| Email |
chung2@jhmi.edu |
| Phone |
(410) 614-4906 |
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Chien-Fu Hung, Ph.D.
Primary Appointment in Pathology
Cervical and ovarian cancers are two gynecological cancers that commonly occur in women. Cervical cancer is the second leading cause of death from cancer in women worldwide, while patients with ovarian cancer have a higher mortality rate than all other patients with gynecologic malignancies.
My research centers primarily on developing immmunotherapeutic, specifically vaccination, strategies for the prevention and treatment of cervical and ovarian cancers. Our lab has developed several strategies to enhance immunologic responses against cancers. Some of these strategies involve targeting an antigen into dendritic cells, targeting an antigen into MHC class I and II processing pathways, enhancing intercellular spreading of antigen, and combining antigen-specific immunotherapy and antiangiogenesis.
Currently, our laboratory has developed an ascitogenic ovarian/peritoneal tumor model that can be used to investigate the interaction of the immune system with the establishment, progression, and treatment of ovarian cancer in immunocompetent mice. Unlike models using human xenografts or human cell lines, which are limited to studies with immunocompromised mice, our model is capable of generating ascites and intraperitoneal tumor growth in immunocompetent C57BL/6 mice after intraperitoneal injection. We are presently investigating DNA vaccine strategies encoding ovarian tumor antigens identified by microarray and SAGE in this tumor model.
Publications
Hung CF, He L, Juang J, Lin TJ, Ling M, Wu TC. Improving DNA vaccine potency by linking Marek's disease virus type 1 VP22 to an antigen. J Virol. 2002, 76(6):2676-82.
Cheng WF, Hung CF, Chai CY, Hsu KF, He L, Ling M, Wu TC. Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen. J Clin Invest. 2001, 108(5):669-78.
Hung CF, Cheng WF, Hsu KF, Chai CY, He L, Ling M, Wu TC. Cancer immunotherapy using a DNA vaccine encoding the translocation domain of a bacterial toxin linked to a tumor antigen. Cancer Res. 2001, 61(9):3698-703.
Hung CF, Wu TC. Improving DNA vaccine potency via modification of professional antigen presenting cells. Curr Opin Mol Ther. 2003 Feb;5(1):20-4. |
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| Email |
roden@jhmi.edu |
| Phone |
(410) 502-5161 |
Related Websites
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Ovarian Cancer
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Richard B.S. Roden, Ph.D.
Primary Appointment in Pathology; Secondary Appointments in Gynecology and Obstetrics, and Oncology
Member, Graduate Program in Pathobiology
The oncogenic genotypes of human papillomavirus (HPV), typified by HPV16, are the primary etiologic agent of cervical cancer. Papillomavirus has only two capsid proteins, L1 and L2. Both capsid proteins represent promising targets for prophylactic intervention. Our primary research goal is to prevent cervical cancer through the development of a preventative vaccine that is active against all oncogenic types of HPV.
Little is known about the pathogenesis of ovarian cancer and there is currently no screening test for its detection while still confined to the ovary. Our goal is to identify novel tumor antigens of significance in the biology of ovarian cancer and applicable as biomarkers for early detection or targets for immunotherapy.
Publications
Yang R, Murillo FM, Lin KY, Yutzy WH 4th, Uematsu S, Takeda K, Akira S, Viscidi RP, Roden RB. Human papillomavirus type-16 virus-like particles activate complementary defense responses in key dendritic cell subpopulations. J Immunol. 2004 Aug 15;173(4):2624-31.
Roden RB, Ling M, Wu TC.Vaccination to prevent and treat cervical cancer. Hum Pathol. 2004 Aug;35(8):971-82. Review.
Yang R, Murillo FM, Cui H, Blosser R, Uematsu S, Takeda K, Akira S, Viscidi RP, Roden RB.Papillomavirus-like particles stimulate murine bone marrow-derived dendritic cells to produce alpha interferon and Th1 immune responses via MyD88. J Virol. 2004 Oct;78(20):11152-60.
H Naora, Y Yang, FJ Montz, JD Seidman, RJ Kurman, and RBS Roden 'Aserologically identified tumor antigen encoded by a homeobox gene promotesgrowth of ovarian epithelial cells' Proc. Natl. Acad. Sci. USA 200198:p4060-4065
Naora, H, Montz, FJ, Chai, C-Y, and RBS Roden. The homeobox geneHOXA7 encodes an autoantigen associated with aberrant mullerian differentiation in epithelial ovarian neoplasia. Proc Natl Acad Sci U S A.2001 Dec 18;98(26):p15209-14. |
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| Email |
bronnett@jhmi.edu |
| Phone |
(410) 614-2971 |
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Brigitte Ronnett, M.D.
Primary Appointment in Pathology; Secondary Appointment in Gynecology and Obstetrics
My research interests are focused on clinicopathologic, immunohistochemical, and molecular studies in gynecologic pathology. A particular interest is the pathology of ovarian mucinous tumors, including the distinction of primary ovarian mucinous tumors from metastatic mucinous carcinomas and the relationship of these tumors to pseudomyxoma peritonei. Other areas of interest include gynecologic cytopathology and diagnostic immunohistochemistry.
Publications
Ronnett BM, Yan H, Kurman RJ, Shmookler BM, Wu L, Sugarbaker PH. Patients with pseudomyxoma peritonei associated with disseminated peritoneal adenomucinosis have a significantly more favorable prognosis than patients with peritoneal mucinous carcinomatosis. Cancer 2001;92:85-91.
Seidman JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol 2003;27:985-993.
Ansari-Lari MA, Staebler A. Zaino RJ, Shah KV, Ronnett BM. Distinction of endocervical and endometrial adenocarcinomas: immunohistochemical p16 expression correlated with human papillomavirus (HPV) DNA detection. Am J Surg Pathol 2004;28:160-167.
Ronnett BM, Kajdacsy-Balla A, Gilks CB, Merino MJ, Silva E, Werness BA, Young RH. Mucinous borderline ovarian tumors: points of general agreement and persistent controversies regarding nomenclature, diagnostic criteria, and behavior. Hum Pathol 2004;35:949-960.
Elishaev E, Gilks CB, Miller D, Srodon M, Kurman RJ, Ronnett BM. Synchronous and metachronous endocervical and ovarian neoplasms: evidence supporting interpretation of the ovarian neoplasms as metastatic endocervical adenocarcinomas simulating primary ovarian surface epithelial neoplasms. Am J Surg Pathol 2005;29:281-294 |
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Ie-Ming Shih, M.D., Ph.D.
Primary Appointment in Pathology; Secondary Appointment in Pathology
Member, Gradutate Program in Pathobiology
Our laboratory focuses on the studies to: a) understand the molecular changes leading to the development of ovarian carcinoma; and b) develop molecular diagnostic tools for early cancer detection including ovarian cancer and other types of cancer.
Specifically, we will determine the molecular genetic alterations during the progression of ovarian serous carcinomas with molecular and morphologic correlations. For this aim, we will employ an array of new technologies to achieve our goals. Besides the conventional cell and molecular biology methods, we will employ digital karyotyping, digital PCR analysis, serial analysis for gene expression, somatic cell knockout, nanobiotechnology, mathematical and computer simulation. Further studies will focus on specific molecular or genetic alterations (i.e., new oncogenes or tumor suppressors) to determine their biological functions in the development of cancer and to assess their clinical significance. Engineered mouse models will also be used to assess the functional roles of newly identified genes. Finally, we will develop the body fluid-based assays to analyze molecular and genetic tumor markers we identified for molecular cancer diagnostics. The successful development of molecular diagnostic approaches may hopefully provide a simple and cost effective tool to detect and follow ovarian carcinomas, which would greatly facilitate clinical management of this deadly disease.
Collaborators: Drs. R. Kurman, B. Vogelstein, R. Roden, T-L Wang.
Publications
Shih, I.-M., Sheu, J. J., Santillan, A., Nakayama, K., Yen, M. J., Bristow, R. E., Vang, R., Parmigiani, G., Kurman, R. J., Trope, C. G., Davidson, B. & Wang, T. L. Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma. (2005) Proc Natl Acad Sci U S A 102, 14004-9.
Chen Y-C, Pohl G, Wang TL, Morin PJ, Risberg B, Christesen GB, Yu A, Davidson B, Shih IM. Apolipoprotein E is required for cell proliferation and survival in ovarian cancer. Cancer Res, 65:331-337, 2005.
Pohl G, Ho C-L, Kurman RJ, Bristow R, Wang T-L, Shih IM. Inactivation of the MAPK pathway as a potential target-based therapy in ovarian serous tumors with KRAS or BRAF mutations. Cancer Res, 65:1994:2000, 2005.
Shih IM and Wang TL. Exploring cancer genome using innovative technologies. Curr Opin Oncol, 17:33-38, 2005.
Ho C-L, Kurman RJ, Dehari R, Wang T-L, Shih IM. Mutations of BRAF and KRAS precede the development of ovarian serous borderline tumors. Cancer Res, 64:6915-6918, 2004.
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Russell S. Vang, M.D.
Primary Appointment in Pathology; Secondary Appointment in Gynecology & Obstetrics
My research interests have included clinicopathologic and immunohistochemical studies of epithelial and non-epithelial tumors of the ovary. Currently, I am in the process of investigating various immunohistochemical markers that may help distinguish metastatic carcinoma involving the ovary from primary ovarian mucinous tumors. In addition, I am undertaking two major clinicopathologic studies of surface epithelial-stromal tumors of the ovary. One involves the histologic reproducibility of the W.H.O. classification of carcinomas. This study, linked with clinical and molecular features, may provide modifications for the current histologic classification system. The other study pertains to serous borderline tumors of the ovary (atypical proliferative serous tumor and non-invasive micropapillary serous carcinoma). Using a large population-based cohort from Denmark, it is hoped that this study will clarify the behavior of both micropapillary serous borderline tumors and tumors with extra-ovarian implants.
Publications
Vang R, Gown AM, Zhao C, Barry TS, Isacson C, Richardson MS, Ronnett BM. Ovarian mucinous tumors associated with mature cystic teratomas: Morphologic and immunohistochemical analysis identifies a subset of potential teratomatous origin that shares features of lower gastrointestinal tract mucinous tumors more commonly encountered as secondary tumors in the ovary. Am J Surg Pathol 2007;31:854-69.
Vang R, Gown AM, Farinola M, Barry TS, Wheeler DT, Yemelyanova Y, Seidman JD, Judson K, Ronnett BM. p16 expression in primary ovarian mucinous and endometrioid tumors and metastatic adenocarcinomas in the ovary: Utility for identification of metastatic HPV-related endocervical adenocarcinomas. Am J Surg Pathol 2007;31:653-63.
Vang R, Gown AM, Barry TS, Wheeler DT, Yemelyanova A, Seidman JD, Ronnett BM. Cytokeratins 7 and 20 in primary and secondary mucinous tumors of the ovary: Analysis of coordinate immunohistochemical expression profiles and staining distribution in 179 cases. Am J Surg Pathol 2006;30:1130-39.
Vang R, Gown AM, Wu LS, Barry TS, Wheeler DT, Yemelyanova A, Seidman JD, Ronnett BM. Immunohistochemical expression of CDX2 in primary ovarian mucinous tumors and metastatic mucinous carcinomas involving the ovary: Comparison with CK20 and correlation with coordinate expression of CK7. Mod Pathol 2006;19:1421-8.
Vang R, Ronnett BM. A practical approach to mucinous tumors involving the ovary: Distinction of primary from metastatic tumors and prediction of site of origin for metastases of uncertain origin. Pathol Case Rev 2006;11:18-30. |
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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
T. W. Kim, C.-F. Hung, M. Ling, J. Juang, L. He, J. M. Hardwick, S.
Kumar, and T.-C. Wu (2003) Enhancing DNA vaccine potency by
co-administration of DNA encoding anti-apoptotic proteins. J. Clin.
Invest. 112: 109-117.
T. W. Kim, C.-F. Hung, D. Boyd, L. He, D. Kaiserman, P. I. Bird, and
T.-C. Wu (2004) Enhancement of DNA Vaccine Potency by Co-administration
of Tumor Antigen Gene and DNA Encoding Serine Protease Inhibitor-6
(Serpinb9). Cancer Research 64: 400-405.
Lora Hedrick Ellenson and T.-C. Wu (2004) Focus on endometrial and
cervical cancer. Cancer Cell 5: 533-538
T. W. Kim, C.-F. Hung, J.-H. Lee, L. He, D. A. K. Boyd, J. M. Hardwick
and T.-C. Wu (2005) Modification of Professional Antigen-Presenting
Cells with Small Interfering RNA In Vivo to Enhance Cancer Vaccine
Potency. Cancer Research (in press). |
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| Email |
ayemely1@jhmi.edu |
| Phone |
(443) 287-7980 |
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Anna V. Yemelyanova, M.D.
Primary Appointment in Pathology
My research interests include clinic-pathologic, immunohistochemical, and molecular characterization of endometrial cancer. I am currently studying various immunohistochemical markers that may assist in pathologic diagnosis of these tumors and further explore their pathogenesis. The other area of my interest concerns cervical cancer related to high risk human papillomavirus (HPV); I am investigating viral protein expression as potential biomarkers useful in diagnosis and clinical management of pre-malignant cervical lesions.
Publications
Yemelyanova A, Vang RS, Judson K, Wu LS, Ronnett BM; Distinction of Primary and Metastatic Mucinous Tumors Involving the Ovary: Analysis of Size and Laterality Data by Primary Site with Re-evaluation of an Algorithm for Tumor Classification
Am J Surg Pathol, 2008; 32(1): 128-38.
Yemelyanova A, Cosin J, Bidus MA Boice CR, Seidman JD; Pathology of stage I versus stage III ovarian carcinoma with implications for pathogenesis and screening. Int J Gynecol Cancer. 2008; 18(3):465-9.
Yemelyanova A, Mao TL, Nakayama N, Shih IM, Kurman RJ: Low-grade Serous Carcinoma of the Ovary Displaying a Macropapillary Pattern of Invasion. Am J Surg Pathol 2008; 32(12):1800-6.
Yemelyanova A, Vang R, Seidman JD, Gravitt PE, Ronnett BM. Endocervical Adenocarcinomas With Prominent Endometrial or Endomyometrial Involvement Simulating Primary Endometrial Carcinomas: Utility of HPV DNA Detection and Immunohistochemical Expression of p16 and Hormone Receptors to Confirm the Cervical Origin of the Corpus Tumor. Am J Surg Pathol, 2009; 33(6):914-24.
Yemelyanova A, Ji H, Shih IM, Wang TL, Wu LS, Ronnett BM; Utility of p16 Expression for Distinction of Uterine Serous Carcinomas from Endometrial Endometrioid and Endocervical Adenocarcinomas: Immunohistochemical Analysis of 201 Cases. Am J Surg Pathol (E-pub, 2009).
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