Our Science – Simpson Website

R. Mark Simpson, D.V.M., Ph.D.

Laboratory of Cancer Biology and Genetics Staff Scientist (Facility Head) National Cancer Institute Building 37, Room 2000 37 Convent Drive Bethesda, MD 20892 Phone:   301-435-7176 Fax:   301-480-1138 E-Mail:   simpsoma@mail.nih.gov

Biography

Dr. Simpson is a doctor of veterinary medicine graduate of the University of Georgia. He completed postgraduate clinical training in veterinary pathology and research training leading to a Ph.D. in comparative biomedical science at the Louisiana State University. He is specialty board certified by The American College of Veterinary Pathologists. Dr. Simpson was a faculty member and hematopathologist at the North Carolina State University Veterinary Medical Teaching Hospital. Subsequently he became a staff scientist with the National Institute of Allergy and Infectious Diseases intramural research program. In May 2001, Dr. Simpson joined the NCI Center for Cancer Research to establish and head the Molecular Pathology Unit, Laboratory of Cancer Biology and Genetics. He is founding director of a new initiative to provide interdisciplinary training for veterinarians, in both diagnostic pathology and human disease-oriented medical research, to increase the synergy for comparative biomedical research interactions. This program is a component of the NIH Graduate Partnership Program and training leads to a Ph.D. and eligibility to certify as a veterinary pathologist. Dr. Simpson is adjunct graduate professor or clinical professor at 4 colleges of veterinary medicine.

Research

The Molecular Pathology initiative includes both applied research and collaborations aimed at developing new reagents, methods, and technologies in preclinical diagnostic medicine. Thus, efforts are aimed at enhancing capabilities to integrate molecular and systemic aspects of disease mechanisms. Designing and employing state of the art medical and pathology investigative tools to the study of animal models and patient tissue will help promote translational phenotype comprehension, and therefore improve model predictability for human cancer diseases. The Unit also operates a PhD-granting research training program in comparative molecular pathology through a university- NCI graduate partnership program. Through its training program, the MPU both extends comparative pathology expertise provided by veterinarians to the CCR and it conducts research, which serves as a source of research training experience for its GPP molecular pathologist trainees. The program’s vision of comparative biomedical scientist training includes pathologist as investigator and collaborator, vertically-integrated from basic discovery to translational research application.


The molecular pathology unit, headed by Dr. Simpson, serves as a CCR resource with 4 main spheres of activity focused on translational research within the NCI Center for Cancer Research:

• Developing molecular diagnostics for research
• Training in comparative and molecular pathology
• Research investigation and animal model validation
• Noninvasive diagnostic and molecular medical imaging

Applied research includes studies to evaluate use of an ovarian cancer animal model to pilot discovery of protein biomarkers with potential clinical diagnostic utility. Among gynecological cancers, ovarian cancer is a significant cause of death in women. Due to the occult nature of early disease and the vague nonspecific symptoms caused, ovarian cancer diagnosis is often delayed until the disease has spread within the abdomen. Additional challenges exist in managing patients due to recurrence of cancer following initial treatments. A means to detect ovarian cancer, or its recurrence, in patient serum would be a significant benefit to current diagnostic paradigms. Diagnosis based upon serum CA125 tests is hampered due to less than optimal sensitivity and specificity, thus new tests to diagnose ovarian cancer are needed. Current research is aimed at validating serum proteins that can be localized to cancer cell origin, and in investigating their validity for diagnostic or staging use. Biomarker correlates of ovarian cancer burden are particularly challenging in a clinical setting due to the way ovarian cancer spreads throughout the abdominal cavity. Animal models are an important adjunct to the ovarian cancer diagnosis research field. In this research, candidate proteins are detected in serum of mice with staged abdominal carcinomatosis using mass spectrometry. Putative biomarkers are validated. Correlations with tumor burden can be attempted in the carcinomatosis model using human cancers engineered with reporter markers that permits cancer cells to be tracked longitudinally during experimental disease. This model is permitting efforts to link cancer detection methods with ovarian cancer burden.

A second line of research is aimed at examining premalignant cellular injury due to oncogenic Ras activation. The Ras oncogene may become dysregulated in some cancers and promote cancer by stimulating uncontrolled cell proliferation. There are a host of other Ras-Mitogen-activated protein kinase (MAPK) pathway dysfunctional consequences. Pathway molecular mechanisms are being investigated outside the context of cell cycle influences of Ras activation by overexpression of Ras oncogene in cardiac myocytes, which are limited in their ability to enter the cell cycle. Oncogenic Ras activation in the myocardium results in a premalignant injury with significant cellular hypertrophy rather than cell proliferation. At the levels of the organ and organismal biology in the model, cardiomyopathy and heart failure, similar to some human cardiomyopathies associated with Ras-MAPK pathway activation, results. Conditional expression of Ras within a cardiomyopathy model is leading to identification of proteins involved in hypertrophy and with post translational modifications to these proteins important to injury due to aberrant Ras expression. Findings are anticipated to have relevance to early network derangements in some cancers associated with oncogenic Ras, as well as potential for informing pathogenesis of some cardiomyopathies. Research aims include identification of candidate targets for therapeutic modulation.

This page was last updated on 9/17/2008.