The Alt laboratory studies mechanisms that maintain genomic stability in mammalian cells. The programmed recombination and hypermutation events in lymphocytes and the general DNA repair mechanisms involved in these processes are a focus. The laboratory also studies mechanisms that promote and prevent oncogenic translocations. Approaches range from molecular genetics and biochemistry to animal models.
The Altshuler lab studies human genetic variation and develops laboratory and analytical methods for associating genotype and phenotype. Our main focus is type 2 diabetes, with projects in prostate cancer, lupus, and other diseases. Long-term, we hope to apply genetic information to improve diagnostics and therapeutics in the clinic.
The Ausubel laboratory uses genetic, genomic, and chemical genetic approaches to: (1) elucidate the molecular basis of microbial pathogenesis in the bacterial pathogens Pseudomonas aeruginosa and Pseudomonas syringae and (2) identify the components of the signaling pathways involved in the host innate immune response in the plant Arabidopsis thaliana and the nematode Caenorhabditis elegans.
The Blower Lab is interested in understanding both how and why RNA is targeted to microtubules during mitosis. We primarily use cell free extracts from the African clawed frog Xenopus laevis to study how RNA influences the assembly of microtubules into a dynamic bipolar spindle.
Constance Cepko and her colleagues study the development of the central nervous system of vertebrates, with an emphasis on the development of the retina. They are also studying the mechanisms of photoreceptor degeneration, and working towards gene therapy for prevention of blindness.
We use quantitative whole genome and proteome measures to guide computational modeling of regulatory and enzymatic networks in microbial and mammalian cells. We develop technologies based on bioinformatics, microarrays, mass-spectrometry, automation, multiplexing, microfluidics, and homologous-recombination genome engineering. We have recently used these to discover new regulatory motifs involved in cell-cycle control, stress response, and many other network components.
We are investigating mechanisms underlying germline maintenance and accurate meiotic chromosome segregation at the molecular level. We are exploring meiotic chromosome dynamics, particularly, the interplay between changes in chromosome configuration/structure during meiosis, and homologous chromosome pairing, synapsis, and DNA double-strand break repair. We are also investigating the roles of histone demethylases in germline maintenance and double-strand break repair. Our studies combine genetic,...
The step by step differentiation of embryonic cells into different types of neurons lays the foundation for our sensory responses, motor commands, and cognitive behaviors. Our research explores this exquisite differentiation program in mammals using a combination of genetic and molecular biological methods.
We study the cellular response to genotoxic stress. We have uncovered a signal transduction protein kinase cascade that phosphorylates over 700 proteins in response to DNA damage and controls genomic stability. Using synthetic biology we also develop genetic technologies such as genome-wide viral libraries of shRNAs for genetic screening in mammals to identify genes important for cancer and growth control.
We study TNF-induced fate decisions in mammalian cells. TNF is particularly interesting because it induces both pro-survival and prodeath signals. Combining mathematical modeling and single-cell measurements, we exploit variability in response in a cell population to explore how these signals are integrated in time and space to control cell fate.
Jim Gusella and his colleagues use genetic strategies to investigate the pathogenesis of disorders of human nervous system, including both identification of causative genes and modifiers of pathogenesis and characterization of their mechanism of action. Current efforts involve Huntington’s disease, Parkinson disease, neurofibromatosis, autism, meningioma and a variety of chromosome translocation-associated developmental disorders.
We aim to understand the genetic basis of traits related to body size (obesity, height and pubertal timing), and certain common diseases (diabetic nephropathy and asthma). We use association studies, informed by population genetics, statistical considerations and gene expression data, to identify genes that influence these polygenic traits in humans.
Work in my lab is focused on understanding how signals in the brain lead to particular patterns of behavior. We utilize a combination of behavioral, genetic, biochemical, imaging, and electrophysiological techniques to study signaling in the brain of the worm C. elegans.
The broad interest of our lab is to characterize the biology of stem cells in normal lung and lung cancer. We use a combination of mouse genetics, cell biology and genomics approaches in our studies. We hypothesize that lung stem cell biology will contribute to understanding the cellular and molecular basis of lung diseases.
The Kingston lab is interested in understanding the fundamental mechanisms of how eukaryotic enzymes can modify chromatin. One focused approach is to isolate chromatin-modifying proteins and to test such complexes in functional assays, with the thesis that assay outcomes will inform the in vivo function of these protien machines. Another important goal is to understand how long-range chromatin interactions are established in the cell nucleus, and this effort is leading to new strategies...
The Kucherlapati laboratory is involved in cloning and characterization of human disease genes with a focus on human syndromes with a significant cardiovascular involvement, use of genetic/genomic approaches to understand the biology of cancer and the generation and characterization of genetically modified mouse models for cancer and other human disorders.
The Kunkel laboratory works on understanding the pathogenesis and genetics underlying the muscular dystrophies. They are attempting therapy of the muscular dystrophies in mice through the use of adult stem cells from muscle. Recently, they have developed zebrafish models of the human dystrophies in an attempt to screen for suppressor mutations. They have also expanded their genetic research into looking at complex disease
traits such as Autism and Interstitial Cystitis.
We study chromatin organization and epigenetic regulation, using X chromosome dosage compensation in Drosophila as a model system. Studies of dosage compensation in mammals and fruitflies suggest that RNAs can play a key role in chromosomal targeting of chromatin modifying complexes. The mechanistic roles of the RNAs within such complexes remain to be understood.
Philip Leder is interested in understanding the genetic interactions that give rise to cancer.
Our lab studies how male (XY) and female (XX) cells use a mechanism called X-chromosome inactivation to achieve equality of sex chromosome gene expression. Our studies are focused on three noncoding RNA loci whose actions coordinate the many steps of X-chromosome inactivation. We are also interested in the mechanistic and evolutionary relationship between X inactivation and imprinting. Recent work by the Lee Lab suggests that imprinted X-chromosome inactivation is directly connected to meiotic sex...
My laboratory works on the elucidation of pathways that are controlled by a growing family of breast and ovarian cancer suppressor genes. This family, which includes BRCA1 and 2, encode proteins that, at a minimum, contribute to the normal cellular responses to DNA damage and to genome integrity control, in general. In particular, we have emphasized an effort to understand how the functions of these gene products contribute to breast and ovarian cancer suppression, in particular.
Work in our lab is focused on determining genetic signals that control heart morphogenesis and physiology. I employ the zebrafish as a model organism and am characterizing a series of mutants with developmental defects affecting the cardiovascular system. New screens are currently being designed to identify genes and molecules that can regenerate cardiac tissue.
We study how the human genome varies in structure and how such structural and copy-number variation influences molecular phenotypes in cells and disease risk in populations. We develop experimental technology for discovering and typing genome structural variants. We recently discovered large, common deletion polymorphisms that appear to influence body weight and Crohn's disease via regulatory effects on nearby genes, and are working to understand how these and other regulatory polymorphisms influence human...
Dr. Mulligan's laboratory is primarily interested in the development of methods for introducing genes into mammalian cells, and the application of those methods in a number of areas of cell biology, developmental biology, virology and medicines. The current research activities of his laboratory are focused in three general areas: (i) the control of hematopoiesis, (ii) manipulation of the immune response via gene transfer, and (iii) the development of new mammalian gene transfer vectors.
The various projects in my laboratory are connected by one central theme: we seek to understand all facets of the V(D)J rearrangements that generate diversity within the vertebrate immune system. Specifically we are studying the enzymatic and regulatory machinery involved, the mechanism of the reaction, and the role of chromatin structure in the regulation of recombination events during lymphoid development. In addition, we are interested in how errors in this process lead to various human diseases.
The general interest of our laboratory is to understand the mechanisms by which cells and tissues talk to each other to coordinate the formation of specific structures during development and to maintain homeostasis. We study these questions in Drosophila using classic genetics as well as state-of-the-art genomic and proteomic methodologies. Current interests are in muscle development, cell migration and stem cell biology.
The Reich laboratory studies population mixture as a foundation for medical, evolutionary and population genetics. Human population history is often explained as a series of “splits”: the divergence of human and chimpanzee ancestors 5-7 million years ago, the spread of modern humans into Eurasia 40,000-100,000 years ago, and the spread into the Americas by at least 15,000 years ago.
The Ruvkun lab uses C. elegans molecular genetics and genomics to study miRNA and RNAi pathways. We also use genome-wide RNAi analysis to study various biological process in C. elegans including molting, insulin signaling, fat deposition, and longevity.
Our lab is using new technologies to couple rapid identification of interesting genes with methods for studying the consequences of their expression in an organismic context. We have developed an efficient type of expression cloning of signal transduction intermediates that allows us to rapidly identify cDNAs encoding genes that engage a number of known transduction pathways. In addition, we continue to work on methods for creating mutant cell lines that have lesions in signal transduction pathways,...
Christine Seidman is interested in dominant-acting mutations in sarcomere protein genes that cause hypertrophic cardiomyopathy in humans. The Seidman lab has made a murine model of this disease and demonstrated that these mutations lead to altered Ca2+ concentrations in myocytes. Ca2+ channel blockers reduce the hypertrophic response to sarcomere protein gene mutations in mice.
Jonathan Seidman is interested in dominant-acting mutations in sarcomere protein genes that cause hypertrophic cardiomyopathy in humans. The Seidman lab has made a murine model of this disease and demonstrated that these mutations lead to altered Ca2+ concentrations in myocytes. Ca2+ channel blockers reduce the hypertrophic response to sarcomere protein gene mutations in mice.
Our laboratory is interested in the molecular mechanisms underlying plant responses to growth and stress hormones, nutrients, environmental stresses, and pathogens. We use a combination of genetic, genomic, biochemical and cellular approaches to discover key regulatory genes, and elucidate their functions and actions in the control of these central signal transduction pathways from receptors/sensors to transcription factors and target genes in plants.
My laboratory research is focused on the origin, early evolution and laboratory synthesis of life, and the in vitro directed evolution of functional biopolymers.
The laboratory studies the genetic basis by which form and structure are regulated during vertebrate development. We combine classical methods of experimental embryology with modern molecular and genetic techniques for regulating gene expression during embryogenesis.
Our goals are to understand how protein interaction, or “interactome”, networks are organized at the scale of the whole cell, how such global organization contributes to biological processes, how the interactome varies in time and space, and how perturbations in interactome networks contribute to human disease.
Members of the Warman laboratory are committed to identifying genetic causes of skeletal disease, to understanding how the responsible genes participate in the biologic processes of skeletal growth and homeostasis, and to using this knowledge to improve human health. Patients affected by genetic disorders of the skeleton are the impetus for scientific inquiry in the Warman lab, but in addition to the human genetic approach, the lab also relies on model organism approaches, and cellular,...
Research in our laboratory focuses on understanding eukaryotic gene expression and chromatin structure, using the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe.
We study the mechanisms by which homologous chromosomal regions/genes/sequences influence each other at the level of chromosome behavior, genome integrity, gene expression, and chromatin structure. To this end, we conduct genetic, molecular, and bioinformatic analyses, focusing on homologue pairing, transvection (such as enhancer action in trans), mitotic recombination, ultraconserved elements, dosage, and chromatin structure in Drosophila and humans.
