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
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