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Personal profile

Research interests

Dr. Shanmughapriya Santhanam's research has focused on the mechanisms by which mitochondrial calcium uptake is tightly regulated during health and disease. Calcium (Ca2+) is a unique cellular ion and is the key regulator of multiple cellular processes including mitochondrial function and dysfunction. Mitochondrial Ca2+ (mCa2+) uptake is precisely controlled by the Ca2+ selective channel, the Mitochondrial Ca2+ Uniporter (MCU). Dr. Santhanam’s research contributed to the understanding of how MCU, a hetero‐oligomeric complex is regulated by a suite of proteins.

Despite active research on identifying the molecular make‐up of MCU as a multifaceted oligomeric complex, an understanding of the molecular mechanism of MCU regulation remains obscure. While many Ca2+ channels including InP3R, RyRs, and CRAC exhibit Ca2+‐dependent feedback mechanisms, it is unclear whether there exists a divalent cation‐dependent control of MCU activity. Dr. Santhanam’s recent research program is focused on how to fine tune MCU activity by mitochondrial matrix Mg2+. Her interest in this field was promulgated by recent resolution of the MCU’s atomic structure and the identification of the MCU regulating acidic patch (MRAP) at the N‐terminal domain by their group in collaboration with Dr. Peter Stathopulos of Western University in Ontario, Canada. To understand the regulation of MCU by matrix Mg2+, her research utilizes a CRISPR/Cas9‐mediated gene targeting strategy to develop novel loss/gain of function mouse models for the mitochondrial Mg2+ channel, Mrs2p.

Because mMg2+ plays a dominant role in the regulation of MCU‐mediated Ca2+ uptake, Dr. Santhanam believes any changes in free mMg2+ levels due to mMg2+ entry or changes in matrix phosphate, ATP or ADP levels will be sensed by the MRAP domain of MCU and thus regulate MCU channel activity. Elucidation of the regulatory mechanism of MCU‐mediated Ca2+ uptake by mMg2+ will optimally yield new avenues for maintaining metabolic plasticity in myocytes thereby facilitating adaptation to increased workload and disease states.

Education/Academic qualification

Postdoctoral Fellow, Temple University School of Medicine

… → Feb 2019

PhD, Bharathidasan University

… → Mar 2013

External positions

Review Editor, Frontiers in Cell and Developmental Biology

Review Editor, Frontiers in Physiology

Fingerprint Dive into the research topics where Shanmughapriya Santhanam is active. These topic labels come from the works of this person. Together they form a unique fingerprint.

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Projects 2017 2019

Ion Channels
Energy Metabolism
Homeostasis
Oxidative Phosphorylation
Divalent Cations

Research Output 2008 2019

  • 1577 Citations
  • 24 h-Index
  • 62 Article
  • 3 Review article
  • 2 Comment/debate
5 Citations (Scopus)

A Selective and Cell-Permeable Mitochondrial Calcium Uniporter (MCU) Inhibitor Preserves Mitochondrial Bioenergetics after Hypoxia/Reoxygenation Injury

Woods, J. J., Nemani, N., Shanmughapriya, S., Kumar, A., Zhang, M., Nathan, S. R., Thomas, M., Carvalho, E., Ramachandran, K., Srikantan, S., Stathopulos, P. B., Wilson, J. J. & Madesh, M., Jan 23 2019, In : ACS Central Science. 5, 1, p. 153-166 14 p.

Research output: Contribution to journalArticle

Open Access
Calcium
Signal transduction
Mutagenesis
Ruthenium
Poisons

Blockade of MCU-Mediated Ca 2+ Uptake Perturbs Lipid Metabolism via PP4-Dependent AMPK Dephosphorylation

Tomar, D., Jaña, F., Dong, Z., Quinn, W. J., Jadiya, P., Breves, S. L., Daw, C. C., Srikantan, S., Santhanam, S., Nemani, N., Carvalho, E., Tripathi, A., Worth, A. M., Zhang, X., Razmpour, R., Seelam, A., Rhode, S., Mehta, A. V., Murray, M., Slade, D. & 12 others, Ramirez, S. H., Mishra, P., Gerhard, G. S., Caplan, J., Norton, L., Sharma, K., Rajan, S., Balciunas, D., Wijesinghe, D. S., Ahima, R. S., Baur, J. A. & Madesh, M., Mar 26 2019, In : Cell Reports. 26, 13, p. 3709-3725.e7

Research output: Contribution to journalArticle

Open Access
AMP-Activated Protein Kinases
Lipid Metabolism
Lipids
Liver
Homeostasis
4 Citations (Scopus)

Chemically synthesized Secoisolariciresinol diglucoside (LGM2605) improves mitochondrial function in cardiac myocytes and alleviates septic cardiomyopathy

Kokkinaki, D., Hoffman, M., Kalliora, C., Kyriazis, I. D., Maning, J., Lucchese, A. M., Santhanam, S., Tomar, D., Park, J. Y., Wang, H., Yang, X. F., Madesh, M., Lymperopoulos, A., Koch, W. J., Christofidou-Solomidou, M. & Drosatos, K., Feb 1 2019, In : Journal of Molecular and Cellular Cardiology. 127, p. 232-245 14 p.

Research output: Contribution to journalArticle

Cardiomyopathies
Punctures
Cardiac Myocytes
Ligation
Reactive Oxygen Species
1 Citation (Scopus)

Mitochondrial dysfunction in human immunodeficiency virus-1 transgenic mouse cardiac myocytes

Cheung, J. Y., Gordon, J., Wang, J. F., Song, J., Zhang, X. Q., Prado, F. J., Santhanam, S., Rajan, S., Tomar, D., Tahrir, F. G., Gupta, M. K., Knezevic, T., Merabova, N., Kontos, C. D., McClung, J. M., Klotman, P. E., Madesh, M., Khalili, K. & Feldman, A. M., Apr 1 2019, In : Journal of Cellular Physiology. 234, 4, p. 4432-4444 13 p.

Research output: Contribution to journalArticle

Viruses
Cardiac Myocytes
Muscle Cells
Transgenic Mice
HIV-1

Trpm2 enhances physiological bioenergetics and protects against pathological oxidative cardiac injury: Role of Pyk2 phosphorylation

Miller, B., Wang, J. F., Song, J., Zhang, X. Q., Hirschler-Laszkiewicz, I., Santhanam, S., Tomar, D., Rajan, S., Feldman, A. M., Madesh, M., Sheu, S. S. & Cheung, J. Y., Sep 1 2019, In : Journal of Cellular Physiology. 234, 9, p. 15048-15060 13 p.

Research output: Contribution to journalArticle

Focal Adhesion Kinase 2
Phosphorylation
Energy Metabolism
Muscle Cells
Wounds and Injuries