Evan Rosen, M.D., Ph.D.

Epigenomic and Transcriptional Analysis of Adipocyte Biology

Our laboratory is interested in the biology of the adipocyte in health and disease.  Many projects within the lab are centered on the idea that understanding the transcriptional pathways by which adipocytes develop and govern their physiology can lead to therapeutic advances. We are also working on mechanisms by which adipocytes regulate insulin sensitivity and metabolic homeostasis both internally and systemically.
Much of our work involves integrating epigenomic and expression data to yield insights into novel transcriptional pathways in adipocyte biology. The predictions generated by these unbiased approaches are then validated using a variety of ‘wet lab’ approaches, including gain- and loss-of-function studies in vitro and in vivo.  For example, we have used modified histone mapping to identify six novel transcription factors regulating adipogenesis, lipolysis, lipogenesis, and thermogenesis. More recently we have turned to modeling disease states in adipocytes, such as insulin resistance, using similar approaches. These studies are being performed in cell culture and in vivo, including a large effort in human subjects.

References:

1. Eguchi J, Yan QW, Schones DE, Kamal M, Hsu CH, Zhang MQ, Crawford GE, Rosen ED. Interferon regulatory factors are transcriptional regulators of adipogenesis.  Cell Metabolism. 2008; 7:86-94. PMCID:PMC2278019

2. Xu Z, Yu S, Hsu CH, Eguchi J, Rosen ED. The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II is a critical regulator of adipogenesis.  Proc Natl Acad Sci USA. 2008; 105: 2421-2426. PMCID:PMC2268152

3. Mikkelsen TS, Xu Z, Zhang X, Wang L, Gimble JM, Lander ES, and Rosen ED. Comparative epigenomic analysis of murine and human adipogenesis. Cell. 2010. 143; 156-169. PMCID:PMC2950833

4. Eguchi J, Wang X, Yu S, Kershaw EE, Chui PC, Dushay J, Estall JL, Klein U, Maratos-Flier E, and Rosen ED. Transcriptional control of adipose lipid handling by IRF4. Cell Metabolism. 2011; 13: 249-259. PMCID: PMC3063358

5. Wrann CD, Eguchi J, Bozec A, Xu Z, Mikkelsen T, Gimble J, Nave H, Wagner EF, Ong S-E, and Rosen ED. FOSL2 promotes adipocyte-specific leptin gene expression in humans and mice. Journal of Clinical Investigation, 2012; 122:1010-1021. PMCID:PMC3322535

6. Kang S, Akerblad P, Kiviranta R, Gupta RK, Kajimura S, Griffin MJ, Min J, Baron R, Rosen ED. Regulation of early adipose commitment by Zfp521. PLoS Biology, 2013;10(11): e1001433. PMCID: PMC3507953

7. Eguchi J, Kong X, Tenta M, Wang X, Kang S, and Rosen ED. Interferon regulatory factor 4 regulates obesity-induced inflammation through regulation of adipose tissue macrophage polarization. Diabetes, 2013; 62:3394-403. PMCID:PMC3781469 [Available on 2014/10/1]

8. Griffin MJ, Zhou Y, Kang S, Zhang X, Mikkelsen TS, Rosen ED. Early B-cell factor-1 (Ebf1) is a key regulator of metabolic and inflammatory signaling pathways in mature adipocytes. J Biol Chem. 2013, 288:35925-39. PMCID:PMC3861642 [Available on 2014/12/13]

9. Rosen ED and Spiegelman BM. What we talk about when we talk about fat. Cell, 2014, 156:20-44. PMCID:
PMC3934003 [Available on 2015/1/16]

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