Matt Miller, M6G
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MSTP Learning Community: Flocks MSTP Entry Date: June 13, 2016 |
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PhD Program: Genetics |
Mentor: Chris Adams, MD, PhD |
Regulation and Role of p21 in Skeletal Muscle Atrophy
Skeletal muscle atrophy is a common and debilitating disease with many diverse causes. Despite the broad clinical impact, there are currently no pharmacologic therapies to prevent or reverse skeletal muscle atrophy. This is partly explained by the fact that the molecular basis of skeletal muscle atrophy remains largely unexplored and thus poorly understood. The transcription factor ATF4 has emerged as a key driver of muscle atrophy in several clinically important scenarios. Previous work has shown that this effect is mediated through increased expression of the ATF4 target gene p21 in skeletal muscle fibers. My studies build upon initial findings to more deeply investigate and understand the upstream mechanisms that control p21 expression in skeletal muscle, the pathophysiological consequences of a targeted reduction in muscle p21 expression and the downstream mechanism by which p21 promotes muscle atrophy.
Awards:
2016 - Edward Heath Award (outstanding communication of laboratory achievements), Medical Student Research Day, Sept 9
2017 - The Thomas A. Weingeist Award for Ophthalmology Research, Medical Student Research Day, Sept 15
2019 - Knights Templar Eye Foundation Travel Grant - Spring 2019
2022 - Karolinska Institute-Mayo Collaborative Travel Award - Fall 2022
2023 - FEBS Open Bio Poster Prize, Advances in Skeletal Muscle Biology in Health and Disease Conference
Teaching:
2020 Fall - MICR:2158 - General Microbiology Laboratory
Education:
2015 - BA, Anthropology, Biology - Grinnell College
Publications:
Giacalone JC, Miller MJ, Workalemahu G, Reutzel AJ, Ochoa D, Whitmore SS, Stone EM, Tucker BA, Mullins RF. Generation of an immortalized human choroid endothelial cell line (iChEC-1) using an endothelial cell specific promoter. Microvasc Res. 2019 May;123:50-57. doi: 10.1016/j.mvr.2018.12.002. Epub 2018 Dec 18. PubMed PMID: 30571950; PubMed Central PMCID: PMC7401191.
Ebert SM, Rasmussen BB, Judge AR, Judge SM, Larsson L, Wek RC, Anthony TG, Marcotte GR, Miller MJ, Yorek MA, Vella A, Volpi E, Stern JI, Strub MD, Ryan Z, Talley JJ, Adams CM. Biology of Activating Transcription Factor 4 (ATF4) and Its Role in Skeletal Muscle Atrophy. J Nutr. 2022 Apr 1;152(4):926-938. doi: 10.1093/jn/nxab440. PMID: 34958390; PMCID: PMC8970988.
Basisty N, Shulman N, Wehrfritz C, Marsh AN, Shah S, Rose J, Ebert S, Miller M, Dai DF, Rabinovitch PS, Adams CM, MacCoss MJ, MacLean B, Schilling B. TurnoveR: A Skyline External Tool for Analysis of Protein Turnover in Metabolic Labeling Studies. J Proteome Res. 2022 Sep 27. doi: 10.1021/acs.jproteome.2c00173. PMID: 36165806.
Miller MJ, Marcotte GR, Basisty N, Wehrfritz C, Ryan ZC, Strub MD, McKeen AT, Stern JI, Nath KA, Rasmussen BB, Judge AR, Schilling B, Ebert SM, Adams CM. The transcription regulator ATF4 is a mediator of skeletal muscle aging. Geroscience. 2023 Aug;45(4):2525-2543. doi: 10.1007/s11357-023-00772-y. Epub 2023 Apr 4. PMID: 37014538; PMCID: PMC10071239.
Marcotte GR, Miller MJ, Kunz HE, Ryan ZC, Strub MD, Vanderboom PM, Heppelmann CJ, Chau S, Von Ruff ZD, Kilroe SP, McKeen AT, Dierdorff JM, Stern JI, Nath KA, Grueter CE, Lira VA, Judge AR, Rasmussen BB, Nair KS, Lanza IR, Ebert SM, Adams CM. GADD45A is a mediator of mitochondrial loss, atrophy, and weakness in skeletal muscle. JCI Insight. 2023 Nov 22;8(22):e171772. doi: 10.1172/jci.insight.171772. PMID: 37815864; PMCID: PMC10721312.
Miller MJ, Gries KJ, Marcotte GR, Ryan Z, Strub MD, Kunz HE, Arendt BK, Dasari S, Ebert SM, Adams CM, Lanza IR. Human myofiber-enriched aging-induced lncRNA FRAIL1 promotes loss of skeletal muscle function. Aging Cell. 2024 Jan 31:e14097. doi: 10.1111/acel.14097. Epub ahead of print. PMID: 38297807.