Sathyadev Unudurthi, Ph.D.

More than 6 million Americans suffer from Heart Failure (HF) and it is a leading cause of hospitalization in people older than 65 years, world-wide. Inflammation is an important driver of pathogenesis in heart failure (HF). Cardiac inflammation is like a double-edged sword. On one hand, it plays an important role of clearing the dead cells after injury or infection, but, chronic cardiac inflammation leads to cardiac fibrosis, and eventually to cardiac dysfunction. There is a need to develop mechanisms that enable us to tightly regulate cardiac inflammation and fine tune the inflammatory response in heart.

My research interests focus on understanding the role of membrane proteins in fine-tuning cardiac inflammation. Specifically, the cell surface receptor Fibroblast growth factor inducible 14 (Fn14), is highly expressed in heart, and it’s ONLY known ligand is Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK). We are currently exploring the role of TWEAK/Fn14 pathway in various cardiac cell types and how this pathway regulates cell-cell communication to promote cardiac inflammation and fibrosis. Studies in the lab span from cardiac cell biology, inflammation, cardiac fibrosis to murine models of heart failure. We employ a wide array of experimental techniques in our research, including in vitro techniques such as cardiac cell culture, flowcytometry, RNA sequencing and generation and culture of human iPSC-CMs. Some of the in vivo techniques include transaortic constriction (TAC) and Myocardial Infarction (MI) surgeries, 2D echocardiography and whole animal imaging.

Sathyadev Unudurthi, Ph.D.
Instructor, Masonic Medical Research Institute
Email –
Phone - 315-624-7475

 


Dr. Unudurthi obtained a PhD in Biological Sciences from National University of Singapore. He conducted his postdoctoral studies at The Ohio State University, Columbus, on spectrin based regulation of cardiac rhythmicity and cardiac inflammation. He was awarded an American Heart Association postdoctoral fellowship to study βIV spectrin dependent regulation of STAT3 signaling in heart. He discovered that βIV spectrin – STAT3 complex was essential for regulation of the cardiac response to stress, and disruption of this complex could be protective against pressure overload induced heart failure. Dr. Unudurthi was recruited to MMRI as an Instructor in Dr. Maria Kontaridis’s lab to unravel inflammatory and fibrotic mechanisms underlying maladaptive cardiac remodeling. Specifically, Dr. Unudurthi’s work focuses on studying the role of TWEAK-Fn14 pathway in regulating inflammation and fibrosis in cardiac tissue.

Honors:

- Outstanding Research Scientist Award, DHLRI Research Day 2019

Professional Memberships

- American Heart Association

- Heart Failure Society of America

- Heart Rhythm Society

Education

- Ph.D., National University of Singapore, Singapore

Funding

- Completed Research Support

- AHA postdoc fellowship 16POST30980042, S. Unudurthi (PI), 2016 - 2018

  1. Unudurthi, SD, Nassal, DM, Patel, NJ, Thomas, E, Yu, J, Pierson, CG et al.. Fibroblast growth factor-inducible 14 mediates macrophage infiltration in heart to promote pressure overload-induced cardiac dysfunction. Life Sci. 2020;247 :117440. doi: 10.1016/j.lfs.2020.117440. PubMed PMID:32070706 .
  2. Gratz, D, Winkle, AJ, Dalic, A, Unudurthi, SD, Hund, TJ. Computational tools for automated histological image analysis and quantification in cardiac tissue. MethodsX. 2020;7 :22-34. doi: 10.1016/j.mex.2019.11.028. PubMed PMID:31890644 PubMed Central PMC6931069.
  3. Greer-Short, A, Musa, H, Alsina, KM, Ni, L, Word, TA, Reynolds, JO et al.. Calmodulin kinase II regulates atrial myocyte late sodium current, calcium handling, and atrial arrhythmia. Heart Rhythm. 2020;17 (3):503-511. doi: 10.1016/j.hrthm.2019.10.016. PubMed PMID:31622781 PubMed Central PMC7056561.
  4. Patel, NJ, Nassal, DM, Greer-Short, AD, Unudurthi, SD, Scandling, BW, Gratz, D et al.. βIV-Spectrin/STAT3 complex regulates fibroblast phenotype, fibrosis, and cardiac function. JCI Insight. 2019;4 (20):. doi: 10.1172/jci.insight.131046. PubMed PMID:31550236 PubMed Central PMC6824442.
  5. Makara, MA, Curran, J, Lubbers, ER, Murphy, NP, Little, SC, Musa, H et al.. Novel Mechanistic Roles for Ankyrin-G in Cardiac Remodeling and Heart Failure. JACC Basic Transl Sci. 2018;3 (5):675-689. doi: 10.1016/j.jacbts.2018.07.008. PubMed PMID:30456339 PubMed Central PMC6234521.
  6. Hulsurkar, M, Quick, AP, Wehrens, XH. STAT3: a link between CaMKII-βIV-spectrin and maladaptive remodeling?. J. Clin. Invest. 2018;128 (12):5219-5221. doi: 10.1172/JCI124778. PubMed PMID:30418170 PubMed Central PMC6264720.
  7. Unudurthi, SD, Nassal, D, Greer-Short, A, Patel, N, Howard, T, Xu, X et al.. βIV-Spectrin regulates STAT3 targeting to tune cardiac response to pressure overload. J. Clin. Invest. 2018;128 (12):5561-5572. doi: 10.1172/JCI99245. PubMed PMID:30226828 PubMed Central PMC6264732.
  8. Unudurthi, SD, Greer-Short, A, Patel, N, Nassal, D, Hund, TJ. Spectrin-based pathways underlying electrical and mechanical dysfunction in cardiac disease. Expert Rev Cardiovasc Ther. 2018;16 (1):59-65. doi: 10.1080/14779072.2018.1418664. PubMed PMID:29257730 PubMed Central PMC6064643.
  9. Knierim, E, Gill, E, Seifert, F, Morales-Gonzalez, S, Unudurthi, SD, Hund, TJ et al.. A recessive mutation in beta-IV-spectrin (SPTBN4) associates with congenital myopathy, neuropathy, and central deafness. Hum. Genet. 2017;136 (7):903-910. doi: 10.1007/s00439-017-1814-7. PubMed PMID:28540413 .
  10. Radwański, PB, Ho, HT, Veeraraghavan, R, Brunello, L, Liu, B, Belevych, AE et al.. Neuronal Na+ Channels Are Integral Components of Pro-arrhythmic Na+/Ca2+ Signaling Nanodomain That Promotes Cardiac Arrhythmias During β-adrenergic Stimulation. JACC Basic Transl Sci. 2016;1 (4):251-266. doi: 10.1016/j.jacbts.2016.04.004. PubMed PMID:27747307 PubMed Central PMC5065245.
  11. Unudurthi, SD, Wu, X, Qian, L, Amari, F, Onal, B, Li, N et al.. Two-Pore K+ Channel TREK-1 Regulates Sinoatrial Node Membrane Excitability. J Am Heart Assoc. 2016;5 (4):e002865. doi: 10.1161/JAHA.115.002865. PubMed PMID:27098968 PubMed Central PMC4859279.
  12. Unudurthi, SD, Hund, TJ. Late sodium current dysregulation as a causal factor in arrhythmia. Expert Rev Cardiovasc Ther. 2016;14 (5):545-7. doi: 10.1586/14779072.2016.1155451. PubMed PMID:26886049 .
  13. Liu, B, Ho, HT, Brunello, L, Unudurthi, SD, Lou, Q, Belevych, AE et al.. Ablation of HRC alleviates cardiac arrhythmia and improves abnormal Ca handling in CASQ2 knockout mice prone to CPVT. Cardiovasc. Res. 2015;108 (2):299-311. doi: 10.1093/cvr/cvv222. PubMed PMID:26410369 PubMed Central PMC4614688.
  14. Glynn, P, Musa, H, Wu, X, Unudurthi, SD, Little, S, Qian, L et al.. Voltage-Gated Sodium Channel Phosphorylation at Ser571 Regulates Late Current, Arrhythmia, and Cardiac Function In Vivo. Circulation. 2015;132 (7):567-77. doi: 10.1161/CIRCULATIONAHA.114.015218. PubMed PMID:26187182 PubMed Central PMC4543581.
  15. Unudurthi, SD, Wolf, RM, Hund, TJ. Role of sinoatrial node architecture in maintaining a balanced source-sink relationship and synchronous cardiac pacemaking. Front Physiol. 2014;5 :446. doi: 10.3389/fphys.2014.00446. PubMed PMID:25505419 PubMed Central PMC4244803.
  16. Makara, MA, Curran, J, Little, SC, Musa, H, Polina, I, Smith, SA et al.. Ankyrin-G coordinates intercalated disc signaling platform to regulate cardiac excitability in vivo. Circ. Res. 2014;115 (11):929-38. doi: 10.1161/CIRCRESAHA.115.305154. PubMed PMID:25239140 PubMed Central PMC4224970.
  17. Glynn, P, Unudurthi, SD, Hund, TJ. Mathematical modeling of physiological systems: an essential tool for discovery. Life Sci. 2014;111 (1-2):1-5. doi: 10.1016/j.lfs.2014.07.005. PubMed PMID:25064823 PubMed Central PMC4144804.
  18. Onal, B, Unudurthi, SD, Hund, TJ. Modeling CaMKII in cardiac physiology: from molecule to tissue. Front Pharmacol. 2014;5 :9. doi: 10.3389/fphar.2014.00009. PubMed PMID:24550832 PubMed Central PMC3912431.
  19. Hund, TJ, Snyder, JS, Wu, X, Glynn, P, Koval, OM, Onal, B et al.. β(IV)-Spectrin regulates TREK-1 membrane targeting in the heart. Cardiovasc. Res. 2014;102 (1):166-75. doi: 10.1093/cvr/cvu008. PubMed PMID:24445605 PubMed Central PMC3958619.
  20. Unudurthi, SD, Hotta, K, Kim, CY. Engineering the polyproline II propensity of a class II major histocompatibility complex ligand peptide. ACS Chem. Biol. 2013;8 (11):2383-7. doi: 10.1021/cb400594q. PubMed PMID:24001370 .
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