Joseph A. Adams, Ph.D.
Professor of Pharmacology
Our laboratory is interested in understanding how phosphorylation controls the splicing of mRNA and complexity of the human proteome. We focus attention on two families of enzymes, the SRPKs and CLKs, that phosphorylate and regulate the biological activities of SR proteins, an essential group of splicing factors that guide the assembly of the spliceosome and the selection of splice-sites in mRNA. These enzymes are not only essential for normal splicing function but are also over-expressed in many cancers making them viable targets for drug intervention in human diseases. Our laboratory applies various biochemical, biological and structural techniques to understand how these enzymes work at both the molecular and cellular levels to affect SR protein function and splicing outcomes.
B.E. Aubol, J. M. Wozniak, L. Fattet, D. J. Gonzalez, & J.A. Adams (2021) “CLK1 Reorganizes the Splicing Factor U1-70K For Early Spliceosomal Protein Assembly,” Proc Natl Acad Sci U S A., 118 (14) e2018251118.
B.E. Aubol, L. Fattet, & J.A. Adams (2021) “A conserved sequence motif bridges two protein kinases for enhanced phosphorylation and nuclear function of a splicing factor,” FEBS J. 288(2), 566-581.
L.-T. Gou, D.-H. Lim, W. Ma, B. E. Aubol, Y. Hao, X. Wang, J. Zhao, Z. Liang, C. Shao, X. Zhang, H. Li, X. Zhang, R. Xu, D. Li, M.G. Rosenfeld, P. L. Mellon, J. A. Adams, M.-F. Liu, & X.-D. Fu (2020) “Initiation of Parental Genome Reprogramming in Fertilized Oocyte by Splicing Kinase SRPK1-Catalyzed Protamine Phosphorylation,” Cell, 180(6), 1212-1227.
A. George, B.E. Aubol, L. Fattet, & J.A. Adams (2019) “Disordered Protein Interactions for An Ordered Cellular Transition: Transporting CLK1 To the Nucleus On the Back of Its SR Protein Substrate,” J. Biol. Chem. 294, 9631-9641.
B.E. Aubol, P. Serrano, L. Fattet, K. Wüthrich & J.A. Adams (2018) “Molecular Interactions Connecting the Function of the Serine-Arginine-rich protein SRSF1 to Protein Phosphatase 1,” J. Biol. Chem. 293, 16751-16760.
B.E. Aubol, G. Wu, M.M. Keshwani, M. Movassat, L. Fattet, K.J. Hertel, X.-D. Fu & J.A. Adams (2016) “Release of SR Proteins from CLK1 by SRPK1: A Symbiotic Kinase System for Phosphorylation Control of Pre-mRNA Splicing” Mol. Cell 63, 218-28.