Vaibhav Sidarala, PhD 
Assistant Professor 
Department of Biomedical Sciences
Joan C. Edwards School of Medicine

Weisberg Applied Engineering Complex
1628 Third Ave., Suite 4113 Huntington, WV 25703

Mitochondria are dynamic bioenergetic organelles capable of regulating their own structure and function depending on cellular metabolic demands. While primarily responsible for ATP production, mitochondria also serve as biosynthetic hubs, providing key metabolic signaling molecules involved in nutrient metabolism, protein homeostasis and hormone secretion. These diverse functions are supported by coordinated fusion-fission events, termed as mitochondrial dynamics, which together regulate several aspects of mitochondrial function including the mtDNA maintenance, cristae remodeling, metabolic flux, respiratory capacity and quality control. Our research focuses on delineating the roles of mitochondrial dynamics in both physiological and adaptive cellular responses, and the pathological mechanisms that may be involved in metabolic diseases such as type 2 diabetes (T2D).

Current Research Direction: Pancreatic β-cells are specialized endocrine cells responsible for insulin secretion to maintain glucose homeostasis. Mitochondrial function is crucial for glucose-stimulated generation of ATP and other metabolic signals necessary for insulin granule exocytosis. In addition to their physiological function, β-cells are inherently capable of modulating their secretory capacity to ensure glucose homeostasis under states of overnutrition and insulin resistance. However, impairments in this compensatory adaptation, due to underlying environmental factors including aging, result in insulin insufficiency and T2D onset. We are interested in delineating the regulatory roles of mitochondrial dynamics in β-cell responses and investigating whether abnormalities in mitochondrial structure may contribute to age-associated defects in β-cell function and T2D.

Project 1: Mitochondrial fusion in β-cell metabolism: Mitochondrial connectivity by fusion ensures the maintenance of crucial elements of mitochondrial function, including respiration, protein homeostasis and metabolite availability. This project will investigate the regulatory roles mitochondrial fusion proteins, Mfn1 and Mfn2, in key metabolic and signaling pathways involved in insulin secretion. High-resolution live-cell imaging will be utilized to visualize how mitochondrial fusion proceeds upon varying nutrient stimulation and metabolic stressors. Multiomic analyses, metabolic biosensors and other biochemical analyses will be performed in genetic models of fusion deficiency to elucidate how mitochondrial dynamics regulate metabolic pathways essential for physiological and compensatory β-cell responses.

Project 2: Mitochondrial dynamics in β-cell development: Nutritional status during early life has profound implications on β-cell development, with neonatal obesity potentially predisposing offspring to developing T2D. This project will examine whether alterations in mitochondrial fission (Drp1) and fusion (Mfn1/2) proteins within developing β-cells influence susceptibility to failure later in life. iPSC-β-cell differentiation protocols and transgenic mouse models will be utilized to assess β-cell development, physiological function, and responses to diet-induced obesity.