Signal transduction is central to theunderstanding of cancer cell growth, metastasis and the molecular basis ofcancer response to therapy. With the advent of proteomics, future cancertreatment strategies could be tailored to target specific signaling pathwaysfor an individual, based on an individual tumor?s genetic background. Thus,it is possible that new adjuvant therapies can be developed and used withexisting treatment regimens to target differential expression of signalingproteins in patients predicted to be non- or poor responders. Our overallresearch goal is to identify molecular changes in cell signaling proteins thatoccur in cancer and target these proteins or genetic changes for thedevelopment of new therapies. Project #1: will address the role of PI3-kinase mediated signaling in angiogenesis and the identification of noveldownstream signaling proteins as targets for anti-angiogenic therapy. Project#2: will address the signal transduction pathways that govern neutrophilactivation and how these signals might differ in cancer patients who haveundergone blood and marrow transplantation. Project #3: will examine howcellular signals induce expression and activation of DNA repair enzymes inovarian cancer with a special emphasis on angiogenesis. Project #4: willaddress the role of cytochrome P450-1A1 and -1A2 isoforms in carcinogenesisand will use molecular modeling techniques to design novel inhibitors thatcould prevent metabolism of environmental pollutants into carcinogens.Project #5: proposes to design new microfluidic methods for proteomicanalysis that will rapidly evaluate protein expression from small sample sizesfor identification. Each of these molecular changes will be analyzed asindicators for prognosis, diagnosis, treatment and outcome and may reveal astrategy for treating patients who respond poorly to conventional therapies.These projects will be led by junior faculty, who will be mentored by anadministrative core. To support these research efforts, two core facilitiesare also proposed for fluorescence activated cell sorter/cell separator (FACS)and mass spectrometry. In addition, faculty recruitment in the area of signaltransduction and cancer are also proposed, which will expand the critical massof cancer research scientist who study signal transduction in cancer andencourage greater collaborative efforts. Our long term goal is to create astrong basic science core that will support cancer research/education andclinical treatment for the citizens of WV and the surrounding Appalachiaregion.
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