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$10.7 Million NIH Grant to University of Maryland Schools of Dentistry and Medicine Funds Study of New Ways to Predict, Prevent, and Treat Sexually Transmitted Infections

A $10.7 million grant to the University of Maryland School of Dentistry and the University of Maryland School of Medicine will fund the collaborative study of biomarkers associated with sexually transmitted diseases such as chlamydia, in hopes of finding new ways to predict the infection and developing new vaccines or treatments. The five-year grant from the National Institute of Allergy and Infectious Diseases is the renewal of a previous $12 million, five-year grant awarded in 2009, bringing the project's total to $22.7 million.



The health effects of infections such as chlamydia and gonorrhea are significant and widespread. Chlamydia trachomatis genital infections are the most common bacterial infectious disease in America, with 2.8 million cases reported annually. Neisseria gonorrhoeae, or gonorrhea, causes 820,000 infections in America each year. These infections together cause most of the 750,000 cases of pelvic inflammatory disease seen each year in the U.S. Pelvic inflammatory disease, in turn, is a leading cause of infertility and life-threatening conditions such as ectopic pregnancy in women.

"We believe that this project will generate new essential knowledge into the mechanisms of sexually transmitted infection and disease as they occur, both in the human host and within the microbes that cause chlamydia and gonorrhea," says co-principal investigator Patrik Bavoil, PhD, professor and chair of the Department of Microbial Pathogenesis at the School of Dentistry.

"We will be identifying human and microbial biomarkers that will tell us who is most susceptible to infection, who is most susceptible to severe disease, even in the absence of symptoms," adds Bavoil, who is also an adjunct professor in the Department of Microbiology and Immunology at the School of Medicine. "These biomarkers could also provide us with new targets for novel ways to prevent and treat STIs and STDs long before these microbes have a chance to endanger a woman's reproductive health."

The research is an example of an emerging field of genomics, the study of the microbiome - the bacteria or microbes that live on and in the human body. These microbes interact with the human genome, and in the case of infections such as chlamydia and gonorrhea, they also interact with the genetics of the pathogen causing the infection. Bavoil's and Ravel's research will examine this interaction.

"This grant is particularly significant because it is the first time that a comprehensive systems biology approach will be utilized to conduct STD research with the ultimate goal of developing knowledge to prognose, diagnose, prevent and treat sexually transmitted infection and disease," says co-principal investigator Jacques Ravel, PhD, professor of the Department of Microbiology and Immunology at the School of Medicine and associate director for genomics at the School of Medicine's Institute for Genome Sciences. "By looking at how human genetics and the microbiome affect and influence infections in humans, we can gain a much better understanding of how to protect against these types of infection, which is critical for improving public health."

The new grant establishes a Cooperative Research Center on Sexually Transmitted Infection led by the two schools of the University of Maryland, Baltimore and including an international consortium of researchers from many other institutions, including the Johns Hopkins University, the University of New South Wales, Australia, Duke University, Loyola University Chicago, the University of Idaho, and the University of Virginia.

The previous research grant awarded in 2009 established a Cooperative Research Center that forms the foundation for this new grant renewal. The original grant established STI Network Groups, consisting of multiple networks of sexual partners in which at least one partner is infected with gonorrhea or chlamydia. Participants in these STI Network Groups agree to submit genital swab samples so that the scientists can analyze changes in the vaginal and urogenital microbiome over time. This clinical core of the research project involves Katrina S. Mark, MD, instructor in the Department of Obstetrics, Gynecology and Reproductive Services at the School of Medicine and Rebecca M. Brotman, PhD, MPH, assistant professor of the Department of Epidemiology and Public Health at the School of Medicine and a research scientist at the Institute for Genome Sciences.

Researchers at the University of Maryland and the partner institutions will examine the samples taken from participants in the STI Network Groups and will analyze them using cutting edge genomic, immunologic and genetic techniques. The scientists will try to identify molecular biomarkers to help them predict who is at risk for STIs and who is less likely to become infected based on the subject's own genetics, the subject's genital microbiome composition and function and the pathogen's unique genome. The scientists hope to use those biomarkers to develop new diagnostic and therapeutic techniques for STIs.

The research grant funds three main projects. One project will examine whether host genetics play an important role in determining susceptibility to STIs and predicting the severity of the resulting disease. That project will examine the role of human genetic variance in dictating the outcome of the "dialog" between the pathogen, the microbiota and the host.

Another project, led by Bavoil and a collaborator in Sydney, Australia, focuses upon identifying certain biomarkers of chlamydia infection, chlamydia/gonorrhea co-infection and pelvic inflammatory disease. It will examine the possibility of translating these biomarkers into clinical tools for diagnoses and prevention.

Ravel will lead another project aimed at using a systems biology approach to identify biomarkers of the penile and vaginal microbiomes, the genetic variation of the host and the genetics of the pathogens associated with increased or decreased risk of infection by chlamydia, gonorrhea or both.

Ravel will further support the project by leading a genomics core to leverage the state-of-the-art capabilities of the Institute for Genome Sciences' Genomics Resource Center and Informatics Resource Center.

Posting Date: 07/29/2014
Contact Name: Karen Robinson
Contact Phone: 410-706-0023
Contact Email: karobinson@umaryland.edu