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| May 17, 2008 |
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Mark P. Kamps (mkamps@ucsd.edu)
Through disease-focused courses, Molecular Pathology students learn the molecular basis of human diseases that interest them most, as well as the use of currently available therapeutics. Unique to the Molecular Pathology track is training in Histology (normal tissue structure) and in Histopathology (diseased tissue structure). With this training, Molecular Pathology students become experts in evaluating the phenotype of knockout mice produced to test the comprehensive or tissue-specific function of a protein or produced as models to confirm disease etiologies and detect effective cellular or molecular therapies. Molecular Pathology trainees may rotate and perform thesis research with any member of the BMS faculty. An example of a typical project in a Molecular Pathology faculty lab is illustrated below. In this case, student Greg Wang pursues the molecular mechanism by which a chromosomal translocation protein containing an N-terminal transcriptional activation domain and a C-terminal histone methyltransferase domain (see illustration) causes human acute myeloid leukemia. He discovers that this fusion oncoprotein prevents the normal differentiation of mouse marrow myeloid stem cells into neutrophils and macrophages, and causes them to proliferate indefinitely as stem cells in cell culture. Greg uses a mouse model to demonstrate that stem cells immortalized by the oncoprotein cause acute myeloid leukemia. Using his cultured progenitors, he performs genomic microarray analysis and discovers that the fusion oncoprotein enforces transcription of Hox and Meis1 genes, which are known effectors of the stem cell phenotype and whose coexpression has previously been shown to cause myeloid leukemia. Greg then identifies which biochemical functions of the fusion oncoprotein are required for its transcriptional activation of the Hox gene locus, for stem cell expansion, and for leukemia formation. Greg finishes his research by focusing on how the normal version of this histone methyltransferase, which targets Lys36 on histone H3, regulates the expression of Hox genes during development because it likely represents one component of a regulatory protein complex, and mutations in other members of that complex are likely to block differentiation in other types of stem cells cancers (e.g. acute lymphoid leukemia, neuroblastoma, carcinoma). 
Finally, the Departments of Pathology and Medicine are committed to providing BMS students with interactive settings to understand the presentation, progression, diagnosis, and current treatments to human disease, as well as to appreciate the current state of clinical and translational research being performed on promising therapeutics. Accordingly, both departments sponsor training opportunities that allow students to compliment their strengths in hypothesis-driven bench research with a practical knowledge of the clinical needs in diagnosing and treating disease. Students that take advantage of these opportunities will better appreciate the most important aspects of human disease upon which to focus their future research efforts. They will also be more likely to pursue diagnostic or therapeutic applications of their research because they understand opportunities in this arena and they understand the activities of academic medical groups, which include clinical trials and use of patient material. These opportunities are summarized in the Med-into-Grad Website. Participating Faculty: Faculty members from the current Molecular Pathology Graduate Program will become members of this track. Required General Coursework for BMS students: BMS students take a core curriculum that provides the foundation to allow them to specialize in any of the offered tracks, focus areas, or customized study. In the Fall quarter, "Molecules to Organisms" provides a systematic approach to current Biomedical Research, using analysis of selected topics to focus on the process of research discovery and its critical evaluation. "Seminar in Biomedical Research" includes attendance at one of the UCSD seminar series and is designed to provoke critical discussion of the presented findings and scientific approaches in a small group setting. BMS students also take short courses in statistical analysis of data and ethics in research in the third quarter of their first year.
Students may select from the seminar series and journal clubs sponsored by other advanced training tracks. |
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News
Molecular Pathology focuses on understanding the biochemical & genetic mechanisms that cause human disease and on deriving new cellular & molecular forms of disease treatment. In the laboratories of Molecular Pathology faculty, students have the opportunity to investigate mechanisms that cause a broad assortment of human diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, endemic and tropical diseases, diseases of autoimmunity & inflammation, and genetic disorders. The pathologies causing these diseases result from a panoply of molecular mechanisms that alter normal cell biology or tissue viability, including those that regulate intracellular signaling, cell division, energy production, transcription, lineage-specific differentiation, cell death, the extracellular environment, and the immune response.