Training

STD/AIDS Research Training Fellowship Program

Bacterial STD Research Track

Sheila Lukehart, Ph.D. and Walter Stamm, M.D., Co-Directors

Overview: The training program in Bacterial STD's is designed to provide each trainee with extensive and in-depth expertise in his/her area of interest in order to insure future success as an independent scientist. This aim is achieved principally through close personal supervision of each trainee's research in the laboratory of one or more of the faculty members in the Bacterial STD track. Often, physician trainees in this track have mentors in both clinical and basic science departments in order to insure optimal supervision in both aspects of their training. Additionally, broad training experiences are also emphasized to provide every predoctoral and postdoctoral trainee with a comprehensive overview of the public health, clinical, microbiological and behavioral aspects of bacterial STDs.

Trainees include predoctoral students (who have completed departmental general examinations and have been accepted as Ph.D. candidates), as well as Ph.D. and M.D. postdoctoral fellows. The training program includes laboratory-based research, formal course work, seminar series, and supervised writing of publications and grant proposals. The track directors and the primary mentors assess each fellow's training needs and review the progress of each trainee at least yearly. These meetings serve to identify areas of strength or concern; recommendations and evaluations are communicated to the trainee and the mentor. Additionally, progress of predoctoral trainees is monitored by their dissertation committees in twice-yearly meetings; written evaluations of these meetings are provided to the students and their mentors.

Didactic Curriculum, Seminar Training Opportunities, and Mentoring.

Pre-doctoral training: Pre-doctoral trainees will complete all course work and dissertation requirements of the UW to obtain a doctorate in their respective departments. Relevant courses are taught by the Departments of Microbiology, Pathobiology, Immunology, Medicine, Pathology, and Laboratory Medicine, and by the interdisciplinary Cellular and Molecular Biology program.

Post-doctoral training: All Ph.D. and M.D. postdoctoral trainees with their mentors select didactic opportunities to complement their backgrounds. Each MD trainee completes a one month rotation in the Clinical Microbiology Laboratory at UWMC or HMC. During this month, the trainee works at the bench under the direction of the laboratory supervisor, focusing primarily on bacterial disease. Training includes classical approaches to bacterial isolation and identification, as well as antimicrobial susceptibility testing, pharmaceutical drug monitoring, specialized assays such as serum bactericidal levels, newer diagnostic techniques such as PCR and other molecular amplification techniques, and approaches to molecular strain typing such as RFLP, PFGE, and others. Relevant courses described above are also taken as needed.

Seminar opportunities. In addition to Core Curriculum and didactic courses, a number of seminars provide additional opportunities for trainees to broaden their exposure to relevant basic science, clinical, and public health issues. These include: (1) weekly Seminars of Departments of Microbiology, Pathology, Pathobiology and Immunology; (2) monthly Bacterial Pathogenesis Work-in-Progress meeting in which trainees in present their ongoing research; and (3) the every-other week Laboratory Medicine Grand Rounds. Trainees attend at least 4 seminars per month. All trainees present their ongoing work at the Annual CFAR/STD CRC Symposium for trainees and New Investigators described above, and/or at the Annual STD/AIDS Retreat. Pre-doctoral and post-doctoral trainees also attend and present their work at annual research retreats organized by their home Departments and receive critical feedback from attending faculty and fellow trainees, and interact more informally with faculty and their peers.

Faculty: Twenty-four faculty from clinical and basic science departments participate in this track.

Research Training Opportunities: Research opportunities in the Bacterial STD track are supported by the UW STD Cooperative Research Center (AI 31448), the Molecular Immunology of STD program project (AI 34616), the Vaginal Microbicides for Prevention of STD program project (AI 39061), the Pathogenic Mechanisms in Urinary Tract Infections program project (DK53369),and the Specialized Center of Research (SCOR) on Sex and Gender Affecting Women's Health (AR049075), as well as multiple individual grants from the National Institutes of Health, the Centers for Disease Control, and private foundations. Ongoing research opportunities described below for training faculty concerns the pathogenesis, immunology, and clinical and molecular epidemiology of T. pallidum, N. gonorrhoeae, C. trachomatis, H. ducreyi, and Mycoplasma/Ureaplasma infections; the epidemiology and pathogenesis of urinary tract infections; and the discovery of etiologic agents in STD syndromes such as urethritis and salpingitis. The research of 8 senior and 3 new training faculty in this track is described below.

• Stamm, Walter MD. Current research is being conducted in two main areas: urinary tract infection and chlamydial infections. The studies on UTI aim to better understand their pathogenesis by studying host-parasite interactions. The studies with Chlamydia trachomatis address: 1) development and evaluation of improved molecular methods for diagnosis of C. trachomatis infections; 2) use of molecular genetic techniques to study the pathogenesis of C. trachomatis infections; and 3) studies in humans and in a primate model of the pathogenetic mechanisms operative in PID.
  
  
• Lukehart, Sheila PhD. The Lukehart laboratory focuses on the pathogenesis of syphilis and the immune response to Treponema pallidum in humans and in animal models. The current major interest is the newly-identified polymorphic tpr gene family of T. pallidum, which comprises 2% of the T. pallidum genome and is hypothesized to encode surface-exposed antigens that are major targets of the protective immune response, may be involved in immune evasion, and are promising vaccine candidates. Ongoing projects include the cloning and characterization of major T cell antigens of T. pallidum, investigation of cytokine induction by these antigens, identification of surface molecules that are targets of opsonization, and the molecular basis for neuroinvasion and the immunologic response to T. pallidum within the CNS.
  
  
• Centurion, Arturo MD. Dr. Centurion is defining the function and cellular localization of the Tpr proteins of T. pallidum, and studying the hypothesis that at least some of the Tpr antigens are surface exposed, and may function as virulence factors (porins, proteins interacting with integral membrane and cytoplasmic molecules in the host). He is trying to determine the function of the TprK antigens by identifying protein-protein interactions using yeast two-hybrid and phage display systems.
  
  
• Lampe, Mary PhD. Dr. Lampe's research concerns 1) sensitivity of C. trachomatis to currently available microbicides and novel, naturally occurring antimicrobials; 2) the identification of Chlamydia antigens that give rise to murine cytotoxic T lymphocyte lines specific for, and able to lyse, C. trachomatis infected cells; 3) the functional analysis of the C. trachomatis PmpD protein.
  
  
• Marra, Christina MD Dr. Marra heads a multi-center study to determine how often central nervous system (CNS) infection with Treponema pallidum persists after neurosyphilis therapy in HIV-1-infected and -uninfected individuals, and what biological mechanisms contribute to control of CNS T. pallidum infection. She also uses two functional neuroimaging techniques to determine changes in brain activation in response to HAART in HIV-1-infected individuals; Chairs the national Adult AIDS Clinical Trials Group (AACTG) Neurology Subcommittee; and collaborates with the University of Hawaii to examine the role of CSF CTL in clearing HIV-1 from the CSF
  
  
• Patton, Dorothy PhD. The Patton lab studies C. trachomatis in macaque models. These studies include the role of topical microbicides in prevention of sexual transmission of chlamydia in vaginal and rectal macaques models. Evaluation of antibiotic and anti-inflammatory treatments for existing chlamydial disease; the immunologic responses to chlamydia, and genetic predisposition to PID.
  
  
• Roberts, Marilyn PhD. The laboratory's major interest is in the genetic mechanisms and regulation of antibiotic resistance. Antibiotic resistance genes are used as models for examining gene transfer and gene spread through natural bacterial populations and identifying new antibiotic resistance genes.
  
  
• Stapleton, Ann MD. The Stapleton laboratory studies interactions of microbes with mammalian glycosphingolipids on epithelial cell surfaces using urinary tract infection as a model. We have defined glycosphingolipid molecules that bind specific uropathogenic E. coli and are selectively expressed in the urogenital epithelium of females at increased risk of urinary tract infection by virtue of their genetic background. Current studies focus on studying the role of caveolae in infections of urogenital epithelia, including a recently established system of primary culture of vaginal epithelial cells.
  
  
• Totten, Patricia PhD. The Totten laboratory focuses on the pathogenesis of chancroid and the discovery of novel organisms associated with STD syndromes. She is using a primate model to examine the role of these potential virulence factors in chancroid. She is extending her findings, exploring the association of novel organisms with STD syndromes, having Mycoplasma genitalium is associated with nongonococcal urethritis in men and endometritis and cervicitis in women by studies of other syndromis; and is continuing studies that appear to implicate novel organisms associated with salpingitis in women using rDNA PCR amplification and DNA sequencing.
  
  
• Van Voorhis, Wesley MD, PhD. Dr. Van Voorhis participaties in studies of the immune response and function of a newly discovered group of variable surface proteins of Treponema pallidum called Treponema pallidum repeat (Tpr) proteins. With Drs. Caroline (Stebeck) Cameron and Lukehart, he is studying other potential vaccine candidates for T. pallidum, looking for T. pallidum surface molecules that can be opsonized by immune serum, identified by molecular subtraction or genomic analysis approaches.
  
  
• White, Ted PhD. Note: Dr. White; Dr. Jeanne Marrazzo (whose work is described in Public Health Track), and Drs. McClelland and Holmes (International Track) are studying fungal, bacterial, and protozoal causes of vaginal infections. Dr. White's interests involves molecular mechanisms contributing to virulence of Candida albicans; and on resistance to antifungal drugs in Candida, a rapidly emerging problem in the HIV-infected population and a problem spreading to other immune-compromised populations. Virulence factors of interest include secreted aspartyl proteinases that suppress immune function, molecules involved in the adhesion and invasion of Candida to the oral mucosal, and signal transduction molecules that allow the cell to vary its repertoire of virulence factors.