A team of UTHSC researchers in the College of Pharmacy has been awarded a $3.3 million grant from the National Institutes of Health for their study of drug-resistance mechanisms of a fungal pathogen responsible for fatal lung infections. Jarrod R. Fortwendel, PhD, associate professor in the Department of Clinical Pharmacy and Translational Science, and P. David Rogers, PharmD, PhD, professor and director of Clinical and Experimental Therapeutics in the Department of Clinical Pharmacy and Translational Science in the College of Clinical Pharmacy, are dual principal Investigators on the study titled “Non-cyp51A-mutation Mediated Triazole Resistance in Aspergillus fumigatus.”
The project focuses on a fairly common fungus species called Aspergillus fumigatus. The fungus produces airborne spores that are harmless to people with healthy immune systems. But for those with weakened immune systems, inhaling Aspergillus spores can cause life-threatening infection in the lungs or sinuses. Drug-resistant forms of this pathogen have developed, rendering ineffective the few primary therapies available.
It is generally believed that resistance in Aspergillus causes mutations of the gene cyp51A, the cellular target of drug therapies. Despite this correlation, the investigative team has recently shown that in the majority of cases, these mutations do not explain drug resistance. In their proposed study, Drs. Fortwendel and Rogers will use the latest genetic and genomic techniques to uncover novel molecular mechanisms underpinning resistance, in order to preserve existing drugs and guide the development of new ones.
Dr. Fortwendel has been studying the pathogen since 2005. “Although I have been studying how this organism causes disease for quite some time, the problem of antifungal resistance of Aspergillus has only recently been appreciated in the United States. The timing of our collaboration was a key part of our success,” he said.
Dr. Rogers has worked on antifungal drug resistance for over 20 years and is currently completing a six-year term as an NIH Study Section member on the Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section. “By combining unique cutting-edge tools developed in the Fortwendel lab with the expertise of our group in teasing out the genetic basis of antifungal resistance, particularly the dissertation work of Dr. Jeff Rybak under our direction, we are uniquely positioned to gain a comprehensive understanding of resistance to this important class of antifungal,” he said. Dr. Rogers also holds the First Tennessee Endowed Chair of Excellence in Clinical Pharmacy and is director of the UTHSC Center of Excellence for Pediatric Experimental Therapeutics.