Robert Bowser, Associate Professor
Associate Director, CMP Graduate Program
PhD, Yale University, 1991
Email: Bowserrp@upmc.edu.
Dr. Bowser's research interests are in determining the molecular and cellular basis of neurodegenerative diseases and the search for biomarkers to aid in diagnostics and drug discovery. His lab has identified protein biomarkers for amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) using proteomic techniques. Mass spectrometry based proteomics has identified protein profiles within the cerebrospinal fluid and blood that can distinguish ALS from control 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. The protein identity for some of these protein biomarkers has been determined and efforts to explore how these proteins contribute to the pathogenesis of ALS are underway using cell culture models, transgenic animals, and human spinal cord tissue samples. Additional projects include determining how the protein biomarker panel changes during disease progression and to use these biomarkers to test drug effectiveness in clinical trials. We are performing similar proteomic studies using the transgenic animal model for ALS and hopefully will identify biomarkers common to the animal model and humans with this disease. We collaborate with numerous clinicians and pharmaceutical companies to perform these experiments, and will soon be measuring biomarkers within ALS patients during clinical drug trials. Dr. Bowser is also the Director of the Center for ALS Research at the University of Pittsburgh (http://www.alsresearchcenter.org/).
Another research focus within his lab is how cell cycle proteins and cell adhesions protein that function during brain development and neurite outgrowth contribute to neurodegeneration. Studies have focused on Alzheimer's disease (AD) and ALS. We hypothesize that the activation of cell cycle proteins and cell-cell adhesion molecules, 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. Cell culture model systems are being utilized to determine the function of these proteins during cell differentiation and neuronal cell death. We are interested in understanding how regulated gene expression via altered chromatin structure controls both brain development and neurodegeneration.
Trainees in Dr. Bowser's laboratory have the opportunity to investigate the mechanisms of neurodegeneration in human neurologic diseases and 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.
Recent Publication
Bowser R, and Lacomis D. (2009). Applying proteomics to the diagnosis and treatment of ALS and related diseases. Muscle & Nerve, 40(5): 753-762.
Lustgarten JL, Visweswaran S, Hogan WR, Bowser R, and Gopalakrishnan V. (2009). Knowledge-based variable selection for rule learning on proteomic data. BMC Bioinformatics, http://www.biomedcentral.com/1471-2105/10/S9/S16. PMCID: PMC2745687.
Henkel JS, Beers DR, Wen S, Bowser R, and Appel SH. (2009). Decreased mRNA expression of tight junction proteins in lumbar spinal cords of ALS patients. Neurology, 72(18): 1614-1616.
Jing Z, Caltagarone J., and Bowser, R. (2009). Altered subcellular distributon of c-Abl in Alzheimer's disease. J Alz Dis, 17(2): 409-422.
Bonneh-Barkay D, Bissel SJ, Wang G, Nicholl GCB, Darko SW, Medina-Flores R, Murphey-Corb M, Rajakumar PA, Nyaundi J, Mellors JW, Bowser R, Wiley CA. (2008). YKL-40 is a cerebrospinal fluid biomarker of SIV encephalitis and binds to the extracellular matrix modulating biological activity of bFGF. Am J Pathol, 173: 130-143. PMCID: PMC2438291.
Ryberg H, and Bowser, R. (2008). Protein biomarkers for amyotrophic lateral sclerosis. Expert Rev Proteomics, 5(2): 249-262.
Ranganathan S, Nicholl GCB, Henry S, Lutka F, Sathanoori R, Lacomis D, and Bowser R. (2007). Proteomic profiling of cerebrospinal fluid reveals significant protein alterations between antemortem and postmortem ALS and control samples. Amyotrophic Lateral Sclerosis, 8: 373-379.
Dunckley T, Craig DW, Huentelman MJ, Pearson J, Szelinger S, Joshipura K, Halperin R, Stamper C, Letizia D, Hesterlee SE, Pestronk A, Levine T, Bertorini T, Graves MC, Mozaffar T, Jackson CE, Bosch P, Barohn R, Lomen-Hoerth C, Rosenfeld J, O'Connor DT, Zhang K, Crook R, Hutton M, Ryberg H, Mitsumoto H, Bowser R, Miller RG, Appel SH, and Stephan DA. (2007). Whole genome analysis of persons with sporadic amyotrophic lateral sclerosis. New Eng J Med, 357: 775-788.
Gruzman A, Wood WL, Alpert E, Prasad MD, Miller RG, Rothstein JD, Bowser R, Hamilton, R, Wood TD, Cleveland DW, Lingappa VR, and Liu J. (2007). Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis. Proc Natl Acad Sci USA, 104: 12524-12529. PMCID: PMC1941502.
Caltagarone J, Jing Z, and Bowser, R. (2007). Focal adhesions regulate A? signaling and cell death in Alzheimer's disease. Biochim et Biophys Acta (BBA) - Molecular Basis of Disease, 1772: 438-445. PMCID: PMC1876750.
