Division of Biomedical Research
Professor / Division Chief
Research in my laboratory focuses on Autosomal Dominant Polycystic Kidney Disease (ADPKD), a disease caused by mutations in the genes PKD1 or PKD2, which code for polycystin-1 and-2 (PC-1 and PC-2), respectively. ADPKD, the main genetic cause of renal failure in adults, is characterized by the growth of fluid-filled cysts arisen from renal tubules. We have demonstrated angiogenesis in ADPKD kidneys, a process that may support cyst growth, facilitate fluid secretion into the cysts, and cause vascular malformations and renal bleeding. We also discovered that interleukin-8 (IL-8) is constitutively expressed in ADPKD kidneys and in cyst cells in culture, but only when induced by hypoxia in normal renal-tubule cells. IL-8 is a growth factor and angiogenic cytokine. ADPKD cyst cells also express IL-8 receptors, suggesting the existence of a proliferative autocrine loop. The central aim of our present studies is to test novel potential treatments for ADPKD based on the inhibition of signaling pathways involved in angiogenesis and cyst growth using in-vitro and in-vivo models of the disease.
Professor of Medicine & Cell Physiology
Vice Chairman, Department of Internal Medicine
Chief, Division of Nephrology & Hypertension
Endowed Chair, University Medical Center
Research in my laboratory is focused primarily on the pathogenesis and pathophysiology of diabetic nephropathy. Renal disease from diabetes is the leading cause of end stage renal failure and is fast growing due to the epidemic of obesity and diabetes all over the world. For several years my research was aimed at addressing the role of some newer pathogenic factors and cytokines in diabetic milieu such as nitric oxide and oxidative stress both in vivo and vitro. Recently we characterized ZSF rat, a new rodent model with phenotypic manifestations of human metabolic syndrome and histological features of human model of nephropathy in type II diabetes (J Am Soc Neph 2007). Angiotensin-nitric oxide interactions in vivo and vitro, mechanisms of insulin resistance including the role of angiotensin, pathogenic role of AMP protein kinase, identification of candidate genes and role of angiogenesis in diabetic nephropathy are some of the ongoing research projects in our laboratory.
Afzal Siddiqui, Ph.D.
1. Schistosomiasis afflicts over 200 million people in 76 different countries; and an additional 600 million people are at risk of acquiring the infection. There is no vaccine available to protect against this infection. We have identified a vaccine candidate, Sm-p80, which plays a pivotal role in the surface membrane renewal of schistosomes, a phenomenon employed by hemo-helminths to evade host immunity. We are testing prophylactic and therapeutic efficacy of Sm-p80-based vaccine using DNA, prime/boost and as well as conventional immunization schemes in mouse and nonhuman primate models. The development of a schistosome vaccine would be a major breakthrough and could save up to 4.5 million DALYs annually. Our ongoing studies will provide proof of concept in order to move the vaccine into human trials.
2. Infection of humans with Strongyloides stercoralis usually results in an asymptomatic chronic disease of the gastrointestinal tract that can remain undetected for decades. In patients on chronic corticosteroid therapy, hyperinfection can occur with the dissemination of larvae to other organs which results in high mortality rates (>80%). We have hypothesized that the major cause of hyperinfection is due to the direct effect of corticosteroids on the parasite and not due to general immune suppression of the host by corticosteroids. To elucidate this phenomenon we have isolated a corticosteroid receptor from S. stercoralis which is a daf-12 gene. Daf-12 is the first identified heterochronic gene that coordinates stage-specific programs and plays an instructive role in the dauer pathway of C. elegans. We are now studying the role of daf-12 in the development of hyperinfection syndrome.
Professor, Chief of Endocrinology Division
Department of Internal Medicine
Barry J. Maurer, M.D.
His research on retinoid, "vitamin A derivatives" as tumor-selective differentiation or cytotoxic agents, mechanisms of drug resistance and drugs to modulate resistance in childhood and adult cancers, development of novel preclinical testing models for childhood and adult cancer drug development, and clinical testing therapeutic approaches for cancer.
Department of Internal Medicine
Genetics of neurodegenerative disorders mainly fontotemporal dementia (FTD), cotocobasal degeneration (CBD), progressive supranuclear palsy (PSP) and Alzheimer’s, movement disorders. Genetic determinants of the outcome of traumatic brain injury (TBI), Genetics of criminal behavior, craniofacial disorders, Study of disease haplotypes in MAPT region on chromosome 17, perform association and linkage studies to identify new genes for dementias.