Last Updated: 11/29/11
The Johns Hopkins University SPORE in Cevical Cancer
T.C. Wu, M. D., Ph.D.
Professor
Departments of Pathology, Oncology, Obstetrics and Gynecology and Molecular Microbiology and Immunology
The Johns Hopkins University
Tel: (410) 614-3899
Fax: (443) 287-4295
OVERALL ABSTRACT
SPORE (Specialized Program of Research Excellence) in Cervical Cancer at the Johns Hopkins University School of Medicine, University of Alabama at Birmingham and University of Colorado brings together a highly interactive, multidisciplinary, and inter-institutional program of translational research in cervical cancer. The SPORE includes four integrated projects spanning the fields of prevention and treatment of cervical cancer. Project I: L1 Capsomeres as a Next Generation Preventive HPV Vaccine is led by Robert Garcea, M.D., Richard Roden, Ph.D., and Warner Huh, M.D. Project II: Development of a Pan-Oncogenic HPV Preventive Vaccine is led by Richard Roden, Ph.D., and Warner Huh, M.D. Project III: A phase I clinical trial to assess the immunogenicity, safety, tolerability and efficacy of HPV DNA-Vaccinia prime booster vaccination with locally applied TLR agonists in patients with HPV-16+ cervical intraepithelial neoplasia 3 (CIN3) is led by Cornelia Trimble, M.D., Drew Pardoll, M.D., Ph.D. and T.-C. Wu, M.D., Ph.D. Finally, Project IV: A phase I clinical trial to assess the safety and immunogenicity of repeated, cluster particle-mediated epidermal delivery (PMED) of the DNA vaccine, pNGVL4a-CRT-E7(detox), in patients with operable Stage IB1 cervical cancer associated with HPV-16 is led by Ronald Alvarez, M.D., Cornelia Trimble, M.D. and T.-C. Wu, M.D., Ph.D. These four projects are supported by four Cores that provide the critical and supportive infrastructure essential to efficient and effective translational research. The Administration/Communication Core (Core A) is led by T.-C. Wu, M.D., Ph.D. and Edward Partridge, M.D. Core B (the Biostatistics/ Data Management Core) is led by Mei-Cheng Wang, Ph.D., and Alan Cantor, Ph.D. The Tissue /Pathology Core (Core C) is led by Anna Yemelyanova, M.D. and Lawrence Lamb, Ph.D. Finally, the Core D is the Immunology Core and is led by Raphael Viscidi, M.D. and Chien-Fu Hung, Ph.D. The SPORE also includes a Developmental Research Program for rapid funding of novel research ideas and a Career Development Program to facilitate career development of individuals with interest in translational cervical cancer research.
PROJECT I: L1 CAPSOMERES AS A NEXT GENERATION PREVENTATIVE HPV VACCINES
Principal Investigators:
Robert Garcea, M.D.
Richard Roden, Ph.D.
Warner Huh, M.D.
Co-Investigators:
Balasubramanyam Karanam, Ph.D.
Laura Winn Jones, R.N.
The recent development of prophylactic vaccines protective against “high risk” human papillomaviruses (HPV) is a landmark in medicine. The current vaccine is composed of recombinant virus-like particles (VLPs) of the major capsid protein, L1, including the high risk HPV types 16 and 18. Phase II/III clinical trials have shown >95% efficacy of these VLP preparations in preventing HPV 16, 18 infection, and thus hopefully preventing the eventual development of about 70% of cervical cancers associated with these types. Despite this success the VLP vaccines have the adverse attributes of high cost ($360 for the initial three immunizations in the USA) and a requirement for refrigeration (i.e., cold chain). We have previously characterized the immunogenic properties of VLP subunits, pentameric L1 capsomeres, and compared these “subunits” to VLPs in a canine infection model. In this model capsomeres appeared near equivalent to VLPs in inducing protection against infection. Capsomeres are purified after recombinant expression of L1 in E. coli as a GST-fusion protein, at levels suggesting a significant reduction in manufacturing expense. The protein is readily purified, and can be precipitated, resuspended, and stored at room temperature without loss of immunogenicity. In the context of an ongoing NCI RAPID award GST-L1 capsomeres have been proposed as a “next generation” HPV vaccine that might be ideally suited for production and use in underdeveloped countries of the world where cervical cancer is particularly prevalent. We propose to use the GST-L1 protein that has been GMP produced (by Shantha Biotechnica), vialed, and toxicology screened under the auspices of a RAPID award for study in a phase I human trial. In aims 1 and 2 we propose a dose escalation scheme of 15 subjects at each of three dose levels (10, 50, 500 micrograms), repeated three times, with concomitant analysis of toxicity, development of neutralizing antibodies, cytotoxic T-cell responses, and possible adverse effects of GST antibody development. In the third aim, laboratory studies with clinical specimens and animal experiments will test new adjuvant strategies including Toll-like receptor activation, and evaluate the effects on humoral immunity of antigen spacing and linking by comparing capsomeres, cross-linked capsomeres, and VLPs. Knowledge of L1 capsomere structure and interaction with the innate immune system will be utilized to generate longer-lived and broader immunity with lower and fewer doses. The results of this project will determine whether the GST-L1 preparation can proceed to further phase II testing.
PROJECT II: DEVELOPMENT OF A PAN-ONCOGENIC HPV PREVENTATIVE VACCINE
Principal Investigators:
Richard Roden, Ph.D.
Warner Huh, M.D.
Co-Investigator:
Laura Winn Jones, R.N.
The two HPV capsid proteins, L1 and L2, are both independent protective antigens. Vaccination with HPV L1 virus-like particles (VLP) induces neutralizing antibodies and protection in patients with strong type restriction. Broad protection against the >15 known oncogenic HPVs is necessary for the eventual cessation of cytologic screening and eradication of cervical cancer. We propose L2 as a single conserved protective antigen. We have shown in rabbits and mice that vaccination with L2 11-200 produced in bacteria protects against both the homologous virus type as well as evolutionarily distant heterologous types (i.e. remarkably, vaccination with HPV16 L2 11-200 protects against rabbit papillomavirus infection) supporting the possibility of an L2-based pan-oncogenic HPV vaccine. Furthermore, we have shown that vaccination with L2 induces cross-neutralizing antibodies in patients. Unlike current multivalent L1 VLP vaccines, a single L2-based antigen produced in E. coli is inexpensive to produce. As such, a pan-oncogenic HPV type that is less costly to produce would have its greatest impact in underserved areas in the US and in developing nations. The Rapid Access to Preventive Intervention Development (RAPID, NCI) program is producing GMP-grade fusion protein comprising L2 11-200 of HPV6, 16 and 18 in tandem (L2 11-200x3) with alum adjuvant for this proposed clinical trial.
HYPOTHESIS 1: Vaccination of patients with HPV L2 11-200x3 polypeptide in alum adjuvant is safe.
Specific Aim #1: To perform a double-blinded, placebo-controlled, dose escalating Phase I trial to evaluate the safety HPV L2 11-200x3 polypeptide vaccination in healthy women.
HYPOTHESIS 2: Vaccination of patients with HPV L2 11-200x3 polypeptide in alum adjuvant induces high titers of broadly neutralizing antibodies.
Specific Aim #2: To determine the dose ranging for HPV L2 11-200x3 in alum with respect to titers of neutralizing antibody and also the spectrum of HPV types neutralized in comparison to Gardasil®. HPV infection is restricted to the epithelium and does not enter the bloodstream, yet passive transfer of neutralizing IgG into the bloodstream is protective. Where does the antibody meet and neutralize HPV?
HYPOTHESIS 3: Transudation of L2-specific HPV neutralizing antibody into the genital tract is the relevant correlate of protection.
Specific Aim #3: To determine whether passive transfer of mice with IgG or IgM from patients vaccinated with HPV L2 11-200x3, HPV16 L1 capsomeres or Gardasil will confer protection from vaginal challenge of mice with HPV pseudovirion and compare the minimal neutralizing antibody titers required for protection.
PROJECT III: A PHASE I TRIAL TO ASSESS THE IMMUNOGENICITY, SAFETY, TOLERABILITY AND EFFICACY OF HPV DNA-VACCINIA PRIME BOOSTER VACCINATION WITH LOCALLY APPLIED TLR AGONISTS IN PATIENTS WITH HPV-16+ HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESIONS (SILs)
Principal Investigators:
Cornelia Trimble, M.D.
Drew Pardoll, M.D., Ph.D.
T.-C. Wu, M.D., Ph.D.
Co-Investigators:
Elizabeth Sauter, R.N.
Mihaela Paradis
Our long term goal is to develop immune therapies for disease caused by Human Papillomavirus (HPV). While the field of cancer immunotherapy has shown proof of principle in humans, namely that established malignancies can be recognized and eradicated by a tumor-specific adaptive T cell response, reproducibly achieving this effect has been difficult. One reason may be that therapeutic vaccines tested to date have not been immunogenic enough to eliminate established disease. Another reason may be immunologic suppression directly mediated by developing and progressing tumors, which are operative in the lesion microenvironment. This project will test the hypothesis that HPV-specific adaptive T cell responses can be elicited by therapeutic vaccination in subjects with high grade cervical dysplasia (CIN3), and that the application of a topical TLR7 agonist, imiquimod, directly on the lesion, will enhance access of CD8+ T cells to the lesions. CIN3 lesions are relatively accessible, and some of them do regress within our 15-week study window. The disease provides rational, non-self antigenic targets for therapeutic vaccination. This project will test a heterologous DNA prime, recombinant vaccinia-based boost regimen to enhance the immune response against HPV16 E6 and E7, which are expressed in a functionally obligate manner in cervical cancer and its precursor lesion, high grade cervical dysplasia (CIN3). This project also provides the opportunity to analyze target lesions directly to determine if we can identify evidence of mechanisms that would mitigate the function of immune effector responses, namely, impairment of homing and function of immune cell subsets. In fact, we found that CD8+ T cells accumulate at CIN3 lesions, but in the case of persistent disease, fail to access lesional epithelium. While patterns of immune cell infiltration have been identified to predict clinical outcome in the clinical setting of invasive disease, to our knowledge, they have not been identified early in disease, before development of an overtly invasive phenotype. This work is an opportunity to study immune responses that are localized to incipient neoplasia, and immune homeostatic mechanisms that could be locally uncoupled to enhance both access and function of effector immune cells to eliminate disease.
PROJECT IV: A PHASE I TRIAL TO ASSESS THE SAFETY AND IMMUNOGENICITY OF REPEATED, CLUSTER PARTICLE-MEDIATED EPIDERMAL DELIVERY (PMED) OF THE DNA VACCINE, pNGVL4a-CRT-E7(detox), IN PATIENTS WITH HPV-16-ASSOCIATED STAGE 1B1 CERVICAL CANCER
Principal Investigators:
Ronald Alvarez, M.D.
Cornelia Trimble, M.D.
T.-C. Wu, M.D., Ph.D.
Co-Investigators:
Mihaela Paradis
We have shown that cluster intradermal vaccination of CRT/E7DNA (with a short interval between vaccinations) more rapidly induced E7-specific immune responses and generated better therapeutic effects against E7-expressing tumors compared to DNA vaccination with longer intervals. These findings prompted us to propose a phase I trial to investigate whether the repeated, cluster intradermal CRT/E7 DNA vaccination is safe and can generate E7-specific CD8+ T cell immune responses in patients with HPV-16 associated stage 1B1 resectable cervical cancer. We plan to vaccinate two cohorts of patients, one before and one after tumor resection. The proposed trial using cluster vaccination regimen permits us to complete the vaccination regimen before tumor resection allowing us to assess the influence of DNA vaccination on tumor microenvironment without compromising the standard care. Clinical grade pNGVL4a-CRT/E7(detox) DNA vaccine has been manufactured by NCI RAID program and formulated in the proprietary ND-10 gene gun device by PowderMed/Pfizer for intradermal vaccination. The proposed trial will be performed at the University of Alabama at Birmingham, which has one of the highest populations of stage IB1 cervical cancer patients. Specifically for Aim 1, we plan to evaluate the safety/toxicity associated with repeated, cluster intradermal pNGVL4a-CRT/E7 (detox) DNA vaccination via gene gun in patients with HPV 16-associated stage IB1 cervical cancer, using a dose-escalating regimen. For Aim 2, we plan to characterize systemic HPV-16 E6 and E7-specific humoral and T cell-mediated immune responses in stage IB1 cervical cancer patients receiving the DNA vaccination via gene gun. For Aim 3, we will characterize the presence of HPV-16 E6 and E7-specific CD8+ T cell immune responses in the tumor and draining lymph nodes in selected stage IB1 cervical cancer patients receiving the DNA vaccination via gene gun. Lastly, Aim 4 will include determining the subset population of immune cells infiltrating the tumor bed, B7H-1 and STAT-3 expression in tumor microenvironment and to determine the apoptotic tumor cell death in stage IB1 cervical cancer patients receiving the DNA vaccination via gene gun. The successful implementation of the proposed study will allow us to assess the systemic and local antigen-specific immune responses following repeated cluster intradermal DNA vaccination using the ND-10 gene gun device in HPV-16 associated stage IB1 cervical cancer.
CORE A: ADMINISTRATION AND COMMUNICATION CORE
Principal Investigators:
T.-C. Wu, M.D., Ph.D.
Edward Partridge, M.D.
Co-Investigators:
Katherine Liu, M.S.
Lucy Wangaruro
Tracey Reid
The Administration/Communication Core (Core A) will facilitate coordination and oversight of all Program activities. This core will include a basic science director (Dr. T.-C. Wu) and a clinical research director (Dr. Edward Partridge). Dr. Wu will be responsible for coordinating basic scientific efforts and the coordination of individual projects. Dr. Partridge will oversee patient identification, enrollment, and patient monitoring in the context of the Core. This resource will also fund a Clinical Research Coordinator who will interact with the Biostatistics/Data Management Core (Core B), the Tissue/Pathology Core (Core C) and the Immunology Core (Core D), as well as with personnel from each individual project to ensure that all patient information, specimens, and results are properly collected and recorded in the computerized database. Appropriate monitoring of patient safety, adverse events, and data management and confidentiality will be provided by the data safety monitoring board, as well as the Clinical Research Management Group. The Administrative Core includes key administrative personnel and will also coordinate essential Program interactions including preparing applications and progress reports for the SPORE, all planning and evaluation activities, arranging and publicizing SPORE activities, coordinating advisory committee meetings, producing annual reports and performing analysis of budgetary matters.
CORE B: BIOSTATISTICS AND DATA MANAGEMENT CORE
Principal Investigators:
Mei-Cheng Wang, Ph.D.
Alan Cantor, Ph.D.
Co-Investigators:
Hui-Yi Lin, Ph. D.
Hui-Chien Kuo, M.S.
Charlotte Bragg
The primary objective of the Biostatistics/Data Management Core is to facilitate and manage experimental design and statistical data analysis through consultation and collaboration at Johns Hopkins University, University of Alabama at Birmingham and University of Colorado at Boulder. The specific aims of the Core include biostatistical consultation and support to all projects in the program, by assisting in the study design, data collection, quantitative modeling, publication, as well as interpretation, visualization and analysis of data arising in the course of program activities. The Core will also provide assistance with the identification and solution of complex database tasks arising in the course of project activities - this includes integration of clinical and basic research databases and interfaces for data entry, data retrieval, patient or sample tracking, and procedures to ensure data quality, integrity, and confidentiality at JHU and UAB. This database will provide a centralized means to produce interim reports of projected progress, patient accrual, processing of specimens, completeness of data gathering, and monitoring of patient drop out or loss to follow-up. The Core also provides the infrastructural support, programming, and computer maintenance necessary for the biostatistical and data management activities within the program. Finally, the Core continues to provide support for the SPORE website development and maintenance.
The Biostatistics/Data Management Core is led by Dr. Mei-Cheng Wang, Ph.D. from Johns Hopkins University and Dr. Alan Cantor, Ph.D. from University of Alabama at Birmingham. The Core is comprised of biostatisticians and supporting personnel from both JHU and UAB. All projects and other cores of the SPORE will be supported by the Biostatistics/Data Management Core.
CORE C: TISSUE AND PATHOLOGY CORE
Principal Investigators:
Anna Yemelyanova , M.D.
Lawrence Lamb, Ph.D.
Co-Investigators:
Brigitte Ronnett, M.D.
Robert Giuntoli, Ph.D.
Michael Conner, M.D.
Patti E. Gravitt, Ph.D.
This Tissue/Pathology Core provides well-characterized human biological specimens to researchers participating in the Johns Hopkins Cervical Cancer SPORE and other similar research efforts. In the first funding period, this core collected over 78,000 individual aliquots from over 3524 patients enrolled by the SPORE in Cervical Cancer and has distributed 6332 aliquots to date. This core also banked over 28,000 aliquots from 838 patients to date from a clinical trial and two epidemiologic studies of the JHU Breast Cancer and Head and Neck SPOREs at no additional cost. In addition to the growing need for sophisticated sample acquisition, investigators increasingly depend on expert pathology support to ensure proper tissue preparation and characterization for selected studies. This Core will also provide expert pathologic evaluation of specimens and technical support.
Specifically, this core will:
- Obtain informed consent and collect specimens from patients for translational research without compromise of patient care or confidentiality;
- Collect cervical carcinoma and pre-malignant lesions, as well as normal tissue from patients, including those enrolled in clinical trials for the SPORE projects;
- Collect blood, secretions and exfoliated cells (e.g. cervical scrapes) from patients, including those enrolled in clinical trials for the SPORE projects;
- Process and store clinical specimens following SOPs to address the requirements of all SPORE investigators;
- Input specimen information into central database system and track specimen distribution and transport;
- Characterize tissue specimens with respect to site of origin, pathologic grading and staging, and proportion of neoplastic and stromal tissue;
- Use well-defined mechanisms for prioritization of the distribution of requested specimens to investigators within and external to the Johns Hopkins SPORE;
- Provide quality-controlled specimens in a timely fashion as inexpensively and efficiently as possible;
- Route specimens for histologic and virologic analyses e.g. immunohistochemical staining, in situ hybridization, tissue microarraying, and HPV testing and typing, immunophenotyping, or laser-capture microdissection in fee per service diagnostic facilities;
- Support the development and implementation of immunologic assays. The samples are tracked using a password-protected database that will be web enabled for access by our projects at UAB and UC.
The activities of this Core will be integrated with those of the Administrative/Clinical Core A, the Biostatistics and Data Management Core B and the Immunology Core D to ensure that specimens and clinical information are appropriately catalogued and disseminated.
CORE D: IMMUNOLOGY CORE
Principal Investigators:
Raphael Wiscidi, M.D.
Chien-Fu Hung, Ph.D.
Co-Investigator:
Shiwen Peng, Ph.D.
The Immunology Core (Core D) is a new core that was established after discussion by the SPORE Internal and External Advisory Committees and in response to the previous critique of our renewal application. The principal goal of the Core is to establish standardized assays of cellular and humoral immune responses to the vaccines being developed and tested by the four projects of the SPORE program. Standardization will be achieved by use of uniform reagents and protocols, trained personnel and stringent quality control measures. Centralized performance of these assays will facilitate head-to-head comparisons of vaccines that use the same primary immunological outcome measures and provide for efficient use of resources. Because some SPORE investigators have a financial interest in the vaccines that are being tested, assessment of immunogenicity by an independently directed laboratory will also allay concerns over possible conflicts of interest. The services provided by the Core to the individual projects are the following. For Project I, the assays include serum IgG-specific HPV 16 L1 virus like particle (VLP) enzyme linked immunosorbent assay (ELISA) and HPV 16, 31 and 33 in vitro pseudovirion neutralization assays. The latter 2 types are included to assess possible cross neutralization of genetically related types. For Project II, the Core will perform an ELISA to detect serum IgG directed against the vaccinogen, HPV L2 11-200x3 protein and in vitro pseudovirion neutralization assays for HPV 6 and 11 and 15 high risk HPV types. For the subset of subjects vaccinated with Gardasil, serum samples will be tested in the HPV 16 VLP ELISA and HPV 6, 11, 16, 18, 31, 33 and 45 pseudovirion neutralization assays. For Projects III and IV, the Core will perform IFN-gamma ELISPOT assays on unfractionated peripheral blood mononuclear cells (PBMC) following overnight stimulation with pools of E6 or E7 peptides. The CD8+ and CD4 + phenotype of the responding lymphocytes will be confirmed by intracellular cytokine staining and flow cytometry. Secondary immunologic assays, assays specific to an individual project and novel immunologic assay development will be performed and perfected by the investigators within the individual projects and only transferred to the Immunology Core when fully optimized and standardized.
The Immunology Core will interact extensively with the individual projects as well as the Tissue/Pathology Core (Core C), which will provide specimens, and the Biostatistics/Data Management Core (Core B), which will perform data analyses.
DEVELOPMENTAL RESEARCH PROGRAM
Directors:
Drew M. Pardoll, M.D., Ph.D.
T.-C. Wu, M.D., Ph.D
The Developmental Research Program is an important component of the SPORE and critical to the long-term fight against cervical cancer. It provides an avenue for soliciting new research ideas and for developing innovative high-risk, but high-impact projects to stimulate cervical cancer research in the context of the SPORE. Pilot studies provide investigators with the resources to conduct translational research consistent with the SPORE's objectives. This program will encourage participation from a broad range of investigators at Johns Hopkins by providing support for pilot projects with the potential to develop into more fully developed translational projects. It will also encourage and facilitate the development of new research directions, methodologies, and collaborations.
CAREER DEVELOPMENT PROGRAM
Directors:
T.-C. Wu, M.D., Ph.D.
Edward Partridge, M.D.
The Career Development Program will allow the Cervical Cancer SPORE to attract and stimulate young investigators to carry out translational research related to cervical cancer. Candidates will submit an application and be evaluated through a careful selection process involving a career development committee headed by Dr. T.-C. Wu as well as the SPORE steering committee. Dr. Robert J Kurman will assist the translational and clinical efforts of awarded investigators. Recipients of the award will be reviewed annually and investigators are required to submit an annual progress report subject to the aforementioned review process.
LIST OF INVESTIGATORS
Ronald Alvarez, M.D.
Professor
University of Alabama at Birmingham
Division of Gynecologic Oncology
176F Room 10250
619 19th Street South
Birmingham, AL 35249
Alan Cantor, Ph.D.
Professor
University of Alabama at Birmingham
Division of Preventative Medicine
Medical Towers 647
717 11th Avenue South
Birmingham, AL 35205
Michael Conner, M.D.
Professor
University of Alabama at Birmingham School of Medicine
North Pavillion 3538
619 19th Street South
Birmingham, AL 35249
Robert Garcea, M.D.
Professor
University of Colorado Boulder
Molecular, Cellular, and Developmental Biology
347 UCB
Boulder, CO 80309
Robert Giuntoli, M.D.
Assistant Professor
Johns Hopkins University School of Medicine
600 North Wolfe Street, Phipps 281
Baltimore, MD 21287
Patti Gravitt, Ph.D.
Associate Professor
Johns Hopkins University School of Public Health
615 N. Wolfe Street, Room E6148
Baltimore, MD 21205
Warner Huh, M.D.
Professor
University of Alabama at Birmingham
Division of Gynecologic Oncology
176F Room 10250
619 19th Street South
Birmingham, AL 35249
Hui-Yi Lin, Ph.D.
Assistant Professor
University of Alabama at Birmingham
Division of Preventative Medicine
Medical Towers 637
1717 11th Avenue South
Birmingham, AL 35205
Chien-Fu Hung, Ph.D.
Associate Professor
Johns Hopkins University School of Medicine
1550 Orleans Street, CRB II Room 307
Baltimore, MD 21231
Robert Kurman, M.D.
Professor
Johns Hopkins University School of Medicine
401 North Broadway, Weinberg 2242
Baltimore, MD 21231
Lawrence Lamb, Ph.D.
Professor
University of Alabama at Birmingham
Department of Medicine
Tinsley Harrison Tower 541
1530 3rd Ave South
Birmingham, AL 35294
Drew Pardoll, M.D., Ph.D
Professor
Johns Hopkins University School of Medicine
1650 Orleans Street, CRB I Room 444
Baltimore, MD 21231
Edward Partridge, M.D.
Professor
University of Alabama at Birmingham
Obstetrics & Gynecology
North Pavilion 2555
619 19th Street South
Birmingham, AL 335249
Shiwen Peng, Ph.D.
Research Associate
Johns Hopkins University School of Medicine
1550 Orleans Street, CRB II 310
Baltimore, MD 21231
Brigitte Ronnett, M.D.
Professor
Johns Hopkins University School of Medicine
401 N. Broadway, Weinberg 2242
Baltimore, MD 21231
Richard Roden, Ph.D
Professor
Johns Hopkins University School of Medicine
1550 Orleans Street, CRB II Room 308
Baltimore, MD 21231
Michael Straughn, M.D.
Professor
619 19th Street South
OHB Room 538
Birmingham, AL 35249
Cornelia Trimble, M.D.
Associate Professor
Johns Hopkins University School of Medicine
600 N. Wolfe St., Phipps 225
Baltimore, MD 21287
Raphael Viscidi, M.D.
Professor
Johns Hopkins University School of Medicine
600 N. Wolfe Street, Blalock 1153
Baltimore, MD 21287
Mei-Cheng Wang, Ph.D
Professor
Johns Hopkins University School of Public Health
615 N. Wolfe St., Hygiene E3039
Baltimore, MD 21205
T.-C. Wu, M.D., Ph.D
Professor
Johns Hopkins University School of Medicine
1550 Orleans Street, CRB II Room 309
Baltimore, MD 21231
Anna Yemelyanova, M.D.
Assistant Professor
Johns Hopkins University School of Medicine
401 N. Broadway, Weinberg 2242
Baltimore, MD 21231
