The CMP program embraces a tissue based approach to research and features active programs in basic cancer research, molecular diagnostics, neurodegenerative diseases, liver biology, transplantation, and gene therapy.
Cancer Biology
This is an exciting time in the area of cancer research. Advances are being made in understanding many important aspects including carcinogenesis, metastasis, and genetics. This is leading to novel markers along with treatment strategies. Faculty members in conjunction with the University of Pittsburgh Cancer Institute, which is a National Cancer Institute Comprehensive Cancer Center, are at the forefront of these discoveries. The latest technologies including chip-based microarrays, SAGE, proteomics and others are being applied to further our knowledge of cancer pathobiology. Cancer has classically been defined as a disease of cell and tissue architecture and this background is being addressed with state of the art approaches. Faculty members in the program focus on many aspects of cancer research including the role of cell structure, cell-cell and cell-ECM interactions, genetic alterations, growth factors, novel markers and treatment strategies. The treatment approaches being studied include gene therapy, immunological based therapies as well as differentiation and apoptotic agents. The cancer types that are studied are diverse and include liver, prostate, bladder, renal, brain and gastrointestinal as examples. There are many exciting opportunities in this area of investigation.
Liver Growth and Differentiation
Pathology faculty members are defining the molecular mechanisms that dictate liver cell formation and development with the goal of replacing liver function, rebuilding a damaged liver, or correcting genetic defects in liver tissue. Studies use cell culture and whole animal models to examine the effects of growth factors, cytokines, biomatrix molecules and their receptors, as regulators of key pathways of hepatocyte differentiation. Hepatocyte growth factor and its receptor (c-met), discovered as part of these studies, as well as interleukin-6 are examined in depth as mitogenic and motogenic regulators. Current projects include the use of cultured human liver cells as a "bridge" therapy for patients waiting for a liver transplant, investigations of hepatic growth factors and gene regulation, hepatocyte culture and in vitro organogenesis, liver gene therapy, and hepatic cancer. This is a collective effort by many laboratories within the department.
Pathogenesis of Neurodegeneration
Research into the brain has greatly expanded as we explore the "universe between our ears." Delineating the cellular and molecular mechanisms of how the brain develops, functions and responds to stress goes hand in hand with understanding the alterations that lead to the numerous diseases of the brain. The study of acute and chronic disorders of the nervous system represents another focus within the CMP program. Experimental neuropathologists are in the unique position to link basic science discoveries with clinicians that treat the patients. Students have the opportunity to utilize patient derived tissues to evaluate pathologic characteristics of human disease and to develop relevant hypotheses to be tested in model systems.
Pathology faculty comprise key members of the University of Pittsburgh Alzheimer's Disease Research Center, the Parkinson's Disease Center of Excellence, the Pittsburgh Institute of Neurodegenerative Diseases, the Center for Neuroscience and the McGowan Institute for Regenerative Medicine. The clinical centers treat a large number of patients, facilitating translational studies, imaging studies (MRI, fMRI, PET, CT), and tissue based studies into the mechanisms of disease. Pathology faculty pioneered the use of molecular biologic techniques to assess viral burden and neurologic damage due to viral infection of the central nervous system. Major current themes include mitochondrial dysfunction and the basic regulation of autophagy in neuron injury responses, proteomic analysis of signaling pathways in Parkinson's disease, and investigations into the role of neuroinflammation in viral encephalopathies and Alzheimer's disease. Both in vitro and in vivo model systems are used to identify mechanisms that induce neurodegeneration or regenerative repair. Our Division of Neuropathology is a national leader in teaching the next generation of scientists that investigate diseases of the brain.
Facilities
The main office and laboratories for the Department of Pathology are located in the Biomedical Science Tower on the University's Pittsburgh campus at the School of Medicine. Additional laboratories are located in UPMC Presbyterian University Hospital and Scaife Hall, the University of Pittsburgh Cancer Institute, UPMC Magee-Womens Hospital, and Magee-Womens research Institute. All buildings are either interconnected or in close walking distance. All laboratories contain state of the art equipment, and the department of Pathology has centralized core facilities for electron microscopy, laser confocal microscopy, DNA sequencing, photography, and histology. These facilities are strengthened by the close proximity with the Molecular Diagnostics Laboratories of the UPMC hospitals, directed to the analysis of molecular components needed for diagnostic evaluation of tumors, genetic diseases, infectious agents, etc. For additional description of the basic science and clinical facilities of the department, please check our website.
Molecular Diagnostics
Molecular Diagnostics is a rapidly growing translational area in pathology and medicine that bridges discoveries in molecular pathogenesis by basic scientists and the migration of these discoveries to useful clinical assays by physicians involved in the care of patients.
In addition to research programs of its own faculty, the Division of Molecular Diagnostics collaborates in a variety of ways with basic investigators in numerous departments within the University of Pittsburgh. We offer an invaluable clinical overview, as well as specific suggestions of where a new technology developed by a basic investigator's laboratory might most usefully be focused for diagnostic application or additional peer-supported investigation. We also collaborate and provide materials necessary to carry out pilot experiments. For investigators with a newly discovered disease-causing gene, the Division's CLIA-certified clinical laboratory can implement clinical genetic testing so results can be provided to research patients for purposes of counseling and clinical decision making. Full transfer of assays to the clinical laboratory at a point in the research also can remove from the investigator the research-slowing and ongoing burden of testing for 'your gene' for multiple colleagues when other projects need more immediate attention. With appropriate IRB and laboratory consents, samples can be designated for other research purposes allowing the investigator potentially new sources with relatively little investment of effort. Investigators interested in performing specific focused research on groups of samples not readily available in a short period of time may be able to take advantage of the Division's stored archives of samples covering a number of years. With its vast experience of developing and trouble-shooting molecular-based assays, the Division can also be a valuable resource for specific problems basic research may be encountering with recently-introduced techniques, and we're always happy to interact with basic investigators, postdocs and graduate students.