BADERC- Evan Rosen

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

Novel Transcriptional Pathway in 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 identifying new transcriptional pathways in adipocyte biology, often through integrated use of epigenomic and expression data. For example, using DNAse hypersensitivity analysis and computational motif finding, we identified a role for interferon regulatory factors (IRFs) and COUP-TFII in adipogenesis. We are now actively studying the role played by these factors in the biology of the mature adipocyte as well, using both cell culture and in vivo models. We have expanded our analysis as well, using genome-wide chromatin state mapping of modified histone marks to identify regions where important regulatory events are occurring in human and murine adipogenesis, and we discovered a host of new factors that regulate differentiation in this way as well.

Other work in the lab is centered on early B cell factors (EBFs) in adipocyte biology, and the metabolic role of Lcn2, a novel secreted adipokine.

References:

Houstis NE, Rosen ED*, Lander ES*. Reactive oxygen species play a causal role in multiple forms of insulin resistance. Nature. 2006; 440:944-948. *co-senior authors
Jimenez MA, Akerblad P, Sigvardsson M, Rosen ED. A critical role for Ebf1 and Ebf2 in the adipogenic transcriptional cascade. Molecular and Cellular Biology. 2007; 27:743-757.
Mukherjee A, Sidis Y, Mahan A, Raher MJ, Xia Y, Rosen ED, Bloch KD, Thomas MK, Schneyer AL. FSTL3 deletion reveals roles for TGF-beta family ligands in glucose and fat homeostasis in adults. Proc Natl Acad Sci USA. 2007;104:1348-53.
Yan QW, Yang Q, Mody N, Graham TE, Hsu CH, Xu Z, Houstis NE, Kahn BB, Rosen ED. The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes. 2007; 56: 2533-40.
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.
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.






			Evan Rosen, M.D., Ph.D. Novel Transcriptional Pathway in 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 identifying new transcriptional pathways in adipocyte biology, often through integrated use of epigenomic and expression data. For example, using DNAse hypersensitivity analysis and computational motif finding, we identified a role for interferon regulatory factors (IRFs) and COUP-TFII in adipogenesis. We are now actively studying the role played by these factors in the biology of the mature adipocyte as well, using both cell culture and in vivo models. We have expanded our analysis as well, using genome-wide chromatin state mapping of modified histone marks to identify regions where important regulatory events are occurring in human and murine adipogenesis, and we discovered a host of new factors that regulate differentiation in this way as well. Other work in the lab is centered on early B cell factors (EBFs) in adipocyte biology, and the metabolic role of Lcn2, a novel secreted adipokine. References: Houstis NE, Rosen ED, Lander ES. Reactive oxygen species play a causal role in multiple forms of insulin resistance. Nature. 2006; 440:944-948. co-senior authors Jimenez MA, Akerblad P, Sigvardsson M, Rosen ED. A critical role for Ebf1 and Ebf2 in the adipogenic transcriptional cascade. Molecular and Cellular Biology. 2007; 27:743-757. Mukherjee A, Sidis Y, Mahan A, Raher MJ, Xia Y, Rosen ED, Bloch KD, Thomas MK, Schneyer AL. FSTL3 deletion reveals roles for TGF-beta family ligands in glucose and fat homeostasis in adults. Proc Natl Acad Sci USA. 2007;104:1348-53. Yan QW, Yang Q, Mody N, Graham TE, Hsu CH, Xu Z, Houstis NE, Kahn BB, Rosen ED. The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes. 2007; 56: 2533-40. 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. 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.