Our research program focuses on the regulation of fat tissue development, function, and energy homeostasis. Adipose tissue is categorized into two types: white adipose tissue (WAT) and brown adipose tissue (BAT). In general, white fat expands massively during obesity and aging with lipid overload. Conversely, brown fat, a distinct tissue dissipates energy in the form of heat through uncoupled respiration. Increasing the activity of brown fat is considered an attractive therapeutic strategy to help reduce obesity and associated metabolic disease(s). Specifically, conversion of white to brown fat phenotype (brown-like/beige cells) is correlated with protection against metabolic disease. As reported, Early B cell factor 2 (EBF2) is a key transcription factor in brown fat development. However, the mechanisms by which transcription factors regulate brown fat size, functionality and maintenance of pre-adipose stem cells under various metabolic conditions remain elusive. Therefore, we seek to identify key molecules or metabolites and genetic pathways that control adiposity and associated complications in mammals.
The following are our major research focus:
1. Transcriptional and epigenetic regulation of brown and beige adipocytes.
2. Elucidate the lipid signaling and RNA processing pathways that control the specializations of white and brown fat development and function.
3. Uncover the molecular connection between age induced adiposity and metabolic complications.
We employ a wide range of approaches including molecular genetics combined with biochemistry and molecular biology to address our specific questions. Also, we explore conditional knockout mouse model(s) and metabolic pathways to dissect the spatiotemporal regulation and contribution of brown adipose tissue for a healthy phenotype.
- Shapira SN, Lim HW, Rajakumari S, Sakers AP, Ishibashi J, Harms MJ, Won KJ, Seale P. (2017). EBF2 transcriptionally regulates brown adipogenesis via the histone reader DPF3 and the BAF chromatin remodeling complex. Genes Dev. 31(7):660-673.
- Harms MJ, Lim HW, Ho Y, Shapira SN, Ishibashi J, Rajakumari S, Steger DJ, Lazar MA, Won KJ, Seale P. (2015) PRDM16 binds MED1 and controls chromatin architecture to determine a brown fat transcriptional program. Genes Dev. 29(3):298-307.
- Wang W, Kissig M, Rajakumari S, Huang L, Lim HW, Won KJ, Seale P. (2014) Ebf2 is a selective marker of brown and beige adipogenic precursor cells. Proc Natl Acad Sci USA. 111(40):14466-14471
- Rajakumari S, Wu J, Ishibashi J, Lim HW, Giang AH, Won KJ, Reed RR, and Seale P. (2013) EBF2 Determines and Maintains Brown Adipocyte Identity. Cell Metab. 17(4):562-574.
- Rajakumari S, and Daum G. (2010) Multiple functions as lipase, steryl ester hydrolase, phospholipase and acyltransferase of Tgl4p from the yeast Saccharomyces cerevisiae. J Biol Chem. 285(21):15769-15776.