Fields of Research
- Drug Discovery and Precision Medicine
- Molecular Basis of Disease
We are currently developing cellular models for fibrolamellar carcinoma. The main genetic lesion in this liver cancer creates a novel fusion kinase called DNAJ-PKAc. Our goal is to understand the mechanisms of oncogenesis and to develop better therapeutic approaches to target this intractable cancer.
My research focuses on the organization and structure of anchored kinase and phosphatase complexes. Our combined biochemical, cell biological and structural work has allowed us to develop a more current concept of a “solid-state” mechanism of PKA action whereby A-kinase anchoring proteins are core regulators of spatiotemporally restricted cAMP responses. Currently my group is examining mis-regulation of AKAPs and PKA function in cancer, with particular emphasis on fibrolamellar carcinoma, a rare liver cancer that affects young adults and which lacks good therapeutic options. Together, this work provides the foundation for ongoing efforts to develop therapeutics that act on discrete signaling complexes with the expectation that such compounds will be more specific and selective, and have fewer side effects than currently available drugs.
Awards and Honors
In the News
- Health Sciences Building
- K-wing K316
Currently looking for students/postdocs
Turnham RE*, Smith FD*, Kenerson HL, Omar MH, Golkowski M, Garcia I, Bauer R, Lau HT, Sullivan KM, Langeberg LK, Ong SE, Riehle KJ, Yeung RS, Scott JD. An acquired scaffolding function of the DNAJ-PKAc fusion contributes to oncogenic signaling in fibrolamellar carcinoma. Elife. 2019 May 7;8. doi: 10.7554/eLife.44187. PubMed PMID: 31063128; PubMed Central PMCID: PMC6533061. *contributed equally
Smith FD, Esseltine JL, Nygren PJ, Veesler D, Byrne DP, Vonderach M, Strashnov I, Eyers CE, Eyers PA, Langeberg LK, Scott JD. Local protein kinase A action proceeds through intact holoenzymes. Science. 2017 Jun 23;356(6344):1288-1293. doi: 10.1126/science.aaj1669. PubMed PMID: 28642438; PubMed Central PMCID: PMC5693252.
Smith FD*, Reichow SL*, Esseltine JL, Shi D, Langeberg LK, Scott JD, Gonen T. Intrinsic disorder within an AKAP-protein kinase A complex guides local substrate phosphorylation. Elife. 2013 Nov 5;2:e01319. doi: 10.7554/eLife.01319. PubMed PMID: 24192038; PubMed Central PMCID: PMC3814001. *contributed equally
Smith FD, Langeberg LK, Cellurale C, Pawson T, Morrison DK, Davis RJ, Scott JD. AKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascade. Nat Cell Biol. 2010 Dec;12(12):1242-9. doi: 10.1038/ncb2130. Epub 2010 Nov 21. PubMed PMID: 21102438; PubMed Central PMCID: PMC3042953.