Recent News in the Zihai Li Lab
Dr. Li Inducted into Association of American Physicians
Dr. Zihai Li will be inducted to the Association of American Physicians (AAP), which is a distinguished honor society for senior physician scientists. Dr. Li is already an inducted member of the American Society of Clinical Investigation (ASCI).
A leader in the field of GP96/GRP94 chaperone research, Dr. Li established its roles in immunity, development, and cancer by advancing the knowledge of its client network, structure-function relationship, and co-chaperone CNPY3. He also uncovered a TGFbeta-GARP axis and the role of platelets in immuno-tolerance. Additionally, he discovered CNPY2 as a key initiator of the unfolded protein response.
Dr. Ansa-Addo Receives ACS-IRG Sub-Award
Dr. Ephraim Ansa-Addo received an MUSC Hollings Cancer Center American Cancer Society Institutional Research Grant (ACS-IRG). The goals of his study are to 1) determine the potential for moesin blockade to improve T cell responses in cancer and 2) determine whether moesin could serve as a potential therapeutic target in combination with PD-1 blockade.
Dr. Li’s Work Featured in May 2017 Online Cover of Science Immunology & EurekAlert.
Cancers adapt to single therapies, making combination therapies the approach of choice. Complementary therapies that decrease immunosuppression may boost the efficacy of immunotherapies. Now, the laboratory of Dr. Zihai Li reports that targeting platelets improves adoptive T cell therapy of multiple cancers. They found that transforming growth factor β (TGFβ) from platelets decrease T cell function largely through the expression of the TGFβ-docking receptor, GARP. These data suggest that combining immunotherapy with platelet inhibitors may be a complementary approach to cancer therapy. This work, highlighted in a EurekAlert! Public Release, was first published in Science Immunology. In fact, it is featured in the journal’s May 2017 Online Cover (see image below).
Moesin’s Potential as Therapeutic Target Reported in JCI & Highlighted in eCancerNews & EurekAlert
Researchers in the laboratory of Dr. Zihai Li published a manuscript titled, “Membrane-organizing Protein Moesin Controls Treg Differentiation and Antitumor Immunity via TGF-β Signaling,” in The Journal of Clinical Investigation (JCI). They report that moesin, a membrane-domain organizing protein, controls Treg function as well as the abundance and stability of TGF-beta receptors on the surface of cells, providing a potential therapeutic target for cancer immunotherapy. This report was highlighted in eCancerNews as well as EurekAlert. The manuscript’s first and corresponding authors are Drs. Ephraim Ansa-Addo and Zihai Li (respectively).
Dr. Zihai Li & Ms. Alessandra Metelli Appear in EurekAlert. Article About a Novel Cancer Immunotherapy
Ms. Metelli and Dr. Li, highlighted in EurekAlert!, are first and senior authors respectively on a journal article published in the December 15, 2016 issue of Cancer Research. The article, “Surface Expression of TGFβ Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer,” reported that GARP promotes both metastasis and immune suppression effects in breast cancer. The report gives the first clues that GARP could be a diagnostic marker for cancer, creating perhaps an opportunity to develop new treatments. "This discovery is fundamentally important to how TGF-beta utilizes GARP to promote cancer and down-regulate the immune system, but it also creates an opportunity for both diagnostics and therapeutics," said Dr. Li.
Alessandra Metelli & Dr.Ephraim Ansa-Addo ReceiveOral Presentation & Travel Awards for the Society of Immunotherapy Meeting - September 2016
Alessandra Metelli will present on cancer promotion and immune tolerance via cancer cell-intrinsic surface expression of GARP.
Dr. Ephraim Ansa-Addo will present on how the lack of moesin improves adoptive T cell therapy by potentiating anti-tumor functions.
Dr. Li Receives 2016 Peggy Schachte Research Mentor Award
Dr. Zihai Li is the recipient of the prestigious Peggy Schachte Research Mentor Award for 2016. The award is aimed at a faculty mentor or other colleague who is widely recognized as an outstanding research mentor and who encourages and supports the advancement of others as successful, extramurally funded investigators. Mentoring the next generation of biomedical researchers has been a highlight of Dr. Li’s career. He shares his passion and energy for discovery with his mentees.
Dr. Feng Hong Receives $30,000 ACS-IRF Award
The project, titled “Roles of CNPY2 in regulating UPR-associated Liver Cancer,” has the following aims:
Aim 1: Determine the mechanisms of CNPY2 in regulating hepatocellular carcinoma (HCC).
Aim 2. Determine whether CNPY2 can serve as a potential therapeutic target for treatment of HCC.
Harnessing the Immune System to Fight Cancer
Learn about how Dr. Li and other laboratories here at MUSC are using the bodies own immune system to fight cancer in a video produced right here on campus.
Progressnotes 2015: Multi-institutional Collaboration
working to develop a new class of cancer therapeutics was featured in the MUSC Progressnotes 2015 Year in Review Issue.
"Dr. Zihai Li, Chair of the Department of Microbiology and Immunology, is leading a multi-institutional team to develop a new class of grp94-based cancer therapeutics.
Precision therapies target specific mutations to knock out pathways involved in cancer development. Cancer is devious, however, and can develop resistance to these therapies by using redundant pathways. Zihai Li, M.D., Ph.D., Chair of the Department of Microbiology and Immunology, has shown that the heat shock protein grp94 is a master regulator of many oncogenic pathways, making it an attractive drug target. A grp94 inhibitor could block multiple cancer-associated pathways at once, reducing the likelihood of resistance.
In September 2015, MUSC Hollings Cancer Center and its partners Memorial Sloan Kettering and the University at Buffalo were awarded a five-year $6.8 million program project grant from the National Institutes of Health to elucidate the underlying biology and structure of the heat shock protein grp94 and to develop grp94 inhibitors for clinical trial. The award will fund three projects and two cores to accelerate the development of grp94-based cancer therapeutics.
Li is the national principal investigator for the grant, will head up its administrative core, and will lead a project to use genetic, biochemical, and immunological tools to elucidate the mechanisms by which grp94 promotes cancer and to assess the therapeutic potential of grp94 inhibitors against triple-negative breast cancer.
Gabriela Chiosis, Ph.D., of Memorial Sloan Kettering, whose laboratory has previously developed successful inhibitors against other heat shock proteins, will head the Medicinal Chemistry core and develop identified grp94-inhibiting compounds into pharmacologically viable agents for clinical trial. Structural biologist Daniel T. Gewirt, Ph.D. of the University at Buffalo will map the atomic structure of grp94 so that new inhibitors can be identified and engineered for better selectivity and binding capacity.”