Zhirui Wang, PhD

Dr. Wang works with the Plastic and Reconstructive and Transplant divisions within the Department of Surgery.

Education & Training

DVM, Veterinary Medicine, Shanxi Agricultural University, Shanxi, China (1982).

Master of Science, Veterinary Microbiology and Immunology, Shanxi Agricultural University, Shanxi, China (1988).

PhD, Molecular Biology, Justus-Liebig-University of Giessen, Giessen, Germany (1995).

Research Associate, Hepatitis B virus (Famciclovir induced HBV mutation), Molecular Virology, Viral Hepatitis Lab, INSERM, U271, Lyon, FRANCE (09/1995-10/1996).

Research Associate, Molecular Biology (High-resolution physical map of porcine genome), College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA (11/1996-11/1998).

Research Associate, Protein Engineering, Targeted Drug Delivery Systems, Molecular Biology, Novartis Pharmaceuticals, Summit, New Jersey. Assigned to Dr. David Neville’s lab at NIMH, Bethesda, Maryland, USA (12/1998-09/2000).

Research Fellow, Protein Engineering, Targeted Drug Delivery Systems, Molecular Biology, NIMH, National Institutes of Health, Bethesda, Maryland, USA (10/2000-09/2007).

Professional Experience

University of Colorado, Denver / Anschutz Medical Campus

Department of Surgery/ Division of Plastic & Reconstructive Surgery/ Division of Transplant Surgery, Associate Professor of Surgery, 08/2018 – Present

Massachusetts General Hospital / Harvard Medical School, Boston, MA

Harvard Medical School, Assistant Professor of Surgery, 07/2013 –07/2018

Harvard Medical School, Instructor of Surgery, 11/2012 – 06/2013

Department of Surgery, Associate Immunologist, 04/2017 – 07/2018

Department of Surgery, Assistant Immunologist, 11/2012 – 03/2017

Transplantation Biology Research Center, Senior Research Scientist, 10/2007-10/2012

Core Leader & Technical Director, Massachusetts General Hospital / Dana Farber Harvard Cancer Center Recombinant Protein Expression and Purification Core Facility, 12/2008 – 12/2014

College of Veterinary Medicine, Shanxi Agricultural University, Shanxi, China

Department of Veterinary Medicine, Lecturer, Veterinary Microbiology and Immunology, 09/1985 - 12/1991

Department of Veterinary Medicine, Instructor, Veterinary Microbiology and Immunology, 01/1982 - 08/1985

Research Overview

Wang laboratory’s main interest and expertise is using unique diphtheria toxin resistant yeast Pichia pastoris expression system as a platform to develop diphtheria toxin-based recombinant immunotoxins for specific depletion of targeted cell populations. The developed immunotoxins will be used for treatment of cancer and autoimmune diseases as well as transplantation tolerance induction. Wang laboratory has developed following immunotoxins. 1) Anti-human CCR4 immunotoxin for targeting CCR4⁺ tumors and Tregs. 2) Ontak^®-like IL-2 fusion toxins (human, porcine and murine versions) for depleting IL-2R⁺ cells including CD25⁺ Tregs. 3) IL2-CCR4 bispecific immunotoxin for targeting human CD25⁺and/or CCR4⁺ tumors and Tregs. 4) Anti-porcine CD3 immunotoxin for depleting porcine CD3⁺ T-cells. 5) Anti-human CD19 immunotoxin for targeting human CD19⁺ tumors. 6) Porcine CTLA-4 fusion toxin for depleting porcine CD80⁺ or CD86⁺ antigen presenting cells. CCR4 immunotoxin, human IL-2 fusion toxin and IL2-CCR4 bispecific immunotoxin have the potential to have pharmaceutical applications in humans.

https://www.ncbi.nlm.nih.gov/myncbi/1tuQXiD9Vj6kb/bibliography/public/

Current Projects

IL2-CCR4 bispecific immunotoxin

Previously, we have developed diphtheria toxin based recombinant Ontak^®-like human IL2 fusion toxin (IL2 fusion toxin) and anti-human CCR4 immunotoxin (CCR4 immunotoxin). Recently, we further constructed an IL2-CCR4 bispecific immunotoxin. The bispecific immunotoxin was significantly more effective than either IL2 fusion toxin or CCR4 immunotoxin alone using human CD25⁺CCR4⁺ cutaneous T-cell lymphoma (CTCL)-bearing immunodeficient NSG mouse model. The bispecific immunotoxin is a promising novel targeted therapeutic drug candidate for treatment of human CD25⁺ and/or CCR4⁺ tumors including CTCL. In addition, the surface receptors CCR4 and CD25 are also expressed on effector Tregs. Therefore, the bispecific immunotoxin also has the potential to deplete tumor infiltrating CCR4⁺ or/and CD25⁺ Tregs and improve tumor immunity. Our overall goal is to move this promising therapy into clinic.

Human EGF fusion toxin

We are collaborating with Dr. Shi-Long Lu’s laboratory in Department of Otolaryngology to develop a diphtheria toxin-based recombinant human EGF fusion toxin for targeting EGFR+ head and neck squamous cell carcinoma (HNSCC).

CD45 immunotoxin

We are developing recombinant anti-CD45 immunotoxins (porcine and human versions) to deplete CD45+ lymphocytes transiently as a novel-conditioning agent for hematopoietic stem cell transplantation. Our overall goal is to develop a CD45 immunotoxin-based novel conditioning protocol without irradiation and without graft versus host disease (GVHD).

Porcine IL-3 Fusion toxin

We are developing a diphtheria toxin-based recombinant porcine IL-3 fusion toxin for depleting porcine IL-3 receptor positive cells (CD123+ cells). We will use this porcine IL-3 fusion toxin to deplete CD123+ plasmacytoid dendritic cells (pDCs) for treatment of lung and skin fibrosis in swine model. It is reported that pDC is very important for transplantation tolerance induction. We will use this porcine IL-3 fusion toxin to deplete porcine CD123+ pDC to break the established organ transplantation tolerance to investigate the pDC-mediated tolerance mechanism.

Anti-porcine CD154 nanobody

We are screening a high-affinity anti-porcine CD154 nanobody from a yeast surface display based camelid nanobody library. We will use the screened anti-porcine CD154 nanobody to block the CD40-CD40L pathway to induce organ transplantation tolerance and treat autoimmune diseases. We will also use the screened anti-porcine CD154 nanobody to construct a recombinant anti-porcine CD154 immunotoxin for depleting activated porcine CD154+ T cells for inducing organ transplantation tolerance and treating autoimmune diseases. We plan to use this rapid platform to screen out more useful nanobodies.