To gain in-depth knowledge of mitochondrial
organization and functions, we utilize multidisciplinary approaches including cell and molecular biology techniques, protein biochemistry, calcium flux analysis,
cellular respiration measurements, omics-based approaches, live-cell imaging, mutant and transgenic mouse models, and in vivo physiological methods.
Current Projects
Calcium is the second most abundant metal ion in the biological system and regulates numerous cellular functions by binding distinct calciumsensing domains or motifs present on numerous proteins. The calcium concentration varies greatly between different cellular compartments,
and thus calcium sensors are strategically localized for subcellular/organelle-specific signaling. Mitochondria actively regulate their calcium
concentration and contain calcium sensors to mediate anterograde and retrograde signaling. Mitochondrial calcium participates in cellular
energy production through the regulation of bioenergetics yet can also promote different modes of cell death. Calcium is also involved in the
regulation of mitochondrial trafficking, structural homeostasis, and dynamics. Dysregulation of mitochondrial calcium flux has been linked to
numerous cellular dysfunctions, including chronic oxidative burden, autophagy, and sensitization for cell death, which are the central hallmarks
of the multiple pathologies. We aim to identify the new regulators and regulatory events associated with mitochondrial calcium-sensing/flux and
their role in animal physiology using protein biochemistry, high-end imaging-based approaches, and genetic manipulations.
The mitochondrial proteome includes around two thousand proteins. Around 99% of the mitochondrial proteins are nuclear-encoded that are synthesized on the endoplasmic reticulum, or cytosol, or the mitochondrial surface. These mitochondrial proteins are subsequently imported into the mitochondria. Multiple post-translational modifications and protein quality control processes are involved in mitochondrial protein import, folding, assembly into multimeric protein complexes, protein functions, and regulated turnover. Defects in mitochondrial protein quality control machinery result in mitochondrial dysfunction that leads to the failure of cellular homeostasis and the onset of diseases. Our research aims to identify the molecular determinants of the mitochondrial protein quality control mechanisms and delineate the associated molecular events that lead to disease onset.
Heart diseases are the number one cause of death in the US and represent substantial health and economic burden. Mitochondrial dysfunctions
and mitochondria-initiated cell death signaling are the primary cause of cell loss associated with the progression of heart failure. Our research
focuses on the identification of new molecular regulators and events associated with the mitochondrial (dys)functions and mitochondria-initiated
cell death signaling. We aim to characterize the molecular consequences of these signaling events using mouse genetics and physiology-based
in vivo methods.
Alzheimer's disease (AD) presents a growing public health challenge, particularly among older Americans, with projections indicating a significant surge by 2050. Despite extensive research, a considerable knowledge gap still exists in understanding the molecular and cellular mechanisms underlying AD. Recent studies have highlighted the critical role of mitochondria in AD progression, particularly noting early dysfunction and calcium overload as key contributors. Our aim is to dissect how calcium signaling and the mitochondrial protein quality control system contribute to the onset of AD, and how these can be targeted to mitigate the disease. Furthermore, we are mapping the heterogeneity of mitochondrial calcium across different brain cells and explore how each cell's contribution affects AD progression. This includes investigating how various brain cells, including glial and vascular cells, manage calcium flux.
Lab Highlights
Postdoctoral Fellows
- Kannan BN, PhD
- Shiridhar, PhD
Visiting Fellows
- Vidyarashmi Hanehalli, BS
Undergraduate Students
- Brianna Thompson
- Ivy Greene
- Leilani Whyte
- Ajay Roy
- Matt Walker
- Jennifer Breglio
- Lenora Paige Ingram
- Harshita Dasari
High-School Students
- Bhanuka Ariyawansa
- Anika Ramanujam
- Chan An
- Enoch Edwin
2025
- 09/2025: New research grant: The lab has been awarded a five-year NIH/NIGMS R35 MIRA grant to investigate calcium sensing and mitochondrial homeostasis.
- 09/2025: Promotion: Shiridhar promoted to Assistant Professor (non-tenure track).
- 06/2025: New research grant: The lab received an American Heart Association grant to study mitochondrial protein lactylation in heart failure.
- 05/2025: Publication: Anupriya and Natasha’s review article on mitochondrial connection to Alzheimer’s disease and heart failure has been published in the journal Current Opinion in Physiology.
- 03/2025: Trainee grant: Shiridhar received a Career Development Award grant from the American Heart Association.
- 03/2025: Publication: Shiridhar’s commentary article “enhancing VEGF therapy in T2D wounds with PLCγ2 epigenetic targeting” has been published in the journal Molecular Therapy.
2024
- 12/2024: Trainee grant: Ashlesha received a postdoctoral fellowship grant from the American Heart Association.
- 10/2024: Publication: Our commentary article “ERMCS Ca2+ transmission fuels cell division” has been published in the journal Trends in Cell Biology.
- 10/2024: Publication: Shani’s review article on calcium signaling in mitochondrial intermembrane space has been published in the journal Biochemical Society Transactions.
- 06/2024: New research grant: The lab received two American Heart Association grants to study TRIM-NHL proteins in cardiac aging and MICU1's role in protein quality control for heart health.
- 03/2024: Publication: Our review article on MICU1's calcium sensing beyond mitochondrial calcium uptake has been published in the journal Biochim Biophys Acta Molecular Cell Research.
2023
- 08/2023: Publication: Ashlesha’s review article on post-translational modifications and protein quality control of mitochondrial channels and transporters has been published in the journal Frontiers in Cell and Developmental Biology.
- 07/2023: New research grant: The lab has received a significant research grant from Alzheimer's Association to study the mitochondrial protein quality control and calcium flux in Alzheimer's disease.
2022
- 12/2022: First trainee grant: Ashlesha received a postdoctoral fellowship grant from the American Heart Association.
- 11/2022: First research grant: Laboratory received a research grant from the Harold S. Geneen Charitable Trust Awards Program for Coronary Heart Disease Research.
- 03/2022: First Trainee: Dr. Ashlesha Kadam joined as a Postdoctoral Fellow in Tomar lab.
- 01/2022: Tomar lab opened in Section of Cardiovascular Medicine, Department of Internal Medicine at Wake Forest University School of Medicine.
