2015 ANNUAL REPORT Executive Summary 2015 ANNUAL REPORT Executive Summary

CONTENTS

2 PRESIDENT’S MESSAGE

7 RESEARCH Research Activities, 8 Research Investigators, 9 Research Highlights, 10

15 EDUCATION Educational Activities, 16 Education Highlights, 17 Meetings & Courses Program, 22 Cold Spring Harbor Laboratory Conferences, 22 Cold Spring Harbor Laboratory Courses, 24 Cold Spring Harbor Asia Conferences, 25 Banbury Center Meetings, 26 Front cover Photograph by Derek Hayn/Centerbrook Watson School of Biological Sciences, 27 This report is written and produced by CSHL Press Publications, 28 the Department of Public Affairs of Cold Spring Harbor Laboratory. For more information, 29 FINANCIAL REPORTS please contact: Chief Operating Officer’s Report, 30 Public Affairs Financial Statements, 32 Cold Spring Harbor Laboratory Consolidated Balance Sheet, 32 One Bungtown Road Cold Spring Harbor, NY 11724 Consolidated Statement of Activities, 33 Consolidated Statement of Cash Flows, 34 Cold Spring Harbor Laboratory (CSHL) is a 516.367.8455 private, not-for-profit research and education [email protected] www.cshl.edu 35 INSTITUTIONAL ADVANCEMENT institution at the forefront of efforts in molecular Institutional Highlights, 36 biology and genetics to generate knowledge Vice President, Communications Dagnia Zeidlickis Honor Roll of Donors, 37 that will yield better diagnostics and treatments Community Support, 42 for cancer, neurological diseases, and other Managing Editors Phil Renna Board of Trustees, 43 major causes of human suffering. Peter Tarr, Ph.D. Laboratory Leadership, 44 PRESIDENT’S MESSAGE

to “spread the grants as widely as possible,” a form of scientific socialism that does not bode well for the fu- ture of American science. At the same time, however, opportunities abound in many areas of science, includ- ing cancer, neuroscience, plant biology and quantitative biology—areas of focus at Cold Spring Harbor. Fortunately, with very strong support from our Board of Trustees and supporters of CSHL, we have seen a dramatic increase in our endowment. But this precious resource should support the core of what makes CSHL one of the leading research institutions in the world of basic discovery science. Having recognized this, it has been increasingly obvious that there are many instances in which we can add value to our science and translate Bruce Stillman, Ph.D. these discoveries they will make an impact in the clinic —and this is particularly the case for cancer. asic research is a central, defining activity of With this background, we took the initiative in 2015 Cold Spring Harbor Laboratory. It is the wellspring B of entering into a strategic affiliation with Northwell of both new knowledge and technological advances that Health, previously known as the North Shore-LIJ make new discoveries possible. Health System. It’s an alliance that I expect to be trans- This discovery science is expensive, and getting more formative. It will provide an unprecedented opportunity expensive every year. Inflation in the biomedical sector to add value to certain of our discoveries and multiply outpaces that of the broad US economy, mostly due to the impact of our research. the wide use of advanced tech- nologies that require expen- sive equipment or reagents. We also pay a premium for The urgency of speeding the translation of basic research into clinical advances is captured in this picture of pancreatic cancer the highly trained personnel patient Gail Poinelli conferring with CSHL’s Dr. David Tuveson (right) and Northwell Health’s Dr. Craig Devoe. The brave Ms. who are needed to offer ever Poinelli, who lost her battle with the illness in 2016, is one of over 40,000 Americans whose lives are claimed by pancreatic cancer annually. increasingly high-tech meth- ods to our faculty, postdoc- toral fellows and students. At The sweet spot of the affiliation is translational cancer- re innovative trials. Patients will be receiving advanced the same time, we continue search, which includes the development of new cancer di- treatments and diagnostics they would not otherwise be to see an erosion of the total agnostics and therapeutics and the training of a new gen- offered, and benefit from them years before they would amount of support any high- eration of research-capable cancer clinicians. Northwell be available to patients elsewhere. At the same time, ly meritorious scientist can It’s an alliance that I expect to be transformative. Health is one of the largest integrated health systems Northwell’s large patient intake provides our scientists obtain from federal sources in the nation. Its recently expanded Cancer Institute, with opportunities to perform cancer research using tu- with over 200 academic oncologists and clinicians, is mor samples from precisely defined subsets of patients. such as the National Institutes It will provide an unprecedented opportunity to part of a system of care encompassing 21 hospitals and As we move further into the era of targeted therapy, of Health and the National ...multiply the impact of our research. 400 outpatient physician practices throughout the New assembling appropriate patient cohorts becomes ever Science Foundation. At the York metropolitan area. Serving more than 8 million more critical if we want to speed the time it takes to NIH and NSF, policies imple- people, Northwell treats some 19,000 new cancer cases evaluate new treatments. mented in the last four years annually. This makes it one of the most important sites have deliberately limited the Clinician-scientists at Northwell have already begun of cancer treatment in the US. type and amount of funding teaming up with faculty at CSHL. Each team has a spe- that can be awarded to the As CEO Michael Dowling has noted, Northwell’s on- cific disease focus, or a focus within broad types of can- nation’s very best and most cologists will make CSHL’s most promising pre-clini- cer such as particular subtypes of breast or prostate can- productive scientists in order cal research available to cancer patients in the form of cer. Under the leadership of Dr. David Tuveson, deputy

2 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 3 director of CSHL’s NCI-designated Cancer (RNAi) technology developed at CSHL by Gregory of aggressive forms of leukemia called acute myeloid Center and a talented clinician-scientist, Hannon and his team. The 2011 discovery, which Vakoc leukemia (AML). Vakoc discovered that a drug—de- Northwell-CSHL teams have begun to has carried forward, revealed a drug target—a protein veloped for another purpose by collaborating scientists gather periodically at our Banbury Center called BRD4—of unusual potential in the treatment at the Dana Farber Institute—hit the target, virtually to plan and assess their work. Our agree- eliminating AML in mouse models. These studies in- ment additionally supports the education duced a number of pharmaceutical and biotech compa- and training of Oncology Fellows. In this nies to initiate clinical trials that target AML, some of aspect of the alliance, the clinical training of which are now in Phase II, with positive results already oncologists in the Northwell Health system, reported from Phase I studies. This is precisely the kind in conjunction with the Hofstra University- of rapid translation of an important basic scientific re- Northwell Health School of Medicine, will sult that our new alliance with Northwell Health and include an elective period of laboratory its vast clinical system is designed to facilitate. It will research at CSHL. Via summer and full- enable us to pursue translational science with a vigor we year fellowships, a cadre of cancer doctors otherwise could not while keeping our basic discovery in training will engine primed. emerge to play Two of our faculty are now reaping the rewards of de- an active Christopher Vakoc (above) and colleagues in 2011 discovered a cades of meticulous basic research. Adrian Krainer’s re- powerful drug target called BRD4 for AML, an often deadly form search on RNA splicing—which began in the 1990s and of leukemia. Translational work has already led to clinical trials grows out of earlier Nobel Prize-winning work by Louise testing the effectiveness of a drug called JQ1 (red) that “hits” the Chow and Richard Roberts at CSHL and by Sue Berget target (left). and Phillip Sharp at MIT—has made possible the devel- opment of a drug, now in Phase III trials, for the serious productive CSHL basic scientist who had already pub- lished many papers helping to identify the molecular players involved the control of cell division, reported the discovery of yet another factor, which he called Cyclin D. This discovery coincided with the same find- ing by former CSHL Trustee Charles Scherr of St. Jude’s Children’s Hospital, who went on to discover the protein kinase CDK4, which forms a complex with Cyclin D. It soon became clear from the work of Beach and Scherr role in translating the next wave of fundamental discov- that the Cyclin D-CDK4 complex is a critical node in eries about cancer into new diagnostics and therapies. the fundamental decision of whether a cell keeps divid- ing or rests from proliferation. Importantly, it became It’s reasonable to ask how the new alliance will change apparent that most cancer cells have mutations in this the way research is done at CSHL. I want to make clear control pathway, thereby pushing tumor cells on the that it in no way alters our core commitment to basic road to unchecked growth and aggressive cancer. research, which is unshakable. This collaboration adds to our capabilities in a manner illustrated by two con- What is poignant about the 2015 approval of Ibrance is the fact that it came a quarter-century after the fun- ...our commitment to basic research is unshakable. damental discoveries by Beach and Scherr. In the early 1990s, we simply did not know enough about cancer to convert their newly generated knowledge into an ef- trasting stories about basic research. One of these sto- fective anticancer drug. Now we do. Another basic re- ries came to a happy conclusion early in 2015 when the search discovery at CSHL, this one quite recent, makes Food and Drug Administration approved palbociclib the point about our progress vividly, suggesting why the (Ibrance) for the treatment of metastatic breast cancer. time is ripe for a clinical alliance that enhances our abil- It’s a first-in-class inhibitor of CDK4 and CDK6, en- ity to promptly take our basic insights into the clinic. The power of basic research is exemplified in discoveries made by Nicholas Tonks and his team. Twenty-five years ago Tonks zymes called protein kinases that help regulate the cell In 2011, Christopher Vakoc, Scott Lowe and CSHL discovered an enzyme called PTP1B (illustration above) that is now the focus of several drug development efforts with poten- division cycle. In 1991, David Beach, then a highly colleagues performed a screen using RNA interference tial applications in breast cancer, diabetes, obesity and Rett syndrome.

4 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 5 children’s disease, spinal muscular atrophy (SMA). of a scientific odyssey in which Nick has persisted in the Nicholas Tonks’ fundamental discovery 25 years ago of face of doubters in the pharmaceutical industry. Tonks’ the first of what proved a large family of enzymes called team has recently demonstrated their ability to target protein tyrosine phosphatases (PTPs) was the beginning PTP1B—with a drug Nick developed years ago—in cel- lular signaling pathways that play a key role in HER2-positive breast cancer. Phase 1 tri- als will begin at Northwell in the spring of 2016. Other PTP1B-targeting compounds in Tonks’ lab are being evaluated by a major pharmaceutical firm for treatment of diabe- tes and obesity. It’s another illustration of how basic science can pay off in ways that are not contemplated at the outset. We see similar promise in other fields: for instance, in Zachary Lippman’s basic research on the process of branching morphogenesis in plants, which now points to a way of significantly increasing fruit yields; and in Steven Shea’s fundamental research on so- cial behavior in rodents, which has led to unexpected insights into Rett syndrome, an autism spectrum disorder. Basic research has made all of these oppor- tunities possible. To keep our discovery science robust, we were pleased this past year to have been asked to join the ranks of select institutions named as beneficia- ries of the Scientific Philanthropy Alliance. The SPA serves as an impartial advisor to major philanthropists, promoting basic re- search as the driver of new ideas, of new economic wealth and for the education of a new generation of talented new scientists. Several benefactors of the Laboratory or- ganized the SPA, which we thank for pro- Basic research in plant biology in several CSHL labs has led to discoveries viding another line of support for the basic that have the potential to significantly increase the yield of tomatoes, research that is the lifeblood of Cold Spring maize, and other food crops. Harbor Laboratory.

April 2016 RESEARCH 6 Cold Spring Harbor Laboratory RESEARCH ACTIVITIES RESEARCH INVESTIGATORS

CANCER

CANCER Dinu Florin Albeanu nn NEUROSCIENCE Researchers at CSHL are devoted to understanding the genetic, developmental, theoretical, physiological, and Gurinder Atwal nn nn nn fundamental biology of human cancer. Their commit- behavioral approaches. Neuroscience research at CSHL PLANT BIOLOGY ment to studying basic cellular processes reflects the is highly collaborative and can be divided into three Anne Churchland nn premise that understanding how these processes are al- broad themes: sensory processing, cognition, and cogni- Camila dos Santos nn GENOMICS tered in cancer cells will provide a framework for rational tive disorders. In addition, there is an effort to develop therapies. Several technological advances developed at new anatomical methods to improve our understanding Joshua Dubnau nn the Laboratory have given rise to innovative genomic of brain circuits, connectivity, and function. Mikala Egeblad nn QUANTITATIVE BIOLOGY approaches and the development of new mouse mod- els of various cancer types. These provide a powerful PLANT BIOLOGY Grigori Enikolopov nn nn pathway for discovery, characterization, and validation Douglas Fearon Pavel Osten nn of genes that contribute to cancer development and The plant group at CSHL studies fundamental mech- nn progression. A unique aspect of the CSHL cancer pro- anisms in plant development and genetics that impact Hiroyasu Furukawa nn Darryl Pappin nn gram is its cooperative nature. Scientists are encouraged crop productivity, biodiversity, climate change, and the Jesse Gillis Scott Powers to share their ideas and work on questions across labs, development of biofuels. Their research uses Arabidopsis, nn nn nn in a synergistic way that far exceeds the power of any maize, and most recently tomato as model systems, and Thomas Gingeras nn nn Michael Schatz nn nn single laboratory working in isolation. CSHL has been it expands upon the Nobel Prize−winning work done at designated as a Cancer Center of the National Cancer CSHL by Barbara McClintock in the 1940s and 1950s. Christopher Hammell nn nn Stephen Shea nn Institute since 1987. The transposable genetic elements, or “jumping genes,” Molly Hammell nn Jason Sheltzer nn that she discovered are now understood to reprogram NEUROSCIENCE the epigenome and are being used at CSHL for func- Gregory Hannon nn nn Adam Siepel nn tional genomics in Arabidopsis and maize. CSHL has CSHL neuroscientists focus on understanding how neu- Z. Josh Huang nn Raffaella Sordella nn taken part in numerous plant genome-sequencing proj- ral activity and neural circuitry underlie behavior, and Ivan Iossifov nn nn David L. Spector nn how disruptions in these circuits lead to neurological ects including Arabidopsis, rice, sorghum, and maize, as and neuropsychiatric disorders such as Alzheimer’s well as epigenomic sequencing and profiling. David Jackson nn Arne Stenlund nn disease, autism, schizophrenia, and depression. These Leemor Joshua-Tor nn Bruce W. Stillman nn questions are addressed in two model systems—ro- GENOMICS dents and fruit flies—using molecular, cellular, The Genomics Program is composed of faculty work- Adam Kepecs nn Marja Timmermans nn nn ing across disciplines and research areas. Its main re- Justin Kinney nn Jessica Tollkuhn nn search interests are genomic organization; structural variation of the human genome as related to disease; Alexei Koulakov nn nn Nicholas Tonks nn computational genomics and transcriptional model- Adrian R. Krainer nn Lloyd Trotman nn ing; and sequencing technology. Program facilities are located at the main campus and a few miles away at Alexander Krasnitz nn nn nn Glenn Turner nn the Woodbury Genome Center. The investigators con- Je H. Lee nn David Tuveson nn duct research in the areas of human genetics, functional genomics, small RNA biology, and bioinformatics. Dan Levy nn nn Christopher Vakoc nn Bo Li nn Linda Van Aelst nn nn QUANTITATIVE BIOLOGY Zachary Lippman nn nn Doreen Ware nn nn CSHL’s Simons Center for Quantitative Biology (SCQB) brings to questions in biological science the in- Gholson Lyon nn nn Michael Wigler nn nn nn sights of applied mathematics, computer science, theo- Robert Martienssen nn nn nn Anthony Zador nn retical physics, and engineering. Members of the SCQB interact closely with other CSHL researchers and apply W. Richard McCombie nn nn nn Lingbo Zhang nn their approaches to research areas including genomic Alea A. Mills nn Hongwu Zheng nn analysis, population genetics, neurobiology, evolution- ary biology, and signal and image processing. Partha P. Mitra nn nn Yi Zhong nn nn

8 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 9 RESEARCH HIGHLIGHTS

n 2015 Cold Spring Harbor Laboratory celebrated pancreatic tissue directly from cells sampled from can- a neighboring or “downstream” neu- Iits 125th year. Today’s CSHL is renowned for its research cer patients. The cells form tiny spheres called organoids ron, but also recruits a third neuron in Cancer, Neuroscience, Plant Biology, Quantitative that are entirely made up of ductal cells, eliminating the to inhibit the downstream target after Biology and Genomics. Scientists at the Laboratory surrounding cell types that often contaminate samples some delay. They will now use a ge- work together, frequently across disciplines, to solve from the pancreas. They grow within a complex gel- netic mouse model of schizophrenia to biology’s most challenging problems. This collaborative like substance filled with growth-inducing factors and determine if there are any noticeable spirit as well as the scope of the faculty’s research in- connecting fibers. Once they have grown to a sufficient changes in the observed feedforward terests are suggested in this sample of a few of the past size, the organoids can be transplanted into mice, where inhibition in the thalamus-PFC path- year’s important findings. they recapitulate human pancreatic cancer. The Tuveson way; these in turn might suggest novel lab has used organoids to interrogate new therapeutic targets for next-generation schizophre- targets in pancreas cancer; David Spector’s lab has used nia therapeutics. a similar method to study targets in breast cancer. The hope is that by testing drugs in these 3-dimensional hol- Cholinergic warning system low spheres made of tumor cells, and comparing them to a patient’s normal cells—which can also be grown In experiments with mice, Adam Kepecs and colleagues discovered a set of ded- into organoids—we will be able to much better predict In this coronal view of mouse brain, red fluorescence is generated by inhibitory patient treatment outcomes in the clinic. neurons in the PFC; it illuminates any neurons providing input into them— icated neurons in the basal forebrain implying a direct connection with red-labeled neurons in the thalamus. that broadcast messages throughout the cerebral cortex, rapidly informing Biomarker for treatment-resistant prostate cancer activate a pathway that involves the interleukin-6 (IL-6) multiple distributed subregions of any In 2015 a new animal model for prostate cancer called protein, which activates the MYC oncogene that is surprising rewards or punishments. The neurons are RapidCaP emerged from Lloyd Trotman’s lab. It is the expressed specifically in therapy-resistant metastatic cholinergic—they send signals in the form of the only model in mouse in which the cancer metastasizes prostate cancer cells. Using the IL-6 marker or associ- neurotransmitter acetylcholine. Such neurons are to the bone. This is precisely what happens in advanced ated proteins to predict which patients would benefit thought to play an important role in arousal, atten- metastatic prostate cancer. It is crucial to have such a from hormone therapy would be a major advance. The tion and learning, yet their precise role in behav- model, since patient responses to hormone therapy vary hope is that translating the IL-6 discovery into clinics ior has remained mysterious, in part because of the widely, and it’s still unclear why some types of prostate could help stratify patients into good responders and technical difficulty in recording from them in vivo. A pancreatic organoid grown in the Tuveson lab. cancer seem to be resistant to the therapy. Those cases bad responders. Degeneration and loss of cholinergic neurons in the that resist therapy—a minority—are liable to become basal forebrain have been implicated in Alzheimer’s metastatic and are often lethal. Crucially, Trotman’s disease, age-related cognitive decline, and other cog- Brain circuit implicated in schizophrenia Organoids to aid pancreatic cancer research model may help us determine which ones. His team has nitive disorders and dementias. Kepecs’ team showed All cancer research relies on a steady supply of cells, been using this system to trace the mechanisms under- The prefrontal cortex (PFC) plays an important role in how central cholinergic neurons function, using both normal and cancerous, that can be grown in the lying metastatic lesions. So far they have discovered that cognitive functions such as attention, memory and optogenetic methods as mice performed behavioral laboratory. By comparing normal cells to cancer cells, such lesions are very different from primary tumors in decision-making. Faulty wiring between the PFC and tasks that involved rewards or unexpected mild pun- scientists can identify changes that lead to disease. Yet the prostate. Their work has shown that these metastases other brain areas is thought to give rise to a variety ishments. To explain their responses the team con- both types of pancreatic cells of cognitive disorders. Disruptions to one particular structed a computational model which revealed that have been difficult to culture in brain circuit—between the PFC and another part of the modulation of signal strength was proportional the laboratory. Another prob- the brain called the thalamus—have been associated to how unexpected or surprising the mice found the lem in studying pancreas cancer with schizophrenia, but the mechanistic details are reward or punishment. According to the model, if is the fact that many patients unknown. Bo Li and colleagues have now discovered the mice were confident their response was correct, when diagnosed are already an inhibitory connection between these brain areas the reward generated a weak signal. But if they were beyond the point at which sur- in mice that can control the timing of information unsure, the reward came as more of a surprise and gery is useful, making it dif- flow into the PFC. This insight may help explain generated a stronger cholinergic signal. Kepecs sug- ficult or impossible in many what goes wrong in schizophrenia and indicate a path gests that cholinergic broadcasts to the cortex would cases to obtain tumor samples. to new treatments. The team used optogenetic stim- be useful in boosting plasticity, allowing flexibility in To address this, CSHL’s David ulation, a technique in which neurons expressing a neuronal connections that makes learning possible. Tuveson, in concert with the light-sensitive protein are controlled with pulses of Whether a surprise is positive or negative, the fact Lung tissue (blue) colonized by prostate cancer cells. Brown areas indicate, from left to Dutch scientist Hans Clevers, right, the presence of IL-6, an immune system component and possible biomarker, its light, to observe a process called feedforward inhi- that it is unexpected, and the degree to which it is, has developed a method to grow downstream target STAT3, and PCNA, a marker of metastasis. bition, a mechanism in which one neuron excites would be an obvious advantage to the individual.

10 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 11 How a brain circuit controls fear most effective druggable targets for cancer cells, across among investigators working in the three labs. They It is hard to imagine that an intan- different cancer types and subtypes. realized there might be some benefit in applying to a mouse model of Rett syndrome some of the work that’s gible emotion like fear is encoded been done in the Tonks lab in developing small molecule within neuronal circuits, but Bo Li Our probabilistic approach to numbers drugs that inhibit an enzyme called PTP1B, which Tonks and colleagues have found that fear Humans, including pre-verbal babies and adults in discovered 25 years ago. Realizing that metabolic regula- is stored within a distinct region indigenous cultures with no formal mathematical ed- tion appears to be abnormal in Rett syndrome—a large- of the brain. In recent years, they ucation, are capable of estimating numbers of objects. ly unappreciated fact—Navasona Krishnan, a Research have discovered that fear learning Yet while areas of the brain have been identified that Associate who works with Tonks, proposed using inhib- and memory are orchestrated by respond to specific numbers, it has been unclear how itors of PTP1B to see if they might address any of the neurons in the central amygdala. numbers are represented. Scientists have generally as- range of symptoms seen in the disease. He first demon- Now, Li, along with CSHL collab- sumed that the brain represents numbers of objects as strated that PTP1B levels were abnormally elevated in orators Josh Huang and Linda van single, whole values, or “scalars.” However, estimates of the model mice. This was an encouraging sign that in- Aelst, took on the question of what Red cells are neurons identified by a method enabling researchers to trace circuits many other features of the environment—such as ob- between two brain regions—here, the PVT (in the thalamus) and CeL (in the amygdala). hibitors of PTP1B might have a beneficial effect. More controls the central amygdala. They ject depth, height and location—have been shown to exhaustive experiments with several candidate small focused on a cluster of neurons that be “probabilistic,” represented as a range of values. In molecule inhibitors demonstrated that they can signifi- form the PVT, or paraventricular Mastering CRISPR to reveal cancer targets 2015 Anne Churchland and colleagues reported results cantly extend lifespan in male mice that model Rett syn- nucleus of the thalamus. This region is extremely sen- of an experiment combining auditory and visual cues drome and can ameliorate several behavioral symptoms Since assembly of the full human genome sequence in sitive to stress, acting as a sensor for both physical and to test whether people have a scalar or probabilistic of the disorder in model female mice. This was tanta- the early 2000s, scientists have been amassing databases psychological tension. The team found that the PVT is sense of numbers. They determined that even a distinct lizing evidence that Rett symptoms can actually be re- that document or predict how specific stretches of DNA number of objects in the world may be represented in versed, and supports the concept that the disorder may specifically activated as animals learn to fear or as they letters in the genome encode specific segments of pro- the brain not as a single value but as a range of possi- be amenable to treatment with small molecule drugs— recall fear memories. They were able to see that neurons teins, called domains. Among the domains of greatest from the PVT extend deep into the central amygdala. ble values. Subjects could perform an audio-visual task an objective the team continues to vigorously pursue. interest to drug developers are those that form pock- involving a numerical determination with any of three Disrupting the connection significantly impaired fear et-like features on the surface of proteins that other mol- strategies. Some employed only the most reliable piece learning. Perhaps most important, in looking for mo- Fine-tuning plant growth to optimize fruit size ecules can fit into, as keys fit into locks. Drugs are keys of information; others combined auditory and visual in- lecular mechanisms that connect the two structures, the that fit into binding-pocket locks, sometimes for the formation to arrive at an estimate; still others random- A wonderful example of basic science having an import- team used data from people with post-traumatic stress purpose of blocking access to the lock, and other times ly picked one piece of information on which to base ant societal impact is work from Zach Lippman’s lab- disorder to discover that the well-known neural growth to initiate a cascade of signaling inside the cell. Watson their number estimate. These results have important oratory. His discoveries in recent years have identified factor BDNF is the chemical messenger that allows the School doctoral student Junwei Shi spent a year in Chris implications for how we learn and PVT to exert control over the central amygdala. This Vakoc’s lab mastering the new genome editing meth- understand our world. Representing provides a promising target for the future treatment of od called CRISPR-Cas9, which has taken the world of numbers as a range of possible val- anxiety disorders. biology by storm. He and Vakoc used the technique ues allows people to utilize multiple to mimic the effect of drugs bind- streams of information, leading to ing to protein targets on leukemia improved decisions. cells—thousands of different targets in a single experiment. This multi- plexing approach yielded exciting Reversibility of Rett syndrome symptoms results, successfully identifying six previously known targets and re- Another example of collaborative vealing 19 previously undiscovered science at CSHL is newly published ones in just one leukemia screen. work that is the fruit of discussions Each one is a binding pocket that among members of the laboratory if blocked by a drug would result in groups of Nicholas Tonks, Stephen cell death—in other words, a target Shea and Josh Huang. The idea be- that the cancer cell depends upon hind Tonks and colleagues’ 2015 re- in order to thrive. It was a proof of port of an experimental drug treat- principle. The method can be used ment to reverse symptoms of Rett A “Manhattan plot” showing 4 already-known drug targets in leukemia (red spikes) identified in a single CRISPR screen, along with several others not previously by academic labs and by drug de- syndrome, an autism spectrum dis- Diagram illustrating how experimental drug developed in Tonks lab inhibits PTP1B discovered (grey spikes). velopers to generate catalogs of the order, can be traced to a discussion in mice modeling Rett syndrome, by releasing the brake on BDNF-TRKB signaling.

12 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 13 of CSHL Nobel laureate Barbara McClintock, this year solved a 30-year-old mystery that had cost growers of the oil palm tree hundreds of millions of dollars in ru- ined crops. In the 1980s, a new method of generating plantations brimming with clones of the highest-yield- ing specimens of the oil palm plant met with unantic- ipated disaster. Corporate investors were astonished to observe that the finest hybrids, cloned in culture dishes, often grew into barren adults bearing desiccated, worth- less fruits. These plants displayed a mutant form that scientists called “mantled.” Martienssen’s work, aimed at more completely understanding how epigenetic mecha- nisms influence and even control plant development and evolution, traced the problem to a transposable element lodged within the oil palm gene called MANTLED. This “jumping gene” is an example of the myriad ge- More stem cells in the meristem (bottom row) correspond with more nomic invaders that lay (mostly) dormant within and flowers (top row) and larger fruit (middle). The Lippman lab identified between genes in all forms of life. This particular invader, a set of genes that controls stem cell production in tomato. or one very similar to it, was first spotted in rice plants, and had been named karma. Martienssen and colleagues a number of things that can be done by growers to discovered that in mantled plants, a methyl mark pres- increase fruit yield. This year Lippman and colleagues ent in healthy plants was missing at a location in karma identified a set of genes that control stem cell production called a splice site. When the splice site is unmethylated, in tomato. Mutations in these genes explain the origin the RNA message copied from the gene encodes a mu- of mammoth beefsteak tomatoes. More important, the tant protein that gives rise to plants with worthless fruit. research suggests how breeders can fine-tune fruit size in A simple epigenetic test will readily identify bad karma potentially any fruit-bearing crop, a significant advance and thus enable growers to cull damaged clones at the for agriculture. The secret of the beefsteak tomato, the plantlet stage. It will promote the propagation of healthy team showed, has to do with the number of stem cells high-value hybrid clones and thus reduce the economic in the plant’s growing tip, called the meristem. They pressure on growers large and small to devote additional traced an abnormal proliferation of stem cells to a nat- tropical rainforest territory to oil palm cultivation. urally occurring mutation that arose hundreds of years ago in a gene called CLAVATA3. Selection for this rare mutant by plant cultivators is the reason we have beef- steak tomatoes today. Lippman’s team examined nev- er-before-studied mutant tomato plants, three of which contained faulty genes encoding enzymes that add sug- ar molecules to proteins. Their experiments revealed that the enzymes, called arabinosyltransfersases (ATs), add sugar molecules called arabinoses to CLAVATA3. By adjusting the number of sugars on CLAVATA pro- teins, and through other mutations affecting compo- nents of the pathway, Lippman and colleagues show it is possible to fine-tune growth in ways that could allow breeders to customize fruit size.

Overcoming bad karma The Martienssen lab solved a decades-old mystery, explain- ing the epigenetic factors that cause oil palm clones to grow Epigenetics pioneer Rob Martienssen, whose discover- into trees that yield desiccated “mantled” fruit (right) instead ies confirm and extend the observations and predictions of healthy fruit (left). EDUCATION 14 Cold Spring Harbor Laboratory EDUCATIONAL ACTIVITIES EDUCATION HIGHLIGHTS

Meetings & Courses Program stakeholders in many of the national brain projects ini- interest. About two dozen meetings are organized at Cold Spring Harbor Laboratory’s reputation as one of the tiated around the world over the last one to two years. Banbury each year, for groups of up to 40 invited par- principal crossroads of biology can be attributed to the This meeting, too, was the subject of a detailed article in Science. ticipants. These are recognized internationally as being enormous success of its Meetings & Courses Program. among the best discussion workshops for topics in mo- With roots in the famous Cold Spring Harbor Symposia The Courses program covers a diverse array of topics in lecular biology, molecular genetics, human genetics, series, dating to 1933, the program currently encom- molecular biology, neurobiology, structural studies and neuroscience, and science policy. passes some 55 meetings and 30–35 lab and lecture bioinformatics. Over 750 instructors, lecturers and as- courses held over two-year cycles. Since 2009, a parallel sistants come to teach at CSHL from universities, med- WATSON SCHOOL OF BIOLOGICAL SCIENCES program of meetings has been held in Suzhou, China, ical schools, research institutes and companies around The Watson School of Biological Sciences (WSBS) trains under the aegis of the Cold Spring Harbor Asia pro- the world. In 2015 about 700 trainees—who included the next generation of biologists, offering the Ph.D. gram, a wholly owned subsidiary of the Laboratory. advanced graduate students, postdocs and faculty—at- in biology in as little as 4 years to a limited number tended courses lasting from one to three weeks. of highly accomplished students drawn from around the In 2015 the CSHL Meetings attracted almost 7,600 The Courses program relies heavily upon grants and world. The curriculum is designed to train self-confident, participants to the main campus; when combined with foundation support. In 2015 renewal was secured for self-reliant young scientists to become scholars and to ac- participants in the China meetings, the program drew course funding from the Howard Hughes Medical quire the knowledge that their research and future careers about 10,500 scientists in all. The year saw the contin- Institute, a longtime benefactor. New major multiyear demand. The accomplishments of WSBS students have uation of many successful annual and biennial meet- ings as well as the introduction of several new meet- grants were received from the Helmsley Charitable Trust n 1890, high school biology teachers took courses been spectacular, with more than 250 papers published ings, focusing on Immunology, Probabilistic Modeling in and the National Institute of General Medical Sciences. at Cold Spring Harbor under the aegis of the Brooklyn in the 15 years since the school’s launch. Graduates have I Genomics, and Genome Engineering. The latter meeting The Helmsley Interdisciplinary Fellowship Fund pro- Institute of Arts and Sciences. The Laboratory’s “phage” moved swiftly into faculty positions at leading academic was a 2015 highlight, featuring the CRISPR genome vided major funding to almost 100 scientists to partici- courses of the post-World War II years were intellectual research institutions worldwide. editing technique. It drew over 400 participants from pate in CSHL courses outside their primary disciplines. incubators for the pioneers of molecular biology. Today, The Courses also benefit from the loan of equipment, DNA LEARNING CENTER around the globe and was reported in the journal Science. CSHL carries forward this tradition in a remarkable donation of reagents and technical support from many range of educational offerings for working scientists, The DNA Learning Center (DNALC) has a major im- In June, Cold Spring Harbor Asia Conferences host- companies, whose support is indispensable to ensure scientists in training, and students and teachers in pri- pact not only in the New York metropolitan area, but ed a special meeting in Suzhou, bringing together that the program remains cutting-edge. mary and secondary school systems locally, throughout also globally in pioneering public science education for the United States and overseas. the genome age. With teaching facilities in Long Island and New York City, it brings a hands-on approach to MEETINGS & COURSES PROGRAM learning about biology and genomes to classrooms and CSHL’s reputation as one of the world’s premier hubs of homes of children in primary schools, middle schools, activity in biology and genetics is linked to its Meetings and high schools. Renowned for devising means for & Courses Program. With roots in the legendary annual young people, teachers, and parents to conduct sophis- Symposia in Quantitative Biology series, which began ticated experiments with DNA, the DNALC also has a in 1933, the program organizes more than 60 meetings robust presence on the Internet, powered by a team of and courses annually, covering a wide range of topics in multimedia innovators who bring knowledge of the life the biological sciences. Together, they bring some 9000 sciences to computer, tablet, and cellphone users. scientists to the Long Island campus each year. Partici- pants range from the most accomplished senior inves- COLD SPRING HARBOR LABORATORY PRESS tigators to graduate students and postdocs. Programs With origins in the 1930s, CSHL Press enhances the are put together on the basis of openly submitted ab- Laboratory’s educational mission by publishing origi- stracts and include the discussion of unpublished work. nal work that assists in the advance and spread of sci- A CSHL-styled meetings program that began in 2009 entific knowledge. Sale of its publications enhances thrives in Suzhou, China. the Laboratory’s international reputation for excellence. The Press publishes research and review journals, books, BANBURY CENTER manuals, primers, and other information sources, in Banbury Center, located on the grounds of the historic electronic and print form. Widely reviewed and highly Robertson House, provides opportunities for scientists praised, these publications are made available in a vari- and other leaders in society to discuss topics of common ety of languages.

16 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 17 Banbury Center meeting on “Therapeutic Use of Ketamine for Treating Watson School of Biological Sciences 2015 was very busy at the Banbury Center, the Severe Depression - Risks and Potential” was a fol- Laboratory’s “think-tank” for biology and science- low-up to a meeting held in 2013 on the biology and In 2015 the Watson School wel- and-society issues located on the former Robertson estate pharmacology of an anesthetic drug being used with comed its 17th incoming class and in Lloyd Neck, across the harbor from the main campus. notable success in depression that doesn’t respond to graduated its 12th. The achieve- other treatments and as a suicide preventive. This year’s ments of the graduate program This year, Banbury meetings attracted over 600 par- meeting dealt with the question: why, if ketamine is so continued to grow. The quality of ticipants. One highlight occurred in March, when effective in treating severe depression, is it not wide- scientific publications produced “Exercise Science & Health” attempted a critical review ly used? The answers involve complicated social, eco- by the school’s students remained of the data and examined how far they can be trusted. nomic and regulatory issues. highly impressive. Watson School As is often the case, it was difficult to get members students continued to graduate of different fields with different practices to reach a In 2015 the Banbury website added short reports of considerably faster than students consensus. “HIV-1 & How to Kill a Killer” was the the meetings, as well as descriptions of classic Banbury in comparable Ph.D.-granting in- first meeting on HIV and AIDS to be held at Banbury meetings. These can be accessed from the home stitutions and demonstrated an since the early 1990s. Five participants in those early page www.CSHL.edu/banbury. This year’s meet- ability to secure excellent jobs. meetings were here in 2015. They and other attend- ings, as those of past years, were made possible in Twenty-one graduates have secured ees examined the vexed issue of where the virus hides significant part by generous support of corporate tenure track faculty positions. Sev- in “cured” patients until it reappears years later. The sponsors and underwriters. en have already been promoted to Associate Professor. Graduates have also moved into influential positions in administration, pub- lishing, consulting and industry. The Watson School is known for its unusual commitment to fac- WSBS entering class of 2015. ulty mentoring. Students benefit from a two-tiered mentoring ap- prestigious and highly competitive scholarships and fel- proach, in which each receives an academic as well as a lowships, as in past years. research mentor. The academic mentor is selected first, and provides counsel during the intensive coursework In August, seven new students entered as Members of of the first term, and also during lab rotation periods, at the Class of 2015. They were selected from among 310 the end of which students identify and select a suitable applicants and represent the United States, Lithuania, research mentor. The academic mentor remains active, Russia, the United Kingdom, and Vietnam. Other new serving as sounding board and advocate for students as graduate students entered as visitors from other institu- they work toward their doctoral degree. tions, including seven from Long Island’s Stony Brook University; other current visitors hail from more distant At the 2015 graduation ceremony, 12 WSBS students institutions, including Cornell University and National were awarded Ph.D. degrees, bringing the total since the Centre for Biological Sciences, India. school’s inception to 83. The new graduates are: Özlem (Mert) Aksoy, Mitchell Bekritsky, Sang-geol Koh, From June through August, 20 undergraduates from Nilgün Tașdemir, Elvin Wagenblast, and Susann across the U.S., as well as China and Switzerland, Weissmueller from the Entering Class of 2008, Stephane took up residence at CSHL to take part in the historic Castel, Kristen Delevich, Wee Siong Goh, Ian Peikon Undergraduate Research Program. These “URPs” (cho- and Cinthya Zepeda Mendoza from the Entering Class sen from among 1,047 applicants) had the remarkable of 2009, and Jack Walleshauser from the Entering Class opportunity to perform advanced research in the labo- of 2010. Michael Giangrasso from the Entering Class of ratory of a CSHL faculty member. The URP Program 2013 was awarded a Master’s degree. During the year, along with the equally innovative Partners for the scientific papers published by students of the school Future program, which brings gifted local high school appeared in major journals, bringing the cumulative students to CSHL labs for hands-on research experi- Banbury Conference Center 2015 meeting “HIV-1 & How to Kill a Killer.” total to over 300. Current and former students won ence, are run and managed by the Watson School.

18 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 19 Closer to home, in 2015 the DNALC Cold Spring Harbor Laboratory Press In 2015, the Press built a new distribution platform served 20,570 students who attended field Scientists from around the world have exchanged data that permits direct sales of e-books to individuals and trips at facilities in Cold Spring Harbor and ideas at Cold Spring Harbor Laboratory since its research groups. This new approach has proved popular as well as DNALC West and the Harlem first Annual Symposium more than 80 years ago. The and will be adopted for many future titles. DNA Lab. An additional 8,908 students Laboratory’s Press extends the opportunity to commu- A highlight of the year was the increasing adoption of completed labs in their own schools, led by nicate what’s new and exciting through its growing list bioRxiv, the online distribution service for preprints of DNALC staff, while 1,348 students attended of journals, books, manuals, and digital tools. The goal research papers in the life sciences, founded in 2013. week-long summer camps. The Center’s pop- is to provide scientists with information that is appro- It permits scientists to make their work immediately ular Urban Barcode Project had a successful priate, authoritative, and affordable. available to the research community and receive feed- 4th year, with participating students present- back on draft manuscripts before submitting them to The Press publishes eight journals, has 200 books in ing research posters and giving oral presen- journals. The monthly rate of manuscript submission print and electronic form, and two web services. In tations at the American Museum of Natural doubled between May and December and represented 2015, a new journal joined the list. Subtitled “a journal History. The program trains teachers to be over 1,500 institutions in 40 countries. Launched with of precision medicine,” Cold Spring Harbor Molecular mentors for their students engaged in projects; seed funding from the Laboratory, bioRxiv has since re- Case Studies illuminates the traditional medical case the related Urban Barcode Research Project, ceived critical support from the Lourie Foundation. Its report with advanced laboratory investigations such as The Ötzi exhibit at the DNALC has been extremely popular with students. this year involving students from 30 public emergence demonstrates that the Laboratory is continu- genome sequencing. and 10 private high schools, brings students ing to pioneer new ways of advancing science by sharing DNA Learning Center under the direction of scientist-mentors. Stu- Confidence in this new publication is sus- results and ideas. dent teams supported by teachers from 20 schools in The DNA Learning Center (DNALC) is a world leader tained by the success and reputation of the Nassau, Suffolk, and Queens counties presented project in providing education that prepares students—as well other Press journals. Genome Research and results at the inaugural Barcode Long Island sympo- as their teachers and even family members—to thrive Genes & Development remain in the top- sium in June. Monthly Saturday DNA! Sessions drew in the genome age. When the DNALC was founded in most ranks of journals in their fields. RNA 229 participants, with parents and grandparents joining the late 1980s, the idea of sequencing genomes was just and Learning & Memory provide value children for classes on natural selection, bacteria and an- for more specialized research commu- a gleam in the eyes of a handful of visionary biologists. tibiotics, and genetic engineering, among other topics. Among them was then Laboratory Director James D. nities. Perspectives and Protocols gain Watson, who provided the impetus for a young staff to The year’s highlight was the opening of an exhibit at the ground and usage as essential library develop what has since become a trademark hands-on Dolan DNALC several years in the making. Featuring assets. Online, the Press journals had a approach for introducing young people to a revolution- a precise life-size reproduction of “Ötzi the Iceman,” record download of more than 13.4 mil- ary new science. the mummified remains of a European male who lived lion full-text articles. about 5,300 years ago, the exhibit provides the entry The DNALC’s glowing reputation is partly the fruit of Interest in print books is falling among point for exploration of human origins, a longtime in- scientists—but under the right circum- having instructed over half a million Long Island and terest of the center. Ötzi, in fact, joined an articulated New York metropolitan area students over the last quar- stances, as in 2015, there can still be suf- Neanderthal skeleton and grave cast, a bust recreation ficient demand to make book publishing ter-century. But it also stems from the program’s success of Homo erectus, and skulls of 16 ancient hominids on financially viable. The best sellers were in carrying its instructional methods to far corners of display. Altogether, these exhibits are designed to com- newly released volumes devoted to the the earth. In 2015, the DNALC concluded negotiations plement experiments pioneered by DNALC, in which intricacies of epigenetics and the compu- to develop a DNA Learning Center Asia in Suzhou students use their own DNA as an entrée to the study of tational analysis of genome sequencing, Industrial Park, near Shanghai, China. It’s the high point the human family and its dispersion across the planet. as well as two perennial favorites, At The of a licensing program that began in 2002, which has led Bench, an initiation into experimental to licensed centers in Singapore (2003), Vienna (2006), Ötzi—whose actual remains are on display in a museum science, and the classic compendium of Notre Dame University (2013), Beijing 166 High School in the Italian Alps—is in fact the subject of what is lab techniques, Molecular Cloning. An editorial team at the Press at work on a manuscript. (2014) and Mexico City Health Park (2014). DNALC perhaps the world’s oldest actively investigated murder Asia has been registered as an “internal” Chinese mystery. He was killed on a mountain slope over 10,000 NGO, sponsored by CSH Asia Conferences. It’s being feet above sea level, by an arrow entering his upper body developed on a 270,000-square-foot site, and its first from the rear. The story was first told in an episode of the set of teaching labs will have twice the capacity of the popular PBS science program NOVA in 2012. Under development in 2015, a new installment in the series, Dolan DNALC in Cold Spring Harbor Village. called “Iceman Reborn,” will focus on the creation of the Ötzi replica now on display at the Dolan DNALC.

20 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 21 MEETINGS & COURSES PROGRAM

COLD SPRING HARBOR LABORATORY CONFERENCES COLD SPRING HARBOR LABORATORY CONFERENCES (continued) Title Organizers Title Organizers

Jan. 28–Feb. 1 Systems Biology: Global Regulation of Gene Expression Tim Hughes, Christina Leslie, John Stamatoyannopoulos, August 11–15 Metabolic Signaling & Disease: From Cell to Organism Daniel Kelly, Mitchell Lazar, Susanne Mandrup Sarah Teichmann August 18–22 Eukaryotic mRNA Processing Jean Beggs, Kristen Lynch, Jens Sykke-Andersen March 3–6 Cellular Dynamics & Models Jennifer Lippincott-Schwartz, Wallace Marshall, Ed Munro, August 25–29 Mechanisms of Eukaryotic Transcription Patrick Cramer, Katherine Jones, John Lis Vito Quaranta March 17–21 Systems Biology: Networks Pascal Braun, Suzanne Gaudet, Ben Lehner, Chad Myers September 1–6 Eukaryotic DNA Replication & Genome Maintenance Anne Donaldson, Anindya Dutta, Johannes Walter March 24–28 Wiring the Brain Joshua Huang, Kevin Mitchell September 8–12 Microbial Pathogenesis & Host Response Lalita Ramakrishnan, Raphael Valdivia, Malcolm Whiteway April 8–11 RNA & Oligonucleotide Therapeutics Annemieke Aartsma-Rus, Arthur Krieg, Laura Sepp-Lorenzino, September 15–19 Cell Death David Andrews, Douglas Green, Anthony Letai Bruce Sullenger September 24–27 Genome Engineering: The CRISPR/Cas Revolution Jennifer Doudna, Maria Jasin, Jonathan Weissman April 14–18 Fundamental Immunology & Its Therapeutic Potential James Allison, Eric Pamer, Fiona Powrie, Stephen Smale Sept. 29–Oct. 3 Neurobiology of Drosophila Aaron D’Antonio, Diane O’Dowd April 21–25 The Ubiquitin Family Ronald Hay, Ron Kopito, Cynthia Wolberger October 7–11 Stem Cell Biology Konrad Hochedlinger, Fiona Watt, Marius Wemig April 28–May 2 Telomeres & Telomerase Julia Cooper, Titia de Lange, Roger Reddel October 14–17 Probabilistic Modeling in Genomics Barbara Engelhardt, Thomas Mailund, Adam Siepel May 2–5 Biology of Genomics of Social Insects Guy Bloch, Juergen Gadau, Amy Toth October 28–31 Genome Informatics Janet Kelso, Daniel MacArthur, Michael Schatz May 5–9 The Biology of Genomes Ewan Birney, Michel Georges, Elaine Mardis, Molly Przeworski November 3–7 Cell Biology of Yeasts Martha Cyert, Daniel Lew, Kenneth Sawin May 12–16 Biology of Cancer: Microenvironment, Metastasis Senthil Muthuswamy, Kornelia Polyak, David Tuveson & Therapeutics November 11–15 Single Cell Analysis Nancy Allbritton, Scott Fraser, Junhyong Kim May 18–23 Retroviruses Kathleen Boris-Lawrie, David Evans November 18–21 Behavior & Neurogenetics of Nonhuman Primates Nelson Freimer, Jeffrey Rogers May 26–31 80th Symposium: 21st Century Genetics - Genes at Work Terri Grodzicker, David Stewart, Bruce Stillman December 2–5 Plant Genomes & Biotechnology: From Genes to Networks Todd Mockler, Jane Parker July 16–19 Evolution of Sequencing Technology: A Half-Century Mark Adams, Nigel Brown, Mila Pollock, Robert Waterston December 9–12 Rat Genomics & Models Aron Geurts, Michael Gould, Bina Joe, Enrico Petretto of Progress

Attendees of 2015 meeting “Wiring the Brain.”

22 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 23 COLD SPRING HARBOR LABORATORY COURSES COLD SPRING HARBOR LABORATORY COURSES (continued) Title Instructors Title Instructors

March 13–16 Workshop on Leadership in Bioscience Carl Cohen, Dannielle Kennedy July 27–August 10 John Dueber, Mary Dunlop, Karmella Haynes, Julius Lucks, March 30–April 1 The Genome Access Course Assaf Gordon, Emily Hodges, Gareth Howell, Benjamin King, Pamela Peralta-Yahya, Stanley Qi Jeremy Ward August 4–10 Cellular Biology of Addiction Antonello Bonci, Christopher Evans, Brigitte Kieffer April 8–21 Protein Purification & Characterization Albert Courey, James Lee, Sue-Hwa Lin, Michael Marr, Sergei Nechaev September 2–4 The Genome Access Course (NYGC) Assaf Gordon, Emily Hodges, Gareth Howell, April 8–21 Quantitative Imaging: From Cells to Molecules Hunter Elliott, Jennifer Waters, Torsten Wittmann Benjamin King, Jeremy Ward April 9–21 Cell & Developmental Biology of Xenopus Mustafa Khokha, Karen Liu October 12–27 X-Ray Methods in Structural Biology William Furey, Gary Gilliland, Alexander McPherson, James Pflugrath June 3–16 Single Cell Analysis James Eberwine, Amy Herr, Michael McConnell October 12–27 Programming for Biology Simon Prochnik, Sofia Robb June 3–23 Advanced Bacterial Genetics Diarmaid Hughes, Beth Lazazzera, Fitnat Yildiz Oct. 28–Nov. 3 Computational & Comparative Genomics Aaron Mackey, William Pearson, Lisa Stubbs June 3–23 Mouse Development, Stem Cells & Cancer Mark Lewandoski, Deneen Wellik November 9–22 Antibody Engineering & Phage Display Don Siegel, Gregg Silverman June 3–23 Ion Channels & Synaptic Transmission Tiago Branco, Stephan Brenowitz, Ian Duguid, Paul Kammermeier November 10–22 Advanced Sequencing Technologies & Applications Elaine Mardis, Gabor Marth, William McCombie, June 4–10 Workshop on Autism Spectrum Disorders Daniel Geschwind, Sarah Spence Aaron Quinlan, Michael Schatz June 18–July 1 Statistical Methods for Functional Genomics Harmen Bussemaker, Sean Davis, Olivier Elemento, Rafael Irizarry November 16–18 The Genome Access Course Assaf Gordon, Emily Hodges, Gareth Howell, June 24–30 Workshop on Pancreatic Cancer Dafna Bar-Sagi, Steven Leach, Anirban Maitraa, David Tuveson Benjamin King, Jeremy Ward June 26–July 16 Drosophila Neurobiology: Genes, Circuits & Behavior Karla Kaun, Chi-Hon Lee, Stefan Pulver December 2–6 Scientific Writing Retreat Charla Lambert, Stephen Matheson June 26–July 16 Frontiers & Techniques in Plant Science Mark Johnson, Shin-Han Shiu, Marja Timmermans June 30–July 16 Advanced Techniques in Molecular Neuroscience Cary Lai, Joseph Loturco, Anne Schaefer July 7–20 Vision: A Platform for Linking Circuits, Perception & Behavior Farran Briggs, Andrew Huberman COLD SPRING HARBOR ASIA CONFERENCES July 14–27 Proteomics Michelle Cilia, Ileana Cristea, Katalin Medzihradszky, Darryl Pappin Title Organizers July 21–August 10 Eukaryotic Gene Expression Karen Adelman, Geeta Narlikar, Ali Shilatifard, Dylan Taatjes July 21–August 10 Yeast Genetics & Genomics Grant Brown, Maitreya Dunham, Marc Gartenberg May 4–8 Precision Cancer Biology & Medicine Patrick Tan, Cun-Yu Wang, Paul Workman, Qimin Zhan July 21–August 10 Imaging Structure & Function in the Nervous System Florin Albeanu, Michael Orger, Lucy Palmer, Philbert Tsai, May 11–15 Membrane Proteins: Structure & Function Martin Caffrey, Nieng Yan, Ming Zhou Jack Waters, Karen Zito June 1–5 Lipid Metabolism & Human Metabolic Disorders Pingsheng Liu, (Hongyuan) Rob Yang July 23–August 2 Neural Data Science Mark Reimers, Pascal Wallisch June 8–12 Frontiers of Plant Biology: Epigenetics & Development Xiaofeng Cao, Justin Goodrich, Doris Wagner June 19–22 International Brain Projects Maoyen Chi, Joshua Huang, Liqun Luo, David Stewart June 22–26 Novel Insights into Glia Function & Dysfunction Shumin Duan, Mengsheng Qiu, Bruce Ransom June 29–July 3 Francis Crick Symposium: Advances in Neuroscience Yang Dan, Bai Lu, Botond Roska September 14–18 Molecular Basis of Aging & Disease Adam Antebi, Jing-Dong Jackie Han, Brian Kennedy, Jan Vijg September 21–25 Tumor Immunology & Immunotherapy Xuetao Cao, Sumiya Dalangood, Olivera Finn, Shimon Sakaguchi, Laurence Zitogel October 12–16 Mitochondria Paolo Bernardi, Andrew Dillin, Xiaodong Wang October 19–22 CSHA/ISSCR Joint Meeting Stem Cells: Hongkui Deng, Andrew Elefanty, Gordon Keller, Duanqing Pei From Basic Biology to Disease Therapy October 26–30 Biological Rhythms Carla Green, Joseph Takahashi, Hiroki Ueda, Han Wang November 2–6 Bacterial Infection & Host Defense Kenya Honda, Samuel Miller, Craig Roy, Feng Shao, Jörg Vogel November 9–13 Targeting Cell Death Mechanisms for Douglas Green, Jiahuai Han, Domagoj Vucic, Junying Yuan the Treatment of Human Diseases November 16–20 Development & Pathophysiology of Respiratory Systems Paul Noble, Min Wu December 1–4 Joint Meeting of the Molecular Biology Society of Japan & the Japanese Biochemical Society* December 2–5 CSHA/AACR Joint Meeting - Big Data, Computation Andrea Califano, William Hahn, Satoru Miyano, Xuegong Zhang & Systems Biology in Cancer December 7–11 New Advances in Optical Imaging Guoqiang Bi, Wenbiao Gan, Arthur Konnerth, Akihiro Kusumi of Live Cells & Organisms

Nicholls Biondi Hall provides a brilliant new venue for posters and presentations.

*Adjunct meeting

24 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 25 BANBURY CENTER MEETINGS BANBURYWATSON SCHOOL CENTER MEETINGSOF BIOLOGICAL SCIENCES

2015 WSBS DOCTORAL RECIPIENTS

Thesis Advisor Academic Mentor Current Position

Colleen Carlston Christopher Hammell Hiroyasu Furukawa Clinical Molecular Genetics Fellow, University of Utah Silvia Fenoglio Gregory Hannon Linda Van Aelst Postdoctoral Fellow, Massachusetts Institute of Technology Wee Siong Goh Gregory Hannon Hiroyasu Furukawa Research Fellow, Institute of Molecular and Cellular Biology, Singapore Jack Walleshauser Leemor Joshua-Tor Christopher Hammell Postdoctoral Fellow, Yale University

Title Organizer(s)

February 20–25 Boehringer Ingelheim Fonds Fellows Retreat Sandra Schedler, Claudia Walther March 9–11 Exercise Science & Health Russell Pate, Laurie Goodyear, Timothy Church March 17–20 Brain Rhythms as Potential Targets for Intervention Roi Cohen Kadosh, Marjorie Garvey, Bettina Osborn, in Cognitive Dysfunction Michele Pearson, Bradley Postle April 6–9 Biophysical Properties & Biological Significance Karen Ashe, Robert Tycko of Amyloid-β Assemblies April 14–17 Creating Patient-Specific Neural Cells for the In Vitro Fred Gage, Rudolph Jaenisch Study of Brain Disorders April 19–22 Neuronal Response Variability & Correlation Laurence Abbott, Kanaka Rajan, John Reynolds April 25–27 Wheat Genomics Michael Bevan, Mario Caccamo May 1–3 NIMH Brain Camp VII Joyce Chung, Thomas Insel June 14–17 What Really Improves the Lives of People with Schizophrenia Robert Heinssen, John Kane June 18–20 Integrated Translational Science Center Workshop Laurence Baker, Lee Ellis, Edison Liu, Anne Schott, David Tuveson September 1–4 Mitochondria & Cancer Navdeep Chandel, David Sabatini September 15–18 Therapeutic Approaches to Prion Disease John Collinge, Jeffery Kelly & Other Neurodegenerative Conditions September 20–22 Therapeutic Use of Ketamine for Treating Severe Hakon Heimer, Rhonda Robinson Beale, Jan Witkoswki, Depression - Risks & Potential September 27–30 Therapeutic Development for ALS Lucie Bruijn, Timothy Miller, Dinah Sah, Clive Svendson October 4–7 What is Needed to Harness Chemogenetics for Gary Aston-Jones, Bryan Roth the Treatment of Human Brain Disorders? October 13–16 HIV-1 & How to Kill a Killer: Attempts at Total Steven Deeks, Robert Gallo, Robert Siciliano or Functional Cure of HIV-1 October 18–21 Lustgarten Scientific Meeting David Tuveson November 1–4 The New Era of Precision Medicine in Epilepsy Samuel Berkovic, David Goldstein, Erin Heinzen, Daniel Lowenstein November 11–13 Preventing Inherited BRCA Cancer: A Think Tank for Thomas Bock, Lawrence Brody Innovative Strategies, Milestone Objectives & Research Priorities November 15–18 How Can the Genetics & Neurobiology of Borderline Hakon Heimer, Antonia New, John Oldham Personality Disorder Contribute to Its Diagnosis & Treatment? December 7–10 Tumor Cell Mechanism: Finding New Targets Lewis Cantley, Steven McKnight for Therapeutic Intervention Watson School of Biological Sciences 2015 commencement convocation ceremony.

26 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 27 CSHL PRESS PUBLICATIONS

Serials Epilepsy: The Biology of a Spectrum Disorder, Genes & Development, Vol. 29 (www.genesdev.org) edited by Gregory L. Holmes and Jeffrey L. Noebels Genome Research, Vol. 25 (www.genome.org) Learning and Memory, edited by Eric R. Kandel, Yadin Dudai, Learning & Memory, Vol. 22 (www.learnmem.org) and Mark R. Mayford RNA, Vol. 21 (www.rnajournal.org) Aging: The Longevity Dividend, edited by S. Jay Olshansky, George M. Martin, and James L. Kirkland Cold Spring Harbor Symposia in Quantitative Biology, Vol. 79: Cognition, edited by Cori Bargmann, Daphne Bavelier, History Terrence Sejnowski, David Stewart, and Bruce Stillman The Road to Discovery: A Short History Cold Spring Harbor Protocols (www.cshprotocols.org) of Cold Spring Harbor Laboratory, by Jan A. Witkowski Cold Spring Harbor Perspectives in Biology (www.cshperspectives.org) Other Cold Spring Harbor Perspectives in Medicine Decoding the Language of Genetics, by David Botstein (www.perspectivesinmedicine.org) Orphan: The Quest to Save Children with Rare Genetic Disorders, by Philip R. Reilly Laboratory Manuals CSHL Annual Report 2014, Yearbook Edition Methods in Yeast Genetics and Genomics: A Cold Spring Harbor Laboratory Course Manual, 2015 Edition, by Maitreya J. Banbury Center Annual Report 2014 Dunham, Marc R. Gartenberg, and Grant W. Brown E-books (Kindle editions) Cell Death Techniques: A Laboratory Manual, edited by Ricky W. Johnstone and John Silke Epigenetics, Second Edition, edited by C. David Allis, Marie-Laure Caparros, Thomas Jenuwein, and Handbooks Danny Reinberg; Associate Editor Monika Lachlan The Next-Generation DNA Sequencing Informatics, Orphan: The Quest to Save Children with Rare Genetic Disorders, Second Edition, edited by Stuart M. Brown by Philip R. Reilly Using R at the Bench: Step-by-Step Data Analytics for Biologists, Decoding the Language of Genetics, by David Botstein by Martina Bremer and Rebecca W. Doerge Methods in Yeast Genetics and Genomics: A Cold Spring Harbor Textbooks Laboratory Course Manual, 2015 Edition, by Maitreya J. Dunham, Marc R. Gartenberg, and Grant W. Brown Epigenetics, Second Edition, edited by C. David Allis, Marie-Laure Caparros, Thomas Jenuwein, and Using R at the Bench: Step-by-Step Data Analytics for Biologists, Danny Reinberg; Associate Editor Monika Lachlan by Martina Bremer and Rebecca W. Doerge Aging: The Longevity Dividend, edited by S. Jay Olshansky, Monographs (Topic Collections from Perspectives in Biology and Perspectives in Medicine) George M. Martin, and James L. Kirkland Experimental Design for Biologists, Second Edition, Retinal Disorders: Genetic Approaches to Diagnosis and Treatment, edited by Eric A. Pierce, Richard H. Masland, and Joan W. Miller by David J. Glass Glia, edited by Ben A. Barres, Marc R. Freeman, and Beth Stevens Career Options for Career Options for Biomedical Scientists, edited by Kaaren Janssen and Richard Sever Intellectual Property in Molecular Medicine, edited by Salim Mamajiwalla and Rochelle Seide Audiobook (Audible or iBook editions) Mitosis, edited by Mitsuhiro Yanagida, Anthony A. Hyman, Orphan: The Quest to Save Children with Rare Genetic Disorders, and Jonathan Pines by Philip R. Reilly The Hepatitis B and Delta Viruses, edited by Christoph Seeger and Stephen Locarnini Websites Molecular Approaches to Reproductive and Newborn Medicine, Cold Spring Harbor Monographs Archive Online edited by Diana W. Bianchi and Errol R. Norwitz (www.cshmonographs.org) Size Control in Biology: From Organelles to Organisms, edited by Cold Spring Harbor Symposium on Quantitative Rebecca Heald, Iswar K. Hariharan, and David B. Wake Biology Archive (symposium.cshlp.org) Neurogenesis, edited by Fred H. Gage, Gerd Kempermann, Services and Hongjun Song DNA Recombination, edited by Stephen Kowalczykowski, bioRxiv, the preprint server for biology (www.bioRxiv.org) Neil Hunter, and Wolf-Dietrich Heyer BioSupplyNet, scientific supply directory (www.biosupplynet.com) FINANCIAL REPORTS 28 Cold Spring Harbor Laboratory CHIEF OPERATING OFFICER’S REPORT

s Bruce Stillman right- our Office of Sponsored Programs, write and submit CSHL Endowment Year-End Value and Performance A ly points out in his high-quality federal grant applications. In other words, President’s Message, basic dis- we continue to obtain a bigger slice of a shrinking pie. $500,000,000 covery science, the heart At the same time, the Laboratory has been very success- of Cold Spring Harbor ful in attracting funds from private foundations and Laboratory’s mission, is be- $444m $451m philanthropy. One need only look at the shift in the mix 400,000,000 coming increasingly expen- sive. This is a result of many of our research funding over the last decade. In 2005, $385m factors including escalation federal grants made up nearly 60% of the total, with

private sources at 20%. Ten years later in 2015, federal 300,000,000 in expenses associated with $313m scientific equipment, sup- grants constitute 44%, with private sources at 29%. It plies, and recruitment and is important also to note that the remaining 27% of the retention of the world’s best research budget is now funded by Laboratory sources 200,000,000 scientists. Unfortunately, this including the annual fund and spending from our en- upward expense spiral has dowment funds, both of which are reflective of a highly coincided with a 20% in- energetic and successful fundraising effort. For this we 100,000,000 W. Dillaway Ayres, Jr. flation-adjusted decline in have to thank our Development Office, our Board of the budget of the National Trustees and the many devoted supporters of CSHL. Institutes of Health over the last decade. The Laboratory’s endowment fund, in some respects its 0 2012 2013 2014 2015 CSHL has navigated its way through this challenging lifeblood, has grown impressively from $215 million in 2008 to $450 million at year-end 2015. This growth is environment by excelling in a few critical areas. One of Performance those is the success of our faculty in obtaining federal the result of many generous endowment gifts in addi- Year 2012 2013 2014 2015 grants. Over the last year, their success rate was 46% as tion to investment returns on the funds. Since the 2008 compared to the national average of 17%. This is sim- financial crisis, we have benefitted from strong financial Return 12.4% 16.4% 4.3% -0.2% ply a reflection of the excellence of our research and the markets and a sound investment strategy developed by vigor with which our investigators, in partnership with the Investment Committee of our Board of Trustees. While in calendar year 2015 CSHL investment returns commencement address at the 2016 Watson School were flat, we have not had a down year in the last sev- graduation ceremony. Citing the decline in federal re- 2015 CSHL Sources of Revenue en and in four of those years we achieved double-digit search funding, the Senator expressed deep concern over returns. This combination of fundraising and positive the anti-science discourse in America. In his words, “I investment returns is inarguably good news. However, think there is a clear and present danger that the US Royalty and Auxiliary Activities as stock markets hover near all-time highs and interest will lose its leadership in the years ahead. This will have Endowments Licensing Fees 26% rates remain stubbornly low, it is increasingly difficult a devastating impact across our economy with lower and Board- 1% Corporate to plan for investment returns on the endowment that growth and fewer innovations. We must put a stop to Designated Funds Contributions are substantially in excess of our spending rate. This is a 10% the growth of the tumor of anti-intellectualism and an- and Grants challenge now being addressed. ti-science in our body politic.” 3% So we are doing many things well at the Laboratory Strong words for sure, but a warning worth heeding. If and, as a result, are on much firmer financial footing we become a society where dogma and beliefs supplant than many of our peer institutions. However, there is empirical evidence and facts, it will be difficult even for a big-picture concern over which we have less control. institutions as fine as Cold Spring Harbor Laboratory This problem was well articulated by honorary de- to thrive. gree recipient Senator Tom Harkin, who delivered the

Federal Grants Foundation and Private 34% Contributions and Grants Annual Funds, Interest 22% and Miscellaneous 4%

30 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 31 FINANCIAL STATEMENTS

Consolidated Balance Sheet Consolidated Statement of Activities December 31, 2015 Year ended December 31, 2015 (with comparative financial information as of December 31, 2014) (with summarized financial information for the year ended December 31, 2014)

Temporarily Permanently 2015 2014 2015 2014 Unrestricted Restricted Restricted Total Total

Assets: Revenue and other support: Cash and cash equivalents $ 54,209,176 56,309,959 Public support - contributions and Grants receivable 9,545,355 10,551,528 nonfederal grant awards $ 16,581,343 11,563,092 2,939,437 31,083,872 39,283,518) Contributions receivable, net 30,100,043 58,786,259 Federal grant awards 31,750,274 –---- –---- 31,750,274 27,176,257) Investments 449,931,993 442,830,529 Indirect cost allowances 27,286,692 –---- –---- 27,286,692 23,710,599) Investment in employee residences 6,161,403 5,159,378 Investment return utilized 17,887,633 –---- –---- 17,887,633 16,497,482) Restricted use assets 5,412,103 5,127,815 Program fees 8,681,384 –---- –---- 8,681,384 6,896,378) Other assets 10,270,883 9,983,360 Publications sales 9,737,489 –---- –---- 9,737,489 10,030,061) Land, buildings, and equipment, net 230,619,980 231,650,890 Dining services 4,819,543 –---- –---- 4,819,543 4,322,717) Rooms and apartments 3,880,805 –---- –---- 3,880,805 3,638,654) Total assets $ 796,250,936 820,399,718 Miscellaneous 5,183,130 –---- –---- 5,183,130 6,632,532) Liabilities and net assets: Net assets released from restrictions 43,903,946 (43,903,946) –---- –---- –---- Liabilities: Total revenue and other support 169,712,239 (32,340,854) 2,939,437 140,310,822 138,188,198) Accounts payable and accrued expenses $ 10,048,146 12,510,995 Deferred revenue 8,004,642 5,509,689 Expenses: Interest rate swap 34,052,132 33,623,553 Research 86,078,788 –---- –---- 86,078,788 85,732,121) Bonds payable 95,608,887 95,542,618 Educational programs 19,849,038 –---- –---- 19,849,038 17,213,213) Publications 9,152,372 –---- –---- 9,152,372 9,466,527) Total liabilities 147,713,807 147,186,855 Banbury Center conferences 1,591,739 –---- –---- 1,591,739 1,486,354) Net assets: DNA Learning Center programs 2,001,720 –---- –---- 2,001,720 1,973,519) Unrestricted 342,262,835 325,723,978 Watson School of Biological Sciences Temporarily restricted 192,160,567 236,314,595 programs 3,246,931 –---- –---- 3,246,931 3,422,312) Permanently restricted 114,113,727 111,174,290 General and administrative 17,204,666 –---- –---- 17,204,666 16,603,749) Dining services 5,924,858 –---- –---- 5,924,858 5,704,911) Total net assets 648,537,129 673,212,863 Total expenses 145,050,112 –---- –---- 145,050,112 141,602,706) Total liabilities and net assets $ 796,250,936 820,399,718 Excess (deficiency) of revenue and other support over (under) expenses 24,662,127 (32,340,854) 2,939,437 (4,739,290) (3,414,508)

Other changes in net assets: Investment return excluding amount utilized (7,694,691) (11,813,174) –---- (19,507,865) (31,486) Change in fair value of interest rate swap (428,579 ) –---- –---- (428,579) (15,010,072)

Increase (decrease) in net assets 16,538,857 (44,154,028) 2,939,437 (24,675,734) (18,456,066)

Net assets at beginning of year 325,723,978 236,314,595 111,174,290 673,212,863 691,668,929)

Net assets at end of year $ 342,262,835 192,160,567 114,113,727 648,537,129 673,212,863)

32 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 33 Consolidated Statement of Cash Flows Year ended December 31, 2015 (with comparative financial information for the year ended December 31, 2014)

2015 2014

Cash flows from operating activities: Decrease in net assets $ (24,675,734) (18,456,066) Adjustments to reconcile change in net assets to net cash provided by operating activities: Change in fair value of interest rate swap 428,579 15,010,072 Depreciation and amortization 13,808,887 13,942,830 Donated equipment (1,880,032) – Amortization of deferred bond costs 66,269 66,269 Net depreciation (appreciation) in fair value of investments 4,238,813 (12,908,048) Contributions restricted for long-term investment (3,057,415) (5,020,506) Changes in assets and liabilities: Grants receivable 1,006,173 (2,045,360) Contributions receivable, net 25,537,066 48,392,029 Restricted use assets (284,288) (623,048) Other assets (287,523) 2,357,289 Accounts payable and accrued expenses, net of financing activities (1,848,350) 959,182 Deferred revenue 2,494,953) 299,798) Net cash provided by operating activities 15,547,399) 41,974,441)

Cash flows from investing activities: Capital expenditures (10,897,945) (13,605,145) Proceeds from sales and maturities of investments 44,262,648 75,649,786 Purchases of investments (55,602,925) (121,501,780) Net change in investment in employee residences (1,002,025) (810,514) Net cash used in investing activities (23,240,247) (60,267,653)

Cash flows from financing activities: Contributions restricted for long-term investment 2,939,438 4,001,838 Contributions restricted for investment in capital 117,977 1,018,668 Decrease in contributions receivable 3,149,150 3,209,572 (Decrease) increase in accounts payable relating to capital expenditures (614,499) 1,114,499) Net cash provided by financing activities 5,592,066) 9,344,577 Net decrease in cash and cash equivalents (2,100,783) (8,948,635) Cash and cash equivalents at beginning of year 56,309,959) 65,258,594 Cash and cash equivalents at end of year $ 54,209,176) 56,309,959

Supplemental disclosure: Interest paid $ 3,978,881) 4,013,111

INSTITUTIONAL ADVANCEMENT 34 Cold Spring Harbor Laboratory INSTITUTIONAL HIGHLIGHTS HONOR ROLL OF DONORS

Private philanthropy drives a Lifetime Contributions Lifetime Contributions of Josiah Macy, Jr. Foundation great deal of the most innovative of $5 million+ $1 million+ or $100,000+ in 2015 Mercer Family Foundation Gillian and Eduardo Mestre basic research. The Laboratory Anonymous Paul G. Allen Foundation Mr. and Mrs.* William R. Miller Estate of Donald E. Axinn Angel Foundation is grateful to all donors, who al- Mr. and Mrs. Yuri Milner Dr. and Mrs. Lalit Rai Bahl Anonymous (6) low our science to push beyond Dr. and Mrs. Howard L. Morgan The Arnold and Mabel Gonzalo Río Arronte Foundation Louis Morin Charitable Trust the mainstream. In 2015 we Beckman Foundation BioBay of Suzhou Venture Capital Group Estate of Thomas C. Nelson celebrated the 10th Double Jamie Nicholls and Fran Biondi Booth Ferris Foundation Nimbus Discovery, Inc. Helix Medals Dinner, rais- David Boies, Chairman of Bristol-Myers Squibb Company University of Notre Dame Boies, Schiller & Flexner LLP Burroughs Wellcome Fund ing $4.5 million and honoring OSI Pharmaceuticals The Breast Cancer Research Foundation Louise Parent and John Casaly Katie Couric, Anne Wojcicki and Lucy Southworth Page and Larry Page Mr. and Mrs. Landon T. Clay Mary K. Chapman Trust David Botstein. Thanks to the The Pew Charitable Trusts The Dana Foundation Chen and Shao Anti-Cancer Foundation Amy and John Phelan leadership of our Board of Trust- Mr. and Mrs. Norris W. Darrell Mr. and Mrs. Roderick H. Cushman William and Maude Pritchard ees, this spectacular event put Dart Neuroscience LLC Davenport Family Foundation Charitable Trust CSHL research in the New York Estate of Kathryn W. Davis Michel David-Weill Ride For Life City spotlight. In November, DeMatteis Family Foundation Ira W. DeCamp Foundation Edward P. Evans Foundation Fannie E. Rippel Foundation George D. Yancopoulis, M.D., Mr. and Mrs. Charles F. Dolan The Robertson Foundation - Dolan Family Foundation The Samuel Freeman Charitable Trust Ph.D., President of Regeneron Coleman Fung Foundation Mr. and Mrs. David M. Rubenstein The William Stamps Farish Fund The Saunders Family Laboratories, joined the institu- Estate of Robert B. Gardner, Jr. Mr. Robert L. Garland* tion’s governing body, bringing Mr. and Mrs. Robert A. Gay - Ivor Charitable Fund Kate Medina Guthart and Leo Guthart Eleanor Schwartz Charitable Foundation his unique perspective as a sci- Howard Hughes Medical Institute Genentech, Inc. Kenyon Gillespie Edith and Alan Seligson or 125 years, CSHL research and education W.M. Keck Foundation entist, clinician, and industry leader. A special thank Jacob Goldfield The Seraph Foundation, Inc. programs have been central to the advancement of Mr. and Mrs. David H. Koch F you to trustees and other benefactors for generous gifts Lola Goldring Jeanne and Herbert J. Siegel biology and genetics. Our Long Island campuses, now Laurie J. Landeau Foundation LLC to research programs: Lalit and Kavita Bahl, Jenny and The Florence Gould Foundation Mr. and Mrs. Howard Solomon Mr. and Mrs. Robert D. Lindsay spread over nearly 200 acres, have been centers for the The Grace Family Mr. and Mrs. Erwin P. Staller Jeff Kelter, Mary W. Harriman Foundation, Gladys and Family global exchange of scientific knowledge. Throughout Michael J. Griffin Dr. and Mrs. James M. Stone and Roland Harriman Foundation, and Leslie and Stu The Lustgarten Foundation The Harrison Foundation and The Mary Dr. and Mrs. Karel Svoboda the decades, the Laboratory has prized its stewardship of Lucille P. Markey Charitable Trust Weisbrod. Jim and Liz Watson continued their legacy as Anderson Harrison Foundation Dr. Jerome Swartz life science, with great appreciation for the public and Nancy Abeles Marks philanthropic champions of the Laboratory with a ma- Thomas Hartman Foundation - The Swartz Foundation private funds that have propelled us forward. The G. Harold & Leila Y. Mathers jor gift toward educational programs. for Parkinson’s Research Swim Across America Nassau/Suffolk Charitable Foundation Waclaw T. Szybalski, D.Sc. CSHL supporters are dedicated to seeing the results of Janet Strauss and Jeff Hawkins To celebrate its 125th anniversary, CSHL opened its cam- The Don Monti Memorial Jo-Ellen and Ira Hazan Mr. and Mrs. Paul J. Taubman research benefit mankind. 2015 was a year replete with pus in June to non-scientists—our friends in the com- Research Foundation William Randolph Hearst Foundation Dr. and Mrs. Stuart T. Weisbrod examples of how basic scientific research benefits society. GEN*NY*sis grant from New York The Karches Foundation Whitehall Foundation, Inc. munity. Faculty, students and employees were out in full State Dormitory Authority In April, CSHL entered into a strategic affiliation with force to tour, explain, and share their knowledge with Mr. and Mrs. Jeffrey E. Kelter New York State Empire State F.M. Kirby Foundation, Inc. one of the nation’s largest health systems, Northwell nearly 600 visitors. This event helped inaugurate Nicholls Development Corporation Health—a unique relationship that will invest more Eugenie* and Walter B. Kissinger Biondi Hall, built with a gift from CSHL Chairman Pershing Square Foundation Mr. and Mrs. John Klingenstein than $120 million in cancer research and bring the Jamie C. Nicholls and O. Francis Biondi to host scientific The Honorable and Mrs. Leon Polsky - The Esther A. & Joseph Laboratory’s science more rapidly toward the clinic. The poster sessions for the Meetings & Courses Program. - Hazen Polsky Foundation Klingenstein Fund new partnership underscores the significance of bio- The Quick Family Elise H. Knight The Robertson Family - Banbury Fund medical research to healthcare today. Throughout the year, we welcomed more than 2000 vis- Mr. and Mrs. David M. Knott itors for tours and public lectures about CSHL research St. Giles Foundation The Forrest C. & Frances H. The importance of CSHL can also be felt in the econ- Drs. Marilyn and James Simons Lattner Foundation and education developments. We engaged virtual visi- The Simons Foundation omy. An economic impact study found that the insti- Betsy and Bryan H. Lawrence tors in multimedia experiences about CSHL’s past, pres- Alfred P. Sloan Foundation Mara and Thomas Lehrman tution, directly employing 1,100, indirectly accounts ent and future at www.cshl.edu/125. A special 125th Theodore R. Stanley* The Lehrman Institute for over 500 additional jobs, and annually brings more Anniversary series of public lectures featured luminar- - Stanley Medical Research Institute Mr. and Mrs. Stephen M. Lessing than $140 million in revenue to Long Island from fed- ies in science and society: Dr. Sylvia Earle, National The Starr Foundation Mary D. Lindsay eral grants, private philanthropy, an array of scientific Geographic Explorer in Residence; Peter Neufeld, the Thompson Family Foundation The Litchfield Charitable Trust Mr. and Mrs. James D. Watson Estate of Elisabeth Sloan Livingston educational programs, and commercialization of tech- Innocence Project; Dr. Michael Wigler, CSHL; Dr. Mr. and Mrs. Henry Wendt III Lisa Lourie nologies. The entire study can be found in the About Us David Tuveson, CSHL and the Lustgarten Foundation; The Roy J. Zuckerberg Dr. Robert W. Lourie section of www.cshl.edu. and Dr. Jeremy Farrar, the Wellcome Trust. Family Foundation Mr.* and Mrs.* David L. Luke III 2015 Double Helix honorees Katie Couric, David Botstein and Anne Wojcicki with CSHL President Bruce Stillman. *Deceased

36 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 37 The Carson Family Charitable Trust Laureen and Ragnar M. Knutsen Contributions of $5,000+ Deb Parmet Sondock and Cliff Sondock Mr. and Mrs. Geoffrey de Lesseps The Soref Family - Cathy, Douglas, Mr. and Mrs. Thomas Korossy BankUnited - Alpha/Omega Charitable Foundation Maryn, Rylan and Colton Mitchell & Karen Kuflik Mr. and Mrs. Fred H. Baron Ike, Molly and Steven Elias Foundation Lee Steinberg Charitable Foundation Liz and Rod Berens Claire Friedlander Family Foundation John B. Vermylen Gordon E. Lamb - Jefferson Family Kathy and Gene Bernstein Mr. and Mrs. Ronald A. Gottlieb Craig Weiss - T. Weiss Realty Corp. Charitable Foundation Lisa and Tim Broadbent The Marc Haas Foundation Mr. and Mrs. Richard H. Witmer, Jr. Long Island 2 Day Walk Mr. and Mrs. Eric Carlstrom The Irving A. Hansen Memorial Foundation Karen E. Zoller to Fight Breast Cancer Centerbrook Architects and Planners Mr. and Mrs. J. Tomilson Hill III Dr. and Mrs. Thomas P. Maniatis Rita M. Cleary Drs. Nancy and Ron Israeli Robert L. Marcus Samara P. Cohen Contributions of $2,500+ Annette Kade Charitable Trust Edward E. Matthews Mr. and Mrs. Jonathan Connors Americana at Manhasset 2015 Golf honorees Tom and Trudy Calabrese pictured Robert T. Lindsay Dr. Marcia Kramer Mayer Nancy Parmet Cook and Jim Cook Paul Amoruso - Oxford & Simpson with longtime friend Mary Lindsay. The Meier & Linnartz Family Foundation Mr. and Mrs. Edward C. Meagher The Cooper Family Foundation Realty Svcs., Inc. The Tom and Judy Moore Foundation - Carter, DeLuca, Farrell & Schmidt, LLP Caroline Monti Saladino, President of the Don Monti Memorial Contributions of $50,000+ Dau Family Foundation Erica and Henry Babcock The Morningside Foundation National Grid Foundation Research Foundation, pictured with CSHL scientists at the 2015 Sandy and Nelson DeMille Dominic Bencivenga Ball of the Year. The Monti Foundation is a longtime supporter Elizabeth and Lee Ainslie Mr. and Mrs. Douglas P. Morris Northwell Health Dilworth & Barrese, LLP Bethpage Federal Credit Union of cancer research at CSHL. Ashley and Frank O’Keefe Anonymous Gerry Ohrstrom Lee MacCormick Edwards Drs. Renee A. Fitts and David Botstein The Perkin Fund Cedar Hill Foundation Susanne Olin Charitable Foundation Dr. Steven Brenner William Townsend Porter Foundation Universe Kogaku (America), Inc. Mr. and Mrs. Edward A. Chernoff Mr. and Mrs. George D. O’Neill Diane and Bob Fagiola G. Morgan Browne Christina Renna Foundation Mr. and Mrs. Douglas A. Warner III - MARS Wendy O’Neill Farrell Fritz, P.C. Annie and Peter Cannell Susan Wasserstein and George Sard Deborah Norville and Karl Wellner Casey and Ellen Cogut Dr. and Mrs. John G. Passarelli Michael L. Focazio - Carissa Maringo Fund Muffy Carlstrom Laura and Harry Slatkin Mr. and Mrs. W. Fifield Whitman John and Laura Desmarais Patricia Petersen - Daniel Gale Putney Cloos and Brian Fox Ann Thompson and Jim Childress Mr. and Mrs. James F. Stebbins Joseph M. Willen Genentech Foundation Sotheby’s International Realty The Deane A. and John D. Clay Claus Memorial Vincent and Mary Striano - Advantage Title Agency, Inc. The Clark Gillies Foundation Pfizer, Inc. Gilliam Foundation Cottage Pharmacy & Boutique - Striano Electric Marion Wood Joni Gladowsky Breast Cancer Foundation Mrs. Richardson Pratt, Jr. and Family Glen Cove C.A.R.E.S. Dr. Lester Dubnick Wilhelmus Johannes Van der Goes Breast Cancer Awareness Day - The Spionkop Charitable Trust Jon and Mindy Gray Family Foundation Fidelity Investments Susan Wojcicki Contributions of $1,000+ in Memory of Elizabeth McFarland Mr. and Mrs. Preston V. Pumphrey H2M architects + engineers G & M Earth Moving, Inc. Loren Eng and Dinakar Singh Drs. Marjorie J. van de Stouwe Robin Hadley Carl Girolamo, D.D.S., P.C. Mr. and Mrs. Robert J. Adams Contributions of $10,000+ Hope Geier Smith and Theodore Smith III and Scott Ratner Danielle and Mark Hamer Glencore International AG Diane L. Anderson - The Geier Foundation Mr. and Mrs. Michael Aboff - Aboff’s, Inc. Rauch Foundation - Harvest Real Estate Services Mary Jo and Mark Hoffman Anonymous Friends of TJ Foundation Anonymous Alex Roepers The Hastings Foundation Patricia Janco - Wells Fargo Private Bank Arch Insurance Group Wodecroft Foundation Autism Speaks Amy Falls and Hartley Rogers Joan M. Hutchins Johnston Family Foundation Tricia and Hal Avidano Mr. and Mrs. W. Dillaway Ayres, Jr. Pamela and Richard Alan L. Jakimo KPMG Mr.* and Mrs. Robert H.B. Baldwin Contributions of $25,000+ Blavatnik Family Foundation Rubinstein Foundation Kean Development Company, Inc. Natalia J. Appenzeller and Daniel R. Levy William W. Bancroft Lydia and Douglas* Shorenstein Roger and Lori Bahnik Brandon Sales Corp. The Kebede Family Foundation The Litwin Foundation and Thomas M. Bancroft Families Constance Silveri - The Bahnik Foundation BreastFest of Champions Steven Bruce Klinsky Rusty and Peggy McCormack - Norwood Foundation Bank of America Charitable Foundation Broad Hollow Bioscience Park, Inc. Deborah K. Solbert - The Klinsky Family Charitable Fund Mr. and Mrs. Ronald P. McNavich Baranay Family Foundation Pien and Hans Bosch The Broder Family Foundation Mr. and Mrs. Richard A. Spehr Amanda and Thomas Lister Diane Valente and Fred Miller Nicholas Bartilucci David P. Brown Vivienne and Josh Spoerri Luitpold Pharmaceuticals, Inc. Timothy Moran - D&B Engineers and Architects, P.C. Mr. and Mrs. Thomas J. Calabrese, Jr. Stand Up for Suzanne Mrs. David J. Mahoney Mr. and Mrs. Jeffrey Pash Caroline E. Bassett Calico Life Sciences Grace and Bruce Stillman Masthead Cove Yacht Club Paul J.R. Paternoster Mr. and Mrs. Christopher C. Callaghan Nancy Szigethy The Elena Melius Foundation Dr. and Mrs. Anthony F. Piazza Mr. and Mrs. George W. Carmany III TD Bank Mickie and Jeff Nagel Claudia Ploska Michele and Jim Celestino Anne D. Thomas New York Community Bank Foundation Nicole and Charlie Prizzi Dr. and Mrs. Bayard D. Clarkson Mr. and Mrs. Peter S. Tilles Mr. and Mrs. Wright Ohrstrom Mr. and Mrs. John Pufahl Susan and Glenn Cohen Joan P. Tilney William C. and Joyce C. O’Neil Bernard and Anne Reynolds Barbara Amonson Mr. and Mrs. Edward Travaglianti Charitable Trust Stefanie and Steve Rosner and Vincent Della Pietra Robin and Paul Vermylen Mr. and Mrs. Timothy Q. O’Neill Miriam K. Rothenberg Miki and Dave Donoho Walrath Family Foundation Lauryl and Robert Palatnick Dr. and Mrs. Raju Sarwal Eppendorf North America West Islip Breast Cancer Coalition for David P. Pearson Susan Sawyers Fortunato Sons Contracting, Inc. Long Island Whitney F. Posillico and Charles L. Sawyers, M.D. The Randall and Mary Hack Foundation Deedee and Michael Wigler Mr. and Mrs. John R. Reese Mary F. Smith Family Foundation Susan T. Harris Elisabeth R. Woods Foundation Lari and Frank Russo Stand Up 2 Cancer Yaoqing & Shouying Huang Family Trust Ann Eden Woodward Foundation Drs. Maria and Charles S. Ryan Michele M. Miroff and Carl J. Studer Elizabeth McCaul and Frank Ingrassia The Bradley Zankel Foundation Mr. and Mrs. Michael Shoff Mr. and Mrs. Stanley S. Trotman, Jr. Dr. and Mrs. Joel J. Kassimir Sharon Stamm and Jerome Zeldis John Sobolewski Sandy and Howard Tytel Eddie Chernoff and members of the CAB hear from DNALC Cathy Soref, pictured with CSHL President Bruce Stillman and Robert Sobolewski Executive Director Dave Micklos about the new Ötzi exhibit Andrea B. and Peter D. Klein - The Zeldis Family Charitable Fund United HealthCare Services, Inc. Watson School students Anja Hohmann and Maria Nattestad, sponsored by LIREG. was honored at the 2015 Women’s Partnership for Science lunch. *Deceased *Deceased

38 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 39 Caroline de Chazal and Guy L. de Chazal Mr. and Mrs. Thomas L. Pulling Al Gherlone Cathryn MacInnes Mr. and Mrs. Daniel C. de Roulet Mr. and Mrs. Peter Quick Golf Magazine Dr. Alea Mills Janet and Frank Della Fera Mr. and Mrs. William D. Roche Hersh Fine Art Gallery Michael O’Brien - Fera Pharmaceuticals LLC Lynn and Gerald Rubin Huntington Country Club John O’Leary Meleanor L. Deming Mr. and Mrs. J. Wright Rumbough, Jr. Amy F. Jalbert Louise Parent Nevenka Dimitrova Diane Emdin Sachs Memorial Fund Jewel Dr. Herbert Perr Michael Eisenbud Mr. and Mrs. Peter G. Schiff Jonathan’s Ristorante Justin Rosati Electronix Systems Nancy and Ray Schuville London Jewelers Van Cleef and Arpels Charles Schmall Frederick W. Engel Robin and Enrique Senior Long Island Academy of Fine Art Kathleen Sobolewski CSHL neighbors host dinner parties for visiting scientists at Enzo Life Sciences, Inc. Mr. and Mrs. Owen T. Smith Luce Ristorante Cathy Soref the annual Dorcas Cummings lecture and symposium. Chris Pendergast and Frank Verdone of Ride for Life present- Valerie M. Sokolowski Luitpold Pharmaceuticals, Inc. Dr. Bruce Stillman ed a $300,000 check to Drs. Molly Hammell and Josh Dubnau Robert Feeney Mr. and Mrs. James L. Spingarn Luxottica USA Mary Striano to fund research to investigate the genetic causes of ALS. Christine and Douglas Fox Carol Marcincuk Jean Gale Mr. and Mrs. Thomas L. Spinner, Jr. Mara’s Homemade Ann Maria Studer Carissa Maringo Elizabeth and Giuseppe Bertani Stanley C. Gale Frank Spokane Alecia Mayrock Joan P. Tilney Marie Matthews Jan and Don Bettencourt Mr. and Mrs. Robert J. Gannon Lynne and John Stahler Geraldine M. Moran Sallie and Alex van Rensselaer Dr. Egon Mayer Elizabeth B. Borden E. Maxwell Geddes, Jr. Jody and David Stewart Carol Murray Dr. James D. Watson Ms. Elizabeth McFarland - Katharine Bradford Foundation Paula and Pierre Gonthier Nancy B. Taylor Nikon Instruments, Inc. Dr. Jan Witkowski Jim McManus Dr. William Braden III Lawrence Goodman - Curtis, Mallet- Pamela M. Thye No Limit Fine Wines Rose M. Mooney - Porter Braden Endowment Fund Prevost, Colt & Mosle LLP Mr. and Mrs. Bart T. Tiernan Oheka Castle Hotel and Estate Contributions in memory of Monica Mowery Mr. and Mrs. Pascal Franchot Tone The Paramount Ryan Bradshaw Dora and Bill Grover Posie Arato Francis O’Connor Betsy Soref Trimble John G. Passarelli, M.D. Ronald J. Brecht Lynn and Frank Gundersen TJ Arcati Kevin O’Connor Sarah and Robert Trust Prime - an American Kitchen & Bar Frank Brosens and Deenie Reverend Linda Peyton Hancock Mrs. Richard Barnett Michelle Paternoster Dr. George F. Vande Woude The Printery Brosens Foundation The Hargraves Family Diane Moriarty Berejka Carol Pearl Richard John Walk Red Restaurant Mr. and Mrs. Frank Bynum Mr. and Mrs. Herman M. Heinemann Ellen Brenner Jordan Perlmutter Gerald I. White Rexer-Parkes - The Bynum Family Foundation William A. Herzog Carol A. Buonaiuto G. Jeffrey Poletti Mr. and Mrs. Jeffrey Wilks Rothmann’s Steakhouse C.M.S. Electrical Services, Inc. Mr. and Mrs. Joseph Heyenoort Robert Cafferkey Sooky Powels Steve Winick Frank Russo Mr. and Mrs. William J. Candee III - Cold Spring Motors Dr. Thomas C. Catalano Henry Powles Wolfensohn Family Foundation Raju Sarwal, M.D. Carol and Stephen Canter Cindy and Robert Higginson Harold Cederbaum Lydia & Christopher Reeves Say La Vie Christina Renna Daniel Carbone The Hotchkiss School Josephine & Ted Chodkowski In-Kind Gifts Tom Schaudel Elizabeth Roberts - Syosset Limousine Service, Inc. Frederic B. Ingraham Joan L. Clarkson Cathy Soref Sondra Rubin Mr. and Mrs. Vincent F. Carosella Walter B. James Fund No. 2 Aboff’s, Inc. John Paul Cleary Bruce Stillman Diane Edmin Sachs Mary and Richard Catalano Kathleen M. Csillag W. Dillaway Ayres, Jr. D. Curtis DeForest TD Bank Helen Schmall Jane H. Choate and Victor R. Klein, M.D. Banfi Vintners Leona Dubnick Jan Tozzo Dr. Uta von Schwedler Cosel-Pieper Family Foundation The Kleinknecht Family Foundation Bank of America Alice B. Duffy Edward Travaglianti Martha Seidel The Cunniff Family Lake Grove-Newfield Soccer Club, Inc. Ben’s Garden Tina Duque Catherine Freudenberg Traykovski Andrew Seligson Curtis Cushman Jill and Steven Lampe Besito Mexican Helen Eisenberg Tres Chic Suzanne Shea Lucy P. Cutting Carol and Jim Large Bethpage Federal Credit Union R. Duncan Elder Tres Jolie Salon Susan Sheehy Jane N.P. Mallinson BlueBirdNY Claire Martin Fairman Elizabeth Turnbull Kathleen Sobolewski Mr. and Mrs. Neil T. McGoldrick Brooks Brothers Dr. Richard D. Field Dr. Marjorie van de Stouwe Jason Stewart Bryan McMillen Susan Brunell Ardell Bierman Fox Dan Welden Graham Stillman Dr. and Mrs. Walter C. Meier Barbara Candee Zee Friedman Wild Honey Restaurant Joan Zaborowsky George N. Lindsay, Jr. and Nancy Metz Chelsea Piers Nancy Slaughter Gay Windham House Dr. Mark Zoller Mr. and Mrs. Clarence F. Michalis Edward A. Chernoff Monte Gerbish Leo Model Foundation Cold Spring Harbor Wine Shoppe Nicolo Gianni Contributions in honor of Dr. Kathleen Mooney Cottage Pharmacy Joni Gladowsky Ann and Steve Munn Crew Kitchen and Bar Jamie Nicholls and Fran Biondi Dr. Christopher G. Goff Vicki S. and Stephen V. Murphy Curtis-Mallet, Prevost, Colt & Mosle LLP Trudy Calabrese Teresa Haire Richard P. and Faye Nespola Daniel Gale Sotheby’s International Realty Ed Chernoff Charles E. Harris Charitable Foundation Nelson DeMille Ellen and Casey Cogut Lowell Harwood Andrea Newburger Ether/Ore Jewelry by Nina Fagiola Glenn Cohen Willa Noble Herzog Patricia and Hugh O’Kane, Jr. Farm to Table Catering by Filomena Susan Cohen Thomas Iovino Mrs. William H. Osborn, Jr. Fidelity Kate Seligson Friedman Dr. Andy Kaplan Mr. and Mrs. Richard S. Overton Rebecca and Steve Forster Ginny & David Knott Eli Kaplon Rhoda Parmet Thomas Forster Jordan Linde Allan Lisse Lisa Puntillo and Robert Pascucci Frassanito Jewelers Mary D. Lindsay Susan Petersen Lubow Mr. and Mrs. Nicholas B. Paumgarten David Luke III Jerry Swartz, Hirsh Cohen, Bill Bialek, Bruce Stillman, Jim Candido Fuentes-Felix, M.D. Robert Lindsay William Manos Watson and CSHL neuroscientists at the April 1 dedication of Mr. and Mrs. Robert A. Pilkington Letizia Gentile Students at the Hotchkiss School held a color run fundraiser the Jerome Swartz Centers for Neuroscience. in April to support autism research at CSHL. *Deceased *Deceased

40 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 41 COMMUNITY SUPPORT BOARD OF TRUSTEES

COLD SPRING HARBOR LABORATORY ASSOCIATION CORPORATE Officers Thomas C. Quick ADVISORY BOARD Executive Committee Jamie C. Nicholls William S. Robertson Officers Chairman Officers Peter Klein George Sard Laureen Stanton Knutsen Edward A. Chernoff Frank O’Keefe Robert D. Lindsay Jeffrey A. Nagel Chairman Thomas A. Saunders III President Vice-Chairman Timothy Q. O’Neill James A. Woods Marilyn H. Simons, Ph.D. Charles L. Sawyers, M.D. Whitney F. Posillico Membership Treasurer Caroline Monti Saladino Vice-Chairman Marilyn H. Simons, Ph.D. Tracey DeMatteis Serko Michael Aboff Virginia Knott Leo A. Guthart Lonnie Shoff Paul Amoruso Dinakar Singh Secretary Todd Andrews Treasurer Hope Geier Smith Samuel L. Stanley, Jr., M.D. Debbie Parmet Sondock Rocco S. Barrese Paul J. Taubman Edward Blaskey Directors Heather Lane Spehr Secretary Bruce W. Stillman, Ph.D. Mary Striano Thomas J. Calabrese Elizabeth Ainslie Christopher Callaghan James M. Stone, Ph.D. Nancy Szigethy Bruce W. Stillman, Ph.D. Lori Bahnik John D. Catalano Peter S. Tilles President & CEO Paul J. Taubman Hans E.R. Bosch Richard A. Catalano Lara S. Trafelet Michele Munn Celestino Jonathan Connors W. Dillaway Ayres, Jr. Edward Travaglianti Marjorie J. van de Stouwe, M.D. Edward A. Chernoff Marian Conway, Ph.D. Chief Operating Officer Heather Warren Whitman George Yancopoulos, M.D., Ph.D. Susan A. Cohen Philip D’Avanzo Maria de Lesseps J. Daniel Decker Roy J. Zuckerberg Individual Trustees SCIENTIFIC Nelson DeMille Honorary Directors Gregory DeRosa Robert Dickstein, Ph.D. Lalit R. Bahl, Ph.D. ADVISORY COUNCIL Ronald A. Gottlieb Mary D. Lindsay Brian Fox Honorary Trustees Carolyn Gulotta Tania A. Baker, Ph.D. Anne R. Meier Lawrence Goodman Frederick W. Alt, Ph.D. (Chair) Joel J. Kassimir, M.D. Cathy Cyphers Soref Mark W. Hamer Cornelia Isabella Bargmann, Ph.D. Bayard Clarkson, M.D. Kassahun Kebede Pearl F. Staller Mary Jane Helenek David Boies Norris W. Darrell Angelika Amon, Ph.D. Richard W. Humann Michael R. Botchan, Ph.D. Massachusetts Institute of Technology Robert Isaksen Charles F. Dolan Alan L. Jakimo Charles I. Cogut Cornelia Isabella Bargmann, Ph.D. Patricia Janco-Tupper Helen Ann Dolan The Rockefeller University Jacob Goldfield Neil M. Kaufman Lola N. Grace Joanne Chory, Ph.D. John C. Kean III Leo A. Guthart The Salk Institute for Norman Kelker, Ph.D. David H. Koch Jeffrey E. Kelter Biological Studies Amy Koreen, M.D. Mary D. Lindsay Laurie J. Landeau, V.M.D. David M. Knott* Carol W. Greider, Ph.D. Kyle Markham Laurie J. Landeau, V.M.D. David L. Luke III Johns Hopkins School of Medicine Victoria Meagher Robert D. Lindsay Stephen F. Melore Nancy Abeles Marks Leonid Kruglyak, Ph.D. Robert W. Lourie, Ph.D. University of California, Los Angeles Robert Palatnick Eduardo G. Mestre John G. Passarelli, M.D. Elizabeth McCaul Markus Meister, Ph.D. David Peikon William R. Miller California Institute of Technology Patricia Petersen Howard L. Morgan, Ph.D. Alan Seligson Joseph Roberto Jamie C. Nicholls Kevan M. Shokat, Ph.D. Stephen Ross, Ph.D. James Simons, Ph.D. University of California, Raju Sarwal, M.D. Frank O’Keefe San Francisco; Berkeley Craig A. Weiss Louise M. Parent James D. Watson, Ph.D. Max S. Wicha, M.D. Andrew Whiteley John C. Phelan Henry Wendt III University of Michigan Joseph M. Willen 2015 CSHLA Directors.

42 Cold Spring Harbor Laboratory 2015 Annual Report • Executive Summary 43 LABORATORY LEADERSHIP

EXECUTIVE MANAGEMENT ADMINISTRATIVE DEPARTMENTS Join our Drive for 125 Bruce W. Stillman, Ph.D. Business Development Human Resources Impact the future with a legacy gift to President & CEO & Technology Transfer Katherine G. Raftery Cold Spring Harbor Laboratory James D. Watson, Ph.D. Teri Willey Vice President Oliver R. Grace Professor Emeritus Vice President “I hope my scientific legacy—and I know my financial legacy, through Chancellor Emeritus Information Technology long-term support of pioneering research at CSHL—will benefit human- Culinary Services Hans Erik Aronson kind and our fragile planet on which all life depends. Giving back is far W. Dillaway Ayres, Jr. James Hope Vice President more rewarding than receiving. Chief Operating Officer Director Chief Information Officer I had the very good fortune in the 1970s of 1) doing my Ph.D. research RESEARCH Development Procurement at CSHL under the mentorship of Jim Watson and Ray Gesteland, Charles V. Prizzi Philip Lembo 2) collaborating with Rich Roberts, Rich Gelinas and Louise Chow on David L. Spector, Ph.D. Vice President, Vice President the discovery of split genes and RNA splicing, and 3) being inspired Director of Research Development and encouraged by Barbara McClintock to follow my scientific instincts Public Affairs Sydney Gary, Ph.D. & Community Relations despite their conflicts with accepted dogma and choirs of naysayers.” Director of Research Operations Dagnia Zeidlickis ~Daniel Klessig, Ph.D. Facilities Vice President, Arthur Brings Communications EDUCATION Vice President Banbury Center Chief Facilities Officer Sponsored Programs To discuss making a gift to CSHL, contact Diane Fagiola at Walter L. Goldschmidts, Ph.D. 516-367-8471 or email [email protected] Jan A. Witkowski, Ph.D. Finance & Accounting Executive Director Vice President Lari C. Russo Executive Director Dr. Klessig, a new Helix Society member and former CSHL scientist, is CSHL Press Chief Financial Officer currently a professor at Cornell University’s Boyce Thompson Institute. John R. Inglis, Ph.D. General Counsel Executive Director Charles S. Ryan, J.D., Ph.D. Vice President DNA Learning Center cold spring harbor laboratory is a not-for-profit research and educational institution chartered by the State General Counsel of New York. Less than half of the Laboratory’s annual revenues are derived from federal grants and contracts. It relies David A. Micklos Executive Director heavily on support from the private sector: foundations, corporations, and individuals. CSHL thanks each and every donor, whose contributions have made possible the discoveries and programs reported in this publication. Library & Archives Please consider a variety of ways to give to CSHL Ludmila T. Pollock Executive Director Capital and Endowment Campaign Science Education Meetings & Courses Program Help secure the financial stability of the Laboratory. Strengthen the DNA Learning Center, where young David J. Stewart, Ph.D. people learn about genetics in an interactive environ- Research Support Executive Director ment, and the Watson School of Biological Sciences, Speed the translation of genetic discoveries into which trains the next generation of biology researchers. Office of the President new diagnostic tests and therapeutics. Terri I. Grodzicker, Ph.D. Planned and Estate Gifts Dean of Academic Affairs Annual Fund Support the most innovative young researchers Make a gift from your estate and become a member Watson School in science today. of the Helix Society. of Biological Sciences Alexander Gann, Ph.D. Lita Annenberg Hazen Dean For more information, contact Charlie Prizzi, Vice President for Development, 516-367-6865 or [email protected]

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