Li Zhang, MSc, PhD, MD

Our laboratory's research is focused on the following two major areas:

1) Developing novel adoptive T cell therapy for the treatment of leukemia and lung cancer.

Human CD3+CD4-CD8-CD56- T cells, termed double negative (DN) T cells, compose a small population of peripheral T cells, and their function remains largely unclear. Recently, we have developed a novel protocol by which therapeutic quality and quantity of human DN T cells can be obtained from peripheral blood of healthy donors by ex vivo expansion. More importantly, we have demonstrated that these ex vivo propagated human DN T cells have potent anti-tumour function both in vitro and in patient-derived xenograft models. DN T cells effectively target lung cancer and primary leukemic cells, including those that are resistant to chemotherapy while spare normal blood and bone marrow cells. Unlike conventional T cells, infusion of DN T cells does not cause tissue damage or graft-versus-host disease, supporting the safety of clinical use of DN T cells.  Based on these findings, a phase I clinical trial using DN T cells to treat patients with acute myeloid leukemia and are at high risk of disease recurrence has been proved by Health Canada. As cryopreserved DN T cells from one healthy donor can target leukemic cells obtained from different patients in a non-HLA-restricted manner, it is possible to develop DN T cells as “off-the-shelf” living drugs. We are currently investigating the mechanisms by which these DN T cells selectively recognize and kill cancer cells but not normal cells and tissues, and exploring the possibility of using DN T cells either alone or in combination with other therapies to eliminate cancer cells and prevent disease recurrence.

2) Dissecting cellular and molecular mechanisms involved in immunity and tolerance and their relevance in diseases.

The ability to induce unresponsiveness to our own tissue and transplanted organ grafts while retaining immune responses towards viruses and malignant cells has been a dream of immunologists and clinicians for many years. To achieve this goal requires understanding the cellular and molecular mechanisms that control and regulate immune responses. Another research focus of our laboratory is to understand the cellular and molecular mechanisms governing tolerance and immunity and to translate obtained knowledge into novel therapies for immune related diseases. We study the mechanisms by which regulatory T cells, particularly NK-CD3+ CD4 and CD8 double negative (DN Tregs) control immune responses and prevent graft-vs-host disease and transplant rejection.

Clin Exp Immunol. 2018 Jul 31;:
Achita P, Dervovic D, Ly D, Lee JB, Haug T, Joe B, Hirano N, Zhang L
BMC Plant Biol. 2018 Jun 18;18(1):124
Zhang J, Li Y, Liu B, Wang L, Zhang L, Hu J, Chen J, Zheng H, Lu M
Free Radic Biol Med. 2018 May 24;123:125-137
Hong G, Zheng D, Zhang L, Ni R, Wang G, Fan GC, Lu Z, Peng T
J Exp Clin Cancer Res. 2018 Apr 24;37(1):88
Chen B, Lee JB, Kang H, Minden MD, Zhang L
Sleep Med. 2018 May;45:25-32
Yi XY, Ni SF, Ghadami MR, Meng HQ, Chen MY, Kuang L, Zhang YQ, Zhang L, Zhou XY
Oncotarget. 2016 Aug 23;7(34):55529-55542
Guo XR, Yang ZS, Tang XJ, Zou DD, Gui H, Wang XL, Ma SN, Yuan YH, Fang J, Wang B, Zhang L, Sun XY, Warnock GL, Dai LJ, Tu HJ
J Cell Mol Med. 2018 Jan 29;:
Zhang L, Wang X, Wu Y, Lu X, Chidiac P, Wang G, Feng Q
Clin Cancer Res. 2016 Jun 01;22(11):2697-708
Zhang L, Marrano P, Wu B, Kumar S, Thorner P, Baruchel S
Dose Response. 2017 Oct-Dec;15(4):1559325817744450
Zhang J, Zhou D, Zhang L, Lin Q, Ren W, Zhang J, Nadeem L, Xu G
Cell Death Dis. 2017 Dec 13;8(12):3214
Zhang L, Zhou D, Guan W, Ren W, Sun W, Shi J, Lin Q, Zhang J, Qiao T, Ye Y, Wu Y, Zhang Y, Zuo X, Connor KL, Xu G

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Inaugural Maria H. Bacardi Chair in Transplantation
Research Director, University of Toronto Transplantation Institute
Professor, Department of Laboratory Medicine & Pathobiology, University of Toronto
Professor, Department of Immunology, University of Toronto
Professor, Institute of Medical Sciences, Faculty of Medicine, University of Toronto