Amar Singh, PhD

Assistant Professor, Department of Surgery

Amar Singh

Contact Info

singh423@umn.edu

Administrative Assistant Name
Kelly Swenson

Administrative Phone
612-626-5697

Administrative Email
malon187@umn.edu

Assistant Professor, Department of Surgery


PhD, Immunology - All India Institute of Medical Sciences (AIIMS), New Delhi, India

M.S., Biotechnology - Jawaharlal Nehru University, New Delhi, India

Summary

T cell and B cell Immunity, Immunological Tolerance, Non-Human Primates Immunology

My work primarily focused on understanding the development of the xeno/allo immune response. My main goal is to understand the role of regulatory T and B cells in islets xenoimmunity and to identify the mechanisms critical to the induction of donor-specific regulation of xenoimmunity by Tr1 cells in concert with regulatory cells of myeloid and lymphoid origin. Our recent work published in Nature Communication described, a novel tolerance protocol using a nonhuman primate animal model for optimal clinical translatability. We have considerably extended field knowledge by demonstrating lasting tolerance to islet allografts in monkeys undergoing immunosuppression and determining that the reduction in donor-specific T and B cell clones along with strong, unremitting regulation contributed to this tolerance. Based on the early and late immunological profiles obtained from this ongoing work, our approach is highly promising as a guide for designing improved human tolerance protocols and ultimately curing type-I diabetes. We are firmly convinced that to better understand the immune tolerance mechanisms, it is essential that all immune system components are analyzed simultaneously and inter-relationships between these taken into account. This have recently been made possible by improved system level immune monitoring techniques with the development of novel high-dimensional methods operating at single-cell resolution, such as Mass cytometry (CyTOF: Cytometry by Time-Of-Flight, epiTOF), Imaging Mass Cytometry (IMC) and scRNA-seq. A recent new direction of my work is the analysis of donor reactive lymphocytes turnover using novel TCR tracking approach to understand the interplay of tolerance and cellular islet xenograft rejection. Using these cutting edge technologies, I am studying the immune phenotype of induction, maintenance and loss of tolerance.

Research

Research Summary/Interests

Immunobiology of Tolerance

Publications

  1. Singh A, Ramachandran, S, Graham ML, Daneshmandi S, Heller D, Suarez-Pinzon WL, Balamurugan AN, Ansite JD, Wilhelm J, Yang A, Zhang Y, Palani N, Abrahante JE, Burlak CJ, Miller SD, Luo X, Hering BJ. Apoptotic donor leukocytes induce stable tolerance to islet allografts in short-term immunosuppressed nonhuman primates. Nat Commun. 2019; 2;10(1):3495. doi: 10.1038/s41467-019-11338-y. PMID: 31375697
  2. Safley SA, Graham ML, Weegman BP, Einstein SA, Jody J. Mutch JA, Singh A, Ramachandran S, Garwood M, Sambanis A, Papas KK, Hering BJ and Weber CJ. Noninvasive Fluorine-19 Measurement of Dissolved Oxygen Levels in Acellular Perfluorochemical-Loaded Alginate Microcapsules Implanted in the Peritoneal Cavity of Nonhuman Primates. Transplantation 2019. (doi: 0.1097/TP.0000000000002896). PMID: 31385927
  3. Singh A, Prasad S. The Immune Checkpoint Protein Programmed Death 1 During HIV Infection in Children: Clinical Relevance and Beyond. The Journal of Infectious Diseases, 2019. https://doi.org/10.1093/infdis/jiy669 (An Editorial)
  4. Prasad S, Hu S, Sheng WS, Chaudhury P, Singh A, Lokensgard JR. The PD-1: PD-L1 pathway promotes development of brain-resident memory T-cells following acute viral encephalitis J Neuroinflammation. 2017; 14: 82.
  5. Singh A, Dey AB, Mohan A and Mitra DK. PD-1+ T Cells Inhibit Effector T Cells at the Pathologic Site of Miliary Tuberculosis. Clin Exp Immunol. 2016. 187 (2), 269-283.
  6. Kang HK, Wang S, Dangi A, Zhang X, Singh A, Lei Z, Rosati J, Wilma LSP, Deng S, Chen X, Thorp, Edward B, Hering, BJ, Miller SD and Luo X. Differential role of B cells and IL-17 versus IFN-? during early and late rejection of pig islet xenografts in mice. Transplantation. 2017;101(8):1801-1810
  7. Prasad S, Hu S, Sheng WS, Singh A, Lokensgard JR. Tregs Modulate Lymphocyte Proliferation, Activation, and Resident-Memory T-Cell Accumulation within the Brain during MCMV Infection. PLoS ONE 2015; 10(12): e0145457.
  8. Saurabh A, Thakral D, Mourya MK, Singh A, Mohan A, Bhatnagar AK, Mitra DK, Kanga U. Differential expression of HLA-G and ILT-2 receptor in human Tuberculosis: Localized versus Disseminated disease. Hum Immunol. 2016;77(9):746-53.
  9. Singh A, Mitra DK, Mohan A and Dey AB. Reply to Stephen-Victor et al. J Infect Dis. 2014 doi: 10.1093/infdis/jiu533.
  10. Singh A, Dey AB, Mohan A and Mitra DK. Programmed Death-1 receptor selectively suppress ?-IFN producing NKT cells in human tuberculosis. Tuberculosis 2014;94: 197-206.
  11. Singh A, Dey AB, Mohan A and Mitra DK. Inhibiting PD-1 pathway rescues M. tuberculosis specific IFN-? producing T cells from apoptosis among pulmonary tuberculosis patients. J. of Infectious Dis., 2013;208: 603–15, DOI:10.1093/infdis/jit206. (PMID:23661793)
  12. Singh A, Dey A B, Mohan A, Sharma PK and Mitra DK. Foxp3+ regulatory T cells among tuberculosis patients: Impact on prognosis and restoration of antigen specific IFN-? producing T cells. PLoS ONE. 2012;7 (9): e44728.
  13. Rai AK, Chadeshwar CP, Singh A, Seth T, Srivastava SK, Singh P, Mitra DK. Regulatory T Cells Suppress T Cell Activation at the Pathologic Site of Human Visceral Leishmaniasis. PLoS ONE 2012;7(2): e31551.
  14. Sharma P, Dube D, Singh A, Mishra B, Singh N, Sinha M, Dey S, Kaur P, Mitra DK, Sharma S, Singh TP. Structural basis of recognition of pathogen-associated molecular patterns and inhibition of pro-inflammatory cytokines by camel peptidoglycan recognition protein. Journal of Biological Chemistry 2011; 286(18): 16208-16217.
  15. Sharma PK, Saha PK, Singh A, Sharma SK, Ghosh B, Mitra DK. FoxP3+ regulatory T cells suppress effector T cell function at pathologic site in miliary tuberculosis. Am J Respir Crit Care Med. 2009;179:1061-1077.