Joint Fellowship Training Program
Mentor:
Jan Simak, PhD
Organizational Affiliation and Position:
Visiting Scientist, Laboratory of Cellular Hematology, Division of Hematology, Office of Blood Research and Review (OBRR), Center for Biologics Evaluation and Research (CBER), FDA
Email:
jan.simak@fda.hhs.gov
Telephone:
301-827-3978
Running Title of Program:
Cell Membrane Microparticles In Plasma As Biomarkers In Cancer
Research Project Summary (if applicable):
Cell membrane microparticles (MPs) in blood, 0.1-1.5 m in size, are released from platelets, blood cells, endothelial cells, and some other cell types including cancer cells. MPs are present in circulating blood of healthy donors and their elevated counts have been reported in various pathologies. In addition, it has been documented that MPs exhibit various biological activities and thus may play significant role in many physiological and pathophysiological processes including hemostasis and thrombosis, inflammation, modulation of vascular tone, angiogenesis, stem cell engraftment, or tumor metastasis. Development and validation of immunodetection and functional assays for MP analysis in blood is essential. Screening of MP phenotypes for diagnostic value is needed. We have designed an original three-color flow cytometry assay for the analysis of MPs in plasma and demonstrated the presence of several different phenotypes of MPs in plasma of healthy blood donors. We have done initial studies in patients with paroxysmal nocturnal hemoglobinuria (PNH), sickle cell disease (SCD), and acute ischemic stroke. Correlations have been found between plasma counts of certain MP phenotypes and severity of the disease.
Proposed Project for IOTF Fellow:
The project will focus on studies of MPs derived from platelets, blood cells and endothelial cells, as well as MPs derived from cancer cells, in plasma of cancer patients. Different immunodetection and functional assays for MP analysis will be used. In collaborative studies, MPs will be analyzed in blood samples from patients with different types of cancer (e.g. head and neck cancer, hematologic malignancies) to investigate diagnostic and prognostic utility of MP analysis in cancer.
Regulatory Activity:
Laboratory of Cellular Hematology regulates cellular transfusion products, including red blood cells, platelets, and platelet substitutes. We also regulate devices and solutions used for collection, processing, storage, and pathogen reduction of these products. In addition, bacterial detection assays and leukocyte counting assays for blood product testing are regulated in our laboratory.
Reference(s):
Simak J., Gelderman M.P.: Cell membrane microparticles in blood as diagnostic markers and potentially pathogenic blood product contaminants. Transfusion Medicine Reviews 2006, 20 (1), In press.
Simak J. et al.: Elevated circulating endothelial membrane microparticles in paroxysmal nocturnal haemoglobinuria. Br J Haematol 2004;125(6):804-13.
Simak J.et al.: Release of annexin V-binding membrane microparticles from cultured human umbilical vein endothelial cells after treatment with camptothecin. BMC Cell Biology 2002; 3: 11, 1-10.
