The primary focus of our translational research program is to develop safe and practical immunomodulatory approaches with applications to transplantation, autoimmunity, and cancer. To achieve this goal, we pioneered a proprietary platform technology, ProtEx™, that allows for the generation of novel recombinant immune ligands and their positional display as single agents or in combination on biological and nonbiologic surfaces for localized immunomodulation. We are also assessing various vehicles, including live bacterial vectors and nanoparticles, for targeted delivery of these biologics in vivo to modulate immune effector and regulatory responses for therapeutic purposes. A proprietary lead biologic delivered using hydrogels has shown efficacy for the treatment of diabetes in rodents and nonhuman primates and presently being developed for clinical translation. In parallel, candidate immunostimulatory molecules are also being developed for cancer immunoprevention and immunotherapy using rodent and humanized mouse models. A lead candidate in this category was recently shown to train the immune system for long-term protection against various cancer types, the first report of an unusual finding with significant translational potential for cancer as well as infectious diseases.
1030 Hitt Street, Ste 2004
NextGen Precision Health Bldg
Columbia, MO 65211
- Cancer Immunoprevention/Immunotherapy
Areas of Expertise
- Development of novel biologics
- Immune adjuvants
- Immune checkpoints
- Targeted delivery of biologics
- Type 1 diabetes
Education & Training
MS, Molecular Biology/Biochemistry
University of California, Santa Barbara, CA
PhD, Molecular Biology/Biochemistry
University of California, Santa Barbara, CA
California Institute of Technology, Pasadena, CA
Awards & Honors
- Shirwan, H., Alteration of cell membrane for new functions. US patent US patent 8,728,747, 05/20/2014
- Shirwan, H., Methods of immune modulation with death receptor-induced apoptosis. US patent 8,551,494, 10/08/2013
- Shirwan, H., Alteration of cell membrane for new functions. CA patent 2413237. 09/10/2013
- Shirwan, H., Immune modulation with death-receptor-induced apoptosis. Japanese patent JP 4898049. 01/06/2012
- Shirwan, H., Alteration of cell membrane with FasL. US patent 8,076,096, 12/13/2011
- Shirwan, H., Alteration of cell membrane for new functions. EU patent 1299522. 11/02/2011
- Shirwan, H., K.G. Elpek, and E.S. Yolcu., Immunostimulatory compositions and methods. US patent 8,017,582. 09/13/2011
- Shirwan, H., Fas ligand-avidin/streptavidin fusion proteins US Patent 7,927,602. 08/19/2011
- Shirwan, H., Immune modulation with death-receptor-induced apoptosis. EU Patent 1250055. 09/15/2010
- Shirwan, H., Methods and Compositions for Expanding T Regulatory Cells. US Patent 7,745,215. 06/29/2010
- Shirwan, H., K.G. Elpek, and E.S. Yolcu., Immunostimulatory compositions and methods. US Patent 7,598,345. 10/06/2009
- Shirwan, H., Alteration of Cell Membrane with B7. US Patent 7,238,360. 06/03/2
In the News
Selected peer-reviewed publications (out of 127)
- 1. Lei J*+, Coronel MM +, Yolcu ES+, Deng H, Grimany-Nuno O, Hunckler MD, Ulker V, Yang Z, Lee KM, Zhang A, Luo H, Peters CW, Zou Z, Chen T, Wang Z, McCoy C, Rosales IA, Markmann J*, Shirwan H*, García AJ*.
FasL-microgels induce immune acceptance of islet allografts in nonhuman primates. Sci Adv. 2022 May 13;8(19):eabm9881. doi: 10.1126/sciadv.abm9881. +Equal contribution; *Sharing senior authorship.
Pick of the week by Nature Reviews Bioengineering. Media coverage: https://www.genengnews.com/metabolic-disorders/diabetes/bbiomaterial-prevents-rejection-of-islet-grafts-for-diabetes-therapy/
- Coronel, MM, KE Martin, MD Hunckler, G Barber, EB. O’Neill, JD Medina, E Opri, CA McClain, L Batra, JD Weaver, HS Lim, P Qiu, EA Botchwey, ES Yolcu, H Shirwan*, AJ García*. Immunotherapy via PD-L1-presenting biomaterials leads to long-term islet graft survival. Science Advances. 6(35): eaba5573, 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455180/ *Sharing senior authorship. Media coverage: https://www.sciencedaily.com/releases/2020/08/200831112336.htm
- Shrestha P, Batra L, Tariq Malik M, Tan M, Yolcu ES*, Shirwan H*. Immune checkpoint CD47 molecule engineered islets mitigate instant blood-mediated inflammatory reaction and show improved engraftment following intraportal transplantation. Am J Transplant.20(10):2703-2714, 2020. https://pubmed.ncbi.nlm.nih.gov/32342638/. *Sharing senior authorship.
- Batra L, Shrestha P, Zhao H, Woodward KB, Togay A, Tan M, Grimany-Nuno O, Malik MT, Coronel MM. Garcia AJ, Shirwan H*, Yolcu ES*. Localized immunomodulation with PD-L1 results in sustained survival and function of allogeneic islets without chronic immunosuppression. J Immunol, 204(10):2840-2851, 2020. *Sharing senior authorship.
- Woodward KB, Zhao H, Shrestha P, Batra L, Tan M, Grimany-Nuno O, Bandura-Morgan L, Askenasy N, Shirwan H*, Yolcu ES*. Pancreatic islets engineered with a FasL protein induce systemic tolerance at the induction phase that evolves into long-term graft-localized immune privilege. Am J Transplant. 20(5):1285-1295, 2020. https://www.ncbi.nlm.nih.gov/pubmed/31850658 *Sharing senior authorship.
- 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.
- 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. 192:271-281, 2019. https://www.ncbi.nlm.nih.gov/pubmed/30458362
- 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, 17(8):732739. https://www.ncbi.nlm.nih.gov/pubmed/29867165 Media coverage: https://www.sciencedaily.com/releases/2018/06/180605103500.htm