The McCallion Laboratory studies the roles played by cis-regulatory elements (REs) in controlling the timing, location and levels of gene activation (transcription). Their immediate goal is to identify transcription factor binding sites (TFBS) combinations that can predict REs with cell-specific biological control--a first step in developing true regulatory lexicons. As a functional genetic laboratory, we develop and implement assays to rapidly determine the biological relevance of sequence elements within the human genome and the pathological relevance of variation therein. In recent years, we have developed a highly efficient reporter transgene system in zebrafish that can accurately evaluate the regulatory control of mammalian sequences, enabling characterization of reporter expression during development at a fraction of the cost of similar analyses in mice. We employ a range of strategies in model systems (zebrafish and mice), as well as analyses in the human population, to illuminate the genetic basis of disease processes. Our long-term objective is to use these approaches in contributing to improved diagnostic, prognostic and therapeutic strategies in patient care.

The Philip Wong Lab seeks to understand the molecular mechanisms and identification of new therapeutic targets of neurodegenerative diseases, particularly Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Taking advantage of discoveries of genes linked to these diseases (mutant APP and PS in familial AD and mutant SOD1, dynactin p150glued ALS4and ALS2 in familial ALS), our laboratory is taking a molecular/cellular approach, including transgenic, gene targeting and RNAi strategies in mice, to develop models that facilitate our understanding of pathogenesis of disease and the identification and validation of novel targets for mechanism-based therapeutics. Significantly, these mouse models are instrumental for study of disease mechanisms, as well as for design and testing of therapeutic strategies for AD and ALS.

The Peisong Gao Lab’s major focus is to understand the immunological and genetic regulation of allergic diseases. We have been involved in the identification of the genetic basis for atopic dermatitis and eczema herpeticum (ADEH) as part of the NIH Atopic Dermatitis and Vaccinia Network-Clinical Studies Consortium. Major projects in the Gao Lab include immunogenetic analysis of human response to allergen, identification of candidate genes for specific immune responsiveness to cockroach allergen, and epigenetics of food allergy (FA).

The Alison Moliterno Lab studies the molecular pathogenesis of myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocytosis and idiopathic myelofibrosis. Our research is focused on the genetic and epigenetic lesions associated with MPDs, with the goal of improving diagnosis and treatment for these disorders.

The Jeremy Nathans Laboratory is focused on neural and vascular development, and the role of Frizzled receptors in mammalian development. We use gene manipulation in the mouse, cell culture models, and biochemical reconstitution to investigate the relevant molecular events underlying these processes, and to genetically mark and manipulate cells and tissues. Current experiments are aimed at defining additional Frizzled-regulated processes and elucidating the molecular mechanisms and cell biologic results of Frizzled signaling within these various contexts. Complementing these areas of biologic interest, we have ongoing technology development projects related to genetically manipulating and visualizing defined cell populations in the mouse, and quantitative analysis of mouse visual system function.

The Joseph Mankowski Lab studies the immunopathogenesis of HIV infection using the SIV/macaque model. Our researchers use a multidisciplinary approach to dissect the mechanism underlying HIV-induced nervous system and cardiac diseases. Additionally, we study the role that host genetics play in HIV-associated cognitive disorders.

Research in the J. Hunter Young Lab focuses on the genetic epidemiology and physiology of cardiovascular disease and its risk factors, especially hypertension, diabetes and obesity. Current activities include an observational study of hypertension among African Americans; a genetic epidemiology study of worldwide cardiovascular disease susceptibility patterns; and several population-based observational studies of cardiovascular and renal disease. A recent focus group study found that changes in housing and city policies might lead to improved environmental health conditions for public housing residents.

The James Hamilton laboratory performs pre-clinical experiments and basic studies investigating liver inflammation, fibrosis, and nuclear receptor signaling. In close collaboration with Dr Svetlana Lutsenko in Physiology, their team performs detailed studies of hepatocyte and non-parenchymal cell isolation, culture, biology and genetic manipulation. Working with models of Wilson disease, a disorder of copper overload, they discovered that hepatic nuclear receptor mediated control of lipid metabolism is a preferential and early target of copper toxicity. Furthermore, targeting nuclear receptors with pharmacologic agonists prevents and reverses liver inflammation and fibrosis.

The Joanna Peloquin Lab focuses on inflammatory bowel disease (IBD). We're working on individualized care for IBD patients through functional genomic studies, specifically those related to diet, host and microbiota interactions.

Human induced pluripotent stem cells (hiPSCs) provide unprecedented opportunities for cell replacement approaches, disease modeling and drug discovery in a patient-specific manner. The Gabsang Lee Lab focuses on the neural crest lineage and skeletal muscle tissue, in terms of their fate-determination processes as well as relevant genetic disorders. Previously, we studied a human genetic disorder (familial dysautonomia, or FD) with hiPSCs and found that FD-specific neural crest cells have low levels of genes needed to make autonomous neurons--the ones needed for the ""fight-or-flight"" response. In an effort to discover novel drugs, we performed high-throughput screening with a compound library using FD patient-derived neural crest cells. We recently established a direct conversion methodology, turning patient fibroblasts into ""induced neural crest (iNC)"" that also exhibit disease-related phenotypes, just as the FD-hiPSC-derived neural crest. We're extending our research to the neural crest's neighboring cells, somite. Using multiple genetic reporter systems, we identified sufficient cues for directing hiPSCs into somite stage, followed by skeletal muscle lineages. This novel approach can straightforwardly apply to muscular dystrophies, resulting in expandable myoblasts in a patient-specific manner.