Dr. Hsu is Associate Professor of Internal Medicine in the Division of Geriatric and Palliative Medicine. His laboratory studies genetics and cell biology of aging using C. elegans as a model organism. Current projects have been focused on unraveling the role of Heat-shock Transcription Factor (HSF-1) in specifying longevity, stress resistance, and the onset of age-related neurodegenerative diseases. His group is particularly interested in the cross talks between the insulin signaling and HSF-1 pathway. Another research focus of his group is to study genes that are responsible for the longevity response to dietary restriction (DR). His group is currently interested in the role of protein translation initiation and S-adenosyl-methionine-dependent methylation in DR-mediated longevity extension. Finally, his group is also working on developing new therapeutic agents that can delay the rate of aging using the C. elegans model.
Jun Hee Lee
Dr. Lee focuses on diverse physiologies including growth, development and aging that are controlled by signal transduction networks. Recently, our research has revealed that Sestrin, a stress-inducible protein, is a feedback inhibitor of mTOR signaling, and that loss of Sestrin can cause various chronic mTOR-associated pathologies, such as fat accumulation, mitochondrial dysfunction, cardiac arrhythmia and muscle degeneration. These phenotypes are quite similar to those associated with obesity, aging and lack of exercise, which are currently some of the major public health issues facing our society. We expect that further research on mammalian Sestrin-family proteins may provide a novel way to attenuate aging and prevent or treat age-associated diseases in humans.
Dr. Low is Professor of the Departments of Molecular & Integrative Physiology and Internal Medicine at the University of Michigan Medical School. He is also an Investigator of the Brehm Center for Diabetes Research. Research in his lab is focused on determining how the hypothalamus integrates environmental and interoceptive sensory information to maintain neuroendocrine homeostasis and energy balance. He is an internationally recognized expert in the generation and analysis of mutant mouse models and currently uses a combination of molecular genetic, endocrine, and behavioral approaches to characterize the physiological functions of neuropeptides and G-protein coupled receptors that are highly expressed in hypothalamic neural circuits, particularly proopiomelanocortin (POMC), MC4-receptor, enkephalin, dynorphin, mu-opioid receptor, corticotropin releasing hormone, somatostatin, dopamine, and dopamine D2-like receptors. POMC neurons play a critical role in the regulation of appetite and metabolism and dysfunction in their associated neural circuits can produce morbid obesity. A current major project in the Low lab is to dissect the functional significance of the recently discovered neuronal enhancers in POMC using targeted deletions of individual or multiple enhancer sequences in mutant mice.
Costas A. Lyssiotis
Dr. Costas is Assistant Professor of Molecular & Integrative Physiology. His lab studies the biochemical pathways and metabolic requirements that enable tumor survival and growth and, in particular, how this information can be used to design targeted therapies. Among his many contributions, Dr. Lyssiotis demonstrated that pancreatic cancers are addicted to glucose and glutamine and use these nutrients in previously undescribed pathways to make DNA and to generate free radical-combating antioxidants, respectively.
Dr. MacDougald is the John A. Faulkner Collegiate Professor of Physiology within the Molecular & Integrative Physiology department. To combat the rising incidence of obesity and associated metabolic diseases, the goal of his lab is to investigate how adipocytes throughout the body develop, function, and interact with other cell types near and afar.
Dr. Michele is Associate Professor of Molecular & Integrative Physiology at the University of Michigan Medical School. Dr. Michele's laboratory is interested in the molecular mechanisms of human diseases of skeletal and cardiac muscle. Currently, we are focused on the mechanisms of muscular dystrophy associated with mutations in the transmembrane dystrophin-glycoprotein complex and abnormal glycosylation of the central protein in this complex, dystroglycan. The cellular mechanisms of dystroglycan modification and the resulting pathways leading to muscular dystrophy and cardiomyopathy are currently unclear. We are exploring these pathways using spontaneous mutant, traditional and conditional targeted mouse models as well as human patient samples.
Dr. Omary is the H. Marvin Pollar Professor of Gastroenterology, a Professor Molecular & Integrative Physiology and of Internal Medicine at the University of Michigan Medical School. He is the Chair of the Department of Molecular & Integrative Physiology and co-Director of this program. His research focus involves studying the disease association, function and regulation of the keratin intermediate filament cytoskeletal proteins in digestive organs. He is considered a leader in this field having chaired the Gordon Conference on Intermediate Filaments in 2006. His laboratory generated transgenic mouse models that pointed to the potential importance of keratin polypeptide 8 and 18 (K8/K18) mutations in human liver disease. These animal models led the Omary laboratory to the first identification of K8/K18 mutations in patients with cryptogenic and noncryptogenic forms of chronic liver disease. These studies also showed in animals and humans that the presence of a keratin mutation/variant increases the risk to fibrosis progression. Presently, his group is studying the mechanism of the cytoprotective role of keratins in the liver, pancreas and intestine. Another major area of focus for the Omary laboratory is understanding the pathogenesis and clinical significance of the hepatocyte inclusions, termed Mallory-Denk bodies, that are commonly seen in patients with alcoholic and nonalcoholic steatohepatitis.
William (Bill) Rainey
Dr. William (Bill) Rainey is the Jerome Conn Professor in the Departments of Molecular and Integrative Physiology and Internal Medicine. Dr. Rainey’s group is recognized for its research on the adrenal gland, specializing on adrenal zonation, steroid production and tumor development. The lab group includes post-graduate clinician and basic scientists as well as graduate and undergraduate students. Summer Undergraduate Research Fellows (SURFs) would join ongoing research projects that are applying genomic and metabolomic approaches toward defining the mechanisms controlling normal and pathologic adrenal function.
Dr. Rui is Associate Professor of Molecular & Integrative Physiology. His laboratory studies the physiological and molecular mechanisms of obesity, fatty liver, and type 2 diabetes, using genetic, physiological, molecular and biochemical approaches. Obesity is the primary risk factor for fatty liver diseases and type 2 diabetes and type 2 diabetes is caused by defects in both insulin production and insulin action (e.g. insulin resistance in the liver, muscle, fat and brain). Ongoing areas of study in the Rui laboratory include: (1) examination of the signal transduction pathways in hypothalamic neurons that regulate energy homeostasis and body weight, (2) investigating molecular defects in hypothalamic neural circuits that cause leptin resistance, energy imbalance and obesity, 3) studying glucose and lipid metabolism under both normal and obese conditions and focusing on the hepatic gluconeogenic and lipogenic programs as well as on the molecular mechanisms of insulin resistance in liver, adipose tissue and muscle.
Dr. Shah is Assistant Professor of Molecular & Integrative Physiology at the University of Michigan Medical School. Dr. Shah's laboratory seeks to understand the mechanisms by which cellular oxygen levels regulate colon and liver cancer. Regulation of hypoxia-mediated genes is dependent on the nuclear transcription factor, hypoxia inducible factor (HIF). HIF signaling is critical in the adaptive response to low oxygen levels by activating genes involved in metabolism, angiogenesis, cell proliferation and cell survival. We have developed novel animal models to study accurately the role of hypoxia and HIF in the liver and intestine-derived cancers. In these animal models we have shown that increased HIF signaling leads to liver and intestinal inflammation and chronic induction of HIF signaling leads to vascularized tumors. Our current goals are to identify molecular mechanisms by which HIF regulates colon and liver inflammation and assess if HIF signaling is a critical link between inflammation and cancer.
The Yin laboratory largely focuses on understanding the molecular regulation of circadian rhythms in mammalian system. The core clock proteins are the driving forces to generate and maintain the 24h circadian rhythms. Post-translational modifications of those core clock proteins play important function in determining the basic features of a circadian cycle, including period length, amplitude and phase response. Our lab is currently studying the role of ubiquitination in regulation of circadian oscillation of the core circadian clock proteins. One of our long-term goals is to identify the unique E3 ligase and de-ubiquitin specific protease (USP) for individual clock protein and determine their circadian functions in vivo.