$2.5 Million NIH R01 Grant Will Support Transformative Interdisciplinary Wound Healing Study

A four-year, $2.5 million R01 grant from the National Institutes of Health will help transform innovative research into diabetic wound healing by investigators at the University of Miami Miller School of Medicine.

(From top left) Natasa Strbo, M.D.; Marjana Tomic-Canic, Ph.D.; and Irena Pastar, Ph.D.

The project will focus on how the antimicrobial protein Perforin-2 contributes to infection and impedes diabetic wound healing. In addition, the research is to evaluate the beneficial role of the commensal skin bacteria Staphylococcus epidermidis in prevention of these infections.

“This is a very exciting collaborative study that will utilize cutting-edge technologies to bring the concept of ‘topical probiotics’ to use for prevention and treatment of wound infection in diabetic patients,” said Marjana Tomic-Canic, Ph.D., professor, vice chair of research and the William H. Eaglstein Chair in Wound Healing in the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery.

The project, funded by the National Institute of Diabetes and Digestive and Kidney Diseases, will include a combination of mechanistic human and animal research, in vivo and ex vivo wound models and human tissue collected from patients.

An Unmet Clinical Need

The research could translate to hope for people with chronic, non-healing wounds known as diabetic foot ulcers (DFUs). For about half of the patients, wounds become infected. These infections, in turn, are associated with hospitalization and substantial morbidity, and are frequently the sentinel event leading to lower extremity amputation. This outcome is not uncommon, with approximately one in six DFUs leading to amputation occurring every 30 seconds worldwide.

While S. epidermidis can be protective, the most common harmful bacterium in these infected ulcers is Staphylococcus aureus. Less clear, and one focus of this research, is exactly how S. aureus drives wound changes at a molecular level. The hope is that the molecular underpinnings will reveal new therapeutic targets.

An Interdisciplinary Initiative

The research is a result of team efforts between the Miller School departments of dermatology and microbiology-immunology, stemming from their previous work that focused on the function of Perforin-2 — originally discovered at the University of Miami by the late Eckhard Podack, M.D., Ph.D. — and its role in wound healing, including findings that revealed how S. aureus can ‘hide’ inside a non-healing diabetic foot ulcer and evade antibiotic treatment.

Principal study investigators include Dr. Tomic-Canic; Irena Pastar, Ph.D., research associate professor in the Department of Dermatology and Cutaneous Surgery; and Natasa Strbo, M.D., research associate professor in the Department of Microbiology and Immunology. Rivka Stone, M.D., Ph.D., assistant professor of dermatology, is a project co-investigator.

The ultimate aim is to translate the scientific findings into clinical interventions to help speed healing of these debilitating DFUs. Drs. Pastar and Strbo said that skin and wound microbiome research is entering a new era, and they hope to develop new treatment approaches.

“We are thrilled that we will continue to advance the knowledge and bring new therapies to patients, reducing the complications and amputations,” added Dr. Tomic-Canic.

Visit the NIH study site for more information on the research project, entitled “Prevention of intracellular infection in diabetic wounds by commensal Staphylococcus epidermidis.”

Tags: Department of Microbiology and Immunology, Dr. Irena Pastar, Dr. Marjana Tomic-Canic, Dr. Natasa Strbo, Dr. Philip Frost Department of Dermatology and Cutaneous Surgery, Dr. Rivka Stone, NIH funding