancer through its integrated health system and 11 cancer institutes.

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Hazen Tower is the centerpiece of the courtyard linking CSHL’s Beckman Neuroscience Building and Dolan Hall. At its peak hangs a bronze bell weighing nearly a ton. Above the bell, four letters are inscribed in gold: “a� for adenine, “c� for cytosine, “t� for tyrosine, and “g� for guanine. They’re the building blocks of DNA, the basis of life as we know it. An appropriately shaped helical staircase rises from the ground between the tower’s four brick columns. It winds its way up to a circular platform offering an unobstructed view of the inner harbor.

You don’t have to visit CSHL to hear Hazen ring. Listen to any episode of At the Lab, and you’ll catch the bell in our three-minute podcast’s opening theme.

“One of the things I love about working at Â鶹´«Ã½Ó³»­ is the environment,â€� Â鶹´«Ã½Ó³»­ Assistant Professor Lucas Cheadle says. “Hazen Tower is one of the first landmarks you see from across the harbor. Its spiral staircase is a clear homage to the genetic code that lies within each individual on campus. Performing basic biology research in an environment that is so intertwined with nature creates a synergy that helps propel our work forward.”

Hazen Tower was named in honor of former CSHL Trustee Lita Annenberg Hazen. The late philanthropist was a lifelong supporter of science. In the late ’80s, she became a founding donor of CSHL’s then-budding Neuroscience Program. Her support was key to the construction of the Beckman Neuroscience Laboratory, dedicated in 1991 alongside Dolan Hall and Hazen Tower.

Today, Beckman houses the labs of five CSHL researchers. Professor & HHMI Investigator Leemor Joshua-Tor studies the molecular machinery our cells depend on to function normally. Professor Hiro Furukawa explores how the brain regulates signals passed between neurons. Associate Professor Jessica Tollkuhn studies sex hormones’ roles in the brain. Assistant Professor Gabrielle Pouchelon focuses on the origins of neurodevelopmental disorders. And Assistant Professor Lucas Cheadle investigates how immune cells called microglia interact with the brain. (In fact, you can catch him talking about this topic as part of our Cocktails & Chromosomes series at Industry bar in Huntington, NY.)

As for Lita Annenberg Hazen, the biomedical philanthropist passed away in 1995. However, her contributions have helped ensure the Laboratory’s place at the forefront of neuroscience research. Today, her legacy remains every bit as strong as the tower that bears her name.

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The world around us is constantly changing. And with it, so too do the sights we encounter at any given moment. Yet we instantly adapt to the differences. How do we keep up? How do our brains navigate our continuously changing sensory environment? New Â鶹´«Ã½Ó³»­ (CSHL) Assistant Professor David Klindt aims to answer this question using the power of machine learning. The hope is that making sense of our senses will help Klindt and his colleagues in the CSHL neuroAI program usher in a new generation of more sensitive and sensible artificial intelligence models.

“AI models sometimes break down in cases where biology doesn’t,� Klindt explains. “There’s a lot of expertise in motor skills at CSHL as well as a group of young scientists like myself focused on perceptual skills. I’m excited to work with the community to bring these themes together and help build up the neuroAI initiative as part of CSHL’s new institutional expansion.�

Klindt comes to CSHL from Stanford University, where he did postdoctoral research. Previously, he got his Ph.D. from the University of Tübingen in Germany and went on to work as a machine learning research scientist at Meta. He joins CSHL at a time of tremendous growth. The lab’s neuroAI program is poised for major expansion with the launch of CSHL’s new Foundations for the Future project.

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Â鶹´«Ã½Ó³»­ (CSHL) Professor and Cancer Center Director David Tuveson has been elected to the American Academy of Arts and Sciences. He is one of 250 new members elected to the venerable institution in 2024.

Tuveson is a pioneer in cancer research. His groundbreaking work with cancer organoids—miniature versions of tumors—led to the first mouse models for two types of pancreatic cancer. In 2020, he co-founded the CSHL organoid facility, which stores and develops organoids for cancer research at institutions around the world. Most recently, Tuveson co-founded the American Association for Cancer Research Cancer Centers Alliance. The initiative fosters collaboration and innovation between the nation’s NCI-designated Cancer Centers to advance lifesaving scientific discoveries.

“On behalf of Â鶹´«Ã½Ó³»­â€™s Board of Trustees, faculty, students, and staff, I congratulate David Tuveson on his election to the ,â€� said CSHL President and CEO Bruce Stillman. “This is a very well-deserved honor. Biomedical science has benefited greatly from David’s dedication to pancreatic cancer research and his leadership of the CSHL Cancer Center.â€�

Tuveson joins six other current CSHL faculty members who have been elected to the Academy: President and CEO Bruce Stillman, Director of Research Leemor Joshua-Tor, and Professors Michael Wigler, David Spector, Adrian Krainer, and Rob Martienssen.

“W±ð honor these artists, scholars, scientists, and leaders in the public, non-profit, and private sectors for their accomplishments and for the curiosity, creativity, and courage required to reach new heights,â€� said Academy President David Oxtoby. “W±ð invite these exceptional individuals to join in the Academy’s work to address serious challenges and advance the common good.â€�

Founded in 1780 in the midst of revolution—by John Adams, John Hancock, and others—the Academy’s membership and work have changed greatly over the centuries while remaining faithful to a charter founded on ideals that celebrate the life of the mind, the importance of knowledge, and the belief that the arts and sciences are “necessary to the interest, honor, dignity, and happiness of a free, independent, and virtuous people.� Distinguished members include Benjamin Franklin, Charles Darwin, Albert Einstein, and Jennifer Doudna.

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Travel back in time to any year in Â鶹´«Ã½Ó³»­ (CSHL) Meetings & Courses history. You’d find yourself rubbing elbows with Nobel laureates, groundbreaking researchers, and promising students from a wide range of scientific disciplines. Return to the summer of 1929 and you might encounter two young scientists relaxing in the sun on CSHL’s Blackford lawn.

Ruth Patrick was here studying the relationship between flowering plants and soil composition. Patrick’s companion, Charles Hodge IV, was studying firefly and grasshopper metabolisms. The two young researchers were not only starting out on what would become long and accomplished careers in the life sciences. They were also taking the first steps toward what would become an equally impressive 53-year marriage.

Their son Charles Hodge V recently spoke with CSHL about his parents’ relationship and legacy.

A 2004 documentary looks back on the groundbreaking achievements of environmental science pioneer Dr. Ruth Patrick. Video: PBS

“My parents were devoted to each other,� Hodge says. “They were also passionate about their work. My father was an excellent teacher, instructing generations of scientists at Temple University. And my mother pioneered an entirely new field of research in a time when women simply didn’t have the same opportunities as men.�

Ruth Patrick’s groundbreaking 1948 survey of Pennsylvania’s Conestoga Creek laid the foundation for the fields known today as environmental science and environmental management. These interdisciplinary areas address humanity’s impact on Earth’s ecosystems and the complex issues that arise as a result.

Patrick was especially concerned with water pollution. Her work led to the 1949 “.� She famously found that “the presence of different species often pointed to different types of water.� Today, this idea seems almost intuitive. But Patrick’s studies were the first to link biodiversity and water quality.

It’s no coincidence Patrick’s core thoughts on these issues came to her on the shores of Cold Spring Harbor. Our campus is part of Long Island’s largest National Wildlife Refuge. The 3,200-acre watershed is home to about 25 different species of waterfowl and once supplied up to 90% of New York’s oyster harvest.

CSHL’s 1929 Annual Report (PDF) offers an early glimpse into Patrick’s research:

Miss Ruth Patrick carried out a series of soil tests for hydrogen-ion in Plant communities that had been carefully studied floristically. Her suggestive findings may furnish material for immediate publication, or may be held for additional data.�

According to her son, Patrick considered herself a “steward of the environment.� She would often credit her summer at CSHL with giving her a world-class biology education. “My mother always spoke about the value of summer courses and their importance to her work,� Hodge says. He also points out that in noting Patrick’s “suggestive findings,� CSHL was among the first institutions to recognize her work’s potential.

Patrick would go on to advise five U.S. presidents on water quality and pollution. Congress would call on her to help write the 1972 . In 1996, President . She joined an honor roll of recipients including CSHL’s Barbara McClintock—the first woman to receive the award.

Charles Hodge V and his family had the opportunity to walk in his parents’ footsteps during a recent visit to CSHL. To their delight, they found that in some ways, the lab still looks much like it does in treasured family photos. The lawn where Ruth and Charles IV gathered with friends is still here. The harbor view remains as pristine as ever.

“It was a very special feeling coming to CSHL and seeing the place where my parents’ union began,� Hodge recalls, “a wonderful experience for my family and me.�

For over 130 years, CSHL has been a breeding ground for ideas with the power to change the world. Of course, these ideas don’t just emerge spontaneously out of coursework. They come from people—from families—exchanging life lessons with one another across generational and cultural divides.

“Generations of scientists from around the world have become a part of our vibrant intellectual community,� CSHL President and CEO Bruce Stillman says. “Their exchanges and experiences at CSHL have shaped society and strengthened science worldwide. And it is always a pleasure seeing the Laboratory bring people together who meet for the first time here, end up married, and both have highly successful careers in science.�

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Seeing is believing. But why and how do these perceptions occur? A new addition to the Â鶹´«Ã½Ó³»­ (CSHL) research roster will help answer these critical questions. Â鶹´«Ã½Ó³»­ is excited to welcome new Fellow Mitra Javadzadeh to the Laboratory’s neuroscience faculty.

Javadzadeh studies the neural computations behind visual perception. Her CSHL lab will focus on how the brain switches between concrete and abstract ways of processing visual information. This work could offer new insight into the mechanics underlying perception itself.

“I am excited to be joining the vibrant scientific community at CSHL,� Javadzadeh says. “My lab is interested in understanding visual perception and the strikingly flexible way in which we process the visual world. I am particularly looking forward to stimulating discussions with the Laboratory’s diverse neuroscience faculty.�

Javadzadeh earned her Ph.D. in neuroscience at University College London’s (UCL) Sainsbury Wellcome Center in 2021. Before coming to CSHL, she worked at UCL as a research fellow. Javadzadeh also brings leadership experience to CSHL. She was a 2021 mentor with the .

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Pharmaceutical companies need to make drugs quickly. They need to produce chemical compounds in large amounts. And they need these compounds to have as few harmful side effects as possible. But in reality, many chemical reactions are imperfect and inefficient. Click chemistry is a revolutionary process that allows scientists to cleanly and quickly uncover more sustainable sources for potential new drugs and other synthetic materials. The term comes from chemicals “clicking� together like LEGO bricks. It was coined by K. Barry Sharpless, a pioneer in the field.

Sharpless isn’t just a two-time Nobel laureate. He was also a mentor to two Â鶹´«Ã½Ó³»­ (CSHL) scientists, Cancer Center Director David Tuveson and Professor John Moses. On March 2, CSHL hosted a symposium celebrating the work of Sharpless and exploring “The Future of Click Chemistry.â€� The event featured the field’s top minds from the U.S., Canada, Europe, and Asia, including Sharpless and Moses. Researchers presented their latest advances, pointing to many exciting new directions for the field. Event sponsor (MEC) announced a $100,000 donation to support click chemistry research in CSHL’s Moses and Tuveson labs. Meanwhile, Sharpless stood approvingly alongside his former apprentices.

CSHL Professor John E. Moses and collaborator two-time Nobel laureate K. Barry Sharpless demonstrate click chemistry in action, synthesizing a helical polymer in a matter of minutes.

From Moses’ perspective, the “future of click chemistryâ€� is largely owed to his mentor’s groundbreaking work. Sharpless’ achievements, he said, “opened the doors to revolutionary advances in science, medicine, and drug discovery. His legacy is a testament to the power of simplicity and precision in science, promising new horizons in healthcare.â€�

It’s a legacy that Professors Tuveson and Moses are excited to uphold and build upon for many years to come.

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When it comes to biology, details matter. If a drug isn’t designed to perfectly hit its target, down to a single atom, it may utterly fail. That’s where structural biologists come in. Â鶹´«Ã½Ó³»­ (CSHL) has one of the world’s leading experts.

CSHL Professor & HHMI Investigator Leemor Joshua-Tor specializes in the use of cryo-electron microscopy (cryo-EM). This Nobel-prize-winning technology flash-freezes biological structures in action. The resulting images enable scientists to look at life at the atomic level. Cryo-EM is one of several shared resources empowering next-generation research at CSHL. So, it’s only right that each year next-gen scientists from across the globe come to CSHL for our .

Founded in 2018 by Justin Kollman and Gabriel Lander, this two-week course has become a hallmark of CSHL’s world-renowned . It covers the theory and practice of interpreting high-resolution single-particle cryo-EM structures. Students get access to state-of-the-art equipment along with hands-on training from instructors like Kollman and Lander. They also attend lectures by the field’s top experts.

Recently, cryo-EM technology enabled CSHL Professors Rob Martienssen and Leemor Joshua-Tor to pinpoint the mechanism that controls epigenetic inheritance in plants.

As for Joshua-Tor, her presence is virtually ubiquitous here on campus. In January, she was named CSHL Director of Research. And the director has some words of wisdom for any course attendee. Quoting the late Francis Crick, she says, “All approaches at a higher level are suspect until confirmed at the molecular level.� These words, she adds, “are the basis for all biology. They are the basis of my life—words I live by.�

Of course, as far as imaging goes, it doesn’t get much more molecular than cryo-EM. “The level of magnification we’re doing would be analogous to standing here on Earth, looking up, and reading a street sign on the Moon,� explains Lander. “It’s incredibly powerful.�

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Plant biology and science education are in Â鶹´«Ã½Ó³»­â€™s (CSHL’s) DNA. Recently, two CSHL plant scientists brought their expertise from the lab to the White House lawn for an event hosted by First Lady Jill Biden.

Since 2022, the has used fun Easter-themed activities to teach kids about science, technology, engineering, and mathematics (STEM), among other topics. This year, CSHL plant scientists Janeen Braynen and Audrey Fahey joined in on the action. Braynen and Fahey participated as ambassadors of the  (ASPB). They led interactive science lessons teaching children about plants and the environment.

“It was so much fun getting kids excited and curious about plants and plant biology!� says Fahey. “STEM outreach and educating the community about plants are crucial,� adds Braynen. “It promotes environmental awareness, highlights plants’ vital roles in our ecosystem, and empowers informed decisions toward sustainability. Such efforts contribute to a more knowledgeable and eco-conscious society.�

Back at CSHL, Braynen and Fahey work in the lab of Adjunct Professor Doreen Ware. Apart from their work with ASPB, Braynen and Fahey also engage in STEM outreach through CSHL. Braynen is co-chair of In-House Education with CSHL’s (WiSE) group. Fahey is an advocate and former Co-Community chair with CSHL’s Diversity Initiative for the Advancement of STEM (DIAS).

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Â鶹´«Ã½Ó³»­ (CSHL) chemists have created a new collection of molecular compounds and begun testing them as potential leads in the search for new drugs. Among these molecules, they found several that show promise for development as antibiotics and cancer therapies. Sounds like a eureka moment? Well, sort of. But it’s more a case of hard chemistry made simple.

The new compounds were synthesized using an efficient new way of linking molecules together, developed in the lab of CSHL Professor John Moses. Moses calls his innovative process Accelerated SuFEx Click Chemistry (ASCC). It’s one of the latest advances in the Nobel-winning field of click chemistry, pioneered by Moses’ mentor K. Barry Sharpless.

Click chemistry quickly snaps together molecules to create complex new structures. This enables drug developers to assemble large numbers of compounds for further exploration. With Accelerated SuFEx, click chemistry can generate more compounds in fewer steps and with higher yields.

“If you can make molecules, you can test them,� Moses explains. “And with this technology, you can make them fast.�

Moses gives a quick primer on click chemistry during a CSHL Cocktails & Chromosomes talk. Stay tuned to the end to see him bring out his mentor, two-time Nobel laureate K. Barry Sharpless.

Moses and his team used ASCC to create more than 150 individual new compounds, including derivatives of complex natural molecules. In the past, it might have taken months to generate and purify such an assortment of molecules. Moses and his team had them ready within days. They then tested these new molecules on cancer cells and drug-resistant strains of bacteria.

In one set of experiments, Joshua Homer, a research investigator in Moses’ lab, synthesized an array of molecules that were similar to an anti-cancer compound called combretastatin A4. Homer found that two of the new molecules could kill cancer cells that typically resist standard chemotherapy. These molecules could someday lead to a solution for difficult-to-treat types of breast and pancreatic cancers.

The researchers also created molecules that resembled an antibiotic called dapsone. They saw that some of these molecules were effective against dapsone-resistant bacteria. Homer says ASCC could help chemists reengineer other complex antibiotics to overcome pathogens’ hardened defenses.

Looking ahead, Moses and his team will continue to use ASCC to explore new horizons of drug discovery and fine-tune their leads into potential drug candidates. Meanwhile, they hope other researchers will also introduce Accelerated SuFEx technology to their own drug discovery platforms. Summing up the advantages of ASCC, Moses says:

“It’s just a way to find function. You can always improve things and optimize. But let’s get there as quick as possible. Hopefully, we can accelerate the whole process.â€�

In other words, presto chango!

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Climate change threatens crops across the globe. But the problem goes far beyond rising temperatures. One major cause for concern is more acidic soil, a product of increasing rainfall. This can result in aluminum toxicity, putting further stress on global agriculture. A new project at Â鶹´«Ã½Ó³»­ (CSHL) seeks to find solutions at the intersection of genomics and plant biology. CSHL Professors Thomas Gingeras and Rob Martienssen have received a $2 million grant from the National Science Foundation (NSF) to tackle aluminum toxicity. Their work may point the way to more resilient crops and stronger food supplies.

“The climate is rapidly transitioning into much harsher crop cultivation conditions,� Gingeras says. “Aluminum toxicity is a significant stress in acidic soils. It damages roots and makes crops more susceptible to drought and mineral deficiency. These effects contribute to serious food insecurity around the world.�

Gingeras leads a team of scientists from the U.S. and Brazil. They aim to uncover connections between gene regulation and aluminum tolerance in crops. The project will also train scientists on new genomic approaches to addressing the effects of climate change. Their training module will supplement CSHL’s .

“Acidic soils are a global agricultural problem worsened by climate change,â€� Martienssen says. “The NSF has given us a great opportunity to build upon our team’s discoveries on aluminum resistance in maize and sorghum, as well as our genomic technologies.â€�

In addition to CSHL, the team includes Andrea Eveland from the Donald Danforth Plant Science Center, Jurandir Magalhaes from Empresa Brasileira de Pesquisa Agropecuária, and the New York Genome Center’s Michael Zody.

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Over 130 years ago, John D. Jones donated land formerly occupied by his family’s whaling company to the Brooklyn Institute of Arts and Sciences. In 1890, the Institute founded the Biological Laboratory at Cold Spring Harbor (a CSHL forerunner) along the harbor’s western shore. Jones Laboratory—named for the man who made it all possible—was built three years later as the centerpiece of this expansion effort.

Jones has been open ever since. Today, it’s the United States’ oldest laboratory still in continuous use. A National Historic Landmark, the humble one-and-a-half-story building looks much the same as it did in the early days of CSHL—on the outside, at least.

In its first decades, the building hosted some of CSHL’s earliest courses on marine biology and genetics. By the mid-1970s, it had been remodeled to accommodate the lab of CSHL’s first neurobiology researcher, Birgit Zipser. Now, the venerable lab houses CSHL Professor & HHMI Investigator Zachary Lippman’s groundbreaking plant genetics research.

“W±ð work in probably the coolest laboratory building in the country,â€� Lippman says.

In the 1890s, Jones contained several research stations, the Biological Laboratory director’s office, and a small library. The interior was completely redesigned in 1975. Gone were the rustic wooden benches and dividers. In their place stood space-age aluminum cubicles. Each was a self-contained neurobiology lab on a vibration-resistant foundation. Forty years later, CSHL renovated Jones again with a little help from the Lippman lab. The shiny metal pods were scrapped. The building now has an open floor plan reminiscent of Jones’ original 19th-century design.

We work in probably the coolest laboratory building in the country.”

CSHL Professor & HHMI Investigator Zachary Lippman

Since his first day there, Lippman has made sure to honor the building’s long history of biological research. His lab has also made significant contributions of its own to Jones’ legacy. These include new insights into tomato evolution and genetic blueprints for two types of groundcherry.

“When we moved into Jones, Zach had pictures of the laboratory’s original staff printed and framed,� Lippman Lab Manager Gina Robitaille says. “These images serve as a nice reminder that science has been happening in this building for over 130 years. It is incredible to think about all the people who were in this building before us. We’re happy and fortunate to have been a part of the renovation process, for how well it turned out, and to have the opportunity to work here.�

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Is this a scene straight out of the latest Star Trek? No, think much more down-to-earth. What we’re seeing here isn’t the Starship Enterprise on fire in the void. It’s a cross-section of precancerous lesions in the pancreas. These mutated cells have a higher risk of turning into cancer than their healthy counterparts. The image above comes to us courtesy of Â鶹´«Ã½Ó³»­â€™s (CSHL’s) Tuveson lab and Microscopy Core Facility.

Like the intrepid explorers in Starfleet, CSHL Professor David Tuveson and his team are pushing the frontiers of pancreatic cancer research. In 2015, the Tuveson lab pioneered the study of pancreatic cancer organoids—tiny lab-grown tumors. This led to the first mouse models for two types of the deadly disease. These innovations have since become invaluable in preclinical pancreatic cancer research. Recently, the team made another fascinating discovery. They found that mucus plays a key role in the progression of certain types of pancreatic tumors. Yes, that mucus.

“Early-stage pancreatic cancer cells regulate mucus production essentially the same way as cells in your nose, eyes, lungs, and even your intestines,� says Claudia Tonelli, a research investigator in the Tuveson lab.

To get a closer look at how these mutated cells use and produce mucus, the Tuveson lab partnered with Jonathan Preall from CSHL’s Single-Cell Biology Facility. They found that regulating mucus production is essential for the growth and survival of certain types of pancreatic cancer. But the discovery is a double-edged sword. Shutting off mucus regulation slows tumor growth, but also drives cancer cells to transform into deadlier, drug-resistant varieties.

Single-cell sequencing and microscopy aren’t going to cure cancer on their own. Yet, they do provide unprecedented insight into the disease. These technologies make it possible to pinpoint cancer-related proteins (above, in red, green, and white), mucin (the stuff mucus is made of, in yellow), and even individual mucus-related RNA (the cyan dots), with striking clarity. And that empowers Tuveson and his team at CSHL to go where no cancer researchers have gone before.

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Farmers have been playing with plant genomics since before the world knew what genes were. Does one strawberry plant produce sweeter fruits? Encourage its growth over less tasty crops. Voilà! Your strawberry crop is now yummier than ever.

Since the turn of the 21st century, Â鶹´«Ã½Ó³»­ (CSHL) breakthroughs have helped revolutionize the world of plant genomics. As a result, society now has a much better understanding of how plants grow and evolve.

In 2000, CSHL Professors Rob Martienssen and W. Richard McCombie were part of an international team that mapped the genome of the flowering plant Arabidopsis thaliana. Their work helped yield the first plant genome sequence in history.

“It was controversial because it was so expensive, and not everyone was convinced it would move science forward,� says Martienssen. However, in time, the team completed a project that turned out to be “as important as mapping the human genome.�

Understanding which genes control which aspects of plant life has unplugged a fountain of information. Martienssen sees in this new knowledge the potential to meet the demands of a changing world.

“As more plant genomes were sequenced, they helped us come to grips with genes that control plant traits,� he says. “These genes are important for everything from climate resilience to disease resistance to crop yield.�

Martienssen takes us on a tour of CSHL’s corn fields and discusses his work’s possible applications in mitigating climate change.

For example, sequencing the oil palm genome in 2013 led Martienssen’s team to discover the Shell gene that controls oil yield. That finding could have big implications for where and how we get our energy. For example, the Malaysian Palm Oil Board is now applying the discovery toward biofuel production and rainforest preservation efforts. They’re working with Orion Genomics, a company Martienssen and McCombie co-founded.

But that’s not all. The first plant genome sequence also has applications beyond plant breeding and genomics. It has helped shed new light on evolution and human health. Perhaps most importantly, it has opened the door to discoveries that explain how genes are regulated.

“One thing the plant genome gave us was the sequence of transposable elements, which is very important for epigenetics,� Martienssen says. Epigenetics describes how external factors, like behaviors and environment, affect genes. Transposable elements are ‘jumping genes’ first discovered by the late CSHL plant biologist Barbara McClintock. Indeed, the Nobel laureate served as a mentor to a young Martienssen in his early days at CSHL. Her lessons proved pivotal in guiding his own breakthroughs.

“W±ð could really dive into what happened to the genome under epigenetics and control genes by transposable elements,â€� Martienssen says. It might sound technical, but the potential for health and medicine is nothing short of revolutionary.

It has implications for “cancer, neurobiology, everything,� he says.

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Â鶹´«Ã½Ó³»­ Associate Professor and Cancer Center member Tobias Janowitz led a COVID-19 clinical trial with Northwell Health in 2021. When he and Clinical Fellow Hassal Lee reviewed the data, a surprising trend emerged. “The patient roster was very diverse,â€� Janowitz explains. “W±ð’d made no deliberate effort toward that other than conducting the trial remotely.â€�

When it comes to cancer trials, many variables impact patient participation. One measurable factor is distance. On average, people are less likely to sign up for trials more than 30 minutes away. Karen Winkfield, Executive Director of the Meharry-Vanderbilt Alliance and member of the National Cancer Advisory Board, says:

“The biggest reason patients don’t enroll is they’re not asked. They aren’t asked because there may not be clinical trials close to them.�

Now, Janowitz and Lee have developed a new approach that may help clinics recruit patients from more communities. Using data from the U.S. Census Bureau, National Trial Registry, and other publicly funded organizations, the team created population maps for areas around highly active cancer trial sites. They found that high-volume sites are often in affluent neighborhoods with less diverse populations.

“Clinical trials should be accessible to all,� Janowitz says. “Currently, 78 sites host about 94% of all U.S. cancer trials. We offer a new approach for these and other sites to use available data in designing more equitable clinical trials.�

With their new tool, the team analyzed the sites’ neighboring areas. They then identified nearby hospitals serving more diverse communities. Collaborating with these potential satellite sites could help expand patient recruitment efforts.

“For example, if you wanted to diversify the population for a clinical trial, you could use our tool to generate maps with whatever demographics you want,� Lee explains. “It’s transferable to any U.S. area as long as you have Census data.�

Janowitz and his team are now working to expand their analysis to other population segments and trials unrelated to cancer. They hope their new approach will help streamline clinical trials. Winkfield, who co-authored the study, says:

“W±ð can do a much better job of providing access to clinical trials in the communities where it matters most. If we’re able to use this tool to make real collaborations with community health centers and hospitals that are interested, this could be a game changer.â€�

The next step is to measure potential real-world impact. Janowitz and Lee suggest applying their approach to design new cancer trials. If they’re right, the trials will be more readily available to all.

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It’s the most common single-gene neurological disorder in the world. It is typically diagnosed in children. It’s often accompanied by learning challenges. It can lead to tumors in the brain, spinal cord, and throughout the body. It’s called neurofibromatosis type 1 (NF1). One out of every 3,000 people is born with the disease. And there is no known cure. Despite all this, research on NF1 has been historically underfunded.

A new partnership between Â鶹´«Ã½Ó³»­ (CSHL) and the Penny’s Flight Foundation aims to change that. The Foundation has joined with CSHL Professor Linda Van Aelst and Assistant Professors Michael Lukey and Jeremy Borniger to tackle the condition head-on. Their work may lead to new, innovative therapies for NF1 and other neurological disorders. It may also provide new insights into glioblastoma, the most common form of brain cancer.

“W±ð are thrilled about the partnership between Penny’s Flight and CSHL and could not ask for a better partner in the quest to find a cure for neurofibromatosis,â€� says Chad Doerge, who co-founded Penny’s Flight with his wife, Kate Doerge, in honor of their late daughter. “Â鶹´«Ã½Ó³»­ is a beacon of innovation in medical research. As they set their vision on the complex problems presented by NF, we know the resulting science will promise a brighter future for those affected by the disease.â€�

“W±ð will find a cure for NF,â€� adds Kate Doerge. “But we could not do it without the incredible support of generous donors and our CSHL partnership.â€�

Van Aelst, Lukey, and Borniger have taken a multi-pronged, collaborative approach to uncovering the root causes of NF1. Their first project studies how cancer and immune cells interact in NF1-related brain tumors. The team is also investigating links between nerve cells and neurofibromas—small, benign growths. They’ve already uncovered a trait shared among all NF1-associated cancers.

“It has been an absolute delight getting to know and work with Kate and Chad Doerge,� says CSHL’s Sarah Kitt. “Their unwavering dedication to finding a cure for this dreadful disease radiates the love they hold for their daughter and the passion they have to cure NF. We are incredibly grateful to have such remarkable individuals involved with CSHL’s new project.�

was founded to celebrate the life of Penny Doerge and the qualities she personified—joy, artistic expression, and humor—while living with NF1. The Foundation supports much-needed research on neurofibromatosis and related disorders. It works to expand knowledge, inspire others, and make a lasting impact on altering the course of these devastating neurological conditions.

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Ever heard of the jelly bean experiment? A researcher filled a jar with jelly beans. He then asked a student how many were in the jar. Then he repeated the question with another student and another until every student in the class had been tested—each in private. Very few students guessed a number near the actual total. But when the researcher averaged their answers together, something remarkable happened. The mean guess was almost exactly right. There’s a profound lesson here. Looking at things from a wider array of perspectives and experiences provides a more accurate interpretation of reality. In other words, diversity drives a deeper understanding of the world. It’s in this spirit that a young scientist and advocate at Â鶹´«Ã½Ó³»­ (CSHL) has co-authored a new article titled “Rigorous Science Demands Support of Transgender Scientists.â€�

“Modern anti-trans movements and legislation are bolstered by ‘scientific’ arguments that are eerily reminiscent of eugenic science of the early 20th Century,� says CSHL postdoc Simón(e) Sun. “During this wave of anti-trans hate in the U.S. and around the world, it is absolutely crucial that the academy protects and supports transgender scientists. Individuals must use their privilege and influence to advocate for real systemic change. Institutions must enact trans-inclusive policies, and highlight diversity, equity, inclusion, and justice contributions in hiring and promotion. Acknowledging and supporting this work improves both the quality and ethical outcomes of our scientific practice. By including people from all walks of life, we enrich our research with unique perspectives to reveal new ways to explore nature’s beauty.�

Sun is a decorated neuroscientist in Â鶹´«Ã½Ó³»­ Associate Professor Jessica Tollkuhn’s lab. They have been named a senior fellow at the Center for Applied Transgender Studies, a 2023 Hannah Gray Fellow, and a 2022 Leading Edge Fellow.

Their article can be read in full on the .

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What if an alien spaceship were to touch down in your front yard tomorrow? How would you communicate with your unexpected guests? How would anyone for that matter? Now, consider the prospect that any unintended miscommunication might result in interstellar war.

Questions like these form the premise of 2016 sci-fi blockbuster Arrival, starring Amy Adams (The Master, Man of Steel). They’re also near and dear to Â鶹´«Ã½Ó³»­ (CSHL) neuroscientist Arkarup Banerjee. Later this month, Banerjee will present a special screening of Arrival at the Cinema Arts Centre in Huntington, NY.

Watch the trailer for Arrival, co-starring Jeremy Renner (The Avengers, The Hurt Locker) and Forest Whitaker (Ghost Dog: The Way of the Samurai, The Last King of Scotland). Video: Paramount Pictures

The event takes place on Tuesday, March 26 at 7:00 p.m. Join us as Assistant Professor Banerjee discusses “The Mysteries of Language & Communication.� Discover how every species and culture’s unique symbols and codes shape our understanding of the world around us. And uncover the intriguing ways in which our brains navigate the limits and possibilities of language. Our discussion will include a live Q&A.

“The Mysteries of Language & Communication� is part of national science-education initiative , funded by the Coolidge Corner Theatre and Alfred P. Sloan Foundation. Tickets are available now via the .

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You’ve heard the phrase, “Men are from Mars, women are from Venus.� If only it were so simple. The fact is that all of us are from Earth. Yet, there are clear physical and neurological differences between the sexes.

Women comprise half the world’s population. However, when it comes to health conditions that primarily affect women and girls, there’s a lot we still don’t know. Â鶹´«Ã½Ó³»­ (CSHL) is working to fix that.

At CSHL, researchers study fundamental biology with an eye toward improving women’s health. Their explorations into cancer and neuroscience are helping us better understand how our minds and bodies can change over the course of a lifetime, from early development to menopause.

This new knowledge could lead to better treatments and prevention strategies for everything from breast cancer to diabetes. And it may help empower multiple generations of women from all walks of life.

Breast cancer prevention

Studies have shown that women who give birth before age 25 are less likely to develop breast cancer than women who never become pregnant and those who do so later in life. Â鶹´«Ã½Ó³»­ Associate Professor Camila dos Santos wants to know how this works. She suspects the answer might help us find new ways to prevent breast cancer.

The dos Santos lab investigates how pregnancy changes breasts at the molecular level. Their hope is to identify specific changes within breast tissue that provide natural cancer protection. They’ve already uncovered a number of long-lasting changes that occur during pregnancy.

Â鶹´«Ã½Ó³»­ Associate Professor Camila dos Santos speaks about breast cancer prevention during a recent Cocktails & Chromosomes talk at Industry bar in Huntington, NY.

An early insight came when dos Santos was a postdoctoral researcher in the lab of former CSHL Professor Gregory Hannon. There, she discovered the genetic reprogramming that readies pregnant mice’s mammary tissue to reorganize in preparation for breastfeeding. This alters the ways certain genes are regulated, including many involved in cell growth.

It turns out that those changes leave a memory of a first pregnancy written into the breast cells themselves. “One of the things we’ve shown is that cells that have been exposed to pregnancy turn on processes that drive potentially cancerous cells to stall their growth,� dos Santos explains. “And eventually, they die.�

This led to another big discovery. In 2021, dos Santos and her team found that certain cancer-fighting immune cells called natural killer cells become much more prevalent in mice’s mammary tissue after pregnancy. The researchers say these natural-born killers could play a direct role in breast cancer prevention. They might actually patrol the tissue and destroy would-be tumors.

This discovery has also prompted the dos Santos lab to consider how immune cells’ interactions with the breasts might change at other times in women’s lives. They’re particularly interested in exploring changes brought about by menopause that might lessen the immune system’s innate ability to stop cells from becoming cancerous.

“All women during menopausal age are at risk of breast cancer,� dos Santos says. “What are the things that your body is erasing over time that puts it at risk? And can we bring them back to inhibit tumor development?�

Dos Santos notes that the effects of pregnancy on breast cancer risk are age-dependent. While risk is reduced significantly for women who give birth before the age of 25, pregnancy after 35 can increase breast cancer risk. The dos Santos team has begun investigating how, with age, breast cells respond differently to the hormones present during pregnancy. That work could help illuminate how breast cancer prevention strategies might shift over a woman’s lifespan.

Â鶹´«Ã½Ó³»­ Associate Professor Jessica Tollkuhn is also interested in hormones. You might say she’s one of the institution’s leading authorities on the topic. Tollkuhn focuses on the sex hormone estrogen, whose natural fluctuations—day to day and over a lifetime—have significant consequences for our physical and mental wellness.

Demystifying estrogen

The effects of estrogen are perhaps best understood in the context of breast cancer. The hormone can turn on genes that drive the growth of breast cancer cells. And women with certain types of breast cancer benefit from treatments that dampen estrogen’s growth-promoting signals.

Tollkuhn says that observing estrogen’s effects on breast cancer cells has enabled researchers to create more targeted therapies. “Understanding which genes are regulated by these hormone receptors has actually led to the development of better cancer therapeutics,� she explains.

Of course, estrogen’s effects are not limited to cancer cells. The problem is that its impacts on healthy tissue aren’t yet well understood. Tollkuhn is particularly concerned with what happens when estrogen reaches the brain. How does it impact brain development after birth? What about later in life?

Estrogen is known to regulate mood and sleep patterns, protect against strokes, boost cognition, and help control body temperature. In fact, breast cancer treatments that rein in estrogen production can interfere with these functions. This can cause side effects like mood swings and hot flashes.

But until recently, no one really knew which genes estrogen targets in the brain. Tollkuhn’s work suggests that there are hundreds. In experiments with mice, she and her colleagues have found nearly 2,000 genome sites that interact with estrogen receptors in the brain. Her research has also revealed that sex hormones present in the developing brains of young animals influence their aggression levels and parenting abilities later in life.

With a long list of genes controlled by sex hormones, scientists can now explore how specific estrogen targets impact women’s health over the course of our lives. Take, for example, how estrogen levels decline during menopause. Hormone replacement therapies can reduce hot flashes and other symptoms triggered by this natural decline. However, for some women, raising the body’s estrogen levels may increase cancer risk.

Tollkuhn hopes her current work will empower researchers to develop therapies that mimic estrogen’s benefits without triggering undesirable side effects. “Now that we know what the genes are, can we figure out how to potentially activate those genes that are just in the neurons and not in the periphery?� she asks.

When neurons that naturally respond to estrogen are artificially activated in a mouse’s brain, the mouse moves. But when they’re not activated, the mouse stays relatively sedentary. Video: Krause/Ingraham lab

With collaborator Holly Ingraham at the University of California, San Francisco, Tollkuhn has already zeroed in on one gene in the brain whose diminishing activity after menopause may have an effect experienced by many women. That gene is Mc4r. The researchers have found it helps spur a motivation to move.

When estrogen levels decline, Mc4r activity wanes. This may help explain why women often become less active during menopause. Such lifestyle changes can make it harder to maintain a healthy weight and strong bones. So, keeping Mc4r turned up could counter these effects. And that could prevent common age-related conditions like obesity, diabetes, and the bone disease osteoporosis.

Brain-body and beyond

Menopause and pregnancy are just two women’s health issues coming into better focus as a result of CSHL research. There are also Â鶹´«Ã½Ó³»­ scientists studying uterine and ovarian cancers. Others have set their sights on the neuroscience of motherhood. How does the profound experience of raising a child affect our brains? And how do these neurological changes manifest physically?

Questions like these lie at the heart of CSHL’s brain-body initiative. It’s here that the work of cancer scientists like Camila dos Santos and neuroscientists like Jessica Tollkuhn intersects. The two study vastly different biological processes. Yet both recognize that their research has significant implications for women’s health. Their findings could lead to new breast cancer prevention strategies, hormone replacement therapies, and better overall patient experiences.

But more than that, their work stands to empower women of all ages and backgrounds. After all, knowledge is power. And thanks to CSHL research, our knowledge of women’s health grows stronger each day.

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Spinal muscular atrophy, or SMA, is the leading genetic cause of infant death. Less than a decade ago, Â鶹´«Ã½Ó³»­ (CSHL) Professor Adrian Krainer showed this brutal disease can be treated by tweaking a process called RNA splicing. This breakthrough resulted in Spinraza, the first effective treatment for SMA. It also opened a new frontier in drug development. Now, CSHL research could push RNA-splicing drugs even further. Â鶹´«Ã½Ó³»­ Associate Professor Justin Kinney, Krainer, and postdoc Yuma Ishigami have figured out why some splicing-based drugs tend to work better than others.

RNA splicing determines which gene segments are used to build a protein. Krainer had designed Spinraza to home in on the exact spot where the drug would modify the production of a specific protein SMA patients need. Not all splice-modifying drugs are so intentionally constructed. Some have been found to change RNA splicing without scientists fully understanding how. That’s true for a recently approved SMA drug, risdiplam.

To better understand how this drug works, the Kinney and Krainer labs analyzed risdiplam’s interactions with RNA. They also examined RNA’s interaction with another drug, branaplam. The researchers measured the drugs’ effects on splicing throughout the genome and on hundreds of variations of their intended targets. From there, they modeled how each drug identifies its targets among all RNA inside a cell.

What is RNA splicing and how does it work? This video spells it out using hand-drawn infographics.

Both risdiplam and branaplam alter RNA splicing to generate the protein needed to treat SMA. However, the researchers found that risdiplam is more specific. Their quantitative models explain how. In the simplest terms, branaplam binds to RNA in two different ways—whereas risdiplam only binds in one way. This finding could help researchers alter the chemical structure of branaplam so that it might someday treat Huntington’s disease—a fatal, currently incurable neurodegenerative disorder.

The researchers also found something else. Combining splice-modifying drugs that target the same gene segment in different ways usually has a greater effect than either drug alone.

“You get synergistic interactions,â€� Kinney explains. “W±ð found synergy is a general property of splice-modifying drugs. This might provide a basis for using drug cocktails instead of individual drugs.â€�

The finding could help researchers identify drug combinations with the potential to improve patient outcomes. And that could lead to new therapeutic strategies for SMA and other diseases. For example, the Krainer lab recently investigated RNA splicing in pancreatic cancer.

“Our new study provides insights into the action and specificity of splice-modifying drugs,� Krainer says. “This should facilitate the development of more effective drugs and drug combinations for a variety of diseases.�

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Plant genomics has come a long way since Â鶹´«Ã½Ó³»­ (CSHL) helped sequence the first plant genome. But engineering the perfect crop is still, in many ways, a game of chance. Making the same DNA mutation in two different plants doesn’t always give us the crop traits we want. The question is why not? CSHL plant biologists just dug up a reason.

CSHL Professor and HHMI Investigator Zachary Lippman and his team discovered that tomato and Arabidopsis thaliana plants can use very different regulatory systems to control the same exact gene. Incredibly, they linked this behavior to extreme genetic makeovers that occurred over 125 million years of evolution.

The scientists used genome editing to create over 70 mutant strains of tomato and Arabidopsis thaliana plants. Each mutation deleted a piece of regulatory DNA around a gene known as CLV3. They then analyzed the effect each mutation had on plant growth and development. When the DNA keeping CLV3 in check was mutated too much, fruit growth exploded. Danielle Ciren, a recent CSHL School of Biological Sciences graduate who led this study, explains:

“CLV3 helps plants develop normally. If it wasn’t turned on at the exact time that it is, then plants would look very different. All the fruits would be ginormous and not ideal. You have to balance growth and yield. If a plant has giant tomatoes but only two, is that as beneficial as a lower yield? There’s no simple solution. You’re always sacrificing something when you’re trying to get something improved.�

For tomatoes, engineering mutations near the beginning but not the end of the CLV3 gene dramatically affected fruit size. For Arabidopsis, areas around both parts of the gene needed to be disrupted. This indicates something happened over the last 125 million years that made the plants evolve differently. Exactly what occurred remains a mystery. Ciren explains:

“You can’t go back to the common ancestor because they don’t exist anymore. So it’s hard to say what was the original state and how have things been mixed up. The most simple explanation is that there’s a regulatory element that’s conserved in some capacity, and it’s been altered in subtle ways. It is a bit unexpected.�

What is certain is that genetic regulation is not uniform between plant species. Unearthing these genetic differences could help make crop genome engineering more predictable. And that would be a big win not just for science but for farmers and plant breeders across the globe.

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Knowing exactly what’s inside a tumor can maximize our ability to fight cancer. But that knowledge doesn’t come easy. Tumors are clusters of constantly changing cancer cells. Some become common cancer variants. Others morph into deadlier, drug-resistant varieties. No one truly understands what governs this chaotic behavior.

Now, Â鶹´«Ã½Ó³»­ (CSHL) Professor David Tuveson and his team have uncovered a mechanism involved in pancreatic cancer transformation—mucus. During the disease’s early stage, pancreatic cancer cells produce mucus. Additionally, these cells depend on the body’s regulators of mucus production. This new knowledge could help set the stage for future diagnostic or therapeutic strategies.

The unpredictable, shifting nature of tumors makes it challenging to pinpoint the right treatments for patients. “W±ð need to better understand this concept of cell plasticity and design therapy that takes this into consideration,â€� says Claudia Tonelli, a research investigator in the Tuveson lab, who led the study.

To find out what’s behind tumors’ erratic behavior, Tonelli teamed with Jonathan Preall from CSHL’s Single-Cell Biology Facility. Together, the scientists broke down messy clumps of pancreatic tumors into individual cancer cells. From there, they could examine the unique differences between each pancreatic cancer type. And that’s where mucus’ role in cancer differentiation oozed into view.

Making mucus is messy and challenging for cancer cells. It takes a lot of resources to assemble and export these protein blobs. So why do it in the first place? The scientists discovered that low-grade pancreatic cancer cells of a common variety, known as the classical type, depend on mucus to survive and thrive. As the cancer cells mature and transform into the deadlier type, known as basal-like, they seem to grow out of this dependency. Tonelli suspects mucus may provide fledgling cancer cells with protection against the immune system.

While therapeutically targeting mucus in young, vulnerable pancreatic cancer cells may have some advantages, it’s a double-edged sword. When mucus production is blocked, cancer cells stop growing. But this forces some of them to become the deadlier basal-like cancer cells as a survival mechanism.

“W±ð would have to do further studies to be ready to hit the cancers once they have undergone this differentiation,â€� says Tonelli. “Identifying a combination of therapies may be an option.â€�

Knowing what makes pancreatic cancer cells transform may someday help researchers discover better therapeutics. So, while mucus might not be the key to cracking pancreatic cancer, the answer might yet be found right under our nose.

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