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 immunoprevention and 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 and immunoprevention using rodent and humanized mouse models

Selected peer-reviewed publications (out of 118)

  1. Barsoumian HB, Batra L, Shrestha P, Bowen WS, Zhao H, Egilmez NK, Gomez-Gutierrez JG, Yolcu ES, Shirwan H. A novel form of 4-1BBL prevents cancer development via nonspecific activation of CD4+ T and Natural Killer cells. Cancer Res. 2019 Feb 15;79(4):783-794. https://www.ncbi.nlm.nih.gov/pubmed/30770367 Media coverage: https://www.eurekalert.org/pub_releases/2019-02/uol-ism021219.php.
  2. Skoumal M, Woodward KB, Zhao H, Wang F, Yolcu ES, Pearson RM, Hughes KR, García AJ, Shea LD, Shirwan H. Localized immune tolerance from FasL-functionalized PLG scaffolds. Biomaterials. 2019 Feb;192:271-281. https://www.ncbi.nlm.nih.gov/pubmed/30458362
  3. Headen DM, Woodward KB, Coronel1 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. Nature Materials, 2018 Aug;17(8):732-739. https://www.ncbi.nlm.nih.gov/pubmed/29867165 Media coverage: https://www.sciencedaily.com/releases/2018/06/180605103500.htm
  4. 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

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