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

Contact Information
Professor of Chemistry and Biochemistry
Program Director, NIH Training Grant
Sixth College Provost

Office: Pepper Canyon Hall 227
Phone: 858-246-0428
Email: ddonoghue@ucsd.edu
Web: cancertraining.ucsd.edu
Group: View group members
Education
1979 Ph.D., Massachusetts Institute of Technology
1974 B.S., University of Wisconsin, Madison
Appointments
2012-present Provost, Sixth College, UCSD
1992-present Professor, Chemistry and Biochemistry, UCSD
1988-1992 Associate Professor, Chemistry and Biochemistry, UCSD
1982-1988 Assistant Professor, Chemistry and Biochemistry, UCSD
1980-1982 Postdoc, Tumor Virology, 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
I have a long-standing interest in Receptor Tyrosine Kinases (RTKs), a passion which evolved from my graduate work at MIT with Phil Sharp, Bob Weinberg and David Baltimore, and from my postdoctoralwork in Tony Hunter's lab at the Salk Institute. During the past decade, my research interests have also included some non-RTK projects (e.g. cyclin B and cyclin-like proteins such as Spy1, co-discovered in our lab).

More recently, I decided to focus exclusively on the Fibroblast Growth Factor Receptor (FGFR) family of RTKs and their roles in oncogenic and inflammatory signaling pathways, exploiting proteomic and genomic approaches such as mass spec analysis of proteins, and microarray analysis of gene expression to identify novel regulatory phosphorylation sites, protein-protein interactions, and gene interaction networks.

We were the first group to show the potential oncogenicity of FGFR4 in experiments that compared its transforming ability with FGFR1 and FGFR3, representing the first demonstration that activation of FGFR4, in addition to FGFR1 and FGFR3, can induce cellular transformation.

We have also detected sites of phosphorylation within the kinase insert domain (KID) of FGFR2. We are currently exploring whether these residues contribute to the activation of FGFR2 and lead to the recruitment of binding proteins to the KID. We are working towards identification of a novel mechanism of FGFR2 regulation beyond the kinase domain in which the KID also contributes to the activation of FGFR2, and perhaps, to the onset of breast cancers in which FGFR2 has been heavily implicated.

We are now concentrating our research efforts towards understanding the role of FGFR4 activation and its impact on downstream signaling in diseases such as prostate and breast carcinomas. In particular, we are investigating the role of FGFR4 and FGFR2 in the regulation of the Nuclear Factor kappaB (NFkappaB) inflammatory signaling pathway. We have already demonstrated a direct interaction between FGFR4 and IKKbeta, the major regulatory kinase of NFkappaB signaling.

Since our first observation of the oncogenic potential of FGFR4 more than a decade ago, occasional reports have shown the involvement of FGFR4 in diseases, such as prostate and colon cancers. However, only one study has shown that FGFR4 leads to the metastasis of Rhabdomyosarcoma (RMS), a pediatric sarcoma that leads to the formation of tumors in head, neck, and trunk. We are therefore applying our knowledge of FGFR4 signaling to analyze its importance in RMS.
Primary Research Area
Biochemistry
Interdisciplinary interests
Cellular Biochemistry

Selected Publications