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Email tcwu@jhmi.edu
Phone (410) 614-3899

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Cervical Cancer Research Lab


Tzyy Choou (T-C) Wu, M.D., Ph.D.

Primary Appointment in Pathology; Secondary Appointments in Oncology, Obstetrics and Gynecology; Joint Appointment in Molecular Microbiology and Immunology (BSPH)
Member, Graduate Program in Immunology; Member, Graduate Program in Pathobiology; Member, Graduate Program in Molecular Microbiology and Immunology (BSPH)


Each year, approximately 500,000 women worldwide develop cervical cancer and 200,000 women die from this cancer. We are currently developing vaccines and immunotherapeutic strategies for human papillomavirus (HPV)-related cervicalcancer and are running a molecular diagnostic lab for the diagnosis of HPVinfection.

My research focus has been in the area of human papillomavirus (HPV) vaccine development. I have created a unique preclinical murine tumor model that expresses HPV-16 oncogenic proteins, E6 and E7, and simulates specific molecular events in the progression of HPV+ precancerous lesions(CIN 3) to invasive cancer. This preclinical tumor model has been widely used and tested by researchers worldwide for HPV vaccine development. I have focused on identifying vaccine and immunotherapeutic approaches to enhance antigen processing and presentation by dendritic cells, including intracellular targeting and intercellular spreading strategies, for the purpose of prevention and treatment of cervical lesions and cancers. Intracellular targeting directs antigen to different subcellular locations to enhance antigen processing and presentation. Meanwhile, intercellularspreading facilitates the distribution of antigen to neighboring cells by taking advantage of unique intercellular transport properties, allowing for an increase in the amount of antigen presented to effector cells. Recently, I have created an innovative approach that combines both antigen-specific immunotherapy and anti-angiogenesis to treat HPV E7-expressing tumors. The continued development of these strategies will facilitate the development of vaccines that generate a potent immune response and antitumor effect against cervical cancer. I am also actively involved with investigating mechanisms of immune evasion of tumors, identifying new tumor-specific antigens, and applying vaccine strategies to other cancer systems with tumor-specific antigens.

Publications

Lee SY, Kang TH, Knoff J, Huang Z, Soong RS, Alvarez RD, Hung CF, Wu TC. Intratumoral injection of therapeutic HPV vaccinia vaccine following cisplatin enhances HPV-specific antitumor effects. Cancer Immunol Immunother. 2013 Jul;62(7):1175-85. doi: 10.1007/s00262-013-1421-y. Epub 2013 Apr 25. PubMed PMID: 23615841; PubMed Central PMCID: PMC3690484.

Kang TH, Mao CP, Lee SY, Chen A, Lee JH, Kim TW, Alvarez RD, Roden RB, Pardoll D, Hung CF, Wu TC. Chemotherapy acts as an adjuvant to convert the tumor microenvironment into a highly permissive state for vaccination-induced antitumor immunity. Cancer Res. 2013 Apr 15;73(8):2493-504. doi: 10.1158/0008-5472.CAN-12-4241. Epub 2013 Feb 15. PubMed PMID: 23418322; PubMed Central PMCID: PMC3630272.

Lee SY, Huang Z, Kang TH, Soong RS, Knoff J, Axenfeld E, Wang C, Alvarez RD, Chen CS, Hung CF, Wu TC. Histone deacetylase inhibitor AR-42 enhances E7-specific CD8⁺ T cell-mediated antitumor immunity induced by therapeutic HPV DNA vaccination. J Mol Med (Berl). 2013 Oct;91(10):1221-31. doi: 10.1007/s00109-013-1054-9. Epub 2013 May 29. PubMed PMID: 23715898; PubMed Central PMCID: PMC3783646.

Sun Y, Peng S, Qiu J, Miao J, Yang B, Jeang J, Hung CF, Wu TC. Intravaginal HPV DNA vaccination with electroporation induces local CD8+ T-cell immune responses and antitumor effects against cervicovaginal tumors. Gene Ther. 2015 Jul;22(7):528-35. doi: 10.1038/gt.2015.17. Epub 2015 Mar 19. PubMed PMID: 25786869; PubMed Central PMCID: PMC4490060.

Wu CY, Yang LH, Yang HY, Knoff J, Peng S, Lin YH, Wang C, Alvarez RD, Pai SI, Roden RB, Hung CF, Wu TC. Enhanced cancer radiotherapy through immunosuppressive stromal cell destruction in tumors. Clin Cancer Res. 2014 Feb 1;20(3):644-57. doi: 10.1158/1078-0432.CCR-13-1334. Epub 2013 Dec 3. PubMed PMID: 24300786; PubMed Central PMCID: PMC3946442.



 


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