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Shanmughapriya Santhanam, PhD

Shanmughapriya Santhanam, PhD

Assistant Professor, Department of Medicine
Division of Cardiology
Assistant Professor, Department of Cellular and Molecular Physiology
Scientific Program:Mechanisms of Carcinogenesis
SMS8350@psu.edu

Research Interests

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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.

  • India
  • Energy Metabolism
  • Leptospirosis
  • Mitochondria
  • Cardiac Myocytes
  • Proteins
  • Population
  • Calcium
  • Porifera
  • Enzymes
  • Enzyme-Linked Immunosorbent Assay
  • Actinobacteria
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Recent Publications

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2023

Sumaiya, K, Ponnusamy, T, Natarajaseenivasan, K & Shanmughapriya, S 2023, 'Cardiac Metabolism and MiRNA Interference', International journal of molecular sciences, vol. 24, no. 1, 50. https://doi.org/10.3390/ijms24010050

2022

Natarajaseenivasan, K, Garcia, A, Velusamy, P, Shanmughapriya, S & Langford, D 2022, 'Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids', iScience, vol. 25, no. 11, 105407. https://doi.org/10.1016/j.isci.2022.105407
Suriya Muthukumaran, N, Velusamy, P, Akino Mercy, CS, Langford, D, Natarajaseenivasan, K & Shanmughapriya, S 2022, 'MicroRNAs as Regulators of Cancer Cell Energy Metabolism', Journal of Personalized Medicine, vol. 12, no. 8, 1329. https://doi.org/10.3390/jpm12081329

2021

Bisserier, M, Shanmughapriya, S, Rai, AK, Gonzalez, C, Brojakowska, A, Garikipati, VNS, Madesh, M, Mills, PJ, Walsh, K, Arakelyan, A, Kishore, R, Hadri, L & Goukassian, DA 2021, 'Cell-free mitochondrial DNA as a potential biomarker for astronauts’ health', Journal of the American Heart Association, vol. 10, no. 21, e022055. https://doi.org/10.1161/JAHA.121.022055
Sumaiya, K, Langford, D, Natarajaseenivasan, K & Shanmughapriya, S 2022, 'Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies', Pharmacology and Therapeutics, vol. 233, 108024. https://doi.org/10.1016/j.pharmthera.2021.108024

2020

Kang, Y, Datta, P, Shanmughapriya, S & Ozbolat, IT 2020, '3D Bioprinting of Tumor Models for Cancer Research', ACS Applied Bio Materials, vol. 3, no. 9, pp. 5552-5573. https://doi.org/10.1021/acsabm.0c00791
Natarajaseenivasan, K, Shanmughapriya, S, Velusamy, P, Sayre, M, Garcia, A, Gomez, NM & Langford, D 2020, 'Inflammation-induced PINCH expression leads to actin depolymerization and mitochondrial mislocalization in neurons', Translational Neurodegeneration, vol. 9, no. 1, 32. https://doi.org/10.1186/s40035-020-00211-4
Shanmughapriya, S, Langford, D & Natarajaseenivasan, K 2020, 'Inter and Intracellular mitochondrial trafficking in health and disease', Ageing Research Reviews, vol. 62, 101128. https://doi.org/10.1016/j.arr.2020.101128
Mercy, CSA, Muthukumaran, NS, Velusamy, P, Bothammal, P, Sumaiya, K, Saranya, P, Langford, D, Shanmughapriya, S & Natarajaseenivasan, K 2020, 'MicroRNAs Regulated by the LPS/TLR2 Immune Axis as Bona Fide Biomarkers for Diagnosis of Acute Leptospirosis', mSphere, vol. 5, no. 4, e00409-20. https://doi.org/10.1128/mSphere.00409-20
Delierneux, C, Kouba, S, Shanmughapriya, S, Potier-Cartereau, M, Trebak, M & Hempel, N 2020, 'Mitochondrial Calcium Regulation of Redox Signaling in Cancer', Cells, vol. 9, no. 2, 1787. https://doi.org/10.3390/cells9020432
Nemani, N, Dong, Z, Daw, CC, Madaris, TR, Ramachandran, K, Enslow, BT, Rubannelsonkumar, CS, Shanmughapriya, S, Mallireddigari, V, Maity, S, SinghMalla, P, Natarajanseenivasan, K, Hooper, R, Shannon, CE, Tourtellotte, WG, Singh, BB, Reeves, WB, Sharma, K, Norton, L, Srikantan, S, Soboloff, J & Madesh, M 2020, 'Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity', Science signaling, vol. 13, no. 628, eaaz6206. https://doi.org/10.1126/scisignal.aaz6206
Chen, SJ, Bao, L, Keefer, K, Shanmughapriya, S, Chen, L, Lee, J, Wang, JF, Zhang, XQ, Hirschler-Laszkiewicz, I, Merali, S, Merali, C, Imamura, Y, Dovat, S, Madesh, M, Cheung, JY, Wang, HG & Miller, BA 2020, 'Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy', Cell Death and Disease, vol. 11, no. 4, 247. https://doi.org/10.1038/s41419-020-2454-8

2019

Tomar, D, Jaña, F, Dong, Z, Quinn, WJ, Jadiya, P, Breves, SL, Daw, CC, Srikantan, S, Shanmughapriya, S, Nemani, N, Carvalho, E, Tripathi, A, Worth, AM, Zhang, X, Razmpour, R, Seelam, A, Rhode, S, Mehta, AV, Murray, M, Slade, D, Ramirez, SH, Mishra, P, Gerhard, GS, Caplan, J, Norton, L, Sharma, K, Rajan, S, Balciunas, D, Wijesinghe, DS, Ahima, RS, Baur, JA & Madesh, M 2019, ' Blockade of MCU-Mediated Ca 2+ Uptake Perturbs Lipid Metabolism via PP4-Dependent AMPK Dephosphorylation ', Cell Reports, vol. 26, no. 13, pp. 3709-3725.e7. https://doi.org/10.1016/j.celrep.2019.02.107
Woods, JJ, Nemani, N, Shanmughapriya, S, Kumar, A, Zhang, M, Nathan, SR, Thomas, M, Carvalho, E, Ramachandran, K, Srikantan, S, Stathopulos, PB, Wilson, JJ & Madesh, M 2019, 'A Selective and Cell-Permeable Mitochondrial Calcium Uniporter (MCU) Inhibitor Preserves Mitochondrial Bioenergetics after Hypoxia/Reoxygenation Injury', ACS Central Science, vol. 5, no. 1, pp. 153-166. https://doi.org/10.1021/acscentsci.8b00773
Kokkinaki, D, Hoffman, M, Kalliora, C, Kyriazis, ID, Maning, J, Lucchese, AM, Shanmughapriya, S, Tomar, D, Park, JY, Wang, H, Yang, XF, Madesh, M, Lymperopoulos, A, Koch, WJ, Christofidou-Solomidou, M & Drosatos, K 2019, 'Chemically synthesized Secoisolariciresinol diglucoside (LGM2605) improves mitochondrial function in cardiac myocytes and alleviates septic cardiomyopathy', Journal of Molecular and Cellular Cardiology, vol. 127, pp. 232-245. https://doi.org/10.1016/j.yjmcc.2018.12.016
Cheung, JY, Gordon, J, Wang, JF, Song, J, Zhang, XQ, Prado, FJ, Shanmughapriya, S, Rajan, S, Tomar, D, Tahrir, FG, Gupta, MK, Knezevic, T, Merabova, N, Kontos, CD, McClung, JM, Klotman, PE, Madesh, M, Khalili, K & Feldman, AM 2019, 'Mitochondrial dysfunction in human immunodeficiency virus-1 transgenic mouse cardiac myocytes', Journal of Cellular Physiology, vol. 234, no. 4, pp. 4432-4444. https://doi.org/10.1002/jcp.27232
Miller, BA, Wang, JF, Song, J, Zhang, XQ, Hirschler-Laszkiewicz, I, Shanmughapriya, S, Tomar, D, Rajan, S, Feldman, AM, Madesh, M, Sheu, SS & Cheung, JY 2019, 'Trpm2 enhances physiological bioenergetics and protects against pathological oxidative cardiac injury: Role of Pyk2 phosphorylation', Journal of Cellular Physiology, vol. 234, no. 9, pp. 15048-15060. https://doi.org/10.1002/jcp.28146
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