Musser Lab

James Musser, MD, PhD

James Musser, MD, PhD
Professor of Pathology and Genomic Medicine
Houston Methodist Academic Institute

The broadly defined goal of Dr. Musser's research is to advance our understanding of pathogen-host molecular interactions and disease causation. Our laboratory uses a highly integrated interdisciplinary research strategy that employs state-of-the-art techniques, such as whole genome sequencing, transcriptome analysis, molecular population genomic analysis, relevant in vivo model systems and analysis of human patient material to gain new information about the molecular basis of infections caused by the human pathogenic bacterium group A Streptococcus (GAS). All of the laboratory's work involves extensive collaboration with local, national, and international investigators with diverse areas of expertise.

One related project is to identify key vaccine candidates against group A Streptococcus. GAS causes more than 700 million cases of human disease each year globally, yet no licensed vaccine is available, despite decades of study. Dr. Musser's goal is to use a multi-modality experimental strategy involving molecular dissection of the pathogen and host immunologic response, in vivo disease models, and analysis of clinical material to identify one or more protein antigens that protect humans against GAS pharyngitis and invasive disease.

A second project is designed to elucidate the molecular genetic events contributing to epidemics of GAS infection. This work is done in collaboration with several groups of national and international investigators. As a model system, the team uses comprehensive, population-based sample collections of GAS recovered from patients with invasive infections. Extensive (“deep”) comparative genome resequencing and genetic polymorphisms analysis is performed using GAS strains from patients with well-defined clinical phenotypes. The goal of this line of research is to understand precise temporal and geographic patterns of strain spread. In addition, the team seeks to define genetic polymorphisms and virulence regulatory circuits in the pathogen that influence clinical phenotype. Recent work has identified a novel virulence circuit involved in the pathogenesis of necrotizing fasciitis, also known as the “flesh-eating” disease. The research also has vaccine and public health implications.

Finally, Dr. Musser’s group is using a novel integrated reverse-genetic strategy to identify group A streptococcus genes that contribute to decreased susceptibility to beta-lactam and other antibiotics. The emergence of strains of group A streptococcus with decreased susceptibility to beta-lactam antibiotics constitutes a potential public health problem of substantial magnitude.