G R A D U A T E P R OG R A M
Areas of research encompassed by the Pharmacology and Molecular Signaling Program are broad and diverse and, in each area, strong collaborative and synergistic interactions exist between basic researchers and clinical colleagues. The research interests of the faculty in each of our five areas of strength are briefly described here. More details about individual faculty can be obtained by clicking on the name listed below.
Richard Baer directs research into hereditary breast and ovarian cancers, with a focus on specific roles of BRCA genes in tumorogenesis. The primary goal of research in the lab of Jan Kitajewski is to understand growth factor/receptor function in vascular development and oncogenesis, emphasizing a biochemical dissection of the Wnt and Notch signaling pathways. The research of Ramon Parsons focuses on the pathogenesis of breast and brain cancer, with efforts to identify the genetic changes that lead a normal cell to develop into an advanced tumor. The research of Kenneth Olive focuses on evaluating novel drugs for pancreatic cancer, with efforts to understand the biology of how pancreatic tumors respond to therapy and mechanisms of resistance to chemotherapy. The research program of Timothy Wang is centered on understanding the role of inflammation and growth factors in the development of gastrointestinal cancers and also investigates the origin of cancer stem cells.
The research of Penelope Boyden is primarily directed at elucidating the abnormalities in ion channel function occurring as a result of ischemic heart disease and at identifying therapeutic interventions that are effective against these abnormal channel proteins. The long-term goal of the work of Wendy Chung is to define a set of genomic rearrangements important in the etiology of congenital heart disease. Henry Colecraft studies molecular aspects of the functioning of voltage-gated calcium channels and designs inhibitors of these channels for treating cardiovascular and neurological diseases. Robert Kass focuses on the regulation of ion channel expression in normal and genetically-altered cardiac cells and on gene-targeted pharmacology of inherited cardiac arrhythmias. Andrew Marks studies fundamental mechanisms that regulate muscle contraction and molecular defects in this regulation that contribute to heart failure and fatal cardiac arrhythmias. Steven Marx studies the regulation of clinically important ion channels in the heart. The lab of Richard Robinson offer opportunities to carry out research on gene and cell-based therapies for cardiac rhythm disturbances, using stem cells modified to act as pacemakers. Research in the lab of Gordana Vunjak-Novakovic aims to engineer advanced technologies for functional tissue engineering, regenerative medicine and human stem cell research in the context of studying and treating heart disease. Masayuki Yazawa uses human stem cell technology, imaging tools and animal models to investigate how mutants in calcium-related molecules cause developmental disorders in the human heart and brain in order to find new therapeutics.
The research of Joseph Graziano focuses on metal toxicology and the impact of environmental sources of metals, such as arsenic and manganese, on public health. Lloyd Greene studies the mechanisms of neuronal differentiation and degeneration and their regulation by growth factors. The lab of Neil Harrison is interested in the effects of alcohol and
other drugs on synaptic transmission, neuronal excitability and gene expression in the brain.
The research of Rene Hen focuses on the roles of the serotonergic neurotransmitter system in the development of psychiatric disorders and the mechanisms whereby serotonergic drugs alleviate those disorders. Christoph Kellendonk is interested in the role of the dopamine system in the cognitive deficits of Schizophrenia. Joachim Scholz studies cellular and molecular mechanisms of pain, especially chronic pain. Steven Siegelbaum studies mechanisms underlying the regulation of synaptic transmission and neuronal integration that are important for learning and memory. The research of David Sulzer is devoted to understanding the molecular events that control dopamine neurotransmission as well as the neuronal death that underlies neurodegenerative diseases such as Parkinson's and Huntington's diseases.
Andrea Califano works at the interface of computational and experimental biological sciences to reverse engineer metabolic and gene regulatory networks and dissect complex genetic traits in a whole genome context. Steven Feinmark studies the role of lipid-derived signaling molecules in cardiac disease and cancer. Alice Prince has been studying the interactions of bacteria and respiratory epithelial cells to understand the pathogenesis of bacterial infection in cystic fibrosis (CF), focusing on the cytokine signaling systems in normal and CF epithelial cells which are activated by bacterial components. Christian Schindler focuses on signal transduction related to the hematopoietin family of cytokines, particularly the JAK-STAT signaling pathway. Susan Steinberg focuses on the signal transduction pathways that mediate the cardiac actions of GPCRs for catecholamines as well as thrombin so as to identify novel signaling mechanisms that contribute to cardiac cell growth and apoptosis (particularly in the context of heart failure syndromes).
Structural and Chemical Pharmacology
Virginia Cornish uses methods in chemical synthesis and DNA technology to understand protein function at the molecular level, looking at isolated proteins in solution, large protein complexes and, finally, protein function in biological networks in living cells. Qing Fan is interested in understanding the molecular mechanisms by which GPCRs transmit signals across biological membranes and her work combines X-ray crystallography with various biochemical techniques. The research of Wayne Hendrickson uses X-ray crystallography to analyze structure-function relationships of a number of important membrane proteins in several different systems, such as the immune and nervous systems. Jonathan Javitch is interested in structure-function relationships of G protein-coupled receptors (GPCRs) and of neurotransmitter transporters, focusing on these proteins as targets for mood-altering drugs. Jingyue Ju focuses on the design and synthesis of novel molecular tags for biological labeling and imaging, and developing new technologies to study problems in genomics.Brent Stockwell diagrams the interconnected signaling networks underlying cancer and neurodegenerative diseases by designing high-throughput screens in mammalian cells to test tens of thousands of small organic molecules and small interfering RNAs for their ability to affect cellular phenotypes associated with oncogenic signaling or neurodegeneration.