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Avneesh Kumar Singh, PhD

Academic Title:

Associate Professor

Primary Appointment:

Surgery

Location:

MSTF,Rm 434C, 10 S Pine Street

Phone (Primary):

410-706-0320

Fax:

410-706-0321

Education and Training

B.Sc. (Hons.), Zoology, AMU, Aligarh, UP, 202001, INDIA

M.Sc., Zoology, AMU, Aligarh, UP, 202001, INDIA

Ph.D., Zoology (Immunogenetics); SGPGIMS, (LU), Lucknow, UP, INDIA

 

Postdoctoral Training

Dept. of Microbiology & Immunology, Vanderbilt University, Nashville, TN, USA
(Mentor or PI: Dr. Luc Van Kaer, PI, Howard Hughes Medical Institute)

 

PROFESSIONAL EXPERIENCE

2005-2006 Research Scientist [C], Transplantation Biology Branch, NIDDK/NIH Bethesda, MD @ Kelly Services at NIH

2006-2006 Scientist, Central Drug Research Institute, Lucknow, UP, India

2006- 2017 Scientist, Suburban Hospital, Johns Hopkins Medicine, Bethesda, MD

2007- 2017 Co-Investigator in Cardiothoracic Surgery Research Program, NHLBI/NIH, Bethesda, MD

2016-2017 Assistant Professor (PT) Department of Surgery, Johns Hopkins Medicine, Baltimore, MD

Biosketch

Received Dr. K.S. Krishnan Research (DAE) Fellowship from Govt. of India to pursue a doctorate degree in life science and investigated the effect of non-immunological and immunological factors (e.g. HLA, alloantibodies, MLR-Bf, etc.) on kidney allograft rejection and survival.

Postdoctoral Training was done at Vanderbilt University, Nashville, TN,  investigated the role of natural killer T (NK T) cells in autoimmune disease and received Sidney Colowick Award for outstanding postdoctoral research 

Later moved to Cardiothoracic Surgery Research Program, NIH heart center at Suburban hospital, sponsored by NHLBI/NIH, Bethesda as Research Scientist to do research on the pig to baboon preclinical cardiac xenotransplantation model.

The focus of my research is to identify an ideal donor from a genetically modified pig and optimize the immunosuppression for cardiac xenotransplantation to benefit heart failure patients for their better life.

Contributions to Science

  • Demonstrated successful transplantation of the first FDA-approved genetically engineered pig heart into a human.
  • Demonstrated the longest survival of genetically engineered pig hearts in non-human primates.
  • Successfully purified and  expanded baboon naturally occurring CD4+CD25+ Treg cells using irradiated pig PBMC and IL-2, and have demonstrated suppression of autologous effector CD4+CD25neg T-cell and B cells proliferation
  • Demonstrated immunoregulatory role of natural killer T (NKT) cells in autoimmune diseases
  • Reported that the activation of NKT cells by its ligand (i.e. α -galactosylceramide (α-GalCer), isolated from marine sponges) prevents experimental autoimmune encephalomyelitis (EAE), an experimental model of human multiple sclerosis and murine systemic lupus Erythematosus (SLE) autoimmune disease induced by pristine
  • Analyzed the early response of NKT cells to glycolipid antigens and bacterial infection by using specific reagents for tracking these cells

Highlighted Publications

Singh AK, Griffith BP, Goerlich CE, Mohiuddin MM; The Road to the First FDA-Approved Genetically Engineered Pig Heart Transplantation into Human; Xenotransplantation; 2022 Sep;29(5):e12776.; DOI0.1111/xen.12776. Epub 2022 Sep 20.

Griffith BP, Goerlich CE, Singh AK, et al.; Genetically Modified Porcine-to-Human Cardiac Xenotransplantation. N Engl J Med. 2022 Jul 7;387(1):35-44. DOI: 10.1056/NEJMoa2201422. Epub 2022 Jun 22.

Singh AK, Goerlich CE, Shah AM, et al.; “Cardiac Xenotransplantation: Progress in Preclinical Models and Prospects for Clinical Translation” Transpl Int. 2022 Mar 23;35:10171. https://doi.org/10.3389/ti.2022.10171

Mohiuddin MM, Goerlich CE*, Singh AK*, Zhang T, Tatarov I, Lewis B, Sentz F, Hershfield A, Braileanu G, Odonkor P, Strauss E, Williams B, Burke A, Hittman J, Bhutta A, Tabatabai A, Gupta A, Vaught T, Sorrells L, Kuravi K, Dandro A, Eyestone W, Kaczorowski DJ, Ayres D, Griffith BP: “Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months” 2022 Mar 31:e12744. https://doi.org/10.1111/xen.12744 * Contributed equally

Singh AK, Corcoran PC, Lewis BG, et al.; Cardiac xenotransplantation: CD4+CD25HiFoxP3+ T regulatory cells in long-term cardiac xenograft survivors; Xenotransplantation. 2017; Accepted

Mohiuddin MM, Singh AK, Corcoran PC, et al.; Chimeric 2C10R4 anti-CD40 antibody therapy is critical for the long-term survival of GTKO.hCD46.hTBM cardiac xenograft; Nature Communications; 2016 Apr 5;7:11138. DOI: 10.1038/ncomms11138: PMID:27045379

Mohiuddin MM, Singh AK, Corcoran PC, et al.; One-year heterotopic cardiac xenograft survival in a pig to baboon model; American J Transplant. 2014 Feb; 14(2): 488-9.DOI: 10.1111/ajt.12562. Epub 2013 Dec 11; PMID: 24330419

Singh AK, Seavey C, Horvath KA, and Mohiuddin MM: Ex−Vivo Expanded CD4+CD25+Treg Cells Suppress T and B Immune Response; Xenotransplantation; 2012 Mar; 19(2): 102-11; PMID 22497512

Parekh, VV, Wilson MT, Olivares-Villagómez D, Singh AK, et al.; Glycolipid antigen induces long-term NKT cell anergy in mice. Journal of Clinical Investigation 2005 Sep; 115(9): 2572

Singh AK, Wilson MT, Hong S, Olivares-Villagómez, et al.; Natural Killer T Cell Activation Protects Mice against Experimental Autoimmune Encephalomyelitis; J EXP MED 194 (12): 1801-1811 DEC 17 2001

Additional Publication Citations

  • Goerlich CE, Singh AK, Mohiuddin MM. The Immunobiology and Clinical Translation of Genetically Engineered Porcine Hearts for Human Transplantation. Nature Cardiovascular Research volume 1, pages715–726 (2022); https://doi.org/10.1038/s44161-022-00112-x
  • Mohiuddin MM, Singh AK Goerlich CE, . Preclinical rationale and current pathways to support the first human clinical trials in cardiac xenotransplantation. Hum Immunol. 2022 Jul 15; S0198-8859(22)00136-7. DOI: 10.1016/j.humimm.2022.07.001
  • Mohiuddin MM, Goerlich CE, Singh AK, et al., Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months. Xenotransplantation, 2022: p. e12744
  • Griffith BP, Goerlich CE, Singh AK, et al., Genetically Modified Porcine-to-Human Cardiac Xenotransplantation. N Engl J Med, 2022.
  • Goerlich CE, Griffith B, Singh AK, et al., Blood Cardioplegia Induction, Perfusion Storage and Graft Dysfunction in Cardiac Xenotransplantation. Front Immunol, 2021. 12: p. 667093.
  • Goerlich C.E., G.B., Hanna P., Hong S.N., Ayares D., Singh A.K., Mohiuddin M.M., The Growth of Xenotransplanted Hearts Can Be Reduced with Growth Hormone Receptor Knockout Pig Donors. Journal of Thoracic and Cardiovascular Surgery, 2021.
  • Singh, A.K., et al., Cardiac xenografts show reduced survival in the absence of transgenic human thrombomodulin expression in donor pigs. Xenotransplantation, 2019. 26(2): p. e12465
  • Mohiuddin MM, DiChiacchio L, Singh AK, Griffith BP., Xenotransplantation: A Step Closer to Clinical Reality? Transplantation, 2019. 103(3): p. 453-454.
  • DiChiacchio L, Singh AK, Lewis B, et al., Early Experience With Preclinical Perioperative Cardiac Xenograft Dysfunction in a Single Program. Ann Thorac Surg, 2019.
  • DiChiacchio L, Singh AK, Chan JL, et all., Intra-Abdominal Heterotopic Cardiac Xenotransplantation: Pearls and Pitfalls. Front Cardiovasc Med, 2019. 6: p. 95.
  • Cooper, Wijkstrom, Hariharan et al. 2017 Transplantation 101, 1551-1558,
  • Mohiuddin, Singh, Corcoran et al. 2016 Nat Commun 7, 11138,
  • Azimzadeh, Kelishadi, Ezzelarab et al. 2015 Xenotransplantation 22, 310-316,
  • Zhou, Singh, Hoyt, et al. 2014 J Thorac Cardiovasc Surg 148, 1131-1137; discussion 1117,
  • Wang, Zhou, Andreyev Singh, et al. 2014 Exp Cell Res 323, 56-65,
  • Mohiuddin, Singh, Corcoran, et al. 2014 Am J Transplant 14, 488-489,
  • Mohiuddin, Singh, Corcoran, et al. 2014 Xenotransplantation 21, 35-45,
  • Mohiuddin, Singh, Corcoran et al. 2014 J Thorac Cardiovasc Surg 148, 1106-1113; discussion 1113-1104,
  • Singh, Seavey, Horvath, et al. 2012 Xenotransplantation 19, 102-111,
  • Mohiuddin, Corcoran, Singh, et al. 2012 Am J Transplant 12, 763-771,
  • Wang, Zhou, Seavey Singh, et al. 2010 Stem Cell Res 4, 117-128,
  • Horvath, Corcoran, Singh, et al. 2010 Transplant Proc 42, 2152-2155,
  • Corcoran, Horvath, Singh, et al. 2010 Transplant Proc 42, 2149-2151,
  • Singh, Horvath and Mohiuddin 2009 Transplant Proc 41, 418-421,
  • Porter, Horvath-Arcidiacono, Singh et al. 2007 Xenotransplantation 14, 298-308,
  • Singh, Yang, Parekh, et al. 2005 Eur J Immunol 35, 1143-1154,
  • Parekh, Wilson, Olivares-Villagomez, Singh et al. 2005 J Clin Invest 115, 2572-2583,
  • Parekh, Singh, Wilson, et al. 2004 J Immunol 173, 3693-3706,
  • Yang, Singh, Wilson, et al. 2003 J Immunol 171, 2142-2153,
  • Wilson, Johansson, Olivares-Villagomez, Singh  et al. 2003 Proc Natl Acad Sci U S A 100, 10913-10918,
  • Wilson, Singh and Van Kaer 2002 Trends Mol Med 8, 225-231,
  • Singh, Wilson, Hong, et al. 2001 J Exp Med 194, 1801-1811

Published abstracts:

  • Chan, Singh, Thomas, et al. 2016 Journal of Heart and Lung Transplantation 35, S47-S48,
  • Chan, Singh, Thomas, et al. 2016 Circulation 134,
  • Mohiuddin, Singh, Corcoran, et al. 2014 American Journal of Transplantation 14, 488-489,
  • Singh, Seavey, Horvath, et al. 2012 Xenotransplantation 19, 102-111,
  • Singh, Seavey, Corcoran, et al. 2012 Transplantation 94, 68-68,
  • Mohiuddin, Singh, Corcoran, et al. 2012 American Journal of Transplantation 12, 530-531,
  • Mohiuddin, Singh, Corcoran, et al. 2012 Transplantation 94, 70-70,
  • Singh, Seavey, Horvath, et al. 2010 American Journal of Transplantation 10, 21-21,
  • Singh, Seavey, Horvath, et al. 2010 American Journal of Transplantation 10, 298-298,
  • Mohiuddin, Corcoran, Singh, et al. 2010 American Journal of Transplantation 10, 186-186,
  • Horvath, Corcoran, Singh, et al. 2010 American Journal of Transplantation 10, 299-299,
  • Corcoran, Horvath, Singh, et al. 2010 American Journal of Transplantation 10, 300-300,
  • Mohiuddin, Singh, Seavey, et al. 2009 Xenotransplantation 16, 362-363,
  • Mohiuddin, Singh, Corcoran, et al. 2009 Xenotransplantation 16, 357-357,
  • Horvath, Corcoran, Singh, et al. 2009 Xenotransplantation 16, 380-380,
  • Corcoran, Horvath, Singh, et al. 2009 Xenotransplantation 16, 429-429,
  • Azimzadeh, Kelishadi, Ezzelarab et al. 2009 Xenotransplantation 16, 356-356,
  • Singh, Horvath and Mohiuddin 2008 American Journal of Transplantation 8, 562-562,
  • Wilson, Johansson, Olivares-Villagomez et al. 2003 Faseb Journal 17, C82-C83,
  • Singh, Singh, Wang, et al. 2003 Journal of the American Society of Nephrology 14, 383a-383a,
  • Singh, Yang, Wilson, et al. 2003 Faseb Journal 17, C279-C279,
  • Yang, Singh, Hong et al. 2002 Faseb Journal 16, A326-A326,
  • Singh, Wilson, Hong et al. 2002 Faseb Journal 16, A1043-A104,
  • Singh, Hong, Du et al. 2001 Faseb Journal 15, A1212-A1212 

 

Research Interests

Xenotransplantation,  Immunosuppression, Immune response, Cellular, and antibody-mediated rejection, Immune Tolerance

Awards and Affiliations

  • Young Investigator Travel Grant for attending International Xenotransplantation Meeting in Osaka, Japan (2013)
  • The Sidney P. Colowick Award for outstanding postdoctoral research achievements from Vanderbilt University, Nashville, Tennessee (2002)
  • Dr. K. S. Krishnan Research (DAE) Fellowship for pursuing Ph.D. in life sciences (1993)
  • National Merit Scholarship in High School (1985)