Profile
The primary focus of our translational research program is to develop safe and practical immunomodulatory approaches with applications to transplantation, autoimmunity, and cancer immunoprevention and immunotherapy. To achieve this goal, we pioneered a proprietary platform technology, ProtEx™, that allows for the generation of novel recombinant immune ligands and their positional and transient 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 in sustaining the survival of beta cells producing insulin in rodents and nonhuman primates as a treatment for type 1 diabetes. This protocol is presently being developed for clinical translation to treat type 1 diabetes. 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 showed prophylactic efficacy against various tumor types in preclinical models, a first-of-its-kind finding with significant translational potential for cancer and infectious diseases. Our research resulted in the creation of intellectual property, including 25 issued and 8 pending patents, and led to the establishment of licensing agreements with two biotech startups: FasCure Therapeutics and iToelrance, Inc.
Academic Information
Office
1030 Hitt Street, Ste 2004
NextGen Precision Health Bldg
Columbia, MO 65211
United States
Research Interests
- Autoimmunity
- Cancer Immunoprevention/Immunotherapy
- Transplantation
- Vaccinology
Areas of Expertise
- Autoimmunity
- Alloimmunity
- Cancer immunoprevention/therapy
- Development of novel biologics
- Immune adjuvants
- Immunomodulation
- Targeted delivery of biologics
- Vaccines
Education & Training
MS, Molecular Biology/Biochemistry
University of California, Santa Barbara, CA
PhD, Molecular Biology/Biochemistry
University of California, Santa Barbara, CA
Postdoctoral Training
California Institute of Technology, Pasadena, CA
Awards & Honors
- Member, National Academy of Inventors
- Marvin Hall, MD Faculty Scholar in Diabetes
- Outstanding Achievement Award in Transplantation Sciences from The Transplantation Society
- Business First, Partners in Health Care Award
- MediStar 2011 the Crowe Horwath Innovation Award
- American Society of Transplant Physicians-Ortho Award
Issued Patents (out of 29)
- Shirwan, H., A.J. Garcia, E.S. Yolcu, H. Zhao, D. Headen. FasL-engineered biomaterials with immunomodulatory function. US patent 11,602,547, 04/14/2023
- Shirwan, H., Immunomodulation for the long-term prevention and treatment of autoimmune disease and foreign tissue rejection. EU patent EP3313429 B1, 05/10/2021
- Shirwan, H., Alteration of cell membrane for new functions. 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 with FasL. US patent 8,076,096, 12/13/2011
- 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
In the News
Publications
Selected peer-reviewed publications (out of 140)
- Turan, A, M Tarique, L Zhang, S Kazmi, MG Tedla, D Badal, ES Yolcu*, H Shirwan*. Engineering pancreatic islets to transiently co-display on their surface thrombomodulin and CD47 immunomodulatory proteins as a means of mitigating instant blood-mediated inflammatory reaction following intraportal transplantation. J Immunol. 2024 Jun 15;212(12):1971-1980. doi: 10.4049/jimmunol.2300743.PMID:38709159
- Gulen AE, Rudraboina R, Tarique M, Ulker V, Shirwan H*, Yolcu ES*. A novel agonist of 4-1BB costimulatory receptor shows therapeutic efficacy against a tobacco carcinogen-induced lung cancer. Cancer Immunol Immunother. 2023 Nov;72(11):3567-3579. doi: 10.1007/s00262-023-03507-2. PMID: 37605009 *Sharing senior authorship.
- Turan, A, L Zhang, M Tarique, V Ulker, FN Arguc, D Badal, ES Yolcu*, H Shirwan*, Engineering pancreatic islets with a novel form of thrombomodulin protein to overcome early graft loss triggered by instant blood-mediated inflammatory reaction. Am J Transplant, 2023 Mar 1;. doi: 10.1016/j.ajt.2023.02.021. 2023 *Sharing senior authorship.
- Shrestha, P, A Turan, L Batra, AE Gulen, Z Sun, H Tan, N Askenasy, H Shirwan*, ES Yolcu*.
Engineering donor lymphocytes with Fas ligand protein effectively prevents acute graft-versus-host disease. Blood Advances. 2023 Feb 13. doi: 10.1182. Online ahead of print. *Sharing senior authorship. Media coverage - Deng H, Zhang A, Pang DRR, Xi Y, Yang Z, Matheson R, Li G, Luo H, Lee KM, Fu Q, Zou Z, Chen T, Wang Z, Rosales IA, Peters CW, Yang J, Coronel MM, Yolcu ES, Shirwan H, García AJ, Markmann JF, Lei J. Bioengineered omental transplant site promotes pancreatic islet allografts survival in non-human primates. Cell Rep Med. 2023 Mar 21;4(3):100959. doi: 10.1016/j.xcrm.2023.100959. PMID: 36863336 https://pubmed.ncbi.nlm.nih.gov/36863336/
- 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.
- 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