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, Ph.D.
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.
- Ph.D., Biological Sciences, CSIR-Central Drug Research Institute, Lucknow, India, 2015.
- M.Sc., Biotechnology, Dr. Hari Singh Gour University, Sagar, India, 2008.
- B.Sc., Biotechnology, Dr. Hari Singh Gour University, Sagar, India, 2006.
Darpan Raghav, Ph.D.
Darpan is a postdoctoral fellow in the Jadiya lab, where he focuses on investigating the role of mitochondrial protein quality control mechanisms in Alzheimer's disease using loss-and gain-of-function mouse models.
- Fellowship, Department of Biosciences and Bioengineering, Indian Institute of Technology, Bombay, India, 2021 - 2023.
- Ph.D., Biotechnology, National Institute of Technology, Calicut, Kerala, India, 2014 - 2020.
- M.Sc., Life sciences, Central University of Gujarat, Gandhinagar, India, 2012 - 2014.
Sarah is a dedicated Ph.D. student in molecular medicine and translational science at Wake Forest University. She holds the prestigious National Institutes of Health National Research Service Award (NIH-NRSA) predoctoral fellowship (T32) within the Redox Biology and Medicine Graduate Training and Fellowship Program.
- Ph.D. candidate, Wake Forest University Graduate School, Winston-Salem, NC, 2019 - current.
- B.S., Molecular, Cell, and Developmental Biology (with honors), University of California, Santa Cruz, Santa Cruz, CA, 2006 - 2011.
Shatakshi is a dynamic and dedicated visiting research graduate scholar. Within the Jadiya lab, she currently delving into the fascinating world of miRNAs and their impact on mitochondrial calcium signaling in Alzheimer's disease.
- M.Sc., Biotechnology, Devi Ahilya University, Indore, India, 2017 - 2019.
- B.Sc., (H) Biomedical Sciences, Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, Delhi, India, 2014 - 2017.
Rakesh Sharma, Ph.D.
Postdoctoral Research Fellow
Undergraduate Research Intern
Undergraduate Research Intern
Nicole I. Anthony
Center for Precision Medicine Summer Intern
Enhancing Undergraduate Education and Research in Aging to Eliminate Health Disparities (ENGAGED) Summer Intern
High-School Draelos Scholar