Our Science – Simpson Website
R. Mark Simpson, D.V.M., Ph.D.
The Molecular Pathology Unit (MPU), headed by Dr. Simpson, serves as a Center for Cancer Research resource with 4 main spheres of activity:
- Developing molecular diagnostics for research
- Conducting training in comparative and molecular pathology
- Research investigation involving biomarker and animal model validation
- Diagnostic and molecular medical imaging and image analysis
Research includes both applied research and collaborations developing new reagents, methods, and technologies in preclinical diagnostic medicine. Contemporary pathology research conducted by the group enhances capabilities to integrate molecular and systemic aspects of disease mechanisms. The effort serves at the interface of extrapolating findings obtained in model animals to translational clinical relevance mechanistically or in pre-clinical therapeutics. Designing and employing state of the art medical and pathology investigative tools, to the study of animal models and patient tissue, is conducted to promote translational phenotype comprehension and therefore improve model predictability for human cancer diseases.
The laboratory also operates a PhD-granting NIH-wide Comparative Biomedical Scientist Training Program (CBSTP) in comparative molecular research pathology, an NCI-administered NIH graduate partnership program with 5 university graduate schools. Research conducted within the MPU additionally serves as a source of research training experience for its CBSTP trainees, as well as serves to extend comparative pathology expertise provided by the CBSTP molecular pathologist to the CCR and other institutes of the NIH intramural research program. Our training philosophy promotes the pathologist as an investigator and collaborator, vertically integrated from basic discovery to translational research application [http://nih-cbstp.nci.nih.gov/].
The Molecular Pathology Unit is also engaged in biomarker discovery and validation for diagnosis and monitoring of ovarian cancer. Among gynecological cancers, ovarian cancer is a significant cause of death in women. Due to the confounding nature of early disease and the vague nonspecific symptoms caused, ovarian cancer diagnosis is often delayed until the disease has spread within the abdomen making clinical management more difficult. Additional challenges exist in caring for patients with cancer recurrence following initial treatments. A means to detect ovarian cancer at its early stage, or its recurrence following therapy, in patient serum would be a significant benefit to current diagnostic paradigms. Diagnosis based upon serum CA125 tests has 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. An S100A6 protein of cancer origin has been identified in serum, related to tumor burden in an animal model of disseminated ovarian cancer, and shown to correlate with amount present in serum in ovarian cancer patients with advanced stage disease. Follow on functional studies are providing insight into potential influence of S100A6 on propensity for metastasis of both ovarian and breast cancers.
Additional lines of inquiry revolve around development and application of technologies, biorepository quality assurance, and the development and characterization of model systems.
- Development of digital pathology capabilities provides new means to archive, share, analyze and consult on pathological specimens of importance to disease research. The MPU has created an initiative to support investigator application of digital pathology for research, and to implement quantitative image analysis algorithms in pathology research.
- Molecular Pathology Unit investigators are contributing to best practices for biorepository quality assurance standards by applying novel computer-assisted diagnosis and image analysis technology to annotate biospecimens and therefore guide research appropriate biospecimen selection. Biorepository-supported translational research depends on high-quality, well-annotated specimens. Histopathology assessment contributes insight into how representative lesions are for research objectives. Feasibility of documenting histological proportions of tumor and stroma is under development in an effort to enhance information regarding biorepository tissue heterogeneity. Unique automated pattern recognition morphometric image analysis algorithms are developed and applied to quantify histologic tumor and nontumor tissue areas in biospecimen tissue sections. Quantitative image analysis automation minimizes variability associated with routine biorepository pathologic evaluations and will enhance biomarker discovery by helping to guide the selection of study-appropriate specimens.
- Determination of disease-relevant proteomic profiles from limited tissue specimens, such as pathological biopsies and tissues from small model organisms, remains an analytical challenge and a much needed clinical goal. Investigation developed within the lab provides a system to apply mass spectrometry (MS)-based proteomics to obtain a disease-relevant molecular profile from amount-limited specimens that are routinely used in pathological diagnosis.
- The Molecular Pathology Unit organizes and conducts initiatives in comparative oncology. An analysis of similarities of naturally occurring canine melanomas with mucosal melanomas in humans led to a consensus statement on the rational for conducting canine surrogate clinical trials to pilot therapeutic development for human melanoma, with dogs serving as preclinical models.
This page was last updated on 12/6/2013.