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- Yaacov Barak, PhD
Yaacov Barak, PhD
Associate Professor, Department of Obstetrics, Gynecology & Reproductive Sciences
Our lab is investigating the molecular principles that guide placental and fat tissue function. In the case of the placenta, this knowledge will usher in better ways to treat and prevent pregnancy complications and congenital heart disease, and in the case of fat tissue – obesity and type 2 diabetes.
Yaacov Barak, PhD
Research in Brief
Dr. Barak's lab studies two disparate areas that evolved from our earlier molecular genetic research of the nuclear receptor PPARg (Peroxisome Proliferator-Activated Receptor gamma):
- Placental development, as well as its critical influence on fetal heart development.
- Development of fat cells (adipocytes), with current emphasis on adipocyte death, which is rampant in obese animals and human patients, but its mechanisms and physiological significance are poorly understood in the context of obesity and type 2 diabetes.
Current Projects
Our research focuses on the developmental functions of the nuclear hormone receptors PPARgamma and PPARdelta – two key therapeutic targets in metabolic diseases, which also regulate distinct aspects of placental development and metabolism.
Projects in the laboratory investigate how both PPARs regulate placental development and metabolism, as well as the functions of PPARgamma in adipocytes (fat cells), with particular emphasis on its control of adipocyte death and regeneration. Our research integrates hypothesis-based and discovery-driven approaches and utilizes cutting-edge gene targeting, histological, physiological and molecular phenotyping, stem and primary cell cultures, and transcriptional profiling. As our research evolved, second-generation studies now encompass functional analyses of PPAR cofactors and target genes and dissection of the transcriptional mechanisms of PPARs in vivo.
Selected Publications
- Shalom-Barak T, Liersemann J, Memari B, Flechner L, Devor C, Bernardo TM, Kim S, Matsumoto N, Friedman SL, Evans RM, White JH, Barak Y. 2018. Ligand-dependent corepressor (LCoR) is a rexinoid-inhibited PPARgamma-RXRalpha coactivator. Mol Cell Biol. 38:e00107-17.
- Lee S, Pallerla SR, Kim S, Shaffer B, Simerly CR, Chaillet JR, Barak Y. Esrrb-Cre
Excises loxP-Flanked Alleles in Early Four-Cell Embryos. Genesis. 54:53-61, 2016. - Shalom-Barak T, Zhang X, Chu T, Schaiff WT, Reddy JK, Xu J, Sadovsky Y, Barak Y.
Placental PPAR regulates spatiotemporally diverse genes and a unique metabolic
network. Dev Biol. 372:143-155, 2012. - Barak Y, Sadovsky Y, & Shalom-Barak T. PPAR signaling in placental development and
function. PPAR Res, 142082, 2008. - Kim S, Huang L-W, Snow KJ, Ablamunits V, Hasham MG, Young TH, Paulk AC,
Richardson JE, Affourtit J, Shalom-Barak T, Bult CJ, & Barak Y. A mouse model of conditional lipodystrophy. Proc Natl Acad Sci USA,104:16627-32, 2007. - Barak Y & Kim S. 2007. Genetic manipulations of PPARs: Effects on obesity and
metabolic disease. PPAR Res, 12781, 2007. - Shalom-Barak T, Nicholas JM, Wang Y, Zhang X, Ong ES, Young TH, Gendler SJ,
Evans RM, & Barak Y. PPAR controls Muc1 transcription in trophoblasts. Mol Cell Biol, 24:10661-69, 2004. - He W, Barak Y, Hevener A, Olson P, Liao D, Le J, Nelson M, Ong, E, Olefsky JM, &
Evans RM. Adipose-specific peroxisome proliferator-activated receptor knockout causes insulin resistance in fat and liver, but not in muscle. Proc Natl Acad Sci USA, 100:15712-17, 2003. - Barak Y, Liao D, He W, Ong ES, Nelson MC, Olefsky JM, Boland R, & Evans RM.
Effects of peroxisome proliferator-activated receptor on placentation, adiposity, and colorectal cancer. Proc Natl Acad Sci USA, 99:303-08, 2002. - Barak Y, Nelson MC, Ong ES, Jones YZ, Ruiz-Lozano P, Koder A, Chien KR, & Evans RM. PPARgammais required for placental, cardiac, and adipose tissue development. Mol Cell, 4:585-95, 1999.
For additional publications, visit Pubmed.