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James M. Musser, MD, PhD

Chair, Department of Pathology & Genomic Medicine
Fondren Presidential Distinguished Chair, Research Institute
Professor of Pathology and Genomic Medicine, Academic Institute
Director, Center for Molecular & Translational Human Infectious Diseases Research
Houston Methodist
Weill Cornell Medical College


Research Lab


Biography

Following postdoctoral research at the Institute of Molecular Evolutionary Genetics, Pennsylvania State University, and residency training in laboratory medicine at the Hospital of the University of Pennsylvania, Dr. Musser joined the pathology department, Baylor College of Medicine in Houston, Texas. He advanced through the academic ranks from 1991 to 1998, when he was promoted to professor. Dr. Musser served as the chief of the Laboratory of Human Bacterial Pathogenesis at the National Institute of Allergy and Infectious Diseases from 1999-2003. He joined Houston Methodist Research Institute in 2005 and served as co-director and executive vice president until 2010. In addition to holding the Fondren Presidential Distinguished Chair, Dr. Musser is also the chair of the Department of Pathology and Genomic Medicine and the director of the Center for Molecular and Translational Human Infectious Diseases Research. His research focuses on the molecular basis of host-pathogen interactions in group A Streptococcus and Mycobacterium tuberculosis. He serves on several editorial boards, has received many national and international honors and awards, and has published more than 300 research articles and book chapters.

Description of Research

The goal of Dr. Musser's research is to advance our understanding of pathogen-host interactions, broadly defined. His laboratory uses a highly integrated interdisciplinary research strategy that employs state-of-the-art techniques such as 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 >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 investigators. The team uses a comprehensive, population-based sample of serotype M3 strains recovered over 16 years from patients with invasive infections as a model system. The project involves extensive (“deep”) comparative genome resequencing and genetic polymorphisms analysis using GAS strains from patients with well-defined clinical phenotype. 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.

Areas Of Expertise

Mycobacterium tuberculosis Group A Streptococcus
Education & Training

Residency, University of Pennsylvania Health System
MD, University of Rochester
Publications

Predicting ß-lactam resistance using whole genome sequencing in Klebsiella pneumoniae: the challenge of ß-lactamase inhibitors
Hujer, AM, Long, SW, Olsen, RJ, Taracila, MA, Rojas, LJ, Musser, JM & Bonomo, RA 2020, , Diagnostic Microbiology and Infectious Disease, vol. 98, no. 3, 115149. https://doi.org/10.1016/j.diagmicrobio.2020.115149

Genome-wide assessment of streptococcus agalactiae genes required for survival in human whole blood and plasma
Zhu, L, Yerramilli, P, Pruitt, L, Saavedra, MO, Cantu, CC, Olsen, RJ, Beres, SB, Waller, AS & Musser, JM 2020, , Infection and Immunity, vol. 88, no. 10, e00357. https://doi.org/10.1128/IAI.00357-20

Convalescent plasma anti-SARS-CoV-2 spike protein ectodomain and receptor binding domain IgG correlate with virus neutralization
Salazar, E, Kuchipudi, SV, Christensen, PA, Eagar, T, Yi, X, Zhao, P, Jin, Z, Long, SW, Olsen, RJ, Chen, J, Castillo, B, Leveque, C, Towers, D, Lavinder, JJ, Gollihar, J, Cardona, JA, Ippolito, GC, Nissly, RH, Bird, I, Greenawalt, D, Rossi, RM, Gontu, A, Srinivasan, S, Poojary, I, Cattadori, IM, Hudson, P, Josleyn, NM, Prugar, L, Huie, KE, Herbert, AS, Bernard, DW, Dye, JM, Kapur, V & Musser, JM 2020, , The Journal of clinical investigation. https://doi.org/10.1172/JCI141206

Population genomic molecular epidemiological study of macrolide-resistant streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a large clonal population with a pbp2x mutation conferring reduced in vitro ß-Lactam Susceptibility
Southon, SB, Beres, SB, Kachroo, P, Saavedra, MO, Erlendsdóttir, H, Haraldsson, G, Yerramilli, P, Pruitt, L, Zhu, L, Musser, JM & Kristinsson, KG 2020, , Journal of Clinical Microbiology, vol. 58, no. 9, e00638-20. https://doi.org/10.1128/JCM.00638-20

A Single Amino Acid Replacement in Penicillin-Binding Protein 2X in Streptococcus pyogenes Significantly Increases Fitness on Subtherapeutic Benzylpenicillin Treatment in a Mouse Model of Necrotizing Myositis
Olsen, RJ, Zhu, L & Musser, JM 2020, , American Journal of Pathology, vol. 190, no. 8, pp. 1625-1631. https://doi.org/10.1016/j.ajpath.2020.04.014

Treatment of Coronavirus Disease 2019 (COVID-19) Patients with Convalescent Plasma
Salazar, E, Perez, KK, Ashraf, M, Chen, J, Castillo, B, Christensen, PA, Eubank, T, Bernard, DW, Eagar, TN, Long, SW, Subedi, S, Olsen, RJ, Leveque, C, Schwartz, MR, Dey, M, Chavez-East, C, Rogers, J, Shehabeldin, A, Joseph, D, Williams, G, Thomas, K, Masud, F, Talley, C, Dlouhy, KG, Lopez, BV, Hampton, C, Lavinder, J, Gollihar, JD, Maranhao, AC, Ippolito, GC, Saavedra, MO, Cantu, CC, Yerramilli, P, Pruitt, L & Musser, JM 2020, , American Journal of Pathology, vol. 190, no. 8, pp. 1680-1690. https://doi.org/10.1016/j.ajpath.2020.05.014

Group A Streptococcus AdcR Regulon Participates in Bacterial Defense against Host-Mediated Zinc Sequestration and Contributes to Virulence
Makthal, N, Do, H, Wendel, BM, Olsen, RJ, Helmann, JD, Musser, JM & Kumaraswami, M 2020, , Infection and Immunity, vol. 88, no. 8. https://doi.org/10.1128/IAI.00097-20

Human infections caused by clonally related african clade (clade III) strains of candida auris in the greater houston region
Long, SW, Saavedra, MO, Christensen, PA, Musser, JM & Olsena, RJ 2020, , Journal of Clinical Microbiology, vol. 58, no. 7, e02063-19. https://doi.org/10.1128/JCM.02063-19

Streptococcus pyogenes genes that promote pharyngitis in primates
Zhu, L, Olsen, RJ, Beres, SB, Saavedra, MO, Kubiak, SL, Cantu, CC, Jenkins, L, Waller, AS, Sun, Z, Palzkill, T, Porter, AR, DeLeo, FR & Musser, JM 2020, JCI insight, vol. 5, no. 11. https://doi.org/10.1172/jci.insight.137686

Genetic evolution of invasive emm28 Streptococcus pyogenes strains and significant association with puerperal infections in young women in Finland
Gröndahl-Yli-Hannuksela, K, Beres, SB, Hyyryläinen, HL, Kallonen, T, Musser, JM & Vuopio, J 2020, , Clinical Microbiology and Infection. https://doi.org/10.1016/j.cmi.2020.04.004

Genome-Wide Screens Identify Group A Streptococcus Surface Proteins Promoting Female Genital Tract Colonization and Virulence
Zhu, L, Olsen, RJ, Beres, SB, Ojeda Saavedra, M, Kubiak, SL, Cantu, CC, Jenkins, L, Yerramilli, P, Pruitt, L, Charbonneau, ARL, Waller, AS & Musser, JM 2020, , American Journal of Pathology, vol. 190, no. 4, pp. 862-873. https://doi.org/10.1016/j.ajpath.2019.12.003

New pathogenesis mechanisms and translational leads identified by multidimensional analysis of necrotizing myositis in primates
Kachroo, P, Eraso, JM, Olsen, RJ, Zhu, L, Kubiak, SL, Pruitt, L, Yerramilli, P, Cantu, CC, Saavedra, MO, Pensar, J, Corander, J, Jenkins, L, Kao, L, Granillo, A, Porter, AR, Deleo, FR & Musser, JM 2020, , mBio, vol. 11, no. 1, e03363-19. https://doi.org/10.1128/mBio.03363-19

Development and evaluation of a novel protein-based assay for specific detection of KPC ß-lactamases from Klebsiella pneumoniae clinical isolates
Lu, S, Soeung, V, Nguyen, HAT, Long, SW, Musser, JM & Palzkill, T 2020, mSphere, vol. 5, no. 1, e00918. https://doi.org/10.1128/mSphere.0918-19

Reduced in vitro susceptibility of streptococcus pyogenes to ß-lactam antibiotics associated with mutations in the pbp2x gene is geographically widespread
Musser, JM, Beres, SB, Zhu, L, Olsen, RJ, Vuopio, J, Hyyryläinen, HL, Gröndahl-Yli-Hannuksela, K, Kristinsson, KG, Darenberg, J, Henriques-Normark, B, Hoffmann, S, Caugant, DA, Smith, AJ, Lindsay, DSJ, Boragine, DM & Palzkill, T 2020, , Journal of Clinical Microbiology, vol. 58, no. 4, e01993-19. https://doi.org/10.1128/JCM.01993-19

Genetic heterogeneity of the Spy1336/R28—Spy1337 virulence axis in Streptococcus pyogenes and effect on gene transcript levels and pathogenesis
Eraso, JM, Kachroo, P, Olsen, RJ, Beres, SB, Zhu, L, Badu, T, Shannon, S, Cantu, CC, Saavedra, MO, Kubiak, SL, Porter, AR, DeLeo, FR & Musser, JM 2020, , PLoS ONE, vol. 15, no. 3, e0229064. https://doi.org/10.1371/journal.pone.0229064

FASEB 2019: Current Topics in Science Advocacy and Policy
Musser, JM 2019, Journal of biomolecular techniques : JBT, vol. 30, pp. S49-S50.

Polymorphisms in Regulator of Cov Contribute to the Molecular Pathogenesis of Serotype M28 Group A Streptococcus
Bernard, PE, Kachroo, P, Eraso, JM, Zhu, L, Madry, JE, Linson, SE, Ojeda Saavedra, M, Cantu, C, Musser, JM & Olsen, RJ 2019, , American Journal of Pathology, vol. 189, no. 10, pp. 2002-2018. https://doi.org/10.1016/j.ajpath.2019.06.009

Metal sensing and regulation of adaptive responses to manganese limitation by MtsR is critical for group A streptococcus virulence
Do, H, Makthal, N, Chandrangsu, P, Olsen, RJ, Helmann, JD, Musser, JM & Kumaraswami, M 2019, Nucleic Acids Research, vol. 47, no. 15, pp. 8333-8334. https://doi.org/10.1093/nar/gkz641

Metal sensing and regulation of adaptive responses to manganese limitation by MtsR is critical for group A streptococcus virulence
Do, H, Makthal, N, Chandrangsu, P, Olsen, RJ, Helmann, JD, Musser, JM & Kumaraswami, M 2019, , Nucleic Acids Research, vol. 47, no. 14, pp. 7476-7493. https://doi.org/10.1093/nar/gkz524

Environmental pH and peptide signaling control virulence of Streptococcus pyogenes via a quorum-sensing pathway
Do, H, Makthal, N, VanderWal, AR, Saavedra, MO, Olsen, RJ, Musser, JM & Kumaraswami, M 2019, , Nature Communications, vol. 10, no. 1, 2586. https://doi.org/10.1038/s41467-019-10556-8