Research Interests:
FGFRs in Human Cancer
We are studying the significance of Fibroblast Growth Factor Receptors (FGFRs), which are receptor tyrosine kinases in several human cancers, specifically the interaction of FGFRs with the NFκB inflammatory signaling pathway. Preliminary evidence demonstrates that both FGFR2 and FGFR4 interact with IKKβ, an important regulatory protein of the NFκB pathway, and that this interaction negatively regulates NFκB signaling activated by its ligand, TNFα. We are examining the inhibitory effects of FGFR activation upon NFκB signaling in breast cancer cells expressing FGFR2, and in prostate cancer cells expressing FGFR4, using mass spec proteomic approaches to characterize FGFR-associated proteins in signaling complexes. We hope to significantly advance our understanding of how growth factor receptor pathways, controlled by FGFRs, have the ability to assemble signaling complexes that can negatively regulate inflammatory signaling, thereby modulating apoptotic control.
Another area of our research is to determine the biological consequences of the disease-associated polymorphisms (SNPs) in FGFR2. Recent genetic linkage studies have identified single nucleotide polymorphisms within FGFR2 as highly significant for increased risk in postmenopausal invasive breast cancer. We have designed experiments to examine whether FGFR2 expression is altered in an estradiol-dependent manner as a result of these SNPs, and to distinguish between different biological outcomes. The detection of novel proteins associated with FGFR2 by mass spectrometry in the breast cancer cell lines that have been characterized for their polymorphisms should yield interesting results to further our knowledge of this genetic risk factor associated with invasive postmenopausal breast cancer.
Track(s):
MCB
BMS Focus Areas:
Cancer Biology
Developmental Biology
|
News