Archive for May, 2007

Washington University School of Medicine in St. Louis is launching a new effort to study infectious diseases that preferentially affect women. The center for Women’s Infectious Disease Research (cWIDR) will focus on issues such as:

• microorganisms that cause urinary tract infections (UTIs) and other conditions that make urination and intercourse painful or difficult

• infections that lead to premature delivery and vaginitis

• potential contributing roles for microorganisms in life-threatening conditions such as cancer, heart disease, neurodegenerative disorders and diabetes.

“Infectious diseases of women is a tremendously underserved area,” says Scott Hultgren, Ph.D., the Helen L. Stoever Professor of Molecular Microbiology and the center’s director and principal investigator. “UTIs, for example, are one of the most common bacterial infections in women. They’re not fatal, but we need new and improved therapeutics because they’re a very significant cause of suffering, lost work days and health-care expenses.”

According to Hultgren, the center continues a University tradition of innovation and leadership in microbiology and infectious diseases. Stephen Beverley, Ph.D., Marvin A. Brennecke Professor and head of molecular microbiology, founded the center’s predecessor, the Center for Infectious Disease Research (CIDR) in 1997. He recently stepped down as director of CIDR and designated Hultgren as his successor.

Hultgren’s research has long been focused on women’s health and infectious diseases, with studies funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Allergy and Infectious Diseases. He has also been active in the Office of Research on Women’s Health, an agency that coordinates and advises on women’s health research throughout the National Institutes of Health.

Given those interests and experiences, Hultgren decided to reconceptualize CIDR and its goals, altering the center’s name to reflect the changes.

The center for Woman’s Infectious Disease Research is part of the University’s BioMed 21 initiative, which is focusing efforts at Washington University on speedy translation of laboratory discoveries into new approaches for diagnosis and treatment of patients.

According to Larry J. Shapiro, M.D., executive vice chancellor for medical affairs and dean at the School of Medicine, studying gender-specific infections can reveal information that is helpful in a much broader range of diseases.

“Scott’s work with urinary tract infections has led to insight into how the bacteria that cause these infections sometimes defend themselves by cooperating to form a protective shield known as a biofilm,” he says. “Many common infections of both men and women employ this defense against antibiotics and the host immune system, and to improve treatment for these infections we have to devise medicines that can penetrate this shield.”

Other major infectious disease issues specific to women include interstitial cystitis or painful bladder syndrome, a condition estimated to afflict hundreds of thousands of females per year. Symptoms are similar to urinary tract infections and include frequent, painful urination and pain during intercourse. Diagnosis and treatment are difficult because scientists don’t yet know the cause of the condition.

Oral and vaginal infections with streptococcus and other bacteria have been linked to premature delivery in pregnant women. Michael Caparon, Ph.D., professor of molecular microbiology and co-director of the center for Woman’s Infectious Disease Research, plans to bring microbiologists and obstetricians to learn why and determine what can be done.

Fostering collaboration between different disciplines to create new perspectives on the big challenges of biomedicine is a primary goal of BioMed 21. Hultgren plans to establish many connections and collaborations between his center and other research centers, noting the potential for synergy provided by the Center of Genome Sciences and other research groups at the University.

“We see the center for Woman’s Infectious Disease Research as part of a multi-disciplinary network combining a powerful blend of microbial pathogenesis, genomics, structural biology, biochemistry and biophysics, and diverse imaging technologies,” Hultgren says.

As an example, Hultgren’s work with urinary tract infections led to detailed study of pili, fibers produced by the bacteria that cause the infections. Pili allow bacteria to adhere to and invade human tissues, and Hultgren’s laboratory has recently found that they help hold bacteria together in biofilms. These discoveries made it possible to design molecules that block pili formation and may one day lead to improved treatments.

Bacteria also manufacture fibers comprised of substances known as amyloids. Like pili, these materials contribute to biofilm formation and host cell colonization, but they’re much more well-known for the role they play in neurodegenerative disorders and other diseases. Hultgren hopes to recruit experts who can use bacteria to model amyloid formation and design compounds that block their assembly.

“Amyloid plaques in the brain are a primary characteristic of Alzheimer’s disease, a terrible disease affecting women and men, so we plan to offer the inhibitors we develop to neurologists as potential treatments for that disorder,” Hultgren says.

Researchers at the center for Woman’s Infectious Disease Research also will study whether microorganisms are playing a role in serious diseases not previously thought to be related to infection. As evidence of why a search for such connections might prove fruitful, Hultgren highlights the surprising discoveries that infectious agents are responsible for all stomach ulcers and most cervical cancers.

In a newer, more tentative link likely to be further probed at the center for Woman’s Infectious Disease Research, scientists have found that a receptor in the circulatory system responds to both fat deposits and bacterial infections. The receptor is believed to help summon an immune response when it detects the bacteria, and cardiologists speculate that its responsiveness to fat may mean the receptor is also triggering inflammatory responses that contribute to heart disease. If so, blocking the receptors could offer a new path to prevention.

To accelerate the search for new treatments for infectious diseases, Hultgren has established close ties with a local biotech firm, Sequoia Sciences, and with Tom Ellenberger, Ph.D., the Raymond H. Wittcoff Professor and head of Biochemistry and Molecular Biophysics.

“Tom has started a program for high-throughput screening of small molecules with pharmaceutical potential, and Sequoia has a library of approximately 250,000 antibacterial compounds isolated from plants in collaboration with the Missouri Botanical Garden,” Hultgren explains. “As we develop assays that help us know what we’re looking for in a treatment, we’ll be using those two resources to rapidly seek out compounds that meet our criteria.”

The new center and five new faculty positions will be supported in part by funding from the school’s Departments of Medicine, Molecular Microbiology, Infectious Diseases and Cardiology as well as general medical school resources and donors.

“If we can get a synergistic effect going on in terms of the interactions between these and other disciplines, then I really feel we’re going to be able to make a significant difference in women’s health,” Hultgren says.