Brahma Manoja K

The fundamental question of how defective nutrient utilization disrupts the overall metabolic health leading to metabolic diseases always fascinates me. Over my PhD and postdoc training, I developed a strong interest in the understanding of how complex milieu of systemic changes associated with metabolic diseases (diabetes and obesity) mediate cardiovascular complications. I started my early research career as master’s student in Pharmacology conducting research on the role of Na+ influx in pathogenesis of cerebral ischemia, which resulted in first author publication in the Journal of Neuroscience Research. This experience directed my interests to define defective energy metabolism affecting human health. Next, I worked as an in vivo Biologist (preclinical drug discovery) at Piramal Life Sciences Ltd., India, where I evaluated the in vivo anti-diabetic and anti-obese potential of in-house small molecules for DGAT1, GPR40, and PPARgamma as major therapeutic targets. My comprehensive understanding of disturbed lipid and glucose metabolism further motivated me to pursue higher studies in the field of energy metabolism. With a fellowship support from the DK-MCD international PhD program, I started my PhD (in the laboratory of Dr. Guenter Haemmerle and Prof. Rudolf Zechner) at the University of Graz, Austria, whose laboratory discovered adipose triglyceride lipase (ATGL), an enzyme that catalyzes the breakdown of triacylglycerols stored in lipid droplets. My thesis was focused on the impact of fibroblast growth factor 21 (FGF21), a fasting hormone, on cardiac and whole-body energy metabolism. At that time heart was the least investigated organ compared to the established roles of FGF21 signaling in the liver and adipose tissue since 2005. By characterizing a novel cardiomyocyte-specific FGF21 transgenic mouse model and utilizing two mouse models of defective myocardial lipid metabolism, I demonstrated FGF21 as a potential biomarker in response to cardiometabolic stress. My PhD training in lipid metabolism was further complemented by my postdoctoral training under Dr. Adam R. Wende’s mentorship at the University of Alabama at Birmingham (UAB), where I studied glucose-mediated regulation of myocardial metabolism via an epigenetic mechanism. My research was primarily focused on establishing the potential crosstalk between intermediary metabolism of glucose and ketone bodies in the diabetic heart by using transgenic mouse models of altered cardiac glucose metabolism and protein O-GlcNAcylation. I independently developed this project and secured a 2-years American Heart Association postdoctoral fellowship. I collaborated with Prof.s Martin Young, John Chatham, and other investigators at UAB for my American Heart Association fellowship project. This work had significance in providing insights on how hyperglycemia contributes to cardiovascular complications. Next, I as a postdoctoral fellow in the lab of Dr. Esteban Gurzov at the ULB, Brussels. I investigated the role of a BCL2-family protein and an alternate splicing factor in the pathogenesis of beta-cell dysfunction in T1D and T2D by characterizing 2 independent mouse models with beta-cell specific deletion of target genes. During my tenure, I also secured Marie Skłodowska-Curie Actions COFUND fellowship (gracefully denied) on the role of protein tyrosine phosphatase in the pathogenesis of Type 1 diabetes.