Prashant Rajbhandari, PhD
I am a well-trained investigator in obesity, diabetes, and adipose tissue biology. Over the last decade, my work has focused on understanding the mechanisms underlying adipocyte formation, immune functions in adipose tissues, adipose thermogenesis, and adipose endocrine functions in normal and pathophysiological states. I have made a significant contribution to the field of beige and white adipogenesis, and my past work has identified Estrogen Receptor-alpha, RNA-binding protein PSPC1, and transcription co-activator TLE3 in controlling beige and white adipogenesis (Sci. Trans. Med. 2020, JCI 2017 and Genes&Dev 2018). My previous work identified cytokine-mediated interaction between immune cells and adipocytes that ultimately regulates thermogenesis and sympathetic nerve-driven breakdown of lipids in adipocytes (Cell 2018). Besides this, I was also involved in identifying fat and liver-secreted soluble factors, Noggin and Notum, and transcription co-activator PRDM4 in driving energy-burning beige adipogenesis (Cell Metab. 2018, Nat. Chem. Biol. 2016, and Mol. Metab. 2019. Recently, we pioneered a technique for studying single adipocyte transcriptomics and heterogeneity (SNAP-seq) and reported on the role of immune cells in contributing to the formation of functionally diverse adipocytes (eLIFE 2019, corresponding author). Recent work from my lab also leveraged our combinatorial experience in adipose tissue biology and scRNA-seq to discover novel mammary duct secreted factors, “mammokines”, that regulate sex-specific adipocyte metabolism and thermogenesis (Nature 2023, Corresponding and senior author). My previous work has highlighted the importance of adipose stromal components such as adipocyte precursor cells, immune cells, and the sympathetic nervous system in driving adipogenesis, thermogenesis, and lipid mobilization.
My lab is involved in understanding how the adipose tissue microenvironment controls adipocyte form and function, particularly:
1) The contribution of immune cells to adipose metabolism and thermogenesis.
2) Transcriptional mechanism of adipocyte precursor cells (APC) conversion into adipocytes.
3) The role of the mammary ductal epithelium in mammary adipocyte metabolism
My research program is based on our findings:
1) We have challenged the central dogma by showing that deletion of anti-inflammatory signal in adipose tissue blocks immune-adipocyte crosstalk to protect mice from obesity and insulin resistance by altering the chromatin architecture of genes that generate heat from stored lipids.
2) We have discovered two new transcription factors (PATZ1 and GTF2I) involved in differentiating preadipocytes into adipocytes and showed that promoter and promoter-transcription start sites are essential for preadipocyte lineage determination.
3) We have developed a new paradigm in mammary adipose tissuebiology by discovering mammary duct-secreted factors, mammokines, that could have essential roles in mammary adipocyte metabolism.
My research program aims to understand the basic biology of adipose tissue niche in adipocyte function and preclinical manipulation to inform therapies for obesity and diabetes. I aim to identify and study novel factors that control adipose biology using animal models, genomics, biochemistry, molecular and cellular biology, and single-cell technologies.
Adipose, Diabetes, Metabolism
Multi-Disciplinary Training Areas
Disease Mechanisms and Therapeutics (DMT)