Haval Shirwan, Ph.D.

Haval Shirwan, Ph.D.

Research Interests:

The primary focus of our translational research program in immunomodulation is to develop novel vaccines for the prevention and treatment of various immune based disorders ranging from infections, cancer, graft rejection, and autoimmunity.  To achieve this goal, we recently pioneered a patented platform technology designated as ProtEx™ that accomplishes two important goals.  First, it allows for the generation of recombinant novel immunological proteins by fusing the functional domain of any ligand of interest with a modified form of core streptavidin (SA).  The chimeric proteins exist as tetramers and higher structures, owing to the physical properties of SA, and as such have potent immune functions in soluble forms by crosslinking their respective receptors on the surface of immune cells for effective signal transduction.  These chimeric proteins, therefore, have great potential to serve as potent adjuvants for the development of subunit vaccines against cancer and infections.  Second, the chimeric proteins can transiently be displayed on the surface of any biological membrane modified with biotin taking advantage of the unsurpassed affinity of biotin for SA.  This protein display technology serves as a rapid, efficient, safe, and clinically applicable alternative to gene therapy for immunomodulation.  Using ProtEx™ technology, we generated a library of proprietary immunological ligands with distinct functions and have been testing these molecules either individually or in combination to develop “tolerogenic” vaccines for the treatment of graft rejection (including hematopoietic stem cells, pancreatic islets, and solid organs), autoimmunity (with particular focus on type 1 diabetes), and standard vaccines for the prevention and treatment of infections and cancer.

Selected peer-reviewed publications (out of 99)

  1. Sharma, RK, ES Yolcu, and H. Shirwan. SA-4-1BBL as a novel adjuvant for the development of therapeutic cancer vaccines. Expert Rev. Vaccines 13:387-398, 2014.
  2. Hakim F, Y Wang, SX Zhang, J Zheng, ES Yolcu, A Carreras, A Khalyfa, H Shirwan, I Almendros, and D Gozal. Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. Cancer Res, 2014.
  3. Yolcu, E.S. H. Zhao, K. Woodward, and H. Shirwan. Immunomodulation with SA-FasL protein as an effective means of preventing islet allograft rejection in chemically diabetic NOD mice. Transplant. Proc. 45:1889-9, 2013.
  4. Yolcu, E.S., A. Kaminitz, K. Mizrahi, S. Ash, I. Yaniv, J. Stein, H.Shirwan, N. Askenasy. Immunomodulation with donor regulatory T cells armed with Fas-ligand alleviates graft versus host disease. Exp Hematol. 10:903-11, 2013.
  5. Kaminitz, A, E.S. Yolcu, K. Mizrahi, H. Shirwan, N. Askenasy. Killer Treg cells ameliorate inflammatory insulitis in non-obese diabetic mice through local and systemic immunomodulation. Int Immunol. 25:485-94, 2013.
  6. Sharma, RK, ES Yolcu, AK Srivastava, and H. Shirwan.  CD4+ T cells play a critical role in the generation of primary and memory antitumor immune responses elicited by SA-4-1BBL and TAA-based vaccines in mouse tumor models. PLoS ONE 8(9): 16;8(9):e73145. doi: 10.1371/journal.pone.0073145, 2013.
  7. Madireddi, S., R.-H. Schabowsky, A. Srivastava, R.K. Sharma, E.S. Yolcu, and H. Shirwan. SA-4-1BBL costimulation inhibits conversion of naïve CD4+ T cells into CD4+CD25+FoxP3+ T regulatory cells by production of IFN-g. PLoS One 7:e42459, 2012.
  8. Srivastava, A., R.K. Sharma, E.S. Yolcu, V. Ulker, K MacLeod, and H. Shirwan Prime-boost vaccination with SA-4-1BBL costimulatory molecule and survivin eradicates lung carcinoma in CD8+ T and NK cell dependent manner.  PLoS One 7:e48463, 2012.
  9. Kaminitz A., E.S. Yolcu ES, J. Stein, I. Yaniv, H. Shirwan, N. Askenasy. Killer Treg restore immune homeostasis and suppress autoimmune diabetes in prediabetic NOD mice. J. Autoimmun. 37:39-47, 2011.

10.  Kaminitz A, Yolcu ES, Askenasy EM, Stein J, Yaniv I, Shirwan H, Askenasy N. Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice. PLOS One 6:e21630, 2011.

 

Patents Issued (out of 19)