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Previous Clinical Awardees

2009 Clinical Awardees

The 2009 award recipients are listed below with a short description of their project(s).

Awardee: Maple Fung, MD
Effects of variation in the degree of African admixture on renal disease and candidate adrenergic genes in African-American veterans
Award Total: $25,000 - one year

Abstract: In the United States, African-Americans carry a high burden of kidney disease1. Because kidney disease has strong familial relationships2, genetic studies are important, though they are often confounded by complex ancestral genetic backgrounds3. Genetic admixture analyses assist in the determination of genetic contributors to phenotype differences between racial groups and facilitate the identification of genetic differences in complex phenotypes, such as renal disease. Though previous analyses have shown that African-American populations typically contain an average of 20% European admixture4, individual admixture estimates (IAEs) range from subjects with almost complete African ancestry to those with a very high degree of European admixture. Using ancestry-informative markers (AIMs), we will determine IAEs in African-American subjects recruited from a primary care veteran population with essential hypertension. In this study, these estimates will be used to evaluate the effect of ethnicity by genetic admixture on both the risk of renal disease alone and on potential candidate genes polymorphisms within the adrenergic and reninangiotensin systems (RAS) and their risk for renal disease. This invaluable resource of determining AIMs and IAEs will be accessible for use in future studies with this cohort and others that utilize similar genetic markers.

Awardee: Karen Herbst, MD, PhD
Blockade of Receptor Cleavage in Diabetes Mellitus with an MMP Inhibitor

Award Total: $25,000 - one year

Abstract: Obesity and type 2 diabetes mellitus (DM2) are epidemic. Development of obesity is associated with extensive modifications in adipose tissue including adipogenesis, angiogenesis and extracellular matrix proteolysis. Matrix metalloproteinases (MMPs) are a family of resident tissue enzymes that participate in these processes. We identified a new mechanism of insulin resistance where elevated MMPs in the spontaneously hypertensive rat (SHR) cleave extracellular domains of receptors including the insulin receptor resulting in hyperglycemia. Activated MMPs therefore cause insulin resistance in an experimental model of the metabolic syndrome with DM2. Hyperglycemia and receptor integrity were dramatically improved after administration of the broadspectrum MMP inhibitor, doxycycline. In this proposal, we will test the novel hypothesis that reduction of activated MMP levels (by chronic doxycycline administration) serves to restore insulin receptor integrity and improves measures of diabetes in an obese population of human subjects with DM2.

2008 Clinical Awardees

Miguel Goicoechea, MD, Assistant Adjunct Professor of Medicine
UCSD HIV Therapy: Impact of Inhibition of Cellular Drug Transporters on
Intracellular Nucleoside Analogue Triphosphate Concentrations

$25,000 one year award

Based on in vitro studies, cellular nucleoside transporters might mediate extrusion of HIV nucleoside drugs and thus may enable memory CD4 T cells to become viral sanctuaries. The investigator will determine if addition of lopinavir-ritonavir, a protease inhibitor and nucleoside transporter antagonist, to nucleoside-based regimens will inhibit nucleoside efflux pumps and so increase intracellular active drug levels in five patients with HIV.

Barbara H. Jung, MD, Assistant Professor of Medicine, UCSD
BARD1 Splice Variants and Colon Cancer Metastasis

$25,000 one year award

BRCA1-mutant breast cancers have high metastatic potential, and primary colon cancers may lack nuclear BRCA1 activity despite lack of mutations. The investigator will determine if this tumor suppressor gene is inactivated in colon cancers by a different mechanism, ie, failure to be transported to the nucleus. This failure might be mediated by alternatively spliced variants of the BRCA1 chaperone BARD1, which they will measure in colon cancer samples and cell lines by immunohistochemistry and RT-PCR.

Jing Yang, MD, Assistant Professor of Pharmacology, UCSD
Dissecting the Molecular Basis of Ewing's Sarcoma Metastasis

$25,000 one year award

In collaboration between UCSD, Rady Children's Hospital, and St. Jude Children's Research Hospital, the investigators will examine the expression of neural crest transcription factors, Twist, Snail, and Slug, in Ewing's Sarcoma Family of Tumors cell lines and primary human samples. The study will determine if genes that are involved in neural crest cell migration promote metastasis in these tumor cells. Among other studies, the investigators plan to examine the mechanism of action of any candidate genes by studying their loss- and gain of-function in mice and in vitro.