The Rosen lab strives to understand how gene expression networks control the development, function, and pathophysiology of metabolically relevant tissues, with an emphasis on adipose tissue. We employ genetic, genomic, computational, cell biological, and in vivo modeling approaches to questions related to adipogenesis, thermogenesis, insulin action, and inflammation. Current projects include:
1. Single cell approaches to human and murine adipose tissue biology. We have generated large atlases of mouse and human adipose tissue at single cell resolution from different depots and under different nutritional conditions. These atlases are being used to identify unique subpopulations of adipocytes and other cells and to generate hypotheses about cell-cell interactions within the adipose niche.
2. Understanding the role of interferon regulatory factors at the intersection of inflammation and metabolism. We have identified IRF family members as critical transcriptional regulators of adipogenesis, lipolysis, thermogenesis, hepatic glucose metabolism and fatty liver. Studies are also underway to assess the role of IRF3 in mediating leptin’s actions in the hypothalamus. Furthermore, we have identified ISGylation as a downstream effector of inflammation in adipose tissue, and we are pursuing studies to identify ISGylated target proteins.
3. Neuropeptide regulation of adipose biology. We have identified two neuropeptides, oxytocin (OXT) and neurotensin (NTS), with profound effects on adipose lipolysis and thermogenesis. Interestingly, these neuropeptides appear to be released by cells within the adipose niche. In the case of OXT, the contributing cell is a subset of sympathetic neurons, while NTS is derived from local lymphatic vessels.