1. Cancer Immunometabolism
2. Cancer Metabolism
Immunometabolism is an emerging field that investigates the interplay between immunological and metabolic processes. Metabolic processes regulate immune cell response in healthy individuals as well as during various disease states, including cancer. AMPK (AMP-activated kinase) is a master regulator of metabolism in all living beings. AMPK has been demonstrated to regulate the function of various immune cells through metabolic regulation.
1. Loss of AMPK results in an accelerated ovarian cancer progression promoted by an increased immunosuppressive state facilitated by hyper-active myeloid-derived suppressor cells (MDSCs). Current investigations are focused on elucidating the intracellular metabolic regulation of MDSCs by AMPK that dictates MDSC immunosuppressive activity. Identification of the regulation of MDSC's function can enable us to restrict the immunosuppressive cancer immune environment and enhance the immunotherapy.
2. Lifestyle-associated pathologies have an immense effect on the outcome of cancer patients. Unhealthy diets and lifestyles cause chronic metabolic inflammation that can have long-lasting immune reprogramming. We are investigating how the dietary intervention of caloric restriction results in a better immune response, specifically by regulating intracellular macrophage metabolism and polarization. We are testing various forms of caloric restriction approaches in obesogenic and aging models.
3. The development of chemoresistance is the biggest hurdle in the treatment of recurrent ovarian cancer. We are investigating the metabolic adaptations acquired by chemoresistant cancer cells, focusing on energy metabolism and mitochondrial STAT3.
Udumula MP, Sakr S, Dar S, Alvero AB, Ali-Fehmi R, Abdulfatah E, Li J, Jiang J, Tang A, Buekers T, Morris R, Munkarah A, Giri S, Rattan R*. Ovarian Cancer modulates the immunosuppressive function of CD11b+Gr1+ myeloid cells via glutamine metabolism. Mol Metab. 2021;15:101272.
Xia H, Li S, Li X, Wang W, Bian Y, Wei S, Grove S, Wang W, Vatan L, Liu JR, McLean K, Rattan R, Munkarah A, Guan JL, Kryczek I, Zou W. Autophagic adaptation to oxidative stress alters peritoneal residential macrophage survival and ovarian cancer metastasis. JCI Insight. 2020;5.:e141115.
Xia H, Wang W, Crespo J, Kryczek I, Li W, Wei S, Maj T, He M, Liu JR, He Y, Rattan R, Munkarah A, Guan JL and Zou W. Suppression of FIP200 and autophagy by tumor-derived lactate promotes naïve T cell apoptosis and affects tumor immunity. Sci Immunol. 2017;2:eaan4631.
Dar S, Chhina J, Mert I, Chitale D, Beukers T, Kaur H, Giri S, Munkarah A and Rattan R*. Bioenergetic adaptations in chemoresistant cells. Sci Rep. 2017;7:8760.
Postdoctoral training (2006-2011), Mayo Clinic, Rochester, MN
PhD (2005), Medical University of South Carolina, Charleston, SC