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
- 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
- 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.
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