Mitochondria and intracellular calcium flux are critical determinant of aging and age-related neurodegenerative diseases. Neuronal intracellular calcium flux is tightly coupled with mitochondrial calcium uptake. Mitochondrial calcium flux is essential for cellular respiration specifically in excitable cells, like neurons, due to high energy demands. However, excessive mitochondrial calcium uptake can contribute to oxidative stress, mitochondrial and metabolic derangement, and neuronal cell death. Yet to date, our understanding of mitochondrial calcium signaling in neurons is limited, and its role in aging and neurodegeneration remains enigmatic. Utilizing multiple genetically modified rodent models our goal is to dissect how specifically mitochondrial calcium dysregulation contributes to aging and associated neuropathology.
Mitochondrial health is essential for cellular functions and survival. Our lab aims to investigate the mitochondrial quality control pathways, including mitochondrial proteostasis, dynamics, and mitophagy, to determine the mechanisms by which mitochondrial calcium dysregulation and mitochondrial (dys)function contribute to aging and age-related neurodegenerations. We combine mass spectrometry-based profiling (proteomics, metabolomics, lipidomics), confocal and electron microscopy, mouse genetics, and mammalian physiology to understand how perturbing mitochondrial quality control pathway elicits neuronal pathology and how preserving healthy mitochondria can prevent age-associated neuronal dysfunction.
The lab studies the mechanisms of mitochondrial (dys)functions, calcium deregulation, and cell death in neurodegeneration, focusing on Alzheimer’s Disease. Alzheimer’s disease is a major age-related multifactorial pathology and is characterized by irreversible memory loss and the deposition of amyloid-beta plaques and hyperphosphorylated-tau (neurofibrillary tangles), specifically in the brain cortex and hippocampal regions. Enormous scientific endeavor has been focused on unraveling the molecular and cellular mechanisms driving neurodegeneration, but there remains no cure for AD. Indeed, altered mitochondrial signaling is believed to present before the onset of clinical symptoms. We aim to determine the early contributor of this disease and identify new therapeutic targets for AD. The lab evaluates neurodegeneration, cognitive function, and neuropathology using various AD models, including 3xTg-AD, 5xFAD, and App-KI mice, in-vitro cell lines (APPswe), and human AD samples to assess how perturbation of mitochondrial (dys)functions predisposes to AD.
Mitochondrial functions and quality decline with normal aging and are linked with the progression of age-related diseases. We are interested in how mitochondrial (dys)functions and calcium dysregulation contribute to aging and how mitochondrial quality control pathways regulate lifespan. Our lab utilizes various in vivo and in vitro approaches to understand the molecular mechanisms directed at improving mitochondrial quality and function and how these mechanisms could be targeted therapeutically to improve life span.
View the most recent highlighted research articles, book chapters, and publications from the Jadiya lab at Wake Forest University School of Medicine.
Pooja Jadiya, PhD
Pooja received her Ph.D. in Life Sciences from CSIR-Central Drug Research Institute, Lucknow, India where she studied functional genomics and epigenetic alterations in neurodegenerative diseases in the lab of Dr. Aamir Nazir. She completed her postdoctoral training with Dr. John Elrod at Lewis Katz School of Medicine at Temple University, Philadelphia. During postdoctoral training, she discovered that mitochondrial calcium flux plays a key role in the onset of Alzheimer’s disease.
Fellowship, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 2015-2020
Fellowship, Waksman Institute of Microbiology, Rutgers University, Piscataway, NJ, 2015
PhD, Biological Sciences, CSIR-Central Drug Research Institute, Lucknow, India, 2015
MSc, Biotechnology, Dr. Hari Singh Gour University, Sagar, India, 2008
BSc, Biotechnology, Dr. Hari Singh Gour University, Sagar, India, 2006