Haval Shirwan, Ph.D.

Education:Haval Shirwan, Ph.D.

Ph.D., Molecular Biology-Biochemistry, University of California, Santa Barbara, CA; 1987
Research Fellow, California Institute of Technology, Pasadena, CA; 1989
Senior Research Fellow, California Institute of Technology, Pasadena, CA; 1990

Curriculum Vitae

Current Positions:

Dr. Michael and Joan Hamilton Endowed Chair in Autoimmune Disease, School of Medicine
Professor, Department of Microbiology and Immunology
Member, Immuno-Oncology Program, James Graham Brown Cancer Center
Director, Molecular Immunomodulation Program, Institute for Cellular Therapeutics, University of Louisville, Louisville, KY

Contact Information:

Institute for Cellular Therapeutics
Donald Baxter Biomedical Research Bldg., Suite 404
University of Louisville
570 South Preston Street
Louisville, KY 40202-1760
Phone: (502) 852-2066   
Fax: (502) 852-2085        

E-mail:haval.shirwan@louisville.edu

Research Description:

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 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 immunoprevention and therapy using rodent and humanized mouse models.

Representative Publications:

  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, Shirwan H.  Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance.  Nature Materials 2018 Aug;17(8):732-9. doi: 10.1038/s41563-018-0099-0.  https://www.ncbi.nlm.nih.gov/pubmed/29867165
  2. Bowen WS, Svrivastava AK, Batra L, Barsoumian H, Shirwan H.  Current challenges for cancer vaccine adjuvant development.  Expert Review of Vaccines 2018 Mar;17(3):207-15.  https://www.ncbi.nlm.nih.gov/pubmed/29372660  PMCID: PMC6093214.
  3. Srivastava AK, 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 Research 2014 Nov 15;74(22):6441-51.  https://www.ncbi.nlm.nih.gov/pubmed/25252915  PMCID: PMC4233189.
  4. Shirwan H, Sharma RK, Srivastava AK, Yolcu ES.  Costimulatory tumor necrosis factor ligands as adjuvant for the development of subunit-based anticancer vaccines.  OncoImmunology 2(4):e23440, 2013.  https://www.ncbi.nlm.nih.gov/pubmed/23734306  PMCID: PMC3654578.
  5. Sharma RK, Schabowsky R-H, Srivastava A, Elpek KG, Madireddi S, Zhao H, Zhong Z, Miller RW, MacLeod KJ, Yolcu ES, Shirwan H.  4-1BB ligand as an effective multifunctional immunomodulator and antigen delivery vehicle for the development of therapeutic cancer vaccines.  Cancer Research 2010 May 15;70(10):3945-54.   https://www.ncbi.nlm.nih.gov/pubmed/20406989  PMCID: PMC2872138.
  6. Sharma RK, Yolcu ES, Elpek KG, Shirwan H.  Tumor cells engineered to codisplay on their surface 4-1BBL and LIGHT costimulatory proteins as a novel vaccine approach for cancer immunotherapy.  Cancer Gene Therapy 2010 Oct;17(10):730-4. https://www.ncbi.nlm.nih.gov/pubmed/20559332  PMCID: PMC2941532.
  7. Sharma RK, Elpek KG, Yolcu ES, Schabowsky R-H, Zhao H, Bandura-Morgan L, Shirwan H. Costimulation as a platform for the development of vaccines: a peptide-based vaccine containing a novel from of 4-1BBL eradicates established tumors.  Cancer Research 2009 (May 15);69(10):4319-26, 2009. https://www.ncbi.nlm.nih.gov/pubmed/19435920  PMCID: PMC2755220.
  8. Yolcu ES, 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 

PubMed information