Training

STD/AIDS Research Training Fellowship Program

Bacterial STD Research Track

Sheila Lukehart, Ph.D. and Pat Totten, Ph.D., Co-Directors

Overview: The training program in Bacterial & Eukaryotic STD Research provides each trainee with extensive and in-depth expertise to enhance 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 track faculty members. Often, physician trainees in this track have mentors in both clinical and basic science departments to provide optimal supervision in both aspects of their training. Additionally, broad training experiences are also emphasized to provide trainees with a comprehensive overview of the public health, clinical, microbiological and behavioral aspects of bacterial and eukaryotic STDs.

Trainees include predoctoral students who have finished coursework, identified a mentor and developed a research project, as well as PhD and MD postdoctoral fellows. The training program includes laboratory-based or epidemiological research, the core curriculum, seminars, and supervised writing of publications and grant proposals. The track directors and the primary mentors assess each fellow's training needs, suggest additional courses if desirable, 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.

Predoctoral training: Pre-doctoral trainees will complete the STD/AIDS core curriculum as well as all course work and dissertation requirements of their respective graduate programs. Relevant elective courses are taught by faculty in Microbiology, Pathobiology, Immunology, Medicine, Pathology, Molecular & Cellular Biology, and Epidemiology. Courses of particular relevance to our trainees are Molecular Mechanisms of Bacterial Pathogenesis, Molecular Epidemiology of Infectious Diseases, and Antibiotic Resistance Mechanisms.

Post-doctoral training: In addition to the STD/AIDS core curriculum, PhD and MD postdoctoral trainees, with their mentors, select didactic opportunities to complement their backgrounds and to fill any scientific gaps. Each MD trainee completes a 1-month rotation in the Clinical Microbiology Laboratory at UWMC or HMC, focusing on both classical and molecular amplification approaches to bacterial isolation and identification, as well as antimicrobial susceptibility testing and molecular strain typing, including RFLP and PFGE.

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 in Departments of Microbiology, Pathology, Pathobiology and Immunology; (2) monthly Bacterial Pathogenesis Work-in-Progress meetings in which trainees present their ongoing research; and (3) bi-weekly Laboratory Medicine Grand Rounds. Trainees present their ongoing work at the Annual STD & AIDS Research Symposium [where they receive written structured feedback from faculty and fellow trainees] and/or at the Annual Retreat. Predoctoral and post-doctoral trainees also present their work at annual research retreats organized by their home departments.

Faculty: 12 training faculty and 5 resource faculty from clinical and basic science departments participate in this track.

Research Training Opportunities: Ongoing research opportunities described below for training faculty include pathogenesis, immunology, and molecular epidemiology of T. pallidum, N. gonorrhoeae, C. trachomatis, H. ducreyi, Mycoplasma, Toxoplasma and Candida infections; the epidemiology and pathogenesis of urinary tract infections; and the discovery of new potential etiologic agents for STD syndromes such as urethritis, bacterial vaginosis, and salpingitis. Abbreviated research descriptions for 11 senior and 1 junior training faculty are provided below.

• Lukehart, Sheila PhD Program Co-Director, Track Co-Director, Training Faculty The Lukehart lab studies the pathogenesis of syphilis and the immune response to Treponema pallidum in humans and in animal models. Recent focus is on antigenic variation of a surface protein (TprK), the molecular mechanism of sequence variation and its immunological implications. With Drs. Centurion and Van Voorhis, regulation of gene expression of tprK and the functions of other putative outer membrane proteins are also being examined. With Dr. Marra, the lab is examining the pathogenesis of neurosyphilis.
  
  
• Totten, Patricia PhD Track Co-Director, Training Faculty The Totten laboratory focuses on the molecular pathogenesis of sexually transmitted bacteria. This includes Haemophilus ducreyi virulence factors and a primate model for chancroid pathogenesis studies. With Dr. Manhart and others, we demonstrated an association of Mycoplasma genitalium (Mg) with urethritis in men, and cervicitis and endometritis in women. We have shown extensive variation in the genes for two surface exposed proteins of Mg, consistent with recombination with archived partial gene copies distributed throughout its chromosome. We are investigating the genes involved in mediating this variation and the role of gene variation on antigenic variation and immune escape. Finally, we identify novel bacteria associated with idiopathic STD syndromes of the upper reproductive tract in women.
  
  
• Centurion-Lara, Arturo MD Junior Training Faculty The Centurion laboratory, with Dr. Lukehart, focuses on mechanisms of immune evasion in T. pallidum, mechanisms of regulation of gene expression in treponemes, and treponemal species/ subspecies differentiation. With Drs. Lukehart and Marra, we are developing tools for differentiation of syphilis from non-syphilis treponemes as well as for syphilis strain typing.
  
  
• Fredricks, David MD Training Faculty The Fredricks laboratory studies fastidious or cultivation-resistant microbes and their roles in poorly understood human diseases, including bacterial vaginosis (BV). We primarily use PCR and fluorescence in situ hybridization (FISH) to characterize vaginal microbial communities and to correlate bacterial species composition and concentrations with adverse health outcomes such as HIV shedding, HIV acquisition, preterm labor, and pelvic inflammatory disease. These studies are conducted in collaboration with Dr. Marrazzo.
  
  
• Krieger, John MD Training Faculty Dr. Krieger's scope of research has involved research projects in many areas of urogenital infections including: vaginitis, urethritis, prostatitis, epididymitis and genital shedding of HIV. His unique perspective as a the senior practicing urologist in the UW system and one of very few urologists with training in infectious diseases provides a unique background for understanding anatomic and physiological aspects of STD/AIDS. His current research interests focus on prostatitis, interstitial cystitis and implementation of male circumcision to prevent HIV infections. He is an editor or on the editorial boards of five journals including STD and the Journal of Urology and is a consultant to numerous groups on urogenital infections including CDC, WHO and the American Urological Association.
  
  
• Marra, Christina MD Training Faculty Broadly, Dr. Marra's research focuses on infections of the central nervous system (CNS), focusing on neurosyphilis and HIV. Studies include defining predictive algorithms for neurosyphilis risk, new methods to diagnose neurosyphilis, and using molecular techniques to model the course of CNS syphilis. Research projects relating to HIV and the CNS are performed with the national AIDS Clinical Trials Group and with the national Neuro-AIDS Research Consortium. Most recently, Dr. Marra was the protocol chair for ACTG 736, "Cerebrospinal Fluid HIV-1 and Cognitive Function in Individuals Receiving Potent Antiretroviral Therapy.”
  
  
• Parsons, Marilyn PhD Training Faculty Dr. Parson’s research interests include the cell biology of protozoan parasites including Toxoplasma gondii, an important opportunistic pathogen in untreated AIDS patients. Specific focus is on a unique and essential organelle called the apicoplast which is genetically and functionally related to chloroplasts. Because the human host lacks a similar organelle, the apicoplast is an important target for development of anti-parasitic agents. Our work now focuses on the mechanisms and motifs involved in protein trafficking to the membranes of the T. gondii apicoplast.
  
  
• Patton, Dorothy PhD Training Faculty The Patton lab utilizes several macaque models to study the role of the topical microbicides in prevention of sexual transmission of C. trachomatis and Trichomonas vaginalis; to determine immunologic responses to various chlamydial antigens (with Dr. Van Voorhis); to evaluate antibiotic and anti-inflammatory treatments for existing chlamydial PID; to assess pathogenicity of aberrant, non-fusing chlamydial EB (with Dr. Stamm). A new focus of this model is to investigate immunologic factors including the role of Toll-like receptors, which may contribute to ascending vs local cervical chlamydial genital tract infection.
  
  
• Roberts, Marilyn PhD Training Faculty Research interests include antibiotic resistance and mercury resistance genes, the mechanisms of resistance, how resistance spreads through bacterial populations in humans and the environment and ultimately, how these genes affect therapy. Current research includes azithromycin resistance in Neisseria gonorrhoeae associated with acquired macrolide resistance genes, gene expression and spread of these genes through populations, as well as the local epidemiology of N. gonorrhoeae.
  
  
• Rockey, Daniel PhD Training Faculty The Rockey lab focuses on genotypic and phenotypic variation in chlamydiae. With Dr. Stamm, we examine the differences in genotype of an isolate as it compares to the biology of disease in the affected patient and in vitro. Other research centers on tetracycline resistance in Chlamydia suis, which is a function of a Tet(C) resistance allele which integrated into the genome of C. suis. We continue to characterize the nature of this resistance and the possibility that the gene might transfer to other chlamydial strains in vitro. Dr. Rockey is located at Oregon State University, but has very close ties to UW where he serves as Project Director for a UW STD CRC projects, with Dr. Stamm. He travels to UW frequently for ongoing research collaborations and to attend seminars, symposia, and to participate in courses.
  
  
• Van Voorhis, Wesley MD, PhD Training Faculty A major focus is studying the immune response and function of several newly identified putative surface proteins of T. pallidum, with Drs. Centurion and Lukehart. Potential vaccine and diagnostic candidate proteins are being identified using functional, molecular subtraction, or genomic analysis approaches. Another research emphasis, in collaboration with Dr. Patton, is determining the role of cytokine expression by immune cells in the primate model of chlamydial pelvic inflammatory disease.
  
  
• White, Ted PhD Training Faculty Dr. White’s research interests center on Candida albicans, the agent of oral, vaginal and systemic candidiasis (often associated with immune compromised HIV-infected individuals. Specifically, we examine how those fungi respond to antifungal drugs, and the molecular mechanisms behind that response. Recent efforts have concentrated on understanding how fungal cells regulate sterol metabolism, the target of many antifungal drugs.