A5082159477- HIV Research and Treatment
- Reproductive tract infections research
- Immune responses and vaccinations
- Immune Cell Function and Interaction
- Reproductive System and Pregnancy
- Tuberculosis Research and Epidemiology
- Retinal Development and Disorders
- HIV/AIDS Research and Interventions
- Cytomegalovirus and herpesvirus research
- Reproductive Health and Contraception
- Immune Response and Inflammation
- Syphilis Diagnosis and Treatment
- Developmental Biology and Gene Regulation
- Immunodeficiency and Autoimmune Disorders
- Herpesvirus Infections and Treatments
- Gut microbiota and health
- Cervical Cancer and HPV Research
- Animal Disease Management and Epidemiology
- Cell Adhesion Molecules Research
- Sexual function and dysfunction studies
- Hedgehog Signaling Pathway Studies
- Mosquito-borne diseases and control
- HIV-related health complications and treatments
- Photochromic and Fluorescence Chemistry
- Reproductive Physiology in Livestock
Infectious Disease Research Institute
2017-2024
Seattle University
2023
University of Washington
2012-2023
Center for Infectious Disease Research
2010-2017
Fred Hutch Cancer Center
2012
National Institute of Neurological Disorders and Stroke
2012
National Institutes of Health
2009-2012
The separation of the optic neuroepithelium into future retina and retinal pigment epithelium (RPE) is a critical event in early eye development vertebrates. Here we show mice that transcription factor PAX6, well-known for its retina-promoting activity, also plays crucial role development. This seen, however, only background genetically sensitized by mutations cell MITF. In fact, reduction Pax6 gene dose exacerbates RPE-to-retina transdifferentiation seen embryos homozygous an Mitf null...
Abstract Effective contraceptives are a global health imperative for reproductive-aged women. However, there remains lack of rigorous data regarding the effects contraceptive options on vaginal bacteria and inflammation. Among 218 women enrolled into substudy ECHO Trial (NCT02550067), we evaluate effect injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG), copper intrauterine device (Cu-IUD) environment after one six consecutive months use, using...
Adolescent girls and young women represent a key risk group for sexually transmitted infections (STIs). The vaginal microbiota is thought to play an important role in susceptibility STIs such as Chlamydia trachomatis. We compared the of lateral wall endocervix, assessed associations with C. trachomatis infection South African adolescents. endocervical were characterized by amplifying sequencing V4 region 16S rRNA gene diagnosed using molecular methods. Of 72 included, 30 had asymptomatic...
HIV-infected children may require the use of combination antiretroviral treatment (cART) into adulthood. However, regimens are limited to first line and second in many African settings. Therefore, understanding long-term rate virologic failure drug resistance during prolonged is important for establishing strategies pediatric cohorts.Children aged 18 months 12 years initiated first-line cART were followed every 1-3 months, up 5.5 years. Treatment was switched second-line based on clinical...
The pituitary gland is an endocrine organ that developmentally derived from a fold in the oral ectoderm and juxtaposed neural ectoderm. Here, we show absence of Vax1, homeodomain transcription factor known for its role eye optic chiasm development, causes rostral to form ectopic eventually develops into separate second with all cell types neuronal fibers characteristic normal pituitary. induction associated localized expression Fgf10, gene encoding growth recruit ectodermal cells...
Studying SIV infection of natural host monkey species, such as sooty mangabeys, has provided insights into the immune changes associated with these nonprogressive infections. Mangabeys maintain health despite high viremia or dramatic CD4 T cell depletion that can occur following multitropic infection. Here we evaluate double-negative (DN)(CD3+CD4−CD8−) cells are resistant to due a lack surface expression, for their potential fulfill role helper cells. We first determined DN polyclonal and...
Mucosal transmission of HIV predominately occurs during sexual intercourse or breast-feeding and generally results in a successful infection from just one few founder virions. Here we assessed the impact viral inoculum size on both immune events within two groups Rhesus macaques that were non-traumatically, orally inoculated with either multiple low (1000 to 4000 TCID50) high (100,000 doses SIV. In agreement previous studies, more diverse SIV variants observed following dose oral compared...
Abstract In a phase-IIa trial, we investigated the influence of 90 days continuous-delivery tenofovir (TFV) intravaginal rings (IVRs) with/without levonorgestrel (LNG) on genital microbiota Kenyan women. Eligible women (n = 27; 18–34 years; negative for HIV, sexually transmitted infections, and Amsel-bacterial vaginosis) were randomized 2:2:1 to use IVRs containing TFV, TFV/LNG, or placebo. Using vaginal wall IVR swabs at insertion removal, microbial composition was determined using 16S rRNA...
Bacille Calmette-Guerin (BCG) vaccine can elicit good T H 1 responses in neonates. We hypothesized that the pioneer gut microbiota affects cell responses. Infants who are HIV exposed but uninfected (iHEU) display an altered immunity to vaccination. BCG-specific immune were analyzed at 7 weeks of age iHEU, and categorized as high or low. Bifidobacterium longum subsp. infantis was enriched stools responders, while Bacteroides thetaiotaomicron low responders time BCG Neonatal germ-free SPF mice...
Human immunodeficiency virus type 1 (HIV-1) infection is characterized by persistent viral replication in the context of CD4(+) T cell depletion and elevated immune activation associated with disease progression. In contrast, simian (SIV) African-origin sooty mangabeys (SM) generally does not result AIDS despite high loads therefore affords a unique model which to study immunologic contributions nonpathogenic lentiviral outcome. A key feature these natural SIV infections maintenance low...
BACKGROUND. Bacillus Calmette-Guérin (BCG) vaccine is administered at birth to protect infants against tuberculosis throughout Africa, where most perinatal HIV-1 transmission occurs. We examined whether BCG vaccination alters the levels of activated HIV target T cells in HIV-exposed South African infants.
Objective: To determine neonatal immunologic factors that correlate with mother-to-child-transmission of HIV-1. Design: This case–control study compared cord blood natural killer (NK) and T-cell populations HIV-1 exposed infants who subsequently acquired infection by 1 month (cases) to those remained uninfected year life (controls). Control specimens were selected proportional match on maternal viral load. Methods: Cryopreserved mononuclear cells (CBMCs) thawed stained for multiparameter...
Abstract The role of Myeloid-Derived Suppressor Cells (MDSC) in infant immune ontogeny is unknown. Here, we evaluated MDSC frequency and relationship with vaccine responses throughout the first year life a prospective cohort study. Ninety-one South African infant-mother pairs were enrolled at delivery, blood samples collected 0, 6, 10, 14 weeks, 6 months, 9 1 year. frequencies quantified, to childhood vaccines Bacillus Calmette-Guérin (BCG), hepatitis B (HepB), combination diphtheria,...
Sub-Saharan African female adolescents are globally at the highest risk of HIV acquisition, and genital inflammation, microbial dysbiosis, cervical target cell activation thought to contribute this risk. Previously, relationship between these mucosal factors subclinical vaginal Candida colonization or hyphae has not been described, role HIV-susceptible Th17 cells in mediating anti- immunity human tract clearly established.
Infections with mycobacteria, including Mycobacterium tuberculosis (Mtb) and bovis (M. bovis) BCG, are a leading cause of morbidity mortality for HIV-infected persons. In contrast to HIV, nonpathogenic SIV infections sooty mangabeys characterized by lack clinical disease an absence opportunistic infections. The goal this study was identify innate immune responses M. BCG maintained during lentiviral through comparison functional pathogenic HIV or Monocytes were evaluated their ability express...
Abstract T cells in the human female genital tract (FGT) are key mediators of susceptibility to and protection from infection, including HIV other sexually transmitted infections. There is a critical need for increased understanding distribution activation cell populations FGT, but current sampling methods require healthcare provider expensive, limiting ability study these longitudinally. To address challenges, we have developed method sample immune FGT utilizing disposable menstrual discs...
Although effective contraceptives are crucial for preventing unintended pregnancies, evidence suggests that their use may perturb the female genital tract (FGT). A comparative analysis of effects most common on FGT have not been evaluated in a randomized clinical trial setting. Here, we effect three long-acting contraceptive methods: depot medroxyprogesterone acetate(DMPA-IM), levonorgestrel(LNG) implant, and copper intrauterine device (Cu-IUD), endocervical host transcriptome 188 women from...
Abstract HIV infection of humans and SIV Rhesus macaques generally results in onset opportunistic infections (OIs) AIDS when left untreated. In contrast, African monkeys, such as sooty mangabeys, high levels viral replication, but the immune system remains resilient to dysfunction, OIs progression AIDS. Here, we set out identify innate correlates associated with acquisition HIV+ (and lack thereof SIV+ mangabeys), through an ex vivo cytokine transcriptomic assessment PBMC monocyte responses...
Abstract Infants who are human immunodeficiency virus (HIV)-exposed uninfected (iHEU) experience higher risk of infectious morbidity than infants HIV-unexposed (iHUU). We compared tuberculosis (TB) infection prevalence in 418 Bacillus Calmette-Guérin vaccinated sub-Saharan African iHEU and iHUU aged 9–18 months using T-SPOT.TB. Prevalence TB was low did not differ by HIV exposure status.
ABSTRACT T cells in the human female genital tract (FGT) 2 are key mediators of susceptibility to and protection from infection, including HIV other sexually transmitted infections. There is a critical need for increased understanding distribution activation cell populations FGT, but current sampling methods require healthcare provider expensive, limiting ability study these longitudinally. To address challenges, we have developed method sample immune FGT utilizing disposable menstrual discs...
Abstract Coinfection with M. tuberculosis (Mtb) and other Mycobacteria is a leading cause of morbity mortality in HIV+ patients. While neither monocytes nor NK cells are directly infected HIV, several their phenotypic functional properties become altered during chronic infection, both cell types important to the control Mtb. We hypothesized that HIV-related dysfunction may result from impaired monocyte crosstalk cells, which we will evaluate context infection. In fact, have observed decrease...