Qizhi Cathy Yao, M.D., Ph.D.
Department of Surgery
Dr. Yao’s research programs include HIV vaccine development, pancreatic cancer pathogenesis and immunotherapy.
Dr. Yao’s lab is interested in developing non-infectious HIV virus-like particles (VLPs) as candidate HIV mucosal vaccines for both preventive and therapeutic purposes. VLPs formed by structural proteins are highly immunogenic and capable of inducing protective immunity against various viral infections in preclinical studies. We have modified vaccine immunogens into chimeric HIV VLPs which contain influenza viral surface glycoprotein HA or other immunologically functional molecules. We are able to show that the chimeric HIV VLPs can induce enhanced humoral and cellular immune responses against HIV in a mouse model.
We have also studied the basic mechanisms of VLPs induced humoral and cellular immune responses, and other factors that affect these responses. For example, we found that VLP vaccines activate conventional B2 cells and promote B cell differentiation to IgG2a producing plasma cells; that VLPs traffic into lymph nodes upon immunization and can be directly visualized by optical imaging techniques; and that intradermal immunization generates improved responses and might be a preferable delivery route to use for viral and cancer immunotherapeutic studies involving VLPs. Since dendritic cells (DCs) have long been known to be pivotal in initiating immune responses, we are also interested in how VLPs modulate DC functions and will evaluate the efficacy of VLP-pulsed DC vaccines. In addition, we are interested in testing the efficacy of modified chimeric VLP oral-mucosal immunization in non-human primates.
Pancreatic cancer pathogenesis and immunotherapy
Pancreatic cancer has one of the highest mortality rates and ranks as the fourth leading cause of cancer death in North America. Survival statistics are poor because there are no reliable tests for early diagnosis and no effective therapies for metastatic disease. There is a need to better understand the molecular mechanisms of pancreatic cancer tumorigenesis and to develop effective treatment strategies. Yao lab currently focuses on the study of key molecules in pancreatic cancer, including Mesothelin (MSLN) and Trop2 and their mechanisms of regulation. Our laboratory is also interested in the involvement of microRNAs in pancreatic cancer, and how their dysregulation leads to its pathogenesis. We are also currently exploring tumor-associated molecule targeted therapy and RNA interference in vivo.
Tying together all our research interests, our group has shown that vaccination of mice with chimeric virus-like particles containing MSLN significantly inhibited tumor progression, suggesting a new therapeutic vaccine strategy whereby MSLN is targeted as an approach to control pancreatic cancer progression. Similarly, combinational therapy with Trop2 chimeric VLP with gencitabine has shown to have synergistic therapeutic effect on pancreatic cancer on a xenograft mouse model. We are also employing a K-ras mutation spontaneous pancreatic cancer mouse model to study prevention and therapeutic potential of our immunotherapy regimens.
Department of Surgery, Molecular Surgeon Research Center
Baylor College of Medicine, Suite R415
One Baylor Plaza
Houston, TX 77030
M.D. - Southeast University School of Medicine, China
Ph.D. - Emory University School of Medicine
Postdoctoral - Emory University School of Medicine
Li, M., Zhang, Y., Bharadwaj, U., Wang, X., Wang, H., Liu, Z., Rosen, B., Zhang, S., Liuzzi, JP., Cousins, R., Fisher, WE., Brunicardi, FC, Logsdon, CD, Chen, C., Yao, Q. (2007). Aberrant Expression of Zinc Transporter ZIP4 (SLC39A4) Significantly Contributes to Human Pancreatic Cancer Pathogenesis and Progression. Proc. Natl. Acad. Sci. USA. 104 (47): 18636 -41.
Bharadwaj, U., Li, M., Zhang, R., Chen, C., Yao, Q. (2007). Elevated IL-6 and G-CSF in Human Pancreatic Cancer Cell Conditioned Medium Suppress Dendritic Cell Differentiation and Activation. Cancer Research, 67(11):5479-88.
Zhang, R., Bharadwaj, U., Li, M., Chen, C., Yao, Q. (2007). Effects of Pentoxifylline on differentiation, maturation and function of human CD14+ monocyte-derived dendritic cells. Journal of Immunotherapy, 30(1):89-95.
Cubas, R. Li, M., Chen, C. Yao, Q. (2007). Colorectal Cancer: New Advances in Immunotherapy. Cancer Biology and Therapy, 6;6(1).
Li, M*, Bharadwaj, U*, Zhang, R*, Zhang, R. Hong Mu, William E. Fisher, F. Brunicardi, C, Chen, C and Yao, Q. (2008). Mesothelin is a malignant factor and a target for therapeutic vaccine for pancreatic cancer. Molecular Cancer Therapeutics. 7(2):286-96. (*equal contribution)
Huang C, Li M, Chen C, and Yao Q. (2008). Small Interfering RNA therapy in cancer: Mechanism, Potential Targets, and Clinical Applications. Expert Opinions in Therapeutic Targets. 12(5):637-45.
Chen C, Chai H, Wang X, Jiang J, Jamaluddin MS, Liao D, Zhang Y, Wang H, Bharadwaj U, Zhang S, Li M, Lin P, Yao Q. (2008).Soluble CD40 ligand induces endothelial dysfunction in human and porcine coronary artery endothelial cells. Blood.112(8):3205-16.
Bharadwaj, U., Li, M., Chen, C., Yao, Q. (2008). Mesothelin-Induced Pancreatic Cancer Cell Proliferation Involves Alteration of Cyclin E via Activation of Stat3. Molecular Cancer Research. 6(11):1755-65.
Marin-Muller C, Li M, Chen C, Yao Q. (2009). Current Understanding and Potential Immunotherapy for HIV-Associated Squamous Cell Carcinoma of the Anus (SCCA). World J Surg, 33(4):653.
Cubas R, Zhang S, Kwon S, Sevick-Muraca EM, Li M, Chen C, Yao Q. (2009).VLP lymphatic trafficking and generation of immune response after VLP immunization by different routes. Journal of Immunotherapy 32(2):118-128. PMC2717166.
Zhang S, Cubas R, Li M, Chen C, Yao Q. (2009). Virus-like particle vaccine activates conventional B2 cells and promotes B cell differentiation to IgG2a producing plasma cells. Molecular Immunology. 46(10):1988-2001. PMC2702656.
Cubas R, Li M, Chen C, Yao Q. (2009). Trop2: A possible therapeutic target for late stage epithelial carcinomas. Biochim Biophys Act-Reviews on Cancer. 1796(2):309-14.
Li M, Zhang Y, Bharadwa U, Fisher WE, Brunicardi FC, Logsdon CD, Chen C, and Yao Q. (2009). Down-regulation of ZIP4 by RNA Interference Inhibits Pancreatic Cancer Growth and Increases the Survival of Nude Mice with Pancreatic Cancer Xenografts. Clin Cancer Res. 15(19):5993-6001.
Zhang R, Zhang S, Li M, Chen C, Yao Q. (2010).Chimeric CD40L/SHIV virus-like particles enhance dendritic cell activation and boost immune responses against HIV. Vaccine. 28(31):5114-27.
Cubas R, Zhang S, Li M, Chen C, Yao Q. (2010). Murine Trop2 overexpression enhances murine pancreatic cancer growth through activation of the ERK1/2 signaling pathway. Molecular Cancer. 9:253.
Chen C, Zhang Y, Zhang L, Weakley SM, Yao Q. (2010). MicroRNA-196: critical roles and clinical applications in development and cancer. J Cell Mol Med. 15(1):14-23. PMID: 21091634
Cubas R, Zhang S, Li M, Chen C, Yao Q. (2010). Trop2 virus-like particles activate broad anti-tumor immune responses and effectively control pancreatic cancer progression. Journal of Immunotherapy. 34(3):251-63.
Bharadwaj U, Marin-Muller C, Zhang Y, Li M, Chen C, Yao Q. (2011). Mesothelin Overexpression Promotes Autocrine IL-6/sIL-6R Trans-signaling to stimulate Pancreatic Cancer Cell Proliferation. Carcinogenesis. Apr 23. [Epub ahead of print].