MS in Biochemistry and Molecular Biology
University of Madras, Guindy Campus, Chennai, India
MPhil in Biochemistry and Molecular Biology
University of Madras, Guindy Campus, Chennai, India
PhD in Biochemistry and Molecular Biology
University of Madras, Guindy Campus, Chennai, India

Areas of Interest

Research Interests

Studying Complement Immunity in Inflammatory, Autoimmune, and Infectious Diseases.

I worked with Dr. Rick Wetsel, PhD, Director-retired, Center for Immunology and Autoimmune Diseases, at the IMM as a junior faculty since 2015. The lab research niche involves examining the roles of complement proteins in chronic inflammatory diseases and circadian rhythmicity, infectious diseases (Listeria monocytogenes, and Mycobacterium avium models), and autoimmune-associated cardiopulmonary fibrosis.

Chronic inflammation and autoimmunity play a major role in interstitial lung diseases (ILD). Autoimmune rheumatoid arthritis (RA) patients display respiratory symptoms such as bronchiectasis, and alveolar and pleural involvement in association with hypoxia, IgG, IgM rheumatoid factor, and complement immune components indicating immunologic etiology. While complement immune factor C5 breakdown products C5b leads the formation of membrane attack complex (MAC) for opsonization of pathogens and damaged cells, C3a and C5a anaphylatoxin signaling via their cognate receptors C3aR and C5aR1 further exacerbate inflammatory response and contribute to tissue injury.  We have recently demonstrated the roles of C3a and C5a and their receptors in endothelial cell activation, and thence activation and polarization of B lymphocytes and skewing of T lymphocytes towards proinflammatory type1 helper T cells. In vivo study models employ global knockout mice lacking C3ar, C5ar1, and C5ar2 (decoy receptor) functions on C57B6/J background along with their wildtype littermates.

Our current projects include studies on the interactions of complement and circadian rhythm in inflammation and immunity. We are interested in deciphering the effects of circadian regulated C5ar1 signaling in lymphoid tissue pathogenesis. These studies evaluate peripheral lymphoid tissue hypertrophy and B and T lymphocytes activation in mice under different circadian Zeitgeber times. We also use DSS-induced ulcerative colitis mice as a tool to understand the circadian gating in complement-induced intestinal lymphoid tissue (Peyer’s patches) pathogenesis.

The second major project focuses on the novel molecular mechanisms in transcriptional regulation of complement proteins in non-resolvable COVID-19 lung disease using lung tissues from end-stage lung transplant patients, as compared with discarded lung tissues from control donors. We also investigate the role of miRNAs in post transcriptional regulation of complement factors in COVID-19 pathogenesis. For C5ar1 signaling-mediated transcriptional regulation in autoimmune-associated cardiopulmonary fibrosis, we employ mouse model of collagen-induced arthritis (CIA). We study distinct 3’-UTR landscapes in proinflammatory genes resulting in transcript isoforms lacking regulatory miRNA binding sites during chronic inflammation. We are envisaging the role of C5ar1-dependent miRNA functions in the augmentation of fibrogenic development in these rheumatoid mouse lungs.



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Recent Publications.

  • Wang R, Lee JH, Kim J, Xiong F, Hasani LA, Shi Y, Simpson EN, Zhu X, Chen YT, Shivshankar P, Krakowiak J, Wang Y, Gilbert DM, Yuan X, Eltzschig HK, Li W. SARS-CoV-2 restructures host chromatin architecture. Nat Microbiol. 2023; 8(4):679-694.
  • Wilson C, Mertens TC, Shivshankar P, Bi W, Collum SD, Wareing N, Ko J, Weng T, Naikawadi RP, Wolters PJ, Maire P, Jyothula SS, Thandavarayan RA, Ren D, Elrod ND, Wagner EJ, Huang HJ, Dickey BF, Ford HL, Karmouty-Quintana H. Sine oculis homeobox homolog 1 plays a critical role in pulmonary fibrosis. JCI Insight. 2022; 7(10):e142984.
  • Jyothula SSK, Peters A, Liang Y, Bi W, Shivshankar P, Yau S, Garcha PS, Yuan X, Akkanti B, Collum S, Wareing N, Thandavarayan RA, Poli de Frias F, Rosas IO, Zhao B, Buja LM, Eltzschig HK, Huang HJ, Karmouty-Quintana H. Fulminant lung fibrosis in non-resolvable COVID-19 requiring transplantation. EBioMedicine. 2022; 86:104351.
  • Shivshankar P, Li Y-D, Mueller-Ortiz S, and Wetsel RA. In Response to Complement Anaphylatoxin Peptides C3a and C5a, Human Vascular Endothelial Cells Transmigrate and Mediate the Activation of B-cells and Polarization of T-cells. FASEB J. 2020. 34:7540–7560.
  • Mueller-Ortiz, S, Shivshankar P, and Wetsel RAThe second receptor for C5a, C5aR2, is detrimental to mice during systemic infection with Listeria monocytogenes. J. Immunol. 2019. 203(10):2701-2711.

Review articles

  • Shivshankar P, Karmouty-Quintana H, Mills T, Doursout MF, Wang Y, Czopik AK, Evans SE, Eltzschig HK, Yuan X. SARS-CoV-2 Infection: Host Response, Immunity, and Therapeutic Targets.Inflammation. 2022; 45(4):1430-1449.
  • Shivshankar P, Fekry B, Eckel-Mahan K, Wetsel RA. Circadian Clock and Complement Immune System- Complementary Control of Physiology and Pathology? Cell. Infect. Microbiol. Bacteria and Host. 2020; Open Access.