Faculty & Staff at TUC

Research Overview

Research Project While at TU-CA

1) DNA-micro array analysis of reward pathways: 2001-2002

Former project at the Ernest Gallo Clinic & Research Center (EGCRC), at the University of California San Francisco (UCSF). I worked on a project with Dr. Michael Miles. In this lab we studied the underlying molecular changes that produce the process of sensitization in the nucleus accumbens upon exposure to drugs of abuse. Using DNA-chip-array technology genes that are regulated by administration of cocaine and alcohol to mice were evaluated.

My role in this project is to help with an ongoing effort by providing my time and molecular biology expertise as well as my knowledge regarding ethanol-induced gene expression changes.

Lipton P. A. Gayer G. G. Wang L., Miles M.F. Time course of effects of chronic cocaine administration expression in mice Society of Neuroscience,. Abstract, 977.15, 2001.


2)Dynorphinergic and enkephalinergic neuronal pathways 2003-2006

Dr. Robert Messing (Ernest and Gallo Research Center, Co-Director, UCSF) and I collaborated on a project to better elucidate that molecular events that occur in reward centers like the nucleus accumbens when exposed to acute and chronic treatments to drugs with high abuse potential. I developed DNA expression vectors that contain green-fluorescent protein directed by pdynorphin (pdyn-GFP) and penkephalin (pENK-EYFP) tissue specific promoter elements. These constructs were developed to make transgenic mice that would enable the visualization of enkephalenergic and dynorphenergic neurons, a simple gene expression assay, and provide a visual identification for the capture of events produced by acute or chronic use of cocaine, heroine, and ethanol, etc. in brain areas hard to identify microscopically. Elucidating the connections in these meso-limbic reward pathways would provide important insights into drugs of abuse. Once these vectors were constructed, it was confirmed that they were functional by transfecting promoter-reporter constructs into tissue culture cells. Expression was confirmed by the population of fluorescent cells. Next, the expression vectors were injected into mouse embryo cells and transgenic mouse strains were analyzed.

3)Angiotensin II receptor function and glycation 2006-Future

I have received a $24,000 intramural grant to study the regulation of pathways central to many pathologic processes observed in diabetic patients. Specifically, angiotensin-II-AT1 receptor function will be observed under various environmental conditions that occur in patients with diabetes. (see attached grant proposal for details). Briefly, it involves measuring the AT1 receptor function under conditions that promote receptor-glycation. This grant proposal received the highest possible rating.

Research Project Prior to Employment at TUCA

At UCSF, EGCRC, I designed and conducted an innovative research project on a neurophysiological component of alcoholism. I was awarded for my efforts a National Institute of Health grant to research causes of alcoholism with potential for future development and use in the treatment of alcoholism and alcohol abuse. This work produced the discovery that chronic ethanol exposure to a neuronal cell culture system led to increases in Tyrosine Hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, protein and mRNA levels. It was further discovered that these increases in gene expression were at the translational level and independent of known ethanol-induced changes receptor function and second messenger cascades. The TH enhancer/promoter transcriptional activation region responsible for ethanol-induced increases was identified (see bold publications below).

I followed graduate work I was recipient of a Howard Hughes post-doctoral fellowship to investigate neural development with Dr. Richard Scheller, a pioneer in the field of molecular biology and the study of synapse function. Investigated the underlying biochemical mechanisms involved in how extracellular matrix proteins aid in developing neural muscular synapse. This project involved designing recombinant gene expression systems for analysis of rat agrin isoforms. I determined the role of the agrin y-splice variant in binding specificity to heparin and the dystrophin glycoprotein complex (see bold publication below and attached, note authors contributed equally on this project). In addition, I performed immunohistochemical localization of agrin splice variants during rat embryo development using florescence microscopy.