CSHL’s research faculty has a rich history of contributing some of the most fundamental discoveries in molecular biology and genetics. This legacy, which includes 8 Nobel Prize winners, continues to be strengthened today by the 52 faculty members who head cutting-edge laboratories in a broad range of fields, some of which are often and increasingly interdisciplinary. Their efforts and output are consistently, internationally recognized. Thomson Reuters’ Essential Science Indicators, a leading index for institutional performance, has ranked CSHL in the top 1% of institutions most cited in published research and its faculty among the top three in terms of its influence in molecular biology and genetics.
neuronal circuits, sensory coding and synaptic plasticity, neuronal correlates of behavior, olfactory processing
How does the brain encode stimuli from the outside world to give rise to perceptions? What does a smell look like in the brain? The focus of my group is to understand how neural circuits compute sensory-motor transformations across different contexts, senses, and brain states to generate meaningful behaviors.
population genetics, bioinformatics, cancer, stochastic processes, statistical mechanics and information theory
The biological landscape is made up of millions of variables that interact in complex and often seemingly random ways. I am applying principles from physical and computational sciences to the study of biology to find patterns in these interactions, to obtain insight into population genetics, human evolution, and diseases including cancer.
Animals are faced with many decisions. They must integrate information from a variety of sources – sensory inputs like smell and sound as well as memories and innate impulses – to arrive at a single behavioral output. My laboratory investigates the neural circuits that underlie decision-making.
Among the changes that occur during pregnancy, those affecting the breasts have been found to subsequently modify breast cancer risk. My laboratory investigates how the signals present during pregnancy permanently alter the way gene expression is controlled and how these changes affect normal and malignant mammary development.
Ph.D., University of Copenhagen and the Danish Cancer Society, 2000
tumor microenvironment, intravital imaging, tumor-associated myeloid cells, breast cancer
Cancer cells are surrounded by immune cells, blood vessels, chemical signals and a support matrix – collectively, the tumor microenvironment. Most microenvironments help tumors grow and metastasize, but some can restrict tumors. My lab studies how to target the bad microenvironments and support the good ones to combat cancer.
Ph.D., Humboldt University of Berlin, Germany, 2007
neural dynamics and computation, neural circuit models, machine learning, stochastic processes, dynamical systems theory, decision-making, attention
My lab investigates how perception and cognition arise from changes in neural activity. We develop and apply computational methods to discover dynamic patterns in large-scale neural activity recordings. We then create mathematical models to explain how these activity changes emerge from signaling between neurons, ultimately driving behavior.
M.D., Johns Hopkins University School of Medicine, 1968
cancer immunology, pancreatic cancer, mouse models
I’m studying how to harness the power of the immune system to fight cancer. Our underlying premise is that the microenvironment within a tumor suppresses the immune system. We have found a way to eliminate this suppression in the mouse model of pancreatic cancer, which has led to development of a drug for human pancreatic cancer that will enter phase 1 clinical trials in 2015.
The nervous system transmits information by passing chemical signals from one nerve cell to the others. This signal transmission relies on a variety of proteins to receive and transmit the chemical signals. My group studies the structure and function of neurotransmitter receptors and ion channels that regulate fundamental neuronal activities.
gene networks, gene function prediction, guilt by association, neuropsychiatric, hub genes, multifunctionality, computational genomics
Of the tens of thousand of protein-coding genes in the human genome, only a small portion have an experimentally defined function. For the rest, how can we determine what they do? My lab develops computational predictions based on co-expression networks. We are applying our predictions to understand neuropsychiatric disorders.
genome-wide organization of transcription and the functional roles of non-protein coding RNAs
Only a small portion of the RNAs encoded in any genome are used to make proteins. My lab investigates what these noncoding RNAs (ncRNAs) do within and outside of cells, where regulators of their expression are located in the genome, and how perturbations of ncRNAs and their regulators contribute to disease.
To ensure that cells function normally, tens of thousands of genes must be turned on or off together. To do this, regulatory molecules - transcription factors and non-coding RNAs – simultaneously control hundreds of genes. My group studies how the resulting gene networks function and how they can be compromised in human disease.
post-transcriptional gene regulation, control of animal developmental timing, RNA biology
As organisms develop, genes turn on and off with a precise order and timing, much like the order and duration of notes in a song. My group uses model organisms to understand the molecules that control the tempo of development. We also study how changes in the timing of gene expression contribute to diseases like cancer.
development and function of the GABAergic inhibitory circuitry in neocortex, cortical circuits, mouse genetics, developmental plasticity, neurogenomics, autism
Studies the development and organization of neural circuits in the mouse cerebral cortex. His team uses an integrated approach to identify neuronal cell types and discover how they interact to process information and guide behavior, focusing on the motor cortex that controls forelimb movement. His studies of inhibitory interneurons, such as chandelier cells, have implications for understanding schizophrenia and autism.
computational biology, molecular networks, human genetics, human disease, applied statistical and machine learning, biomedical text-mining, molecular evolution
Every gene has a job to do, but genes rarely act alone. Biologists have built models of molecular interaction networks that represent the complex relationships between thousands of different genes. I am using computational approaches to help define these relationships, work that is helping us to understand the causes of common diseases including autism, bipolar disorder, and cancer.
plant development, stem cell signaling, genomics and imaging
My lab studies genes and signals in cells that regulate the growth and shape of plants. We have discovered several genes that control plant architecture by exerting an influence on stem cells. By identifying the genes that control the number of stem cells in corn plants, for example, we’ve discovered a means of boosting the yield of that vital staple.
Our cells depend on thousands of proteins and nucleic acids that function as tiny machines: molecules that build, fold, cut, destroy, and transport all of the molecules essential for life. My group is discovering how these molecular machines work, looking at interactions between individual atoms to understand how they activate gene expression, DNA replication, and small RNA biology.
My lab studies the neurobiological principles underlying cognition and decision-making. Using state-of-the-art technologies, we interrogate neural circuits in rodents as they perform a task. We validate our findings with analogous tasks in humans. We hope to define the neural circuits underlying decisions that will inform the development of new therapies for psychiatric diseases.
From regulating gene expression to fighting off pathogens, biology uses DNA sequence information in many different ways. My research combines theory, computation, and experiment in an effort to better understand the quantitative relationships between DNA sequence and biological function. Much of my work is devoted to developing new methods in statistics and machine learning.
The complexity of the mammalian brain challenges our ability to explain it. My group applies methods from mathematics and theoretical physics to understand the brain. We are generating novel ideas about neural computation and brain development, including how neurons process information, how brain networks assemble during development, and how brain architecture evolved to facilitate its function.
posttranscriptional control of gene expression, alternative splicing, splicing in genetic diseases and cancer, splicing-targeted antisense therapeutics
Our DNA carries the instructions to manufacture all the molecules needed by a cell. After each gene is copied from DNA into RNA, the RNA message is "spliced" - an editing process involving precise cutting and pasting. I am interested in how splicing normally works, how it is altered in genetic diseases and cancer, and how we can correct these defects for therapy.
in silico genomics of cancer, single-cell genomics, inference from noisy biological data, large-scale numerical computing
How does cancer arise? It evolves from innocuous beginnings, as healthy cells accumulate mutations and transform into lethal tumor cells. I am developing mathematical and statistical tools to discover key genetic elements involved in the evolution of cancer, and in particular, metastatic tumors.
single-cell, in situ RNA-seq, non-coding RNA, spatial genomics, cancer microenvironment, pancreatic cancer
Cells are amazingly complex, with the ability to sense, and remember timing, location and history. I am exploring how cells store this information, and how their surroundings influence their communication with other cells. I am also developing various imaging and molecular sequencing methods for tracking genes, molecules, and cells to understand how cancer cells arise and evolve.
computational biology, human genetics, phylogenetics, copy number variation
We have recently come to appreciate that many unrelated diseases, such as autism, congenital heart disease and cancer, are derived from rare and unique mutations, many of which are not inherited but instead occur spontaneously. I am generating algorithms to analyze massive datasets comprising thousands of affected families to identify disease-causing mutations.
synapse, physiology and plasticity, neural circuits, fear processing, reward processing, rodent behaviors related to mental disorders
My group studies the neural circuits underlying cognitive function and dysfunction as they relate to anxiety, depression, schizophrenia and autism. We use sophisticated technologies to manipulate specific neural circuits in the rodent brain to determine their role in behavior. We are interested in changes in synaptic strength that may underlie mental disorders.
Ph.D., Watson School of Biological Sciences at Cold Spring Harbor Laboratory, 2004
plant developmental genetics, mechanisms of phase transitions for flowering time and inflorescence branching, heterosis
My research team studies the genes that determine when and where, and thus how many, flowers are produced on plants. Flowers form on branches called inflorescences, which originate from stem cells. By studying the genes that control how stem cells become inflorescences, we are able to manipulate flower production to improve crop yields.
Ph.D., Rockefeller University, 2003
M.D., Weill Cornell Medical College, 2004
biochemistry, amino-terminal acetylation of proteins, human genetics, neuropsychiatric diseases, whole genome sequencing
My group focuses on human genetics and genomic medicine, with an emphasis on diseases with severe neuropsychiatric manifestations. We collect large family pedigrees and use whole-genome sequencing to define mutations that correlate with the syndromes. We then undertake detailed functional characterization of these mutations to discover fundamental new biology.
With joint appointments at CSHL and Northwell Health, I am working to expand clinical cancer research at our institutions to provide new treatments for patients as well as greater insight into the biology of this complex set of diseases. In my own research, I am collaborating on research in soft-tissue and bone sarcomas to better understand the cancer microenvironment and epigenetics, targeting molecular weaknesses to halt cancer growth.
plant genetics, transposons, development, gene regulation, DNA methylation
Chromosomes are covered with chemical modifications that help control gene expression. I study this secondary genetic code - the epigenome - and how it is guided by small mobile RNAs in plants and fission yeast. Our discoveries impact plant breeding and human health, and we use this and other genomic information to improve aquatic plants as a source of bioenergy.
computational biology, sequence-function relationships, population genetics, protein evolution, machine learning
Some mutations are harmful but others are benign. How can we predict the effects of mutations, both singly and in combination? Using data from experiments that simultaneously measure the effects of thousands of mutations, I develop computational tools to predict the functional impact of mutations in protein coding sequences.
genomics of psychiatric disorders, genomics of cancer, computational genomics, plant genomics
Over the last two decades, revolutionary improvements in DNA sequencing technology have made it faster, more accurate, and much cheaper. We are now able to sequence up to 10 trillion DNA letters in just one month. I harness these technological advancements to assemble genomes for a variety of organisms and probe the genetic basis of neurological disorders, including autism and schizophrenia, better understand cancer progression and understand the complex structures of the genomes of higher plants.
Cells employ stringent controls to ensure that genes are turned on and off at the correct time and place. Accurate gene expression relies on several levels of regulation, including how DNA and its associated molecules are packed together. I study the diseases arising from defects in these control systems, such as aging and cancer.
A theoretical physicist by training, my research is centered around intelligent machines. I do both theoretical and experimental work. The theoretical work is focussed on analyzing distributed/networked algorithms in the context of control theory and machine learning, using tools from statistical physics. My lab is involved in brain-wide mesoscale circuit mapping in the Mouse as well as in the Marmoset. An organizing idea behind my research is that there may be common underlying mathematical principles that constrain evolved biological systems and human-engineered systems.
M.D., Medical School of Charles University, Prague, 1991
Ph.D., SUNY Downstate Brooklyn, 1995
neurobiology of autism and schizophrenia, gene expression-based mapping of brain activity, anatomical mapping of brain connectivity, high throughput microscopy
To understand what’s going wrong in illnesses like autism and schizophrenia, we need to know more about how neural circuits are connected in the healthy brain. We’ve developed advanced imaging methods to draw the first whole-brain activation map in the mouse. Now we’re applying that technology to study changes in brain activity in mice whose behavior models human autism and schizophrenia.
Unlike animals, plants neither have specific organs that see or hear various stimuli, yet, plants are sensitive to their surrounding environment and modify their development according to various external signals. My lab studies how the environment of a plant modulates its growth and development. Understanding environmental control of growth will have far-reaching implications for agriculture, energy production, and many other human activities.
olfaction, audition, communication behaviors, in vivo electrophysiology, individual recognition
When confronted with another individual, social animals use multiple sensory inputs smells, sounds, sights, tastes, touches to choose an appropriate behavioral response. My group studies how specific brain circuits support these natural communication behaviors and how disruptions in these circuits can lead to inappropriate use of social information, as in Autism Spectrum Disorders.
computational biology, population genetics, computational genomics, molecular evolution, gene regulation
I am a computer scientist who is fascinated by the challenge of making sense of vast quantities of genetic data. My research group focuses in particular on questions involving human evolution and transcriptional regulation.
Two challenges in cancer biology guide my work: first, how do tumors become addicted to certain gene products, and second, how do tumors develop resistance to anti-cancer drugs. I focus on the epidermal growth factor receptor (EGFR), which is both addictive when mutated and a common source of drug resistance. We are also identifying new targets for the treatment of lung cancer.
The immense amount of DNA, RNA and proteins that contribute to our genetic programs are precisely organized inside the cell¹s nucleus. My group studies how nuclear organization impacts gene regulation, and how misregulation of non-coding RNAs contributes to human diseases such as cancer.
Despite the development of preventive vaccines, human papillomaviruses (HPVs) still infect more than five million women each year, significantly increasing their risk of cervical cancer. I am working to identify how HPV multiplies so that we may develop drugs that can defeat the virus once it has infected an individual.
cancer, cell cycle, DNA replication, chromatin assembly, biochemistry, yeast genetics
Every time a cell divides, it must accurately copy its DNA. With 3 billion “letters” in the human genome, this is no small task. My studies reveal the many steps and molecular actors involved, as well as how errors in DNA replication are involved in diseases that range from cancer to rare genetic disorders.
small RNA regulation, pattern formation, stem cell function, plant development
At the growing tip of plants sits a reservoir for stem cells, called the meristem, from which new organs, such as leaves, arise. We study genetic networks that distinguish stem cells from their differentiating descendants as well as the role of mobile small RNAs as novel meristem-derived signals that pattern leaves
transcriptional regulation, chromatin, critical periods in neurodevelopment, steroid hormones and behavior
I am interested in how transient events during development program neurons to take on a specific identity and function. More specifically, I am studying how estrogen and testosterone generate sex differences in the brain and behavior.
posttranslational modification, phosphorylation, phosphatases, signal transduction, protein structure and function
Cells must constantly react to what is happening around them, adapting to changes in neighboring cells or the environment. I study the signals that cells use to exchange information with their surroundings. Our group is finding drugs that target these signals and thus can treat diabetes, obesity, cancer, and autism spectrum disorders.
cancer modeling and treatment, senescence and tumor progression, cancer visualization, PTEN regulation
We have recently developed the first genetic mouse model for therapy and analysis of metastatic prostate cancer. Now we can test if and how modern concepts of cancer evolution can outperform the 80-year-old standard of care - hormone deprivation therapy - and turn lethal prostate cancer into a curable disease.
pancreatic cancer, experimental therapeutics, diagnostics, mouse models, cancer genetics
Pancreatic cancer is an extremely lethal cancer. On average, patients who are diagnosed with pancreatic cancer succumb to the disease within 6 months. Research is the only way to defeat pancreatic cancer. My lab is making progress toward finding a cure by detecting the disease earlier and designing novel therapeutic approaches.
chromatin, transcriptional regulation, acute myeloid leukemia, BET bromodomains, lysine methyltransferases
Cancer cells achieve their pathogenicity by changing which genes are on and off. To maintain these changes in gene expression, cancer cells rely on proteins that interact with DNA or modify chromatin. My group investigates how such factors sustain the aberrant capabilities of cancer cells, thereby identifying new therapeutic targets.
signal transduction, Ras and Rho proteins, tumorigenesis, neuronal development and disorders
Normal cell function relies on coordinated communication between all the different parts of the cell. These communication signals control what a cell does, what shape it takes, and how it interacts with other cells. I study these signaling networks to understand how they guard against cancer and neurological disorders.
When we think of evolution, we often think about physical changes, like a plant developing broader leaves to collect more solar energy. Such evolution actually occurs within the plant’s DNA. I am using computational analysis and modeling to visualize how plant genomes have evolved over time, particularly those of staple crops. We are learning from this work to improve the range and yield of modern plants.
human genetic disorders, population genetics, cancer genomics
Devastating diseases like cancer and autism can be caused by spontaneous changes to our DNA—mutations first appearing in the child, or in our tissues as we age. We are developing methods to discover these changes in individuals, tumors, and even single cells, to promote early detection and treatments
My lab studies how circuitry in the brain gives rise to complex behaviors, one of nature’s great mysteries. We study how the auditory cortex processes sound, and how this is interrupted in autism. We also seek to obtain a wiring diagram of the mouse brain at the resolution of individual neurons. Our unusual approach exploits cheap and rapid “next-gen” gene sequencing technology.
I study a type of brain cancer known as malignant glioma, which differs from healthy tissue by a small number of defining characteristics. By forcing glioma cells to adopt these healthy traits, we can stop tumor growth. My group searches for therapeutic ways to force this transition.
Are you really what you eat? Our goal is to uncover the precise mechanisms that link nutrition to organismal health and disease states at the cellular and molecular level. A particular focus in our lab is to understand how dietary perturbations affect the immune system and contribute to the risk of diseases that are associated with immune dysfunction such as cancer.
Ph.D., Massachusetts Institute of Technology, 2015
cancer genetics, aneuploidy, genome dosage imbalances, systems biology
Nearly all tumors exhibit a condition known as aneuploidy – their cells contain the wrong number of chromosomes. We’re working to understand how aneuploidy impacts cancer progression, in hopes of developing therapies that can specifically eliminate aneuploid cancers while leaving normal cells unharmed.
Ph.D., Joint program of Massachusetts Institute of Technology and National University of Singapore, 2013
normal and malignant hematopoietic stem and progenitor cells, self-renewal, cancer metabolism, myelodysplastic syndrome, leukemia
My research group focuses on normal and malignant hematopoietic stem and progenitor cells, specifically early erythroid progenitors and leukemic stem cells. We are currently using both CRISPR/Cas functional genomic and forward chemical biology genetic approaches to uncover critical genes and small chemical compounds regulating the self-renewal of hematopoietic stem and progenitor cells. The ultimate goal of this work is to identify novel therapeutics for drug resistant cancer-related anemias and leukemias through targeting of novel self-renewal pathways and metabolic vulnerabilities.
Research Assistant Professor/Manager, Functional Genomics
Currently the Director of the Functional Genomics Shared Resource at CSHL. His studies focus on shRNA, microRNA, RNA interference, and siRNA. The lab has studied cancer proliferation gene discovery through functional genomics.
Research Assistant Professor/Manager, Animal Imaging
Applies non-invasive imaging methods and develops new imaging reagents to facilitate the use of genetically engineered mouse models of cancer in pre-clinical and basic cancer research. As Director of Animal Imaging, he provides collaborative research support to investigators at both CSHL and neighboring institutions and will an important role in the pre-clinical research facility at CSHL.
Our genome can encode hundreds of thousands of different proteins, the molecular machines that do the work that is the basis of life. I use proteomics, a combination of protein chemistry, mass spectrometry and informatics, to identify precisely which proteins are present in cells - cells from different tissues, developmental stages, and disease states.
Research Assistant Professor/Mgr, Antibody & Phage Display
Studies the creation of engineered biologics such as antibodies, proteins and peptides, for therapeutics and translational medicine. The lab employs protein engineering and chemical biology approaches to develop therapeutic biologics acting on cell signaling machineries in order to abrogate pathological cellular behavior. He is currently the Director of CSHL Cancer Center Antibody Shared Resource- a collaborative resource for high quality antibody development.
Ph.D., Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 1978
Stem cells give rise to all the diverse types of cells that make up our bodies. As we age, neural stem cells in the brain are lost, leading to age-related cognitive decline. I study the signals that control how neural stem cells decide when to divide and what to become, in an effort to understand age-related memory loss and depression.
growth control in mammalian cells, post-transcriptional gene silencing
I explore the processes that cells use to turn genes on and off. My work is focused on understanding a relatively new class of cellular pathways, governed by molecules known as small RNAs, that control gene activation and repression. Our studies of small-RNA biology in early development provide insights into human evolution, diversity, and diseases such as cancer.
genomics, DNA sequencing, genome assembly validation, high performance and multicore computing, parallel algorithms, cloud computing
DNA sequencing efforts produce trillions and trillions of As, Cs, Gs, and Ts each minute - but what do the letters mean? My group develops novel computational methods to extract the information contained in biological sequences. We are applying these tools to discover mutations associated with cancer and autism and to reconstruct the genomes of important plants, animals, and microbes.