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STD/AIDS Research Training Fellowship Program

Bacterial & Viral STD Pathogenesis & Immunology Research Track

Director: Denise A. Galloway, PhD

Overview: The Bacterial & Viral STD Pathogenesis & Immunology Research Track offers laboratory-based or translational research on bacterial and viral STDs, including molecular epidemiology, with the goal of preparing investigators for independent research careers working in pathogenesis, immunology, virology or bacteriology, and molecular epidemiology. Predoctoral trainees participate in course-work and dissertation research leading to a PhD in Microbiology, Pathobiology, Immunology, Molecular and Cellular Biology, or Pathology. Postdoctoral (PhD and MD) trainees receive rigorous focused scientific laboratory training, with MDs working alongside PhDs. The Track Director, Dr. Galloway, is internationally recognized for her research into the mechanisms by which HPV contributes to neoplasia.

Faculty

20 Training Faculty and 4 Junior Training Faculty

Galloway, Denise, PhD Track Director, Training Faculty   
The overall focus of the Galloway Lab is to understand the mechanisms by which viruses, particularly HPV and human polyomaviruses, contribute to human cancers. Research has focused on high risk HPV that are causally associated with all cervical cancers and the majority of anogenital and oropharyngeal cancers. Additional research includes investigating whether genus beta HPVs are involved in squamous cell skin cancers, and the role that the Merkel Cell Polyomavirus plays in Merkel Cell Carcinoma.

Emerman, Michael, PhD Training Faculty   
The Emerman lab studies host-cell interactions of HIV and related viruses. The goal is to understand the molecular and evolutionary basis of virus replication and pathogenesis. The research team studies the evolution and function of host antiviral genes in order to determine how HIV adapted to humans,and how ancient viral infections influenced the susceptibility or resistance of humans to modern lentiviruses.

Fredricks, David MD Training Faculty   
The Fredricks laboratory studies the human indigenous microbiota to determine how changes in microbial communities impact human health. The team uses tools such as broad range 16S rRNA gene PCR to describe microbial diversity in human body sites with a focus on the vaginal microbiota and the common condition bacterial vaginosis (BV). The team also studies the role of novel genital tract bacteria in pelvic inflammatory disease, idiopathic urethritis, cervicitis, HIV acquisition and shedding, and preterm birth.

Fuller, Deborah PhD Training Faculty   
Research is focused on the role of mucosal CD4+/CD8+ T cell responses in control of HIV infection, using the SIV model for AIDS to investigate immune mechanisms of viral control and to design and test new vaccine approaches for prophylaxis and therapy. Projects are driven by 3 primary hypotheses: 1. Mucosal immunity is necessary to control and prevent infection at the site of exposure. 2. Broad specificity in the mucosal CD8 response restricts viral evolution and disables fitness of residual virus in the gut reservoir. 3. Inflammation and immune activation influence effectiveness of prophylactic and therapeutic vaccines.

Gale, Michael, Jr., PhD Training Faculty   
Research is aimed at understanding the innate immune processes that control virus infection and viral oncogenic potential. A major goal is to define in molecular terms virus-host interactions that trigger and regulate innate defenses against hepatitis C virus (HCV), HIV, influenza virus, and West Nile virus. The lab uses in vitro and in vivo models to elucidate key viral and cellular determinants of host defense regulation to define novel therapeutic targets in anti-viral innate immune defenses and oncogenic transformation, aiming to ultimately design strategies to augment innate immune control of these chronic viral infections and limit malignancy progression.

Gottlieb, Geoffrey MD, PhD Training Faculty   
Dr. Gottlieb is the PI of a study in Senegal, West Africa, on the effect of antiretroviral therapy (ART) on HIV-2 disease outcomes, emergence of drug resistance, and genital shedding. He is also involved in understanding the differences between natural history, clinical, immunologic and virologic aspects of HIV-1 and HIV-2 infection. In addition, he has been studying the effects of dual infection with HIV-1 and HIV-2 on disease outcomes and ART in Senegal.

Hybiske, Kevin PhD Training Faculty   
The Hybiske laboratory is broadly interested in the interactions between intracellular pathogens and host cells. A major research focus of the lab is to decipher the mechanisms by which the intracellular pathogens Chlamydia and malaria manipulate cellular function in order to exit host cells and cause infectious disease. Both pathogens have coevolved similar mechanisms to do so. Our ultimate goal is to leverage a thorough understanding of these pathogenic mechanisms as a new, unexplored therapeutic platform.

Koelle, David, MD Training Faculty   
Dr. Koelle's team studies immune responses to infections, pathogen variation, and relationships of host genomics and infection severity. Pathogens include HSV, vaccinia, Merkel cell polyoma virus and Mycobacterium tuberculosis. He uses genomic libraries and genome-spanning ORF sets to interrogate T-cells to high definition. Candidate HSV vaccines are poised to enter phase I trials. The team measures cellular immunity at sites of infection, such as skin, the genital tract, cornea, trigeminal ganglia, and tumor biopsies. Mouse studies focus on vaccine immunogenicity and efficacy in the HSV-2 system. Newer initiatives include T-cell diversity by deep sequencing, HSV genetic diversity, and long-term T-cell memory. Large numbers of T-cell tests for tuberculosis are being run for the CDC.

Lagunoff, Michael, PhD Training Faculty   
The Lagunoff lab is interested in how Kaposi's Sarcoma-associated herpesvirus KSHV alters endothelial cells to cause KS. The team studies multiple aspects of the host-pathogen interactions with a focus on two main areas, viral induction of angiogenesis and viral alterations in host cell metabolism, both likely critical for the formation of this highly vascularized tumor.

Lingappa, Jaisri, MD, PhD Training Faculty   
The Lingappa laboratory studies viral-host interactions that promote virus assembly, and has demonstrated that during assembly the HIV-1 capsid protein Gag progresses through an energy-dependent pathway of assembly intermediates that requires catalytic action of at least two host enzymes, the ATP binding protein ABCE1 and the RNA helicase DDX6. This assembly pathway is initiated when Gag co-opts a novel complex in cells that contain ABCE1, DDX6, and other proteins that may facilitate HIV-1 assembly and packaging. Studies have led to identification of novel small molecules that inhibit replication of HIV-1 and other viruses.

Lingappa, Jairam, MD, PhD Training Faculty   
Research is focused on identifying the role of host factors in modulating host susceptibility to and poor outcomes from infections. Dr. Lingappa has used samples and data derived from recent large HIV-1 prevention clinical trials conducted in Africa to identify genomic factors that reduce host susceptibility to HIV-1. Using technologies such as complete genome sequencing, gene expression analysis and proteomics applied to deeply phenotyped samples, the aim is to understand the host response underlying resistance to HIV-1 in the hope that this response could be elicited in individuals lacking specific genetic traits.

Lukehart, Sheila PhD Training Faculty   
Dr. Lukehart has focused her research on the genetic diversity of the pathogenic treponemes, antigenic variation and molecular pathogenesis of syphilis, and the host immune responses to Treponema pallidum. While her work is largely laboratory-based, she has conducted several clinically relevant investigations, most notably on neurosyphilis, syphilis-HIV interactions, and antibiotic resistance in T. pallidum.

McElrath, M. Juliana, MD, PhD Training Faculty   
Dr. McElrath is Director of the Vaccine and Infectious Disease Division, and PI of the HVTN Laboratory and Seattle VTU. She heads the clinical infectious diseases service at the FHCRC/SCCA. Her research pursues a vaccine that will protect against HIV-1 infection and a deeper understanding of the components of immunity that control of HIV-1. She maintains a successful international HIV vaccine laboratory program, and conducts immunological research in humans in a multicenter setting.

Mullins, James, PhD Training Faculty   
The Mullins lab uses molecular, computational, and virus biology methods to investigate the relationship between HIV and its human hosts, striving to understand the implications of HIV's genetic diversity on the immunopathogenesis of AIDS, with an emphasis on acute/early infection and superinfection. The work focuses on the characterization of HIV nucleotide sequences, the development of web tools for related computational studies, in vitro studies of the growth properties of viral isolates, host genetic polymorphism analysis, and high-throughput analysis of cellular transcription.

Overbaugh, Julie, PhD Training Faculty   
Dr. Overbaugh's laboratory is part of a collaborative team that is pursuing translational research on the molecular epidemiology of HIV-1 transmission. These studies, which include investigators in Seattle and Kenya, include studies of mother-to-infant transmission, natural history studies of transmission and pathogenesis in women, and studies of virus and host factors that contribute to transmission and disease progression in these settings. A central aspect of this work is exploring the role of neutralizing antibodies in limiting HIV transmission and disease, including in individuals who become re-infected with HIV.

Patton, Dorothy, PhD Training Faculty   
The Patton Laboratory utilizes several pigtailed macaque models to study C. trachomatis. Topical microbicides are also tested for effects on vaginal or rectal microflora, as well as changes in epithelial tissues and efficacy in prevention of both cervical and rectal chlamydial infections. Second, the macaque model of pelvic inflammatory disease (PID) characterizes upper genital tract disease resulting from ascending cervical infection. The PID model has been used to evaluate antibiotic and anti-inflammatory treatments for existing chlamydial disease, immunologic responses to Chlamydia including Toll-like receptors, and genetic predisposition to PID. Third, the evaluation of candidate chlamydial vaccine antigens is ongoing.

Smith, Kelly D., MD, PhD Training Faculty   
Dr. Smith's lab investigates the mucosal immune response to infectious pathogens. Much of the work has focused on Salmonella typhimurium infection, and the role of the innate immune system, specifically flagellin recognition. The team is currently dissecting the innate immune pathways that are required for flagellin recognition, and determining how these pathways affect mucosal infections, inflammation and the ability of the host to mount antibody responses. They are harnessing their detailed understanding of flagellin structure and function to develop novel vaccines against broadly conserved HIV epitopes.

Sodora, Donald, PhD Training Faculty   
Dr. Sodora's laboratory has assessed SIV and HIV transmission and disease progression in monkeys and humans. One of the seminal findings is that oral transmission of SIV results in entry of the virus through mucosal tissues in the mouth and esophagus and that the virus spreads to many tissues rapidly. The overall goal of the laboratory is to compare findings from the SIV/monkey models to what is occurring in HIV infected humans.

Stamatatos, Leo, PhD Training Faculty   
Research aims to develop a safe, effective HIV vaccine and to investigate how HIV infection leads to AIDS. Of interest are identifying immunological pathways that lead to development of broadly neutralizing antibodies during natural HIV infection; exploiting these pathways for vaccine-related purposes; and understanding how HIV evolves to avoid the action of such antibodies. Projects focus on HIV envelope structure/function relationship, B cell immunology in the context of HIV infection, HIV evolutionary escape pathways and pathogenesis, and HIV vaccine design.

Totten, Patricia, PhD Training Faculty   
Dr. Totten studies the disease syndromes, risk factors, and treatment efficacies for M. genitalium. She also studies the repercussions of antigenic and phase variation in two surface-exposed proteins expressed by this pathogen, in studies with persistently infected women, primate models for infection, and in vitro experiments. Finally, she is exploring the role of potential recombination enzymes and regulatory factors leading to variation in the genes encoding these proteins and archived copies of these genes.

Centurion-Lara, Arturo MD Junior Training Faculty   
Research focuses on syphilis: 1) identifying the members of the TpCRP (a global transcriptional regulator) regulon in the syphilis spirochete by CHIP and RNA sequencing approaches; 2) studying the genome-wide genetic diversity of syphilis strains to identify adaptive mutations associated with different clinical outcomes; 3) In collaboration with Dr. Sheila Lukehart, studying the implications of diversity of the TprK antigen in immune evasion, and antigenic differences in surface exposed loops of the TprC and TprD antigens and their significance in cross immunity among treponemal species, subspecies and strains.

Frahm, Nicole, PhD, MS Junior Training Faculty   
Research centers on characterization of cellular immune responses induced by HIV-1 infection and by experimental HIV vaccines. In her role as the Associate Director for Laboratory Science at the HIV Vaccine Trials Network, Dr. Frahm's research provides a comprehensive overview of vaccine-induced cellular immunity including innate, T-cell, as well as B-cell responses in the periphery and gastrointestinal tract, encompassing various vaccine platforms aimed at preventing HIV acquisition. Research involving HIV-infected persons aims at defining immune responses associated with natural control of viral replication, including understanding the influence of HIV sequence diversity on recognition by cytotoxic T lymphocytes.

Katzenellenbogen, Rachel, MD Junior Training Faculty   
Dr. Katzenellenbogen studies how the E6 oncoprotein of high-risk HPV 16 affects telomerase activity in cells, and specifically the catalytic subunit of telomerase, hTERT. HPV 16E6 can increase telomerase expression through transcriptional activation of hTERT, but HPV 16E6 also increases hTERT post-transcriptionally through its interaction with NFX1-123. NFX1-123 is an endogenous protein, found in the cytoplasm of epithelial cells, and this protein can bind to and increase the stability of the hTERT mRNA. She is also studying new roles for NFX1-123, HPV 16E6 and RNA processing proteins in cervical cancer, tumorigenesis, and the virus life cycle.

Lund, Jennifer, PhD Junior Training Faculty   
Research focuses on elucidating the basic mechanisms of immunity in the context of virus infection. Specifically, the team uses a mouse model to study how regulatory T-cells affect the anti-viral immune responses to genital HSV-2, influenza, and West Nile virus. We are also investigating immune correlates of protection from HIV infection using a cohort of exposed seronegative individuals, and the potential immune modulatory effects of HIV pre-exposure prophylaxis.




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STD/AIDS Research Training Fellowship Program

Introduction

Training Program Organization

Upcoming Events

Core Curriculum

Application Information

Bacterial & Viral STD Pathogenesis & Immunology Track

Research in HIV/STD Care & Affected Populations Track

Epidemiology & Prevention Interventions for HIV/STD Track

STD/HIV in Maternal, Child, & Adolescent Health Track

Health Metrics & Modeling in HIV/STD Track

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