The temporal and spatial control of gene expression during development is a dynamic process that relies on altering the composition of DNA-associated factors as well as the nuclear organization of the genome. Advances in next-generation sequencing technologies have allowed us to take a precise look at the changes that occur throughout the genome as cells change from one type into another. I have had 19+ years of bench experience studying transcriptional regulation, chromatin structure and protein-DNA interactions. My laboratory is interested in finding out 1) how the genome responds to cell-fate reprogramming by sequence-specific DNA binding proteins and 2) how cell identity is maintained by transcriptional regulators. We are particularly interested in factors that influence cell fate specification in human embryonic stem cells and trophoblast stem cells including the components of the Polycomb Repressive Complex 1.1.
As a member of the Developmental Biology Center, I have collaborated extensively with other laboratories on model organisms such as M. musculus (mouse), D. melanogaster (fruitfly), C. elegans (nematode), D. rerio (zebrafish), G. gallus (chicken) and A. mexicanum (axolotl). I am a strong proponent of reproducible research and have published the full methods of my analyses at github.com/micahgearhart. Our department aims to train the next generations of biologists to embrace genome-wide approaches and apply statistical and critical analyses to their results and interpretations. My goal is not only to collaborate with investigators to analyze and interpret next generation sequencing data, but also to facilitate the transfer of knowledge regarding bioinformatics tools and statistical methods for functional genomics to our researchers and graduate students.
- Kutscher, L. M.; Okonechnikov, K.; Batora, N. V.; Clark, J.; Silva, P. B. G.; Vouri, M.; van Rijn, S.; Sieber, L.; Statz, B.; Gearhart, M. D.; et al. Functional Loss of a Non-Canonical BCOR-PRC1.1 Complex Accelerates SHH-Driven Medulloblastoma Formation. bioRxiv, 2020, 2020.02.06.938035. doi.org/10.1101/2020.02.06.938035.
- Tsukamoto T, Gearhart MD, Kim S, Mekonnen G, Spike CA, Greenstein D. Insights into the Involvement of Spliceosomal Mutations in Myelodysplastic Disorders from an Analysis of SACY-1/DDX41 in Caenorhabditis Elegans. bioRxiv. 2019 December; 12(23):886804. doi: 10.1101/2019.12.23.886804.
- Kotov JA, Kotov DI, Linehan JL, Bardwell VJ, Gearhart MD, Jenkins MK. BCL6 corepressor contributes to Th17 cell formation by inhibiting Th17 fate suppressors. J Exp Med. 2019 Jun 3;216(6):1450-1464. doi: 10.1084/jem.20182376. Epub 2019 May 3. PubMed PMID: 31053612; PubMed Central PMCID: PMC6547868.
- Wang Z, Gearhart MD, Lee YW, Kumar I, Ramazanov B, Zhang Y, Hernandez C, Lu AY, Neuenkirchen N, Deng J, Jin J, Kluger Y, Neubert TA, Bardwell VJ, Ivanova NB. A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs. Cell Stem Cell. 2018 Feb 1;22(2):235-251.e9. doi: 10.1016/j.stem.2017.12.002. Epub 2018 Jan 11. PubMed PMID: 29337181; PubMed Central PMCID: PMC5797497.
- Béguelin W, Teater M, Gearhart MD, Calvo Fernández MT, Goldstein RL, Cárdenas MG, Hatzi K, Rosen M, Shen H, Corcoran CM, Hamline MY, Gascoyne RD, Levine RL, Abdel-Wahab O, Licht JD, Shaknovich R, Elemento O, Bardwell VJ, Melnick AM. EZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent Promoters, Mediate Germinal Center Formation and Lymphomagenesis. Cancer Cell. 2016 Aug 8;30(2):197-213. doi: 10.1016/j.ccell.2016.07.006. PubMed PMID: 27505670; PubMed Central PMCID: PMC5000552.
- Choi SH, Gearhart MD, Cui Z, Bosnakovski D, Kim M, Schennum N, Kyba M. DUX4 recruits p300/CBP through its C-terminus and induces global H3K27 acetylation changes. Nucleic Acids Res. 2016 Jun 20;44(11):5161-73. doi: 10.1093/nar/gkw141. Epub 2016 Mar 6. PubMed PMID: 26951377; PubMed Central PMCID: PMC4914088.
- Lindeman RE, Gearhart MD, Minkina A, Krentz AD, Bardwell VJ, Zarkower D. Sexual cell-fate reprogramming in the ovary by DMRT1. Curr Biol. 2015 Mar 16;25(6):764-771. doi: 10.1016/j.cub.2015.01.034. Epub 2015 Feb 12. PubMed PMID: 25683803; PubMed Central PMCID: PMC4366330.