Robert A. Clark, M.D.
Professor and Chair
Department of Medicine
| Location: | DTL, Room 5.070R |
| Phone: | (210) 567-4810 |
| Fax: | (210) 567-4654 |
| E-mail: | clarkra@uthscsa.edu |
Research Interests:
Neutrophil signal transduction and activation are studied
at cellular and molecular levels. In a project on calcium signaling
the Ca 2+ storage protein calreticulin and the IP3-gated Ca2+
release channel are under study in terms of transcriptional regulation
of gene expression, protein biosynthesis, and structural determinants
of protein function. Another project concerns the respiratory
burst oxidase, a multi-component enzyme responsible for
stimulus-dependent
formation of reactive oxygen species. Recombinant proteins are
used to determine the mechanisms of enzyme activation, considering
phosphorylation, translocation of cytosolic components to membranes,
role of SH3 domains, and the function of the rac GTPases.
Patients with chronic granulomatous disease, a genetic disorder
of oxidase function are studied from cellular, biochemical and
clinical perspectives. Our overall goal is to understand at a
molecular level the neutrophil responses that result in microbial
killing and tissue injury. A new area of interest focuses on a
family of genes that are homologous to the neutrophil oxidase,
but are expressed in many non-myeloid cells where they may be
involved in signaling, cell growth, aging, and host defenses.
We are exploring the role of these oxidases in transcriptional
regulation of genes that are relevant to the biology of aging.
Unique Technical and Clinical Research Capabilities/Instrumentation:
cell biology, molecular biology, protein chemistry, spectroscopy
Publications:
Clark RA. Activation of the neutrophil respiratory burst oxidase. J Infect Dis (Suppl 2):S309-317, 1999.
Li S-L, Schlegel W, Valente AJ, Clark RA. Critical flanking sequences of PU.1 binding sites in myeloid-specific promoters. J Biol Chem 274:32453-32460, 1999.
Lavrovsky Y, Chatterjee B, Clark RA, Roy AK. Role of redox-regulated transcription factors in inflammation, aging and age-related diseases. Exper Gerontol 35:521-532, 2000.
Xu W, Longo FJ, Wintermantel MR, Jiang X, Clark RA, DeLisle S. Calreticulin modulates capacitative Ca2+ influx by controlling the extent of inositol 1,4,5-trisphosphate-induced Ca2+ store depletion. J Biol Chem 275:36676-36682, 2000.
Li S, Valente AJ, Wang L, Gamez MJ, Clark RA. Transcriptional regulation of the p67phox gene: Role of AP-1 in concert with myeloid-specific transcription factors. J Biol Chem 276:39368-39378, 2001.
Key Words:
inflammation, phagocytosis, neutrophil, oxygen radicals, superoxide,
calreticulin, calcium, transcription