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Daniel Donoghue
Fibroblast Growth Factor Receptors (FGFRs) in Human Cancer |
| Contact Information |
| Program Director, NIH Training Grant |
| Chair, Academic Senate, San Diego Division, 2008/2009 |
| Vice Chair, Graduate Education, Dept. Chemistry & Biochemistry |
| Office: UH 6102 |
| Phone: (858) x42463 |
| Email: ddonoghue@ucsd.edu |
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| View group members
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| Education and Appointments |
| 1982 |
Postdoc, Salk Institute
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| 1979 |
Ph.D., Massachusetts Institute of Technology
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| 1974 |
B.S., University of Wisconsin, Madison
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| 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.
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| Primary Research Area: |
Interdisciplinary Specialties: |
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Biochemistry
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Cellular Biochemistry
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| Selected Publications |
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Barnes EA,
Porter LA,
Lenormand JL,
Dellinger RW,
Donoghue DJ,
"Human Spy1 promotes survival of mammalian cells following DNA damage." Cancer Res 13(3701-7):
, 2003. [Go to PubMed]
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Meyer AN,
Gastwirt RF,
Schlaepfer DD,
Donoghue DJ,
"The cytoplasmic tyrosine kinase Pyk2 as a novel effector of fibroblast growth factor receptor 3 activation." J Biol Chem 27(28450-7):
, 2004. [Go to PubMed]
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Barnes EA,
Heidtman KJ,
Donoghue DJ,
"Constitutive activation of the shh-ptc1 pathway by a patched1 mutation identified in BCC." Oncogene 5(902-15):
, 2005. [Go to PubMed]
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Chen J,
Williams IR,
Lee BH,
Duclos N,
Huntly BJ,
Donoghue DJ,
Gilliland DG,
"Constitutively activated FGFR3 mutants signal through PLCgamma-dependent and -independent pathways for hematopoietic transformation." Blood 1(328-37):
, 2005. [Go to PubMed]
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Gastwirt RF,
Slavin DA,
McAndrew CW,
Donoghue DJ,
"Spy1 expression prevents normal cellular responses to DNA damage: inhibition of apoptosis and checkpoint activation." J Biol Chem 46(35425-35):
, 2006. [Go to PubMed]
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McAndrew CW,
Gastwirt RF,
Meyer AN,
Porter LA,
Donoghue DJ,
"Spy1 enhances phosphorylation and degradation of the cell cycle inhibitor p27." Cell Cycle 15(1937-45):
, 2007. [Go to PubMed]
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Golipour A,
Myers D,
Seagroves T,
Murphy D,
Evan GI,
Donoghue DJ,
Moorehead RA,
Porter LA,
"The Spy1/RINGO family represents a novel mechanism regulating mammary growth and tumorigenesis." Cancer Res 10(3591-600):
, 2008. [Go to PubMed]
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Meyer AN,
McAndrew CW,
Donoghue DJ,
"Nordihydroguaiaretic acid inhibits an activated fibroblast growth factor receptor 3 mutant and blocks downstream signaling in multiple myeloma cells." Cancer Res 18(7362-70):
, 2008. [Go to PubMed]
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Ahier A,
Rondard P,
Gouignard N,
Khayath N,
Huang S,
Trolet J,
Donoghue DJ,
Gauthier M,
Pin JP,
Dissous C,
"A new family of receptor tyrosine kinases with a venus flytrap binding domain in insects and other invertebrates activated by aminoacids." PLoS One 5(e5651):
, 2009. [Go to PubMed]
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Salazar L,
Kashiwada T,
Krejci P,
Muchowski P,
Donoghue D,
Wilcox WR,
Thompson LM,
"A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells." Hum Mol Genet 11(1951-61):
, 2009. [Go to PubMed]
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