Daniel Donoghue
Fibroblast Growth Factor Receptors (FGFRs) in Human Cancer

Contact Information
Professor of Chemistry and Biochemistry
Chair, Academic Senate, San Diego Division, 2008/2009
Vice Chair, Graduate Education, Dept. Chemistry & Biochemistry
Program Director, NIH Training Grant

Office: Pepper Canyon Hall 227
Phone: 858-822-5155
Email: ddonoghue@ucsd.edu
Web: chem-faculty.ucsd.edu/donoghue/NIH-TG 
Group: View group members
Education
1979 Ph.D., , Massachusetts Institute of Technology
1974 B.S., , University of Wisconsin, Madison
Appointments
1982 Postdoc, , Salk Institute
Awards and Academic Honors
1989-1993
Recipient of American Cancer Society Faculty Research Award
1988-1994
Co-recipient of Lucille P. Markey Foundation Charitable Trust Funds
1983-1986
Searle Scholars Fellowship
1980-1982
Helen Hay Whitney Fellowship
1977-1979
Health Sciences Fund Fellowship
1974-1975
Phi Kappa Phi Graduate Fellowship
Research Interests
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 NFkappaB inflammatory signaling pathway. Preliminary evidence demonstrates that both FGFR2 and FGFR4 interact with IKKbeta, an important regulatory protein of the NFkappaB pathway, and that this interaction negatively regulates NFkappaB signaling activated by its ligand, TNFalpha. We are examining the inhibitory effects of FGFR activation upon NFkappaB 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.

Primary Research Area
Biochemistry
Interdisciplinary interests
Cellular Biochemistry

Selected Publications