Research Interest Summary
Our group studies two distinct biological systems – the placenta and adipose tissue. In both systems we are employing cutting edge genomic technologies to understand fundamental biological processes and their physiological significance.& In the placenta, we are interested in transcriptional networks that regulate both development and metabolism of the tissue. We are currently investigating:
- The role of PPAR and a novel transcription cofactor in regulation of carbohydrate supply to the embryo during late embryonic development.
- The impact of a novel network of metabolic enzymes downstream of PPARγ on placental fat metabolism.
- The physiological significance of placental glycogen stores. 4. The adverse effects of placenta defects of embryonic heart development.
In adipose tissue, we are currently focusing on a fascinating, hitherto uncharacterized non-apoptotic, non-necrotic mechanism of adipocyte death, and its physiological ramifications on obesity, lipodystrophy (fat degeneration), and diabetes. Our studies of this phenomenon involve state-of-the-art gene manipulation, lineage marking and imaging technologies.
Barak Y, Nelson MC, Ong ES, Jones YZ, Ruiz-Lozano P, Koder A, Chien KR, Evans RM. 1999. PPARγ is required for placental, cardiac, and adipose tissue development. Mol Cell 4:585-595.
Barak Y, Liao D, He W, Ong ES, Nelson MC, Olefsky JM, Boland R, Evans RM. 2002. Effects of peroxisome proliferator-activated receptor δ on placentation, adiposity, and colorectal cancer. Proc Natl Acad Sci USA 99:303-308.
He W*, Barak Y*, Hevener A*, Olson P, Liao D, Le J, Nelson M, Ong E, Olefsky JM, Evans RM (*Co-first authors) 2003. Adipose-specific peroxisome proliferator-activated receptor γ knockout causes insulin resistance in fat and liver, but not in muscle. Proc Natl Acad Sci USA 100:15712-15717.
Shalom-Barak T, Nicholas JM, Wang Y, Zhang X, Ong ES, Young TH, Gendler SJ, Evans RM, Barak Y. 2004. PPARγ controls Muc1 transcription in trophoblasts. Mol Cell Biol 24:10661-10669.
Barak Y, Kim S. 2007. Genetic manipulations of PPARs: Effects on obesity and metabolic disease. PPAR Res. 2007:12781.
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. 2007. A mouse model of conditional lipodystrophy. Proc Natl Acad Sci USA 104:16627-16632.
Barak Y, Sadovsky Y, Shalom-Barak T. 2008. PPAR signaling in placental development and function. PPAR Res. 2008:142082.
Shalom-Barak T, Zhang X, Chu T, Schaiff WT, Reddy JK, Xu J, Sadovsky Y, Barak Y. 2012. Placental PPARγ regulates spatiotemporally diverse genes and a unique metabolic network. Dev Biol. 372:143-155.