Events

 Oct 12, 2026 @ 8:30 a.m.
 WoodCliff Hotel & Spa | 

Hannah Powell - Graduate Student

SF3B1 is an essential early pre-mRNA splicing factor and is also the most frequently mutated splicing factor in cancer. It is known that SF3B1 is phosphorylated during active splicing by various CDKs, including CDK11. Using RT-PCR, I have shown the importance of SF3B1 phosphorylation in splicing and plan to use this technique to link the effect of SF3B1 phosphorylation to the function of essential splicing factor U2AF2, as part of a rebuttal manuscript¹ . Little is known, however, about how the dephosphorylation of SF3B1 is controlled. A protein phosphatase 1 (PP1) subunit called NIPP1 is known to associate with phosphorylated SF3B1, but the binding interface and interaction context is unclear. We hypothesize that NIPP1 acts as a functional counterpart to CDK11 to counterbalance its phosphorylation of SF3B1. I have used X-ray crystallography and isothermal titration calorimetry to reveal a new recognition mode between the phospho-binding domain of NIPP1 and a phosphorylated SF3B1 site. In this period, I used the CDK11 inhibitor OTS 964 and NIPP1 mutants that prevent PP1 and SF3B1 association to show that these conditions affect SF3B1 phosphorylation at sites pT211 and pT313 in cells via Western blotting. Using RNA-sequencing, we have determined that the NIPP1-SF3B1 interface has widespread effects on pre-mRNA splicing across the transcriptome. Going forward, I am preparing samples for mass spectrometry analysis to determine the SF3B1 phosphorylation sites affected by NIPP1 and CDK11. Additionally, I plan to test whether NIPP1 overexpression alters the effects of OTS 964 to support the hypothesis that these proteins act in the same step of splicing. These results show that regulation of SF3B1 phosphorylation by NIPP1 and CDK11 has a functional role in splicing, suggesting a role for these proteins in the broader context of regulating gene expression through a balance of kinase and phosphatase activity.

1. Kirchhoff CL, Powell HR, et al. SF3B1 Phosphorylation Prompts U2AF2 Dissociation for Widespread Control of pre-mRNA Splicing. bioRxiv. Jan 20 2026;doi:10.64898/2026.01.19.700466

 Oct 13, 2026 @ 1:00 p.m.
 Medical Center | Upper S-Wing Auditorium (3-7619)

Kaavya Krishna Kumar, PhD - Assistant Professor, Department of Pharmacology, Weill Cornell Medicine, New York, NY

 Oct 14, 2026 @ 2:00 p.m.
 Medical Center | K307 (3-6408)

Ximena Barros Álvarez, PhD - Principal Scientist II, Structural Biology, Schrödinger Therapeutics Group, Boston, MA

 Oct 15, 2026 @ 3:00 p.m.
 Medical Center | Lower Adolph Aud 1-7619

Ute Kothe, PhD - Professor, Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada

 Oct 21, 2026 @ 2:00 p.m.
 Medical Center | K307 (3-6408)

Sarah E. J. Bowman, PhD - Associate Professor and Director of the National Crystallization Center, Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY

 Oct 28, 2026 @ 2:00 p.m.
 Medical Center | k307 (3-6408)

Paul Whitford, PhD - Professor, Department of Physics, Northeastern University, Boston, MA

 Nov 04, 2026 @ 2:00 p.m.
 Medical Center | K307 (3-6408)

Michael Neugent, PhD - Assistant Professor, Departments of Urology and of Microbiology & Immunology, University of Rochester, Rochester, NY

 Nov 11, 2026 @ 2:00 p.m.
 Medical Center | K307 (3-6408)

Isaac Fianu, PhD - Assistant Professor of Biochemistry, Caltech, Pasadena, CA

 Nov 18, 2026 @ 2:00 p.m.
 Medical Center | k307 (3-6408)

Isaac Fianu, PhD - Assistant Professor, Department of Biochemistry, Caltech, Pasadena, CA

 Nov 19, 2026 @ 3:00 p.m.
 Medical Center | Lower Adolph Aud 1-7619

Eric Wagner, PhD; Makaía Papasergi-Scott, PhD - Professor, Department of Biochemistry & Biophysics, University of Rochester, Rochester, NY; Assistant Professor, Department of Biochemistry & Biophysics and Department of Pharmacology & Physiology; Scientific Director, Structural Biology Imaging Resource, Center for Advanced Research Technologies, University of Rochester, Rochester, NY

 Dec 03, 2026 @ 3:00 p.m.
 Medical Center | Lower Adolph Aud 1-7619

Harmit Malik, Ph.D. - Investigator, Howard Hughes Medical Institute, Professor and Associate Director, Basic Sciences Division, Fred Hutchinson Cancer Center

Dr. Harmit Malik studies genetic conflict, the competition between genes and proteins with opposing functions that drives evolutionary change. His research could have implications for a range of diseases, from HIV to cancer. As part of this work, his team developed an approach for identifying genes that divide one species from another, which could help solve the riddle of how new species evolve. Dr. Malik also studies the evolutionary processes that drive our body’s interactions with viruses, including contemporary scourges like HIV as well as ancient viruses whose fossils litter our genome. With Hutch colleagues, he has characterized the rapidly evolving interface between proteins on human cells and viruses that make us sick. This work has highlighted surprising deviations from “textbook” models of these interactions, and it is revealing gene variants that could influence our susceptibility to infection. — https://www.fredhutch.org/en/people/m/harmit-malik.html

 Apr 12, 2027 @ 9:00 a.m.
 Kornberg Medical Research Building | Class of '62 Aud. and Flaum Atrium