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Dr. Martin Adelmann
Ms. Raquel Cabana
Dr. L. Scott Cram
Dr. Madhu Dikshit
Dr. Sumeet Gujral
Mr. Michael Keeney
Dr. Awtar Krishan
Dr. Mike Ormerod
Dr. Vincent Shankey
Dr. Arvinder Singh
Dr. Ranbir Sobti
Dr. Vivek Tanavde
Dr. William G. Telford
Dr. Rakesh Singal
Mrs. Veena Kapoor
Mr. Ron Hamelik
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 Core Faculty
Dr. Vincent Shankey
Dr. T. Vincent Shankey received Ph.D. in Immunology and Medical Microbiology from the University Of Florida School Of Medicine (1977). He did his postdoctoral training at the University of Pennsylvania, where he investigated the cytogenetics and Immunoglobulin synthesis in Chronic Lymphocytic Leukemia. He has been involved in flow and image cytometry for over thirty years. He was Director of Research for the Urology Department and Scientific Director of the Clinical Flow Cytometry laboratory at Loyola University Medical Center. Chicago, Illinois. He joined the Advanced Technology Center at Beckman Coulter, Miami in 2001.
Lecture
Signal transduction pathways represent the major communication network that transmits signals from cell surface to the nucleus to activate specific genes. These pathways serve an important function in integrating signals from individual pathways and to signal cell death, proliferation and differentiation. This lecture will provide an overview of the basic mechanisms involved in activation of receptor tyrosine kinases followed by a summary of idealized pathways that involve the regulation of cell proliferation (MAP kinase pathways), and cell death/apoptosis (PI3 kinase pathway). We will discuss flow analysis of the MAP kinase pathway, including factors that impact these measurements. Potential clinical use for monitoring chronic myelogenous leukemia responsiveness to STI571 (Gleevec) will be discussed.
Lab
Glevec for the treatment of CML represents one of the first "molecularly targeted" therapies. This drug binds to the ATP binding site in the Abl portion of the Bcr/Abl fusion protein, inhibiting the subsequent phosphorylation of a number of downstream targets, including P-STAT5 and P-Crkl. This leads to inhibition of the G1-S transition in the cell cycle, with subsequent apoptosis of CML cells. We will demonstrate the inhibition of phosphorylation of STAT5 using an antibody specifically targeted to the phosphorylated form of this protein.
Relevant Literature
Chow S, Patel H, Hedley DW. Measurement of MAP kinase activation by flow cytometry using phospho-specific antibodies to MEK and ERK: Potential for Pharmacodynamic monitoring of Signal Transduction inhibitors. Cytometry 46; 72-78, 2001.
Jacobberger JW, Sramkoski RM, Frisa PS, Ye PP, Gottlieb MA, Hedley DW, Shankey TV, Smith BL, Paniagua M, and Goolsby CL. Immunoreactivity of STAT5 phosphorylated on tyrosine 694 as a cell-based measure of Bcr/Abl kinase activity. Cytometry 54A;75-88, 2003
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