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.

Work in the Green Lab is centered on the ribosome. The overall fidelity of protein synthesis appears to be limited by the action of the ribosome, which is the two-subunit macromolecular machine responsible for decoding and translating messenger RNAs (mRNAs) into protein in all organisms. Our work is divided into four general project areas. The longest-standing research area concerns the interactions of eubacterial ribosomes and release factors. The goal is to understand the mechanism of action of release factors on the ribosome. A second research area involves biochemical and structure/function studies of the miRNA pathway, particularly the mechanism of action of the Argonaute proteins and their interacting factors. A third area of work in the lab is centered around regulation of eukaryotic translation, specifically in understanding the mechanism behind various mRNA quality control pathways and the interactions of proteins therein, as well as with the ribosome. The newest area of research in the lab extends our strengths in ribosome biochemistry to characterize the translation status of the cell using the ribosome profiling. We are using this technique to better understand the role of several factors involved in eukaryotic and prokaryotic translation fidelity.

The Gregg Semenza Lab studies the molecular mechanisms of oxygen homeostasis. We have cloned and characterized hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix transcription factor. Current research investigates the role of HIF-1 in the pathophysiology of cancer, cerebral and myocardial ischemia, and chronic lung disease, which are the most common causes of mortality in the U.S.

The Goley Lab is broadly interested in understanding cellular organization and dynamic reorganization, with particular focus on the roles of the cytoskeleton in these phenomena. We use cell biological, biochemical, genetic and structural approaches to dissect cytoskeletal processes with the aim of understanding how they work in molecular detail. Currently, we are focused on investigating the mechanisms underlying cytokinesis in bacteria. A deep understanding of cytoskeletal function in bacteria will aid in the identification of targets for novel antibiotic therapies and in efforts in synthetic biology.