Robert P. Bowser, Ph.D.
Associate Professor, Pathology, Neurobiology- Ph.D. Yale University (1992)
- Office: S-420 Biomedical Science Tower
- Telephone:412-383-7819
- Fax:412-648-1916
- E-mail: bowserrp@upmc.edu
- Website: http://path.upmc.edu/personnel/Faculty/Bowser.htm
Molecular mechanisms in neurodegeneration.
Research Summary:
Dr. Bowser's research interests are in determining the molecular and cellular basis of neurodegenerative diseases. His lab is currently investigating how cell cycle proteins and transcription factors that function during brain development contribute to neurodegeneration in neurologic diseases. Studies have focused on Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). We hypothesize that the activation of cell cycle proteins and transcription factors, initially a compensatory response to neuronal insult, ultimately results in increased stress and cell death. Determining the pathways that result in activation of these cell cycle proteins will lead to new therapeutic strategies for neurologic diseases. Molecular biological approaches, including traditional gene cloning techniques and DNA microarrays, have led to the discovery of novel genes that are expressed at high levels during brain development, lower levels in non-demented adult brain, and re-expressed during the early stages of the disease process. Recent studies have demonstrated that one of our alternatively expressed genes, called FAC1, binds DNA and functions as a transcriptional regulator. FAC1 interacts with other transcription factors that function during the cell cycle, including the retinoblastoma (Rb) protein. We are currently formulating a molecular mechanism important for normal brain development that is re-activated during Alzheimer's disease and ALS. Cell culture model systems are being utilized to determine the function of these interacting transcription factors during cell differentiation and neurite outgrowth. We are interested in understanding how regulated gene expression controls both brain development and neurodegeneration.
Another focus within the lab is to identify protein biomarkers for ALS using proteomic techniques. We are using mass spectrometry based proteomics to protein profile the cerebrospinal fluid of ALS and control subjects. We have identified a series of protein biomarkers that identify ALS subjects with high levels of sensitivity and specificity. We are currently increasing the number of subjects in the study to confirm our findings, and hope to develop a diagnostic test for ALS. Future projects will determine the identity of each protein biomarker and how they function and contribute to the pathogenesis of ALS.
Trainees in Dr. Bowser's laboratory have the opportunity to investigate the mechanisms of neurodegeneration in human neurologic diseases and also to characterize the function of protein biomarkers for ALS. Techniques used within the laboratory include immunocytochemistry of human brain and spinal cord tissue, confocal laser microscopy, cell culture, mass spectrometry based proteomics, and numerous cellular and molecular biological techniques, including gel mobility shift assays, and in vitro cell death assays.
Selected Publications:
Jahroudi, N., Schmaier, A., Sujata, S., Madhi, F, Lutka, F.A., and Bowser, R. Von willebrand factor promoter targets the expression of amyloid precursor protein to brain vascular endothelial cells of transgenic mice. J. Alzheimer’s Disease, 5: 149-158, 2003.