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Research Interests:
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.
Selected Publications:
Ranganathan S., Polshyna A., Lutka F., Nicholl G., Lyons-Weiler J., and Bowser R. (2006). Assessment of protein stability in cerebrospinal fluid by mass spectrometry based proteomics. Clinical Proteomics, 2: 91-102.
Gopalakrishnan V, Ganchev P, Ranganathan S, and Bowser R. (2006). Rule Learning for Disease-specific Biomarker Discovery from Clinical Proteomic Mass Spectra. In BioDM 2006, Lecture Notes in Bioinformatics (LNBI) 3916. J. Li et al. (Eds.) Springer-Verlag, Berlin, Heidelberg, pp 93 - 105.
Chalovich EM, Zhu J-H, Caltagarone J, Bowser R, and Chu CT. (2006). Functional repression of cAMP response element in 6-hydroxydopamine-treated neuronal cell. J Biol Chem, 281: 17870 - 17881.
Caltagarone J., Jing Z., and Bowser, R. (2006). Focal adhesions regulate A¦Â signaling and cell death in Alzheimer's disease. Biochim et Biophys Acta (BBA) - Molecular Basis of Disease, http://dx.doi.org/10.1016/j.bbadis.2006.11.007.
Bowser R., Cudkowicz M., and Kaddurah-Daouk R. (2006). Biomarkers in amyotrophic lateral sclerosis. Expert Rev Mol Diagn, 6: 387-398.
Kolarcik C., and Bowser R. (2006). Plasma and cerebrospinal fluid-based protein biomarkers for motor neuron disease. Mol Diag & Therapy, 10(5): 281-292.
Ranganathan S., Williams E., Ganchev P., Gopalakrishnan V., Urbinelli L., Newhall K., Cudkowicz M.E., Brown R.H.Jr., Bowser, R. (2005). Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. J Neurochem, 95: 1461-1471.
Yu X., Caltagarone, J., Smith, M.A., and Bowser R. (2005). DNA damage induces cdk2 protein levels and histone H2B phosphorylation in SH-SY5Y neuroblastoma cells. J Alzheimer Dis, 8: 7-21.
Strachan G.D., Morgan K.L., Caltagarone J.M., Gittis A., Bowser R., Jordan-Sciutto K.L. (2004). Fetal Alz-50 Clone 1 (FAC1) interacts with the human homologue of the Kelch-like Ech Associated Protein (Keap1). Biochemistry, 43: 12113-12122.
Wilson, C., Henry, S., Smith, M.A., and Bowser, R. (2004). The p53 homologue p73 accumulates in the nucleus and localizes to neurites and neurofibrillary tangles in Alzheimer disease brain. Neuropath Appl Neurobiol, 30: 19-29.
Hamilton, R.L., and Bowser, R. (2004). Alzheimer disease pathology in amyotrophic lateral sclerosis. Acta Neuropathologica, 107: 515-522.
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