Researcher Profile

Researcher Profile

Shanmughapriya Santhanam, PhD

Shanmughapriya Santhanam, PhD

Assistant Professor, Department of Medicine
Assistant Professor, Department of Cellular and Molecular Physiology
Penn State Heart and Vascular Institute
Scientific Program:Mechanisms of Carcinogenesis
sms8350@psu.edu

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.

  • India
  • Energy Metabolism
  • Leptospirosis
  • Cardiac Myocytes
  • Mitochondria
  • Porifera
  • Proteins
  • Population
  • Infection
  • Carcinoma
  • Actinobacteria
  • Enzyme-Linked Immunosorbent Assay

Recent Publications

2019

Tomar, D, Jaña, F, Dong, Z, Quinn, WJ, Jadiya, P, Breves, SL, Daw, CC, Srikantan, S, Santhanam, 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, Santhanam, 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, Santhanam, 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, Santhanam, 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, B, Wang, JF, Song, J, Zhang, XQ, Hirschler-Laszkiewicz, I, Santhanam, 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

2018

Cheung, JY, Wang, JF, Zhang, XQ, Song, J, Davidyock, JM, Prado, FJ, Santhanam, S, Worth, AM, Madesh, M, Haouzi, A & Haouzi, P 2018, ' Methylene Blue Counteracts H 2 S-Induced Cardiac Ion Channel Dysfunction and ATP Reduction ', Cardiovascular toxicology, vol. 18, no. 5, pp. 407-419. https://doi.org/10.1007/s12012-018-9451-5
Natarajaseenivasan, K, Cotto, B, Santhanam, S, Lombardi, AA, Datta, PK, Madesh, M, Elrod, JW, Khalili, K & Langford, D 2018, 'Astrocytic metabolic switch is a novel etiology for Cocaine and HIV-1 Tat-mediated neurotoxicity article', Cell Death and Disease, vol. 9, no. 4, 415. https://doi.org/10.1038/s41419-018-0422-3
Tahrir, FG, Santhanam, S, Ahooyi, TM, Knezevic, T, Gupta, MK, Kontos, CD, McClung, JM, Madesh, M, Gordon, J, Feldman, AM, Cheung, JY & Khalili, K 2018, 'Dysregulation of mitochondrial bioenergetics and quality control by HIV-1 Tat in cardiomyocytes', Journal of Cellular Physiology, vol. 233, no. 2, pp. 748-758. https://doi.org/10.1002/jcp.26002
Santhanam, S, Tomar, D, Dong, Z, Slovik, KJ, Nemani, N, Natarajaseenivasan, K, Carvalho, E, Lu, C, Corrigan, K, Garikipati, VNS, Ibetti, J, Rajan, S, Barrero, C, Chuprun, K, Kishore, R, Merali, S, Tian, Y, Yang, W & Madesh, M 2018, 'FOXD1-dependent MICU1 expression regulates mitochondrial activity and cell differentiation', Nature communications, vol. 9, no. 1, 3449. https://doi.org/10.1038/s41467-018-05856-4
Nemani, N, Carvalho, E, Tomar, D, Dong, Z, Ketschek, A, Breves, SL, Jaña, F, Worth, AM, Heffler, J, Palaniappan, P, Tripathi, A, Subbiah, R, Riitano, MF, Seelam, A, Manfred, T, Itoh, K, Meng, S, Sesaki, H, Craigen, WJ, Rajan, S, Santhanam, S, Caplan, J, Prosser, BL, Gill, D, Stathopulos, PB, Gallo, G, Chan, DC, Mishra, P & Madesh, M 2018, 'MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress', Cell Reports, vol. 23, no. 4, pp. 1005-1019. https://doi.org/10.1016/j.celrep.2018.03.098
Nemani, N, Santhanam, S & Madesh, M 2018, 'Molecular regulation of MCU: Implications in physiology and disease', Cell Calcium, vol. 74, pp. 86-93. https://doi.org/10.1016/j.ceca.2018.06.006
Hirschler-Laszkiewicz, I, Chen, S, Bao, L, Wang, J, Zhang, XQ, Santhanam, S, Keefer, K, Madesh, M, Cheung, JY & Miller, B 2018, 'The human ion channel TRPM2 modulates neuroblastoma cell survival and mitochondrial function through Pyk2, CREB, and MCU activation', American Journal of Physiology - Cell Physiology, vol. 315, no. 4, pp. C571-C586. https://doi.org/10.1152/ajpcell.00098.2018

2017

Dong, Z, Santhanam, S, Tomar, D, Siddiqui, N, Lynch, S, Nemani, N, Breves, SL, Zhang, X, Tripathi, A, Palaniappan, P, Riitano, MF, Worth, AM, Seelam, A, Carvalho, E, Subbiah, R, Jaña, F, Soboloff, J, Peng, Y, Cheung, JY, Joseph, SK, Caplan, J, Rajan, S, Stathopulos, PB & Madesh, M 2017, 'Mitochondrial Ca2+ Uniporter Is a Mitochondrial Luminal Redox Sensor that Augments MCU Channel Activity', Molecular cell, vol. 65, no. 6, pp. 1014-1028.e7. https://doi.org/10.1016/j.molcel.2017.01.032
Alevriadou, BR, Santhanam, S, Patel, A, Stathopulos, PB & Madesh, M 2017, 'Mitochondrial Ca2+ transport in the endothelium: Regulation by ions, redox signalling and mechanical forces', Journal of the Royal Society Interface, vol. 14, no. 137, 0672. https://doi.org/10.1098/rsif.2017.0672
Kanagavel, M, Santhanam, S, Aishwarya, KVL, Ponmurugan, K, Murugan, K, Al-Dhabi, NA & Natarajaseenivasan, K 2017, 'Peptide specific monoclonal antibodies of Leptospiral LigA for acute diagnosis of leptospirosis', Scientific reports, vol. 7, no. 1, 3250. https://doi.org/10.1038/s41598-017-03658-0
Luongo, TS, Lambert, JP, Gross, P, Nwokedi, M, Lombardi, AA, Santhanam, S, Carpenter, AC, Kolmetzky, D, Gao, E, Van Berlo, JH, Tsai, EJ, Molkentin, JD, Chen, X, Madesh, M, Houser, SR & Elrod, JW 2017, 'The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability', Nature, vol. 545, no. 7652, pp. 93-97. https://doi.org/10.1038/nature22082

2016

Scheitlin, CG, Julian, JA, Santhanam, S, Madesh, M, Tsoukias, NM & Alevriadou, BR 2016, 'Endothelial mitochondria regulate the intracellular Ca2+ response to fluid shear stress', American Journal of Physiology - Cell Physiology, vol. 310, no. 6, pp. C479-C490. https://doi.org/10.1152/ajpcell.00171.2015
Anita, K, Premlatha, MM, Kanagavel, M, Akino Mercy, CS, Raja, V, Santhanam, S & Natarajaseenivasan, K 2016, 'Evaluation of combined B cell specific N-terminal immunogenic domains of LipL21 for diagnosis of leptospirosis', International Journal of Biological Macromolecules, vol. 91, pp. 465-470. https://doi.org/10.1016/j.ijbiomac.2016.05.109
Raja, V, Santhanam, S, Kanagavel, M, Artiushin, SC, Velineni, S, Timoney, JF & Natarajaseenivasan, K 2016, 'In vivo-expressed proteins of virulent Leptospira interrogans serovar autumnalis N2 elicit strong IgM responses of value in conclusive diagnosis', Clinical and Vaccine Immunology, vol. 23, no. 1, pp. 65-72. https://doi.org/10.1128/CVI.00509-15
Sivasankari, K, Santhanam, S & Natarajaseenivasan, K 2016, 'Leptospiral renal colonization status in asymptomatic rural population of Tiruchirapalli district, Tamilnadu, India', Pathogens and Global Health, vol. 110, no. 4-5, pp. 209-215. https://doi.org/10.1080/20477724.2016.1222054
Parveen, SMA, Suganyaa, B, Sathya, MS, Margreat, AAP, Sivasankari, K, Santhanam, S, Hoffman, NE & Natarajaseenivasan, K 2016, 'Leptospirosis seroprevalence among blue metal mine workers of Tamil Nadu, India', American Journal of Tropical Medicine and Hygiene, vol. 95, no. 1, pp. 38-42. https://doi.org/10.4269/ajtmh.16-0095
Zhou, J, Ahmad, F, Parikh, S, Hoffman, NE, Rajan, S, Verma, VK, Song, J, Yuan, A, Santhanam, S, Guo, Y, Gao, E, Koch, W, Woodgett, JR, Madesh, M, Kishore, R, Lal, H & Force, T 2016, 'Loss of adult cardiac myocyte GSK-3 leads to mitotic catastrophe resulting in fatal dilated cardiomyopathy', Circulation research, vol. 118, no. 8, pp. 1208-1222. https://doi.org/10.1161/CIRCRESAHA.116.308544
Tomar, D, Dong, Z, Santhanam, S, Koch, DA, Thomas, T, Hoffman, NE, Timbalia, SA, Goldman, SJ, Breves, SL, Corbally, DP, Nemani, N, Fairweather, JP, Cutri, AR, Zhang, X, Song, J, Jaña, F, Huang, J, Barrero, C, Rabinowitz, JE, Luongo, TS, Schumacher, SM, Rockman, ME, Dietrich, A, Merali, S, Caplan, J, Stathopulos, P, Ahima, RS, Cheung, JY, Houser, SR, Koch, WJ, Patel, V, Gohil, VM, Elrod, JW, Rajan, S & Madesh, M 2016, 'MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics', Cell Reports, vol. 15, no. 8, pp. 1673-1685. https://doi.org/10.1016/j.celrep.2016.04.050
Kanagavel, M, Princy Margreat, AA, Arunkumar, M, Prabhakaran, SG, Santhanam, S & Natarajaseenivasan, K 2016, 'Multilocus sequence typing (MLST) of leptospiral strains isolated from two geographic locations of Tamil Nadu, India', Infection, Genetics and Evolution, vol. 37, pp. 123-128. https://doi.org/10.1016/j.meegid.2015.11.008
Narayanan, R, Sumathi, G, Prabhakaran, SG, Santhanam, S & Natarajaseenivasan, K 2016, 'Paediatric leptospirosis: A population based case-control study from Chennai, India', Indian Journal of Medical Microbiology, vol. 34, no. 2, pp. 228-232. https://doi.org/10.4103/0255-0857.180353
Santhanam, S, Lency, A, Kavitha, S & Natarajaseenivasan, K 2016, 'Prolonged aminoglycoside treatment for pelvic inflammatory disease associated ovarian carcinoma', Trends in Medical Research, vol. 11, no. 1, pp. 49-53. https://doi.org/10.3923/tmr.2016.49.53
Santhanam, S, Senthilkumar, G, Arun, S, Das, BC & Natarajaseenivasan, K 2016, 'Risk factors for epithelial ovarian carcinoma in India: A case control study in low-incidence population', International Journal of Cancer Research, vol. 12, no. 1, pp. 61-68. https://doi.org/10.3923/ijcr.2016.61.68
Lee, SK, Santhanam, S, Mok, MCY, Dong, Z, Tomar, D, Carvalho, E, Rajan, S, Junop, MS, Madesh, M & Stathopulos, PB 2016, 'Structural Insights into Mitochondrial Calcium Uniporter Regulation by Divalent Cations', Cell Chemical Biology, vol. 23, no. 9, pp. 1157-1169. https://doi.org/10.1016/j.chembiol.2016.07.012

2015

Sureshkumar, BT, Santhanam, S, Das, BC & Natarajaseenivasan, K 2015, 'A population-based study of the prevalence of HPV in three districts of Tamil Nadu, India', International Journal of Gynecology and Obstetrics, vol. 129, no. 1, pp. 58-61. https://doi.org/10.1016/j.ijgo.2014.10.025
Abdhul, K, Ganesh, M, Santhanam, S, Vanithamani, S, Kanagavel, M, Anbarasu, K & Natarajaseenivasan, K 2015, 'Bacteriocinogenic potential of a probiotic strain Bacillus coagulans [BDU3] from Ngari', International Journal of Biological Macromolecules, vol. 79, pp. 800-806. https://doi.org/10.1016/j.ijbiomac.2015.06.005
Hoffman, NE, Miller, B, Wang, JF, Elrod, JW, Rajan, S, Gao, E, Song, J, Zhang, XQ, Hirschler-Laszkiewicz, I, Santhanam, S, Koch, WJ, Feldman, AM, Madesh, M & Cheung, JY 2015, 'Ca2+ entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance', American Journal of Physiology - Heart and Circulatory Physiology, vol. 308, no. 6, pp. H637-H650. https://doi.org/10.1152/ajpheart.00720.2014
Santhanam, S, Rajan, S, Hoffman, NE, Zhang, X, Guo, S, Kolesar, JE, Hines, KJ, Ragheb, J, Jog, NR, Caricchio, R, Baba, Y, Zhou, Y, Kaufman, BA, Cheung, JY, Kurosaki, T, Gill, D & Madesh, M 2015, 'Ca2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca2+ uniporter gene MCU', Science Signaling, vol. 8, no. 366, pp. ra23. https://doi.org/10.1126/scisignal.2005673
Ganesh, M, Senthamarai, A, Santhanam, S & Natarajaseenivasan, K 2015, 'Effective production of low crystallinity Poly(3-hydroxybutyrate) by recombinant E. coli strain JM109 using crude glycerol as sole carbon source', Bioresource technology, vol. 192, pp. 677-681. https://doi.org/10.1016/j.biortech.2015.06.042
Doonan, PJ, Chandramoorthy, HC, Hoffman, NE, Zhang, X, Cardenas, C, Santhanam, S, Rajan, S, Vallem, S, Chen, X, Foskett, JK, Cheung, JY, Houser, SR & Madesh, M 2015, 'Erratum: LETM1-dependent mitochondrial Ca21 flux modulates cellular bioenergetics and proliferation (FASEB Journal 28 (4936-4949) DOI: 10.1096/ fj.14-256453)', FASEB Journal, vol. 29, no. 8. https://doi.org/10.1096/fj.14-256453ERR
Vanithamani, S, Santhanam, S, Narayanan, R, Raja, V, Kanagavel, M, Sivasankari, K & Natarajaseenivasan, K 2015, 'Lipopolysaccharide specific immunochromatography based lateral flow assay for serogroup specific diagnosis of leptospirosis in India', PloS one, vol. 10, no. 9, e0137130. https://doi.org/10.1371/journal.pone.0137130
Enthumathi, R, Santhanam, S, Sumathi, S, Das, BC & Natarajaseenivasan, K 2015, 'Prevalence of human papillomavirus, cytomegalovirus and chlamydia trachomatis among women with normal cervical cytology and their impact on TLRs expression', Research Journal of Obstetrics and Gynecology, vol. 8, no. 1, pp. 1-9. https://doi.org/10.3923/rjog.2015.1.9
Santhanam, S, Rajan, S, Hoffman, NE, Higgins, AM, Tomar, D, Nemani, N, Hines, KJ, Smith, DJ, Eguchi, A, Vallem, S, Shaikh, F, Cheung, M, Leonard, NJ, Stolakis, RS, Wolfers, MP, Ibetti, J, Chuprun, JK, Jog, NR, Houser, SR, Koch, WJ, Elrod, JW & Madesh, M 2015, 'SPG7 Is an Essential and Conserved Component of the Mitochondrial Permeability Transition Pore', Molecular cell, vol. 60, no. 1, pp. 47-62. https://doi.org/10.1016/j.molcel.2015.08.009
Luongo, TS, Lambert, JP, Yuan, A, Zhang, X, Gross, P, Song, J, Santhanam, S, Gao, E, Jain, M, Houser, SR, Koch, WJ, Cheung, JY, Madesh, M & Elrod, JW 2015, 'The Mitochondrial Calcium Uniporter Matches Energetic Supply with Cardiac Workload during Stress and Modulates Permeability Transition', Cell Reports, vol. 12, no. 1, pp. 23-34. https://doi.org/10.1016/j.celrep.2015.06.017

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