Jeniel Nett, MD, PhD, assistant professor, Infectious Disease, is one of 17 physician-scientists in the United States to be awarded a 2017 Clinical Scientist Development Award from the Doris Duke Charitable Foundation (DDCF). The award aims to help promising physician-scientists build their research programs so they can achieve independent careers.

The grant provides $495,000 over three years for Dr. Nett’s research program, which is investigating how the yeast Candida albicans forms sticky sheets on the surfaces of implanted medical devices. These biofilms cannot be cleared by the human immune system — unlike free-floating Candida cells, which can be attacked by white blood cells called neutrophils.

Candida biofilms on devices such as pacemakers, vascular or urinary catheters, shunts, or artificial heart valves are a serious problem that can lead to systemic infection throughout the body. Candida biofilms on central venous catheters, for example, are estimated to cause 100,000 US deaths and cost $6.5 billion each year.

“In modern medicine, we're commonly using medical devices that remain in place in patients. These devices can become infected with biofilms, and it’s difficult to treat these infections. Part of that is due to an inefficient immune response. This research will look at why white blood cells are not effective in killing these biofilms,” said Dr. Nett.

In 2016, Dr. Nett’s team published a study showing that Candida biofilms prevent neutrophils from mounting a defense response. Normally, neutrophils control overgrowth of Candida by releasing extracellular traps (NETs), a mixture of DNA, histones, and proteins. When Candida cells aggregate into biofilms, though, neutrophils do not release NETs.

Research supported by the funding from DDCF will investigate the theory that Candida biofilms produce glycoproteins on their surface, which inhibits NET release and allows the yeast to invade the immune system. A team of scientists led by Dr. Nett will conduct both laboratory and human clinical studies.

"The goal is to find new drug targets that can be effective," said Dr. Nett.

About the Doris Duke Charitable Foundation
The mission of the Doris Duke Charitable Foundation is to improve the quality of people's lives through grants supporting the performing arts, environmental conservation, medical research and child well-being, and through preservation of the cultural and environmental legacy of Doris Duke's properties. The foundation’s Medical Research Program supports clinical research that advances the translation of biomedical discoveries into new preventions, diagnoses and treatments for human diseases. To learn more about the program, visit www.ddcf.org.

Resources:

• “17 Physician Scientists Win DDCF’s 2017 Clinical Scientist Development Awards,” Doris Duke Charitable Foundation, July 20, 2017
• Johnson CJ, Cabezas-Olcoz J, Kernien JF, Wang SX, Beebe DJ, Huttenlocher A, Ansari H, Nett JE. 2017. The Extracellular Matrix of Candida albicans Biofilms Impairs Formation of Neutrophil Extracellular Traps. PLoS Pathog. 12(9):e1005884.
• Nett JE. 2016. The Host’s Reply to Candida Biofilm. Pathogens 5(1): 33.