Haval Shirwan, Ph.D.

Haval Shirwan, Ph.D.

Research Interests:
The primary focus of our translational research program is to develop safe and practical immunomodulatory approaches with application to transplantation, autoimmunity, and cancer immunotherapy. To achieve this goal, we pioneered a platform technology, ProtEx™, that allows for: i) the generation of novel recombinant immunological ligands with robust immune stimulatory or suppressive functions; and ii) their positional display, as individual molecules or in combinations, on biological and non-biological surfaces for localized immunomodulation. We are also assessing various vehicles, including biomaterial, for targeted delivery of these immunomodulatory molecules in vivo for modulation of immune effector (innate and adaptive) and regulatory cells to achieve therapeutic outcomes. Ongoing studies demonstrated the efficacy of two lead therapeutic candidates in inducing tolerance to allografts in rodent models and are presently being assessed for tolerogenic efficacy in humanized mouse and nonhuman primate models.  This lead immunomodulatory protocol is also being tested in autoimmune models of type 1 diabetes and multiple sclerosis. In parallel, candidate immunostimulatory molecules are also being developed for cancer immunotherapy using rodent and humanized mouse models.

Selected peer-reviewed publications (out of 109)

  1. Headen DM, Woodward KB, Coronel MM, Shrestha P, Weaver JD, Zhao H, Tan M, Hunckler MD, Bowen WS, Johnson CT, Shea L, Yolcu E, García AJ, and Shirwan H. Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance. Nat Mater. 2018 Jun 4. doi: 10.1038/s41563-018-0099-0. https://www.ncbi.nlm.nih.gov/pubmed/?term=shirwan
  2. Bowen WS, Svrivastava AK, Batra L, Barsoumian H, Shirwan H. Current challenges for cancer vaccine adjuvant development. Expert Rev Vaccines. 2018 Mar;17(3):207-215.  https://www.ncbi.nlm.nih.gov/pubmed/29372660
  3. Srivastava A.K., Dinc G, Sharma RK, Yolcu ES, Zhao H, Shirwan H.,SA-4-1BBL and monophosphoryl lipid A constitute an efficacious combination adjuvant for cancer vaccines. Cancer Res. 2014 Nov 15;74(22):6441-51 https://www.ncbi.nlm.nih.gov/pubmed/25252915
  4. Yolcu, E.S. H. Zhao, C. Lacelle, L. Bandura-Morgan, N. Askenasy, and H. ShirwanPancreatic islets engineered with SA-FasL protein establish robust localized tolerance by inducing T regulatory cells in mice. J. Immunol. 187:5901-9, 2011. http://www.ncbi.nlm.nih.gov/pubmed/22068235
  5. Yolcu E.S., Askenasy N, Singh NP, Cherradi SE, Shirwan H. Cell membrane modification for rapid display of proteins as a novel means of immunomodulation: FasL-decorated cells prevent islet graft rejection.  Immunity. 2002 Dec;17(6):795-808 https://www.ncbi.nlm.nih.gov/pubmed/12479825

Click the link below for a complete list of Shirwan’s publications: https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/43609723/?sort=date&direction=ascending

Issued Patents (out of 19)
  1. Shirwan, H., Alteration of cell membrane for new functions. US patent US patent 8,728,747, 05/20/2014
  2. Shirwan, H., Methods of immune modulation with death receptor-induced apoptosis. US patent 8,551,494, 10/08/2013
  3. Shirwan, H., Alteration of cell membrane for new functions. CA patent 2413237. 09/10/2013
  4. Shirwan, H., Immune modulation with death-receptor-induced apoptosis. Japanese patent JP 4898049. 01/06/2012
  5. Shirwan, H., Alteration of cell membrane with FasL. US patent 8,076,096, 12/13/2011
  6. Shirwan, H., Alteration of cell membrane for new functions. EU patent 1299522. 11/02/2011
  7. Shirwan, H., K.G. Elpek, and E.S. Yolcu., Immunostimulatory compositions and methods. US patent 8,017,582. 09/13/2011
  8. Shirwan, H., Fas ligand-avidin/streptavidin fusion proteins US Patent 7,927,602. 08/19/2011
  9. Shirwan, H., Immune modulation with death-receptor-induced apoptosis. EU Patent 1250055. 09/15/2010
  10. Shirwan, H., Methods and Compositions for Expanding T Regulatory Cells. US Patent 7,745,215.  06/29/2010
  11. Shirwan, H., K.G. Elpek, and E.S. Yolcu., Immunostimulatory compositions and methods. US Patent 7,598,345. 10/06/2009
  12. Shirwan, H., Alteration of Cell Membrane with B7. US Patent 7,238,360. 06/03/2007