Amnon Schlegel, MD, Ph.D.
School of Medicine, Internal Medicine, Endocrinology & Metabolism, College of Health, Nutrition and Integratice Physiology, School of Medicine, Biochemistry, Molecular Medicine – Adjunct
Dr. Schlegel’s laboratory takes a multi-pronged approach to identifying andcharacterizing novel genes involved in lipid and glucose metabolism.In one main area of investigation, unbiased, forward genetic screens inzebrafish are used to isolate mutants with lipid phenotypes of interested (e.g.,inappropriate accumulation of lipids in the liver, altered adipose lipid mass).The group then clones and characterizes the affected genes.In a seconda area of investigation, modern genetic methods are used todelete or selectively express genes of therapeutic interest, with a particularemphasis on the control of intestinal lipid handling as a platform for treatingdyslipidemia and atherosclerosis, and on the liver’s control of fasting glucosemetabolism.
The primary focus of our research is understanding signaling cascades regulating ion transportprocesses, particularly in the kidney, but also in other settings such as stroke, circadian rhythmand osmoregulation. We use genetic techniques in Drosophila melanogaster, physiology,behavior and biochemistry to understand the molecular basis of ion transport physiologyrelevant to human physiology and pathophysiology, including electrolyte and tonicitydisorders and high blood pressure.
Con Yost, MD.
School of Medicine, Pediatrics, Neonatology
Corrine Welt, MD.
School of Medicine, Internal Medicine,Endocrinology & Metabolism
My laboratory is focused on the genetics of female reproductive disorders with a goal to understand the etiology, discover genetic markers for early identification and intervention and identify new treatment targets. We have assembled a database of genetic and phenotype data in women with primary ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). We use a genome-wide association approach in women with PCOS to uncover gene variants associated with risk for PCOS through international collaborations. We use whole genome and exome sequencing in familial cases to identify new genes causing POI. We use a translational approach to determine the functional effect of thesemutations and variants and a population-based approach to understand the genetic etiologies of POI and the inheritance of comorbid disease so that women can be identified early based on their family history and genetic profile. The work will ensure that treatment measures are put in place early to preserve fertility,avoid the associated medical consequences of infertility and we identify new treatment options.
The overall goal of my research is to understand the mechanisms regulating vertebrate iron metabolism.One project focuses on elucidating the mechanisms through which the key regulator of cellular iron metabolism, iron-regulatory protein(IRP2), senses and respondsto iron content, and how dysregulation of iron metabolism as a consequence of IRP2 deficiency causes hematological and neurodegenerative diseases and diabetes. Another research project uses the nematode Caenorhabditis elegansas model genetic organism to identify novel iron-and oxygen-regulated genes and pathways that are relevant in vertebrates.
H. Joseph Yost, Ph.D. holds the Richard L. Stimson Presidential Endowed Chair, is the interim co-Director of the Molecular Medicine program, Vice Chairman for Basic Science Research, Department of Pediatrics, and Professor of Neurobiology & Anatomy. His lab is recognized as a founder and leader in the field of vertebrate left-right (LR) development, discovering pathways and mechanisms that convert bilateral symmetry to LRasymmetry, including essential functional and/or structural asymmetries in the heart, brain and digestive system. His group has generated zebrafish genetic models of human congenital heart disease(CHD), adult cardiomyopathies and heart failure, heterotaxy syndrome, ciliopathies, Roberts syndrome, Li-Fraumeni syndrome, colon cancer and rare/orphan diseases in pediatrics, with the long-term goal of increasingthe understanding of biological mechanisms for the advancement of human medicine.
Karin Chen, MD.
School of Medicine, Pediatrics, Pediatric Allergy & Immunology
Katsushiko Funai, Ph.D.
College of Health, Physical Therapy & Athletic Training
Lipids are the most abundant organic constituents in many humans. The rise in obesity prevalence has prompted a need for a more refined understanding of the effects of lipid molecules on cell physiology. In skeletal muscle, deposition of lipids can be associated with insulin resistance that contributes to the development of diabetes. Muscle cells are equipped with the molecular machinery to convert and sequester lipid molecules, thus rendering them harmless. Induction of mitochondrial and lipogenic flux in the setting of elevated lipid deposition, such that occurs with exercise, can protect muscle from lipid-induced poisoning of the cellular machinery. We utilize celllines, genetically-modified mice and primary muscle cells from human subjects to examine mechanisms whereby skeletal muscles develop and/or evade toxic effects of lipid influx.
Kevin Whitehead, MD.
School of Medicine, Internal Medicine, Pediatrics, Cardiovascular Medicine
Pediatrics, Pediatric Cardiology – Adjunct