Musser Lab

Musser 360x318

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 interactions. Our laboratory uses a highly integrated interdisciplinary research strategy that employs state-of-the-art techniques, such as whole genome sequencing, expression microarray analysis, molecular population genetic analysis, relevant in vivo model systems and analysis of host factors to gain new information about the molecular basis of infections caused by the human pathogenic bacterium group A Streptococcus (GAS) and Mycobacterium tuberculosis. All of the laboratory's work involves extensive collaboration with local, national and international investigators with diverse areas of expertise.

One project is to identify key vaccine candidates against group A Streptococcus. This work is performed in collaboration with investigators in the private sector. 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 has a longstanding interest in the genetic epidemiology of human susceptibility to tuberculosis disease. Using a cohort of extensively defined human tuberculosis patients and controls, his team seeks to define human genetic factors that help to determine why some individuals get tuberculosis disease, whereas others who have been exposed to the organism do not. A combination of single nucleotide polymorphism analysis and deep candidate gene resequencing is used, as well as other contemporary human genetic analysis methods.