Michael Washburn, PhD

Professional Background

PhD scientist with long standing experience in quantitative proteomics, systems biology, epigenetics, and chromatin/transcription biochemistry. Now applying 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

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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 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 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.

• Decoding the Assembly and Function of Paralogue Specific SIN3A and SIN3B Human Chromatin Remodeling Complexes and Networks, NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES, PI
• Unraveling idiopathic pulmonary fibrosis endophenotypes; a lung-centric approach to prognostic and therapeutic biomarker validation, National Heart Lung and Blood Institute, Co-I
• Relationships between APP and Mitochondria, National Institute on Aging, Co-I

• Miah M, Huda MN, Islam MR, Gerald D, Khator S, Saha A, Alam J, Thornton JL, Gies A, Bauer MA, Stephens KE, Nagalo BM, Rahman MA, Washburn MP, Miah S. 2026. Loss of FAM60A disrupts Sin3/HDAC control of the Hippo signaling and promotes oncogenic YAP1 activation.. Cell death & disease, 17 (1)
• Arnold L, Yap M, Farrokhian N, Jackson L, Barry M, Ly T, Arjunan P, Kaczorowski-Worthley A, Tews C, Pandey A, Morrison A, Washburn MP, Standing D, Gomez JP, Yellapu NK, Johnson D, Li L, Umar S, Anant S, Thomas SM. 2025. DCLK1-mediated regulation of invadopodia dynamics and matrix metalloproteinase trafficking drives invasive progression in head and neck squamous cell carcinoma.. Molecular cancer, 24 (1), 50
• Liu X, Zhang Y, Wen Z, Hao Y, Banks CAS, Cesare J, Bhattacharya S, Arvindekar S, Lange JJ, Xie Y, Garcia BA, Slaughter BD, Unruh JR, Viswanath S, Florens L, Workman JL, Washburn MP. 2024. An integrated structural model of the DNA damage-responsive H3K4me3 binding WDR76:SPIN1 complex with the nucleosome.. Proceedings of the National Academy of Sciences of the United States of America, 121 (33), e2318601121
• Liu X, Zhang Y, Wen Z, Hao Y, Banks CAS, Lange JJ, Slaughter BD, Unruh JR, Florens L, Abmayr SM, Workman JL, Washburn MP. 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
• Sardiu ME, Gilmore JM, Groppe BD, Dutta A, Florens L, Washburn MP. 2019. Topological scoring of protein interaction networks.. Nature communications, 10 (1), 1118
• Kuchay S, Giorgi C, Simoneschi D, Pagan J, Missiroli S, Saraf A, Florens L, Washburn MP, Collazo-Lorduy A, Castillo-Martin M, Cordon-Cardo C, Sebti SM, Pinton P, Pagano M. 2017. PTEN counteracts FBXL2 to promote IP3R3- and Ca²⁺-mediated apoptosis limiting tumour growth.. Nature, 546 (7659), 554-558
• Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, Florens L, Washburn MP, Skowronski J. 2011. Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein.. Nature, 474 (7353), 658-61
• Takahashi H, Parmely TJ, Sato S, Tomomori-Sato C, Banks CA, Kong SE, Szutorisz H, Swanson SK, Martin-Brown S, Washburn MP, Florens L, Seidel CW, Lin C, Smith ER, Shilatifard A, Conaway RC, Conaway JW. 2011. Human mediator subunit MED26 functions as a docking site for transcription elongation factors.. Cell, 146 (1), 92-104
• Paoletti AC, Parmely TJ, Tomomori-Sato C, Sato S, Zhu D, Conaway RC, Conaway JW, Florens L, Washburn MP. 2006. Quantitative proteomic analysis of distinct mammalian Mediator complexes using normalized spectral abundance factors.. Proceedings of the National Academy of Sciences of the United States of America, 103 (50), 18928-33
• Zybailov B, Mosley AL, Sardiu ME, Coleman MK, Florens L, Washburn MP. 2006. Statistical analysis of membrane proteome expression changes in Saccharomyces cerevisiae.. Journal of proteome research, 5 (9), 2339-47