Michael Washburn, PhD

Professional Background

PhD scientist with long standing experience in quantitative proteomics, systems biology, epigenetics, and chromatin/transcription biochemistry. Now applying innovative proteomic and cellular technologies to the study of chromatin remodeling complexes in cancer.

• PhD, Biochemistry and Environmental Toxicology, Michigan State University
• Post Doctoral Fellowship, Biochemistry, Michigan State University
• Post Doctoral Fellowship, Proteomics, University of Washington

Research

Overview

Applying innovative proteomic and cellular technologies to the study of chromatin remodeling complexes in cancer.

Chromatin Remodeling Complexes and Interaction Networks in Cancer. Critical mutations in chromatin remodeling proteins are routinely found in cancer genomics studies and therapeutics that target chromatin remodeling complexes are of great interest for the treatment of cancer. For example, HDAC 1 and HDAC2 are enzymes whose inhibitors are under investigation in many ongoing clinical trials, and these proteins are members of several distinct protein complexes like the SIN3A and SIN3B protein complexes. SIN3A and SIN3B are paralogues that define distinct protein complexes that play key roles in chromatin remodeling. Mutations in SIN3A are considered potential cancer drivers in diseases like Uterine Corpus Endometrial Carcinoma. In addition, SIN3A and SIN3B have been shown to deferentially regulate breast cancer metastasis. Our laboratory is pursuing ongoing studies regarding the structure and function of HDAC1. HDAC2, SIN3A, and SIN3B protein complexes in normal and diseased states.

Integrated Structural Modeling of Protein Complexes. We seek to develop and integrate new and emerging technologies in pursuit of our studies of the structure and function of chromatin remodeling complexes. To do so, we have been adopting exciting new and powerful cross-linking mass spectrometry technologies . Integration of cross-linking mass spectrometry data with state-of-the-art computational approaches allows one to build structural models of complexes using integrative approaches. We have used these techniques to begin to build integrated structural models of chromatin remodeling complexes like the SIN3A complex and the Spindlin1:SPINDOC protein complex.

ProteoCellomic analysis of Protein Complexes and Protein Interaction Networks. We have a long-standing interest in the study of protein complexes and protein interaction networks and have developed technologies and approaches that seek to advance the field. To do so, we have adopted multifunctional tags like the HaloTag and SNAP-tag. These tags can be used for affinity purification of protein complexes in addition to the study of tagged proteins in live cells. We have developed a serial capture affinity purification (SCAP) approach using these tags where two distinct proteins are tagged with the HaloTag or SNAP-tag and specific and enriched protein complexes that can be isolated using a sequential purification approach. Live cell imaging is then used to investigate the quantitative nature of specific protein interactions. Next, using cross-linking mass spectrometry and computational approaches an integrated structural model of the enriched protein complex can be generated.

• Liu, X, Zhang, Y, Wen, Z, Hao, Y, Banks CAS, Lange, J., J, Slaughter, B., D, Unruh, J., R, Florens, L, Abmayr, S., M, Workman, J., L, Washburn, M., P. 2020. Driving integrative structural modeling with serial capture affinity purification.. Proceedings of the National Academy of Sciences of the United States of America, 117 (50), 31861-31870
• Banks CAS, Zhang, Y, Miah, S, Hao, Y, Adams, M., K, Wen, Z, Thornton, J., L, Florens, L, Washburn, M., P. 2020. Integrative Modeling of a Sin3/HDAC Complex Sub-structure.. Cell reports, 31 (2), 107516
• Adams, M., K, Banks CAS, Thornton, J., L, Kempf, C., G, Zhang, Y, Miah, S, Hao, Y, Sardiu, M., E, Killer, M, Hattem, G., L, Murray, A, Katt, M., L, Florens, L, Washburn, M., P. 2020. Differential Complex Formation via Paralogs in the Human Sin3 Protein Interaction Network.. Molecular & cellular proteomics : MCP, 19 (9), 1468-1484
• Sardiu, M., E, Gilmore, J., M, Groppe, B., D, Dutta, A, Florens, L, Washburn, M., P. 2019. Topological scoring of protein interaction networks.. Nature communications, 10 (1), 1118
• Miah, S, Banks CAS, Ogunbolude, Y, Bagu, E., T, Berg, J., M, Saraf, A, Tettey, T., T, Hattem, G, Dayebgadoh, G, Kempf, C., G, Sardiu, M, Napper, S, Florens, L, Lukong, K., E, Washburn, M., P. 2019. BRK phosphorylates SMAD4 for proteasomal degradation and inhibits tumor suppressor FRK to control SNAIL, SLUG, and metastatic potential.. Science advances, 5 (10), eaaw3113