Robert Bowser, Ph.D.

Research Interests:
Dr. Bowser's research interests are in determining the molecular and cellular basis of neurodegeneration in neurologic diseases. Recent studies in the laboratory have focused upon a group of interacting transcription factors and the role they play in neurodegeneration in Alzheimer’s disease and amyotrophic lateral sclerosis (ALS). We hypothesize that altered function of nuclear transcription factors regulates gene expression and chromatin structure that ultimately dictates the survival or death of the neuron. It is hypothesized that re-expression of developmentally regulated genes in adult post-mitotic neurons and glia, initially a compensatory response to neuronal insult, ultimately result in increased stress and contribute to cell death. Current research projects utilize numerous molecular and cell biologic techniques, including immunofluorescent laser confocal microscopy, transfection of cultured cells, and DNA binding studies, to explore transcription factor function during neurologic diseases. Recent studies demonstrate that a novel transcriptional regulator we identified, FAC1, is re-activated during Alzheimer’s disease and ALS to help regulate neuronal survival via interactions with a group of cell cycle proteins and proteins that control chromatin structure. Cell culture model systems are being used to further explore the function of these proteins during neuronal differentiation and cell death induced by a variety of stimuli. Characterization of nuclear transcriptional mechanisms and upstream activating signal transduction pathways will lead to novel insight into how neurons differentiate and how they die during neurologic diseases, and lead to new therapeutic agents that inhibit the progression of disease.

Opportunities for Fellows:
Fellows in Dr. Bowser’s laboratory will take a lead role in establishing a line of investigation that will produce an independent scientific career. Fellows will have direct oversight of a research technician and will be mentored in developing skills in project development, data interpretation, manuscript writing and grantsmanship. Fellows will be expected to apply for research funding during their fellowship training period.

Opportunities for Graduate Students:
Graduate students are trained to rapidly develop a line of investigation that leads to a thesis project. Current research projects focus on how nuclear proteins that regulate gene expression and chromatin structure function during neurodegeneration. Numerous opportunities exist for graduate students to acquire expertise in molecular and cellular methodologies including subcloning, expressing and purifying gene products, microscopic analysis of cultured cells and tissue sections using light and immunofluorescent techniques, primary cell cultures from the brain and spinal cord of wildtype and transgenic mice, protein-DNA interactions and cell transfections. Graduate students are expected to write manuscripts about their data for publication and present their data at national and international meetings. Graduate students will also receive training in grantsmanship and how to critique manuscripts and grant applications.

Opportunities for Undergraduates:
Undergraduates in the Bowser laboratory work closely with other members of the lab to assist within a project and to eventually develop an independent line of experimental investigation. Undergraduates are encouraged to apply to the summer undergraduate training program within the Department of Pathology in order to obtain more extensive training and research experience.

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Charleen Chu, M.D., Ph.D.

Research Interests:
Dr. Chu's laboratory investigates oxidative regulation of cell signaling in neurodegenerative diseases. One major focus revolves around temporal and spatial regulation of mitogen activated protein kinase (MAPK) signaling and trafficking. We have found that sustained, granular cytoplasmic ERK/MAPK activation contributes to oxidative neurotoxicity. Moreover, granular cytoplasmic aggregates of phospho-ERK/MAPK are observed in substantia nigra neurons in both early and advanced Parkinson’s disease. A second project focuses upon extracellular binding proteins and TGF-beta regulation. Experimental manipulation of reactive oxygen and nitrogen species, kinases, and phosphatases using biochemical, molecular, and cell culture systems is complemented by direct biochemical and immunomicroscopic analysis of diseased human tissues. In addition, transgenic and knockout mice with altered levels of extracellular superoxide dismutase (EC-SOD), a potent regulator of nitric oxide and superoxide bioavailability, are used in neurotoxic Parkinson’s disease models.

Opportunities for Fellows:
A post-doctoral research position is available. Experience with techniques of protein biochemistry and molecular biology are required. US citizenship or permanent resident status preferred. Please send a clear statement of career goals, CV, and 3 references.

Opportunities for Graduate Students:
Graduate students and MD/PhD students are encouraged to contact Dr. Chu about training and research opportunities in the lab.

Opportunities for Undergraduates: Research opportunities for motivated undergraduate trainees can be developed.

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Ronald Hamilton, M.D.

Research Interests:
Dr. Hamilton has research interests in the molecular biology of brain tumors, and neurodegenerative diseases such as Alzhemier's, Lewy Body Dementia, ALS and Parkinson's disease. The pediatric brain tumor research is conducted with Children's Hospital of Pittsburgh in collaboration with Dr. Ian Pollack, a pediatric neurosurgeon and the Children's Oncology Group (COG) and Pediatric Brain Tumor Consortium. As the diagnostic neuropathologist for the Neuropathology Core of the Alzheimer's Disease Research Consortium (ADRC) and Director of the Neuropathology Brain Bank, Dr. Hamilton also collaborates with numerous dementia researchers. Dr. Hamilton’s laboratory investigates aggregation and proteolysis of alpha-synuclein (the main protein component of Lewy bodies) using immunoblots of human tissue, in vitro studies using recombinant protein and an inducible cell system (Tet-off) with a neural cell line (B65). Dr. Hamilton’s laboratory has a weekly journal club focusing on the current literature of alpha-synucleinopathy.

Opportunities for Fellows:
Fellows have the opportunity to engage in immunohistochemical studies of autopsy material for neurodegenerative work and can participate in neuro-oncology work with clinico-pathologic correlations using immunohistochemistry (proliferation rates and other molecular markers of malignancy) or correlation of loss of heterozygosity and tumor progression.

Opportunities for Graduate Students:
Graduate students interested in investigations of proteolysis and aggregation of proteins (such as alpha-synuclein) are welcome.

Opportunities for Undergraduates:
Dr. Hamilton has mentored several undergradute students through Independent Study and Honor Research courses. Students are assigned their own project and are expected to attend the weekly journal lub and are also given the opportunity to participate in the weekly brain cutting sessions and may participate in brain banking.

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David Lacomis, M.D.

Research Interests:
Dr. Lacomis specializes in neuromuscular diseases and neuromuscular pathology. His research interests include (1) the histopathologic features of critical illness myopathy, especially with regard to the loss of myosin thick filaments; (2) histopathologic and electrophysiologic correlation in inflammatory myopathies and peripheral nervous system vasculitis; (3) the use of neurotrophic factors in the treatment of amyotrophic lateral sclerosis; and (4) the use of antioxidants in the treatment of diabetic neuropathy.

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Clayton Wiley, M.D., Ph.D.

Research Interests:
Dr. Wiley's research concentrates on the pathogenesis of neurodegenerative diseases and in particular on viral induced nervous system diseases. Viruses damage the nervous system either by direct infection of neural cells or by secondary effects of an immune response. In recent years his studies have focused on central nervous system (CNS) retroviral infections and have pioneered the use of molecular techniques to quantitatively assess viral burden. This same technology is now being applied to quantify synaptic damage and the CNS immune response. A wide variety of techniques including laser confocal microscopy is employed to measure production of cytokines, neurotrophic factors and potential neurotoxins. While investigations are founded in observations made in human tissues, both animal models and in vitro nervous system cultures are used to test hypotheses. Current laboratory focus is placed on the CD8 depletion model of SIV encephalitis.

Opportunities for Fellows:
Post-doctoral fellows with a solid foundation in either molecular biology or immunology are encouraged to expand their training in the study of neurological disease while at the same time creating their own experimental niche investigating the pathogenesis of lentiviral encephalitis.

Opportunities for Graduate Students:
Graduate student projects are directed along the lines of existing funded studies including: elucidation of monocyte/macrophage trafficking to the brain, pathogenesis of lentiviral encephalitis, alterations in gene expression during lentiviral encephalitis, immune control of lentiviral infected macrophages and in vivo monitoring of CNS macrophage activation

Opportunities for Undergraduates:
At any one time the laboratory sponsors 1 or 2 undergraduate students. Undergraduates begin lab work with routine experiments, and based upon performance, may be paired with fellows or graduates students to carry out more advanced studies.