The Abu-Remaileh Lab is interested in identifying novel pathways that enable cellular and organismal adaptation to metabolic stress and changes in environmental conditions. We also study how these pathways go awry in human diseases such as cancer, neurodegeneration and metabolic syndrome, in order to engineer new therapeutic modalities.
Russ Altman's research is focused on the interaction of genes and drugs and on methods for unraveling these complex relationships with informatics technologies.He is the PI of the Pharmacogenomics Knowledgebase (PharmGKB), the premier repository of information about how human genetic variation impacts drug response phenotypes. He is also PI of the Simbios National Center for Physics-Based Simulation of Biological Structure, which studies the molecular interactions between drugs and their target gene-products. His group also uses text-mining methods to extract information about gene-drug interactions from the published literature and uses data mining and machine learning methods to extract clues about the molecular basis of drug action and side effects. He has collaborated with Euan Ashely and Atul Butte in creating methods for annotating whole human genomes (his focus is on predicting drug responses). He is the Director of the Biomedical Informatics training program.
Euan Ashley's lab is developing new methods to interpret genomic variants in medicine, with a particular focus on cardiovascular biology. He led the team that carried out the first clinical interpretation of a human genome in 2010, and now directs the Clinical Genome Service and Center for Inherited Cardiovascular disease at Stanford. His lab is also studying variants associated with elite athletic performance. Approximately half his lab is devoted to experimental tests of gene function using a variety of cell culture, transgenic, and induced stem cell models to test hypothesis generated by clinical sequencing and association studies.
The Attardi lab seeks to answer which p53-regulated gene networks and which cellular programs facilitate this critical transcription factor’s anti-tumor activity. The research this through CRISPR/Cas9 screens, ATAC-sequencing, genetic mouse models, proteomics, single cell transcriptomic, and a wide variety of other techniques available to us through our large network of collaborators at Stanford.
Julie Baker’s research is centered on understanding the molecular regulation of the first cell fate decisions in the embryo. Her lab incorporates frog embryology, mouse genetics, and human embryonic stem cell technology to explore how gene networks guide cell fate and how improper specification of these cells – particularly the trophoblast – leads to disease. She has been one of the lead investigators on the Stanford March of Dimes Prematurity Center, spearheading an effort to correlate errors of placentation with pregnancy disease. She and Bustamante are also collaborating on a study of altitude adaptation in the highlands of Peru and its implications for preeclampsia. They co-mentor an M.D./Ph.D. student.
Maria Barna’s laboratory is focused on understanding the cellular and molecular basis for how complex three- dimensional tissues are formed during vertebrate embryonic development. Her work on classical mouse skeletal mutants has shown that fundamental aspects of tissue patterning are directed by “specialized ribosomes”, which act to selectively translate subsets of mRNAs harboring unique cis-regulatory elements. Her lab has developed novel translational profiling technologies to delineate how the genomic template is translated into functional proteins within unique cell and tissue types. A second major research focus is developing and employing state-of-the-art imaging and transgenic chicken reporter strains to uncover the earliest morphogenetic events during embryonic development. They are visualizing activation of signaling during organogenesis at single & subcellular cell resolution, providing novel insights into tissue patterning.
Michael Bassik's lab studies how endocytic pathogens such as toxins, viruses, and protein aggregates enter cells, disrupt homeostasis, and cause apoptosis. His lab has developed novel ultra-complex shRNA libraries and CRISPR-based approaches that make it possible to systematically knock down pairs of genes in high throughput screens in cultured cells. This work has facilitated the first systematic genetic interaction maps in mammalian cells. These interaction maps help understand coordinated gene functions, can predict new functions for uncharacterized genes, and make it possible to search for new drug targets.
Philip Beachy studies the biology and mechanism of Hedgehog protein signaling. Past research established how Hedgehog proteins disseminate from localized sites of expression to pattern the embryonic development of brain, spinal cord, axial skeleton, and other organs. He is currently studying Hedgehog signaling during repair and regeneration of a variety of adult tissues, and its effects on stem cell physiology and cancer stem cells. At a mechanistic level, the laboratory studies how lipid-modified Hedgehog signals are packaged and released as multivalent particles which engage the transporter-like protein Patched and its co-receptors.
Gill Bejerano’s lab studies the cis-regulatory architecture of the human genome. Major interests include mapping regulatory elements involved in early limb, forebrain and placenta development, identifying regulatory changes that have contributed to lineage-specific evolutionary traits, and interpreting human sequence variants found during personal genome sequencing and clinical medicine.
Dominique is a plant scientist with a specific focus on developmental biology and plant biology. Correspondingly, she is a professor of Biology at Stanford University and is in association with the Stanford Institute for Stem Cell Biology and Regenerative Medicine
Ami Bhatt's lab characterizes the dynamics of the microbiome in immunocompromised individuals with hematological malignancies, and explores how changes in the microbiome are associated with idiopathic diseases in patients. Her microbiome sequence-based analysis has led to the discovery of a novel bacterium in diseased human tissue.
Alistar Boettiger’s lab aims to understand how long-range interactions between non-consecutive parts of the genome are regulated to control gene expression. Such interactions between cis-regulatory elements (such as enhancers and promoters) are essential for all developmentally regulated genes and lies at the core of cell differentiation. Differences in CRE activity and CRE interactions are likely responsible for much of the genetic variation between individuals in terms of both appearance and health, as the transcribed sequence of genes is highly conserved. We believe the answers to these questions require understanding the 3-D organization of the genome.
The Boyd lab studies healthy and pathogenic human immune responses in the context of vaccination, infectious diseases, and allergy, using a combination of antigen receptor sequence analysis, antibody functional characterization, and cellular immunology experiments.
Anne Brunet’s lab uses a combination of genetics and genomic approaches to investigate the genetic and epigenetic mechanisms regulating longevity in a variety of model systems, from worms to mammals. Her lab studies a pivotal genetic pathway that controls lifespan in an evolutionarily conserved manner (the Insulin-Foxo pathway), and the importance of chromatin modifiers in longevity and regeneration. They have also pioneered new genetic mapping, sequencing and CRISPR approaches in the African killifish N. furzeri, which shows great longevity variation and the shortest known vertebrate lifespan, as a new model system for aging.
Howard is a physician-scientist who has trained in genome science. His research focuses on mechanisms that coordinate the activities of large number of genes in cell fate control. His lab made a series of discoveries that introduced the important and pervasive roles of long noncoding RNAs in biological regulation. Howard has substantial experience in epigenetics and RNA biology, including invention of new methods for epigenomic profiling, map RNA occupancy on chromatin, and define RNA structures genome-wide. His lab pioneered methods to identify key regulators of large-scale transcriptional programs; these methods have been highly fruitful for studies of development, cancer, and aging. The long term goal of my laboratory is to decipher the regulatory information in the human genome for disease diagnosis and therapy.
James Chen’s laboratory has pioneered the use of chemical tools to study developmental signaling pathways. They have discovered and/or characterized several small-molecule modulators of the Hedgehog pathway, such as the first Smoothened antagonists (cyclopamine, SANT-1 through 4, SANT-75) and agonists (SAG and purmorphamine); the first Hedgehog protein blocker (robotnikinin); and antagonists epistatic to Suppressor of Fused (HPI-1 through -4) that includes the first chemical inhibitor of dynein (HPI-4). They have also developed new technologies for embryological studies using zebrafish, including the first caged morpholinos that enable light-controlled gene silencing with spatiotemporal precision. By integrating photoactivatable reagents with caged fluorophores, flow cytometry, and microarray studies, they have dynamically profiled transcription factor targets during embryogenesis, revealing a surprising degree of functional plasticity within a single cell lineage.
Thomas Clandinin research program is focused on three central questions in neurobiology. How do neuronal circuits assemble during development? How are the functions of these circuits maintained during adult life? How do such circuits mediate the complex computations essential to animal behavior? Our work exploits the interplay between the cells and genes that underpin these processes to define new molecular mechanisms that control neuronal connection specificity, synapse maintenance, and to characterize the computational roles of specific circuits. The long term goal of our program is to understand how the genome programs neural circuits across adult life to implement the computations that underpin innate behavior, using the visual system of the fruit fly as a model.
Gerald Crabtree’s laboratory uses genomic analysis and mouse genetics to probe basic processes of chromatin regulation. They are particularly interested in the molecular mechanisms used by chromatin remodeling complexes, including ATP-dependent chromatin regulation by BAF complexes (a remote relative of yeast SWI/SNF). This polymorphic family of chromatin remodeling complexes is mutated in about 16% of all human tumors, and play genetically dominant roles in the development of the human and murine nervous system. The lab has developed novel strains of "Chromatin Indicator and Assay" mice that allow rapid regulation of chromatin at specific loci, facilitating new modeling of chromatin dynamics in living cells.
Christina Curtis's lab studies evolutionary dynamics, novel therapeutic targets, and the genotype to phenotype map in cancer. Her extensive genomic studies of tumor samples have led to a novel "big bang" model of intratumoral heterogeneity, and provides a new quantitative framework for interpreting tumor growth and DNA sequence signatures in cancer patients.
The Engreitz lab combines experimental and computational genomics, biochemistry, molecular biology, and human genetics to assemble regulatory maps of the human genome and uncover biological mechanisms of disease.
Andrew Fire’s lab studies a variety of natural mechanisms that are utilized by cells adapting to genetic change. These include mechanisms activated during normal development and systems for detecting and responding to foreign or unwanted genetic activity. At the root of these studies are questions of how a cell can distinguish "self" versus "non-self" and "wanted" versus "unwanted" gene expression. Much of the current effort in the lab is directed toward a molecular understanding of the RNAi machinery and its roles in the cell. RNAi is not the only cellular defense against unwanted nucleic acid, and substantial current effort in the lab is also directed at the identification of other triggers and mechanisms used in the recognition and response to foreign information in both model systems and in human pathogen surveillance.
The long term goal of Dr. Frydman's research is to understand how proteins fold in living cells. The lab uses a multidisciplinary approach to address fundamental questions about molecular chaperones, protein folding and degradation. In addition to basic mechanistic principles, we aim to define how impairment of cellular folding and quality control are linked to disease, including cancer and neurodegenerative diseases and examine whether reengineering chaperone networks can provide therapeutic strategies.
Polly Fordyce is developing new methods for quantitative, systems-scale measurements of molecular interactions. Using novel micro-fluidic assays, she has studied the relationship between transcription factors, binding affinities, and target gene networks in S. cerevisiae, C. albicans, and humans. This work has helped identify entirely new classes of DNA binding transcription factors, and revealed how amino acid differences between particular TF family members can change binding specificity and gene network interactions. She is currently developing automated spectral encoding methods to create novel polymer bead libraries containing millions of distinct codes, enabling new multiplexed genomic-scale assays that are currently impossible.
Hunter Fraser studies the regulation and evolution of gene expression using a combination of experimental and computational approaches. His work brings together quantitative genetics, genomics, epigenetics, and evolutionary biology to achieve a deeper understanding of how genetic variation within and between species affects genome-wide gene expression and ultimately shapes the phenotypic diversity of life.
Margaret Fuller’s lab investigates the mechanisms that regulate self-renewal, proliferation, and differentiation in adult stem cell lineages. They use the Drosophila male germ line model to investigate how adult stem cells recognize, maintain attachment to, and orient toward their support cell niche, and how the daughters of stem cell divisions enter and then execute the differentiation program. They are also investigating the mechanisms that limit the proliferation capacity of transit amplifying cells and trigger and mediate the switch from proliferation to terminal differentiation in adult stem cell lineages. In addition, they are investigating the mechanisms that regulate the cell type specific cell cycle of meiosis in males and that turn on the cell-type specific terminal differentiation program once germ cells become spermatocytes.
Aaron Gitler’s research is on defining the mechanisms of human neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). They use yeast as a model system to study the effects of protein aggregation on cell biology and to perform unbiased genome-wide screens for modifiers. These studies have allowed them to define conserved cellular pathways affected by aggregation-prone proteins in Parkinson’s and ALS, and to a common human genetic risk factor for ALS.
Hank Greely is a Professor at Stanford Law and a joint faculty in Genetics. His current interests in human genetics focus on prenatal genetic diagnosis, the impacts of clinical whole genome sequencing, and ethical, legal, and social issues in genomic biobanks. His interests in stem cells include legal challenges to stem cell research and ethical issues involving human/non-human chimeras. He also studies human research protections, biological enhancement, and the future of reproductive technologies.
William Greenleaf’s lab leverages the power of high-throughput sequencing methods and cutting-edge optical microscopy to study the relationship between genome sequence and function. The lab studies the relationship between RNA sequence, function, and using a newly-developed RNA array method; detects and quantifies rare genetic and epigenetic variation in cells and single molecules by developing new molecular biology and microfluidic methods, and maps the structure of chromatin in vivo using a power new "assay for transposase accessible chromatin" (ATAC-seq) that can be applied quickly and easily to small numbers of cells.
Stefhan Heller’s lab is interested how the inner ear forms from an early anlage called the otic placode. Our goal is to describe the otic lineage from an early placodal progenitor until it splits up into multiple cell types making up the sensory epithelia, innervating ganglia, and accessory structures. In parallel, we apply knowledge we gained from guiding embryonic and induced pluripotent stem cells along the otic lineage to find ways for treatment of hearing loss. This involves identification of mechanisms of sensory hair cell regeneration in animals such as chickens that recover from hearing gloss, screening for potential regenerative targets that can be activated with drugs, and exploring reprograming as well as cell transplantation strategies.
The Jerby lab studies collective multicellular behaviors in the context of the cancer-immune interplay. They define “immune responses” broadly, as any molecular crosstalk that allows different cells or cell types to jointly detect and repress pathological processes. Our primary goal is to uncover multifactorial immune evasion mechanisms in highly aggressive tumors and use this information to identify interventions that could block tumor formation/progression through targeted immune responses.
KC Huang’s laboratory employs diverse interdisciplinary methods of inquiry to understand the relationships among cell shape detection, determination, and maintenance in bacteria. Current topics of interest are (i) cell-wall biosynthesis, (ii) the regulation and mechanics of cell division, (iii) membrane organization, and (iv) membrane-mediated protein interactions. Ultimately, the manipulation of cell shape may provide a direct tool for engineering complex cellular behaviors. Currently, we are interested in (i) the role of the cell wall in cell-shape determination, (ii) the regulation and mechanics of the cell cycle and cell division, (iii) the spatial and temporal organization of the membrane, (iv) the role of the membrane in transmembrane-protein interactions and ion channel gating, and (v) collective behavior in bacteria.
Daniel Jarosz’s research program focuses on a key paradox in biology: organisms can remain the same for long periods, but they must also diversify to survive in fluctuating environments. The lab studies mechanisms that contribute to this balance between robustness and change. Understanding this paradox at the molecular level offers the potential to thwart human pathologies ranging from cancer to neurodegeneration and multi-drug resistant infections. The lab employs multidisciplinary approaches including biochemistry, genome-scale analyses, high-throughput screening, and quantitative genetic techniques. Current investigations use large- scale screening experiments to study prion-like phenotypic switching yeast, to identify new molecular mechanisms of phenotypic plasticity, and to study how molecules interact with environmental fluctuations to generate biological novelty. A long term aim is to identify methods to manipulate these mechanisms for therapeutic benefit, and to harness their power to engineer synthetic signaling circuits.
Mark Kay’s lab studies new gene transfer vectors for gene therapy. A major interest has been in unraveling the basic mechanisms of vector transduction in vivo. His work on recombinant AAV vectors played an important role in a human factor IX clinical trial that included the first systemic administration of rAAV into humans. His lab has also worked on developing RNA interference vectors for therapeutic applications in liver disorders. Their work on whole mammals has uncovered key mechanistic insights that have resulted in new types of studies to evaluate the mechanism of miRNA loading into mammalian RISC, the identification of new classes of small RNAs derived from tRNAs, and small RNAs that may be generated by RNA-directed RNA transcription in vertebrates. Major accomplishments include inhibition of human viral (HBV) replication in whole animals, and demonstration of toxicity with shRNA over -expression in mammals, resulting in the discovery of rate-limiting processes for RNAi-based therapeutics.
Paul Khavari’s experimental focus is on the mammalian setting, including mouse genetics, human genetics, single cell studies, and new human tissue platforms. The latter encompass human skin regenerated on immune deficient mice as well as organotypic constructs with epithelial and stromal cells embedded within architecturally faithful mesenchyma in vitro. These new models, which we term Multi-Functional Human Tissue Genetics, allow up to 10 alleles or more to be altered simultaneously, permitting genetic experiments with an unprecedented degree of rapidity and complexity.
Seung Kim's lab studies fundamental pathways of hormone secretion, glucose control, and pancreatic islet development using Drosophila, mice, and humans. His development of sensitive assays for glucose control in flies has made it possible to model human diabetes GWAS variants for likely target genes and pathways, and to discover novel hormone pathways that control insulin secretion. His work in mice and humans has identified the important role of Menin, Wnt, PDGF, and NFAT signaling in controlling â-cell proliferation during neonatal development, pregnancy, and aging. Dr. Kim's lab is also combining detailed genomics profiling with cell culture methods to deconstruct and reconstitute pancreas development in vitro, with the long-term goal of developing improved strategies for replacement or regeneration of pancreatic islets of Langerhans.
David Kingsley is using genetics and genomics to identify the molecular basis of evolutionary change in vertebrates. Originally trained as a mouse geneticist,Dr. Kingsley has more recently pioneered the development of both genetic and genomic tools for threespine stickleback fish. By combining genetic mapping, positional cloning, and transgenic rescue experiments, his laboratory has identified specific major genes and mutations that underlie dramatic morphological differences between recently evolved marine and freshwater fish species. He leads an international collaboration to develop a multi-level view of vertebrate evolution, combining whole genome sequencing, developmental biology, and population genetics of evolutionary change in sticklebacks, and applying lessons from this system to several other evolving organisms, including humans.
Karla Kirkegard's lab studies viral, cellular, and host factors that control the replication, recombination, cell-to- cell spread, and host immune response to positive strand RNA viruses like polio. Her work has shown that defective versions of viral products that form oligomeric complexes such as capsids and polymerases, can often behave as genetic dominants in infected cells. This has particular significance for anti-viral drug design, since potentially drug-resistant viruses will usually be generated within cells that already harbor drug susceptible genomes. Her lab is developing the principle of "dominant drug targeting” for poliovirus, Dengue and hepatitis C. Her lab has also elucidated the function of the first long non-coding RNA that controls pathogen susceptibility, based on a classic mouse locus that controls ability to clear Theiler's virus via changes in interferon gamma mRNA synthesis. In both mice and humans, the lncRNA is highly polymorphic, and work is in progress to determine the consequences of these polymorphisms for infectious and inflammatory disease.
Anshul Kundaje's lab develops statistical and machine learning methods to integrate large-scale functional genomic and genetic data, to learn new models of gene regulation, and to decipher the regulatory impact of natural and disease-associated genetic variants. He led computational analysis efforts of two of the largest functional genomics projects to date, the Encyclopedia of DNA Elements (ENCODE) consortium and the Roadmap Epigenomics Project. His lab has deciphered the largest collection of regulatory elements in the human genome; and has obtained fundamental insights into regulatory dynamics and variation across individuals, cell types species, and diseases. His work has helped identify the cell types and pathways most likely affected by common disease-associated SNPS, revealing for example, the important role of immune pathways in shaping susceptibility to Alzheimers disease.
Jin Billy Li’s lab is primarily interested in identifying and understanding sequence variations in RNA and DNA. In particular, they focus on RNA editing, where genomically encoded information is changed in the RNA. Their long-term goal is to map sequence changes in transcriptomes, elucidate their mechanisms, and understand their functions in health and disease. Their approaches include molecular genetics, genomics, computational biology, evolutionary analysis, precise CRISPR engineering in Drosophila, and new technology development.
Kyle Loh: Embryonic stem cells can produce any type of human cell in a dish. Thus they afford an opportunity to recreate, and thus study, basic developmental phenomena (lineage diversification, tissue self-organization and multilineage competence) that are difficult to probe in a developing embryo. However, this opportunity has yet to be fully realized because stem-cell differentiation often yields heterogeneous mixtures of cells that are ill-suited for molecular analysis or cell therapy. We have developed a reductionist system to define the minimal essential inductive and repressive signals necessary for the developmental induction of a given embryonic lineage from differentiating ESCs. These efforts culminated in systematic roadmaps describing the extrinsic signals that guide human ESCs into a variety of endoderm and mesoderm germ layer derivatives (including liver, intestinal, bone and heart progenitors) through a series of bifurcating intermediate steps. The overarching goal is to exploit the resultant highly-pure populations of human tissue progenitors to explore classic questions in developmental biology, using stem-cell differentiation as a technological platform.
The Mourrain lab combines expertise in neuroscience, genetics, epigenetics, developmental biology and engineering to understand why we sleep and how sleep changes our synaptic connection to improve our cognitive performance. To unravel synaptic deficiencies in neurodevelopmental (Fragile X syndrome, Autism) and neurodegenerative disorders (Alzheimer’s, Parkinson’s) as well as during normal aging. Uncover genes and processes important for neuronal regeneration to replace dead or deficient tissue in the brain including retina. To push further our understanding of gene regulation and how non-coding SNPs can be responsible for human diseases.
Hiromitsu Nakauchi's lab is defining fundamental principles of hematopoiesis and niche signaling pathways, and developing innovative new methods for replacing solid organs in vivo. His detailed lineage tracing work in mice has discovered novel self-renewing progenitors and novel myeloid differentiation pathways that revise the conventional hierarchical model of blood cell development. His group has also established a new model for producing donor stem cell-derived solid organs in vivo, using blastocyst complementation with a pancreatogenesis-disabled host mouse embryo, and showing that a functional rat pancreas can develop in an otherwise pancreas deficient mouse (the first truly “exogenic” organ). He is currently extending this work by reconstituting organs in pancreas-deficient pig models, with the exciting prospect of ultimately generating large, functional organs from donor stem cells that can be used for clinical applications in humans.
Roel Nusse’s lab has pioneered the study of oncogenes, particularly the Wnt family pathway. Wnt proteins are essential for the control over stem cells. How this is achieved is far from clear and is the subject of studies in the lab, both in vivo and in cell culture. In vivo, a particular question the lab address with genetic and genomic methodology is how physiological changes, such as those occurring during hormonal stimuli, injury or programmed tissue degeneration, have an impact on the self-renewal signals and on stem cell biology.
Lucy O’ Brien’s lab has developed the Drosophila midgut as a simple invertebrate model to uncover the rules that govern adaptive remodeling. In adult flies, the midgut is a stem cell-based organ analogous to the vertebrate small intestine. We have found that when dietary load increases, midgut stem cells activate a reversible growth program that increases total intestinal cell number and digestive capacity. The midgut is a uniquely tractable model to study adaptive growth; not only can gene expression be manipulated and lineages traced at single-cell and whole-tissue levels, but complete population counts of all cell types are possible. Our goal is to understand how this nutrient-driven mechanism regulates stem cell behavior for lifelong optimization of organ form and function.
Dr. Oro's research interests encompass cancer genomics and tumor evolution, stem cell biology and hair/skin development and regeneration, and definitive molecular and cellular therapeutics. His clinical interests include hair biology, non-melanoma skin cancer, and stem cell-based therapies for genetic skin diseases.
The Petrov lab is interested in a wide range of questions in molecular evolution and molecular population genetics. We do theoretical, computational and experimental work to address these questions. Our primary focus at the moment is on (i) population genetics and molecular mechanisms of adaptation and (ii) genome evolution.
Jonathan Pritchard's lab studies how genetic variation impacts gene regulation and complex traits. He has developed new computational tools for analyzing population structure, history, and adaptation, especially in humans. His lab would like to be able to predict which noncoding variants in the genome are likely to have regulatory effects in any given cell type, and how these link to phenotypic variation and disease. His lab pioneered the analysis of various genomic phenotypes measured in panels of human cells, including RNA-seq, DNase-seq, and mRNA-decay. He has also analyzed the human genome for both hard and soft selective sweeps, producing new insights into population history and regions of the genome under selection.
A major interest of my lab is the mechanism by which stem cells maintain a quiescent state, are activated to undergo proliferative expansion and differentiation, and undergo self-renewal. We focus specifically on stem cells from skeletal muscle, but study comparable processes in stem cells other mesenchymal tissue (e.g. fat) and epithelia (e.g. skin, gut, and neuro-epithelia). Our studies have focused primarily on the Notch and Wnt signaling pathways in these processes.
Research in the lab addresses problems in evolutionary biology and human genetics through a combination of mathematical modeling, computer simulations, development of statistical methods, and inference from
population-genetic data. Noah’s current work covers topics such as human genetic variation, inference of human evolutionary history, the role of population genetics in the search for disease-susceptibility genes, the
relationship of gene trees and species trees, and mathematical properties of statistics used for analyzing genetic variability.
Julien Sage's research program focuses on defining the cellular and molecular mechanisms that control the proliferation and the differentiation of mammalian cells with a particular emphasis on the role of the RB pathway in stem cells in vivo and its impact on subordinate gene regulatory networks. A major discovery of the Sage lab is the identification of adult stem/progenitor cells as cells from which sporadic cancers may initiate following loss of function of the RB pathway, as well as the demonstration that RB normally controls the fate of these populations of stem cells in vivo. A second major achievement is the development and the analysis of mouse models for human neuroendocrine small cell lung cancer (SCLC) and hepatocellular carcinoma (HCC). Recently, the Sage lab has explored the role of the RB pathway in embryonic stem cells, investigating the relationship between the cell cycle machinery and pluripotency factors.
Dr. Sanuli studies the organizing principles of the genome and how these principles regulate cell identity and developmental switches.
Gavin Sherlock's research focuses primarily on the molecular basis of adaptive evolution. His lab uses yeast as an experimental model, and developed a system whereby subpopulations can be tracked during in vitro evolution, such that adaptive events could be inferred. Using this system, they were able to show that clonal interference dominates such experiments, and were also able to subsequently show that there exists a rugged fitness landscape resulting from reciprocal sign epistasis between adaptive mutations. His lab has employed high-throughput sequencing to identify the adaptive mutations and the pathways that they affect in this experimental system. In addition, his lab is using RNA-Seq to characterize the transcriptome of the human fungal pathogen Candida albicans, and also runs several genome databases.
Michael Snyder is Chair of Genetics and a leader in the field of functional genomics and proteomics. His laboratory has launched and applied many technologies in genomics and proteomics, including the development of proteome chips, high-resolution tiling arrays for the entire human genome, methods for global mapping of transcription factor binding sites, paired end sequencing for mapping of structural variation in eukaryotes, and RNA-Seq. These technologies have been used for characterizing genomes, proteomes, and regulatory networks. Seminal findings from the Snyder laboratory include the discovery that much more of the human genome is transcribed and contains regulatory information than was previously appreciated, and a high diversity of transcription factor binding occurs between and within species. He is a cofounder of several biotechnology companies, including Protometrix (now part of Life Technologies), Affomix (now part of Illumina), Excelix, and Personalis, and he presently serves on the board of a number of companies.
Tim Stearns’s work uses genetics, microscopy, and biochemistry to understand fundamental questions in cell biology, including the role of the centrosome and cilia in cell signaling, and how this process goes awry in cancer. The Stearns lab is also investigating the functional consequences of human genetic variation, using "humanized" yeast strains to assay function in vivo.
Lars Steinmetz's lab develops and applies cutting-edge technologies to investigate the genetic basis of complex phenotypes, mechanisms of transcription, and the molecular basis of disease. He pioneered yeast as a model system for dissecting complex, quantitative traits, and has applied novel genomic approaches, including the new tool of reciprocal hemizygosity analysis, to connect quantitative traits to causative genes. He has extensively characterized transcriptomes in yeast, mice, and humans, discovering pervasive non- coding transcription, as well as remarkable variation in the structures of individual transcript molecules. His lab is also using yeast and human cells for disease modeling, including innovative screening assays with strains carrying human patient mutations to identify compounds with therapeutic potential for mitochondrial disorders.
Aaron Staight’s goal is to understand how chromosomes are faithfully transmitted during cell division and how chromosomes are structured and organized in the nucleus. Many cellular processes act on the chromosome to specialize different chromosomal domains for unique functions in the biology of cells. One of the best examples of a specialized chromatin domain is the eukaryotic centromere and kinetochore that forms at a single site on each human chromosome and ensures the proper segregation of the genome during each cell division cycle. The laboratory studies the genetic and epigenetic mechanisms that control the formation of human centromeres and kinetochores. Cells use a variety of different mechanisms to change the function of chromosomes. We have also focused on understanding how RNAs that associate with chromosomes regulate the reorganization of chromatin into silent heterochromatic domains. Our recent efforts have been directed at understanding how long range interactions between chromosomes are used to organize the genome within the nucleus and to control gene expression and chromosome dynamics.
William Talbot uses genetic and genomic approaches to investigate the development and function of the nervous system in vertebrates. He has been at the forefront of zebrafish genetics and genomics since the early 1990s. The Talbot group has exploited the experimental advantages of the zebrafish model system to discover many new genes with conserved, essential functions in the nervous system. Examples include the discovery of Gpr126 as a key receptor triggering myelination in nerves, and the characterization of kif1b as a kinesin motor essential for mRNA localization in oligodendrocytes. Current research focuses on screening for new genes that are essential for myelination and the proper regulation of the immune cells in the brain and spinal cord.
The goal of my lab is to develop, scale up, and broadly disseminate molecular technologies for mapping cells and functional circuits. At the sub-cellular scale, maps document the spatial organization of proteins, RNA, DNA, and metabolites with nanometer precision and temporal acuity on the order of seconds. Maps also chart the connectivity between these molecules, elucidating the circuits and signaling processes that give rise to function.
Alexander Urban’s laboratory investigates the genetic basis of brain development and brain function. His laboratory combines genomics and epigenomics methods with induced pluripotent stem cell biology (iPSCs). Main target disease phenotypes are schizophrenia and related psychoses and the autism spectrum disorders. Dr. Urban's laboratory uses high-resolution genomics technologies such as high-density array CGH and, in particular, next-generation paired-end whole-genome sequencing (an approach of which Dr. Urban is a co- developer) to discover and fine-map disease-relevant CNVs. Then, the molecular mechanisms are investigated by applying next-generation sequencing to measure gene expression, DNA methylation, chromatin regulatory states, and chromosome folding in relevant tissue culture models, in particular in precursors and neurons from iPSC lines from patients with neuropsychiatric disease and disease-associated CNVs.
Anne Villeneuve’s lab investigates molecular mechanisms governing genome inheritance during meiosis. They investigate pairing, synapsis, and regulated recombination between homologous chromosomes using C. elegans. The lab combines functional genomics with traditional genetic strategies to identify components of the meiotic machinery on a genome-wide scale, and analyzes the roles of these components using high-resolution imaging to visualize interactions between homologous chromosomes in the context of intact 3D nuclear architecture. The lab also uses comparative genomics to investigate factors affecting the evolution of rapidly- diverging components of the meiotic machinery. The Villeneuve lab has collaborated with the lab of Dr. Fire to identify connections between endogenous siRNA pathways and the function of reproductive cells.
Irving Weissman's lab was the first to isolate a tissue stem cell from mice and humans (the blood-forming stem cell [HSC]). He has subsequently isolated human brain-forming stem cells and other stem cells, and is studying cancer stem cells in leukemia and other diseases. His lab has used lineage analysis and gene profiling to characterize the stages of development between HSC and mature blood cells. He has also characterized the signaling pathways that guide other bifurcating cell fate decisions during normal development. Weissman has been a leader in the clinical application of both blood and brain stem cells for permanent regeneration of their respective tissues, and he currently serves as the Director of the Institute for Stem Cell Biology and Regenerative Medicine at Stanford.
Monte Winslow’s laboratory uses genome-wide methods to uncover alterations that drive cancer progression and metastasis. The Winslow lab uses unbiased genomic methods and in vivo models to better understand the molecular and cellular changes that underlie tumor progression and each step of the metastatic cascade. They use genetically-engineered mouse models of metastatic cancer in which the resulting tumors recapitulate the genetic alterations and histological progression of the human disease. Given the dearth of human tissue samples from metastatic disease, especially from primary tumors and metastases from the same patient prior to therapy, these models represent a unique opportunity to understand the molecular biography of the most prevalent tumor types. By modulating gene expression in vivo, these models allow them to characterize the function of candidate genes and pathways during tumor progression and metastasis in vivo.
Joanna Wysocka's research is centered on genetic and epigenetic mechanisms that regulate cell fate decisions. Her laboratory studies how the instructions encoded by cis-regulatory elements are interpreted in the context of a cellular state and signaling milieu to establish chromatin states permissive or restrictive for gene expression during development. She is also interested in mechanisms by which future differentiation events are anticipated at the chromatin level and the role such mechanisms may play in determining the developmental plasticity of stem cells. Another area of interest involves understanding the role of neural crest cells in molecular and developmental origins of human facial variation. To address these questions Wysocka's laboratory uses human and mouse in vitro stem cell models, which recapitulate specific developmental decisions and are amenable for large-scale genomic, genetic and biochemical analyses. These studies are complemented with various in vivo embryological models, including Xenopus, chicken and mouse.