M. Geoffrey Rosenfeld, MD

The major focus of the investigation and scientific inquiry has recently centered on global genomic approaches to molecular mechanisms underlying transcriptional programs in development, homeostasis, and disease, emphasizing the neuroendocrine system and the CNS. The ultimate goal is to translate these insights into the development of new therapeutic and preventative approaches. The laboratory has been made seminal contributions to the fields of epigenetic regulatory mechanisms, the enhancer code of development, regulation of enhancers and the discovery of induced eRNAs, the roles of phase separation in ligand-induced enhancer activation/function, genetic regulation of transcriptional mechanisms, nuclear receptors, global genomic strategies, pituitary development, and learning and memory, Additionally, we have contributed to elucidating the mechanisms underlying actions of lncRNAs in transcriptional regulation, diseases of aging, and DNA damage repair in transcription. We have had the privilege of having been in the top twenty most cited scientists in molecular biology and genetics for several decades and for having the work recognized by election to the National Academy of Sciences, USA. In the past eight years, our laboratory has contributed novel concepts to the role of enhancers in cognitive function, nuclear architecture, and eRNAs in programs of gene transcription. It has also introduced several new technologies towards uncovering the relationship between subnuclear architectural structures and specific regulatory chromosomal regions, focusing on enhancers. The lab has uncovered several unexpected features about enhancers, including the potential role of eRNAs in enhancer:promoter interactions and the role of the so-called MegaTrans complex in estrogen-regulated enhancers. Recently, these studies have provided data indicating the key functional role of induced phase transition of enhancer RNPs in cooperative gene activation and regulated alterations in nuclear architecture in gene transcriptional programs. The lab is currently investigating abnormalities in enhancer regulation as a major component of multiple degenerative diseases including sporadic AD using single cell/nucleus global genomic approaches.

Bibliography - 2008 – Present
Selected Publications (of 468 original papers)

Yang M, Lee JH, Zhang Z, De La Rosa R, Bi M, Tan Y, Liao Y, Hong J, Du B, Wu Y, Scheirer J, Hong T, Li W, Fei T, Hsieh CL, Liu Z, Li W, Rosenfeld MG, Xu K. Enhancer RNAs Mediate Estrogen-Induced Decommissioning of Selective Enhancers by Recruiting ERα and Its Cofactor. Cell Rep. 2020 Jun 23;31(12):107803. doi: 10.1016/j.celrep.2020.107803. PubMed PMID: 32579929.

Vinckier NK, Patel NA, Geusz RJ, Wang A, Wang J, Matta I, Harrington AR, Wortham M, Wetton N, Wang J, Jhala US, Rosenfeld MG, Benner CW, Shih HP, Sander M. LSD1-mediated enhancer silencing attenuates retinoic acid signaling during pancreatic endocrine cell development. Nat Commun. 2020 Apr 29;11(1):2082. doi: 10.1038/s41467-020-16017-x. PubMed PMID: 32350257; PubMed Central PMCID: PMC7190832.

Luo Z, Wang X, Jiang H, Wang R, Chen J, Chen Y, Xu Q, Cao J, Gong X, Wu J, Yang Y, Li W, Han C, Cheng CY, Rosenfeld MG, Sun F, Song X. Reorganized 3D Genome Structures Support Transcriptional Regulation in Mouse Spermatogenesis. Science. 2020 Apr 5;23(4):101034. doi: 10.1016/j.isci.2020.101034. [Epub ahead of print] PubMed PMID: 32315832; PubMed Central PMCID: PMC7170994.

Gou LT, Lim DH, Ma W, Aubol BE, Hao Y, Wang X, Zhao J, Liang Z, Shao C, Zhang X, Meng F, Li H, Zhang X, Xu R, Li D, Rosenfeld MG, Mellon PL, Adams JA, Liu MF, Fu XD. Initiation of Parental Genome Reprogramming in Fertilized Oocyte by Splicing Kinase SRPK1-Catalyzed Protamine Phosphorylation. Cell. 2020 Mar 19;180(6):1212-1227.e14. doi: 10.1016/j.cell.2020.02.020. Epub 2020 Mar 12. PubMed PMID: 32169215; PubMed Central PMCID: PMC7190278.

Nott A, Holtman IR, Coufal NG, Schlachetzki JCM, Yu M, Hu R, Han CZ, Pena M, Xiao J, Wu Y, Keulen Z, Pasillas MP, O'Connor C, Nickl CK, Schafer ST, Shen Z, Rissman RA, Brewer JB, Gosselin D, Gonda DD, Levy ML, Rosenfeld MG, McVicker G, Gage FH, Ren B, Glass CK. Brain cell type-specific enhancer-promoter interactome maps and disease-risk association. Science. 2019 Nov 29;366(6469):1134-1139. doi:10.1126/science.aay0793. Epub 2019 Nov 14. PubMed PMID: 31727856; PubMed Central PMCID: PMC7028213.

Benaglio P, D'Antonio-Chronowska A, Ma W, Yang F, Young Greenwald WW, Donovan MKR, DeBoever C, Li H, Drees F, Singhal S, Matsui H, van Setten J, Sotoodehnia N, Gaulton KJ, Smith EN, D'Antonio M, Rosenfeld MG, Frazer KA. Allele-specific NKX2-5 binding underlies multiple genetic associations with human electrocardiographic traits. Nat Genet. 2019 Oct;51(10):1506-1517. doi:10.1038/s41588-019-0499-3. Epub 2019 Sep 30. PubMed PMID: 31570892; PubMed Central PMCID: PMC6858543.

Nair SJ, Yang L, Meluzzi D, Oh S, Yang F, Friedman MJ, Wang S, Suter T, Alshareedah I, Gamliel A, Ma Q, Zhang J, Hu Y, Tan Y, Ohgi KA, Jayani RS, Banerjee PR, Aggarwal AK, Rosenfeld MG. Phase separation of ligand-activated enhancers licenses cooperative chromosomal enhancer assembly. Nat Struct Mol Biol. 2019 Mar;26(3):193-203. doi: 10.1038/s41594-019-0190-5. Epub 2019 Mar 4. PubMed PMID: 30833784; PubMed Central PMCID: PMC6709854.

Tan Y, Jin C, Ma W, Hu Y, Tanasa B, Oh S, Gamliel A, Ma Q, Yao L, Zhang J, Ohgi K, Liu W, Aggarwal AK, Rosenfeld MG. Dismissal of RNA Polymerase II Underlies a Large Ligand-Induced Enhancer Decommissioning Program. Mol Cell. 2018 Aug 16;71(4):526-539.e8. doi: 10.1016/j.molcel.2018.07.039. PubMed PMID:30118678; PubMed Central PMCID: PMC6149533.

Gao WW, Xiao RQ, Zhang WJ, Hu YR, Peng BL, Li WJ, He YH, Shen HF, Ding JC, Huang QX, Ye TY, Li Y, Liu ZY, Ding R, Rosenfeld MG, Liu W. JMJD6 Licenses ERα-Dependent Enhancer and Coding Gene Activation by Modulating the Recruitment of the CARM1/MED12 Co-activator Complex. Mol Cell. 2018 Apr 19;70(2):340-357.e8. doi: 10.1016/j.molcel.2018.03.006. Epub 2018 Apr 5. PubMed PMID: 29628309; PubMed Central PMCID: PMC6258263.

Kim HS, Tan Y, Ma W, Merkurjev D, Destici E, Ma Q, Suter T, Ohgi K, Friedman M, Skowronska-Krawczyk D, Rosenfeld MG. Pluripotency factors functionally premark cell-type-restricted enhancers in ES cells. Nature. 2018 Apr;556(7702):510-514. doi: 10.1038/s41586-018-0048-8. Epub 2018 Apr 18. PubMed PMID: 29670286; PubMed Central PMCID: PMC6021123.