James M. Musser, M.D., Ph.D.
Postdoctoral Research Associate, Pennsylvania State University, University Park, PA (Microbial Pathogenesis)
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 The Methodist Hospital Research Institute in 2005 and served as co-director and executive vice president until 2010. In addition to holding the Fondren Distinguished Endowed 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.
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.
Group A Streptococcus and Mycobacterium tuberculosis.
Makthal N, Rastegari S, Sanson M, Ma Z, Olsen RJ, Helmann JD, Musser JM, Kumaraswami M. Crystal structure of peroxide stress regulator (PerR) from Streptococcus pyogenes provides functional insights into the mechanism of oxidative stress sensing. J Biol Chem. 2013 May 3. [Epub ahead of print] PMID: 23645680
Verhaegh SJ, Flores AR, van Belkum A, Musser JM, Hays JP. Differential virulence gene expression of group A Streptococcus serotype M3 in response to co-culture with Moraxella catarrhalis. PLoS One. 2013 Apr 23;8(4):e62549. PMID: 23626831
Feske ML, Teeter LD, Musser JM, Graviss EA. Counting the homeless: a previously incalculable tuberculosis risk and its social determinants. Am J Public Health. 2013 May;103(5):839-48. PMID: 23488504
Long SW, Williams D, Valson C, Cantu CC, Cernoch P, Musser JM, Olsen RJ. A genomic day in the life of a clinical microbiology laboratory. J Clin Microbiol. 2013 Jan 23. PMID: 23345298.
Oh SY, Maier H, Schroeder J, Richter GS, Elli D, Musser JM, Quenee LE, Missiakas DM, Schneewind O. Vaccine protection against Bacillus cereus-mediated respiratory anthrax-like disease in mice. Infect Immun. 2013 Mar;81(3):1008-17.
Musser JM. S. Burt Wolbach, Rocky Mountain Spotted Fever, and Blood-sucking Arthropods: Triumph of an Early Investigative Pathologist. Am J Pathol. 2013 Feb;182(2):291-3.
Perez KK, Olsen RJ, Musick WL, Cernoch PL, Davis JR, Land GA, Peterson LE, Musser JM. Integrating rapid pathogen identification and antimicrobial stewardship significantly decreases hospital costs. Arch Pathol Lab Med. 2012 Dec 6. PMID: 23216247.
Xiao YL, Kash JC, Beres SB, Sheng ZM, Musser JM, Taubenberger JK. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded autopsy lung tissue sample from the 1918 influenza pandemic. J Pathol. 2013 Mar;229(4):535-45.
Flores AR, Jewell BE, Fittipaldi N, Beres SB, Musser JM. Human disease isolates of serotype m4 and m22 group A Streptococcus lack genes required for hyaluronic acid capsule biosynthesis. MBio. 2012 Nov 6;3(6):e00413-12.
Marquez L, Feske ML, Teeter LD, Musser JM, Graviss EA. Pediatric Tuberculosis: The Litmus Test for Tuberculosis Control. Pediatr Infect Dis J. 2012 Nov;31(11):1144-7.
Kobayashi SD, Musser JM, DeLeo FR. Genomic analysis of the emergence of vancomycin-resistant Staphylococcus aureus. MBio. 2012 Jun 26;3(4).
Wimmer JL, Long SW, Cernoch P, Land GA, Davis JR, Musser JM, Olsen RJ. Strategy for Rapid Identification and Antibiotic Susceptibility Testing of Gram-Negative Bacteria Directly Recovered from Positive Blood Cultures using the Bruker MALDI Biotyper and BD Phoenix. J Clin Microbiol. 2012 Jul;50(7):2452-4
Fittipaldi N, Olsen RJ, Beres SB, Van Beneden C, Musser JM. Genomic analysis of emm59 group A Streptococcus invasive strains, United States. Emerg Infect Dis. 2012 Apr;18(4):650-2.
Olsen RJ, Long SW, Musser JM. Bacterial Genomics in Infectious Disease and the Clinical Pathology Laboratory. Arch Pathol Lab Med. 2012 Nov;136(11):1414-22.
Sun H, Xu Y, Sitkiewicz I, Ma Y, Wang X, Yestrepsky BD, Huang Y, Lapadatescu MC, Larsen MJ, Larsen SD, Musser JM, Ginsburg D. Inhibitor of streptokinase gene expression improves survival after group A Streptococcus infection in mice. Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3469-3474.
Fittipaldi N, Beres SB, Olsen RJ, Kapur V, Shea PR, Watkins ME, Cantu CC, Laucirica DR, Jenkins L, Flores AR, Lovgren M, Ardanuy C, Liñares J, Low DE, Tyrrell GJ, Musser JM. Full-Genome Dissection of an Epidemic of Severe Invasive Disease Caused by a Hypervirulent, Recently Emerged Clone of Group A Streptococcus. Am J Pathol. 2012 Apr;180(4):1522-34.
Bensi G, Mora M, Tuscano G, Biagini M, Chiarot E, Bombaci M, Capo S, Falugi F, Manetti AG, Donato P, Swennen E, Gallotta M, Garibaldi M, Pinto V, Chiappini N, Musser JM, Janulczyk R, Mariani M, Scarselli M, Telford JL, Grifantini R, Norais N, Margarit I, Grandi G. Multi High-Throughput Approach for Highly Selective Identification of Vaccine Candidates: the Group A Streptococcus Case. Mol Cell Proteomics. 2012 Jun;11(6):M111.015693.
Olsen RJ, Laucirica DR, Watkins ME, Feske ML, Garcia-Bustillos JR, Vu C, Cantu C, Shelburne SA 3rd, Fittipaldi N, Kumaraswami M, Shea PR, Flores AR, Beres SB, Lovgren M, Tyrrell GJ, Efstratiou A, Low DE, Van Beneden CA, Musser JM. Polymorphisms in regulator of protease B (RopB) alter disease phenotype and strain virulence of serotype M3 group A Streptococcus. J Infect Dis. 2012 Jun;205(11):1719-29.
Hawiger J, Musser JM. How to approach genome wars in sepsis? Crit Care. 2011 Dec 2;15(6):1007.
Shea PR, Ewbank AL, Gonzalez-Lugo JH, Martagon-Rosado AJ, Martinez-Gutierrez JC, Rehman HA, Serrano-Gonzalez M, Fittipaldi N, Beres SB, Flores AR, Low DE, Willey BM, Musser JM. Group A Streptococcus emm Gene Types in Pharyngeal Isolates, Ontario, Canada, 2002-2010. Emerg Infect Dis. 2011 Nov;17(11):2010-7.
Carroll RK, Beres SB, Sitkiewicz I, Peterson L, Matsunami RK, Engler DA, Flores AR, Sumby P, Musser JM. Evolution of diversity in epidemics revealed by analysis of the human bacterial pathogen group A Streptococcus. Epidemics. 2011 Sep;3(3-4):159-70.
Feske ML, Teeter LD, Musser JM, Graviss EA. Including the third dimension: A spatial analysis of TB cases in Houston Harris County. Tuberculosis (Edinb). 2011 Dec;91 Suppl 1:S24-33.
Feske ML, Teeter LD, Musser JM, Graviss EA. Giving TB wheels: Public transportation as a risk factor for tuberculosis transmission. Tuberculosis (Edinb). 2011 Dec;91 Suppl 1:S16-23.
Shelburne Iii SA, Olsen RJ, Makthal N, Brown NG, Sahasrabhojane P, Watkins EM, Palzkill T, Musser JM, Kumaraswami M. An amino-terminal signal peptide of Vfr protein negatively influences RopB-dependent SpeB expression and attenuates virulence in Streptococcus pyogenes. Mol Microbiol. 2011 Dec;82(6):1481-95.
Horstmann N, Sahasrabhojane P, Suber B, Kumaraswami M, Olsen RJ, Flores A, Musser JM, Brennan RG, Shelburne SA 3rd. Distinct single amino Acid replacements in the control of virulence regulator protein differentially impact streptococcal pathogenesis. PLoS Pathog. 2011 Oct;7(10):e1002311.
Deleo FR, Kennedy AD, Chen L, Bubeck Wardenburg J, Kobayashi SD, Mathema B, Braughton KR, Whitney AR, Villaruz AE, Martens CA, Porcella SF, McGavin MJ, Otto M, Musser JM, Kreiswirth BN. Molecular differentiation of historic phage-type 80/81 and contemporary epidemic Staphylococcus aureus. Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18091-6. Epub 2011 Oct 24.
Wright AM, Beres SB, Consamus EN, Long SW, Flores AR, Barrios R, Richter GS, Oh SY, Garufi G, Maier H, Drews AL, Stockbauer KE, Cernoch P, Schneewind O, Olsen RJ, Musser JM. Rapidly Progressive, Fatal, Inhalation Anthrax-like Infection in a Human: Case Report, Pathogen Genome Sequencing, Pathology, and Coordinated Response. Arch Pathol Lab Med. 2011 Nov;135(11):1447-59.
Carroll RK, Musser JM. From transcription to activation: how group A Streptococcus, the flesh-eating pathogen, regulates SpeB cysteine protease production. Mol Microbiol. 2011 Aug;81(3):588-601.
Shelburne Iii SA, Sahasrobhajane P, Suber B, Keith DB, Davenport MT, Horstmann N, Kumaraswami M, Olsen RJ, Brennan RG, Musser JM. Niche-specific contribution to streptococcal virulence of a MalR-regulated carbohydrate binding protein. Mol Microbiol. 2011 Jul;81(2):500-14.
Musser JM. Third-track pathology: in unambiguous support of the Banbury Conference report. Arch Pathol Lab Med. 2011 Jun;135(6):687-8.
Massilamany C, Gangaplara A, Gardner DJ, Musser JM, Steffen D, Somerville GA, Reddy J. TCA cycle inactivation in Staphylococcus aureus alters nitric oxide production in RAW 264.7 cells. Mol Cell Biochem. 2011 Sep;355(1-2):75-82.
Carroll RK, Shelburne SA 3rd, Olsen RJ, Suber B, Sahasrabhojane P, Kumaraswami M, Beres SB, Shea PR, Flores AR, Musser JM. Naturally occurring single amino acid replacements in a regulatory protein alter streptococcal gene expression and virulence in mice. J Clin Invest. 2011 May 2;121(5):1956-68.
Sitkiewicz I, Green NM, Guo N, Mereghetti L, Musser JM. Lateral gene transfer of streptococcal ICE element RD2 (region of difference 2) encoding secreted proteins. BMC Microbiol. 2011 Apr 1;11:65.
Shea PR, Beres SB, Flores AR, Ewbank AL, Gonzalez-Lugo JH, Martagon-Rosado AJ, Martinez-Gutierrez JC, Rehman HA, Serrano-Gonzalez M, Fittipaldi N, Ayers SD, Webb P, Willey BM, Low DE, Musser JM. Distinct signatures of diversifying selection revealed by genome analysis of respiratory tract and invasive bacterial populations. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5039-44.
Nelson MI, Tan Y, Ghedin E, Wentworth DE, St George K, Edelman L, Beck ET, Fan J, Lam TT, Kumar S, Spiro DJ, Simonsen L, Viboud C, Holmes EC, Henrickson KJ, Musser JM. Phylogeography of the spring and fall waves of the H1N1/09 pandemic influenza virus in the United States. J Virol. 2011 Jan;85(2):828-34.
Kennedy AD, Porcella SF, Martens C, Whitney AR, Braughton KR, Chen L, Craig CT, Tenover FC, Kreiswirth BN, Musser JM, DeLeo FR. Complete nucleotide sequence analysis of plasmids in strains of Staphylococcus aureus clone USA300 reveals a high level of identity among isolates with closely related core genome sequences. J Clin Microbiol. 2010 Dec;48(12):4504-11.
Shea PR, Virtaneva K, Kupko JJ 3rd, Porcella SF, Barry WT, Wright FA, Kobayashi SD, Carmody A, Ireland RM, Sturdevant DE, Ricklefs SM, Babar I, Johnson CA, Graham MR, Gardner DJ, Bailey JR, Parnell MJ, Deleo FR, Musser JM. Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus. Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4693-8.
Beres SB, Carroll RK, Shea PR, Sitkiewicz I, Martinez-Gutierrez JC, Low DE, McGeer A, Willey BM, Green K, Tyrrell GJ, Goldman TD, Feldgarden M, Birren BW, Fofanov Y, Boos J, Wheaton WD, Honisch C, Musser JM. Molecular complexity of successive bacterial epidemics deconvoluted by comparative pathogenomics. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4371-6.
Olsen RJ, Sitkiewicz I, Ayeras AA, Gonulal VE, Cantu C, Beres SB, Green NM, Lei B, Humbird T, Greaver J, Chang E, Ragasa WP, Montgomery CA, Cartwright J Jr, McGeer A, Low DE, Whitney AR, Cagle PT, Blasdel TL, DeLeo FR, Musser JM. Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis. Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):888-93.
Olsen RJ, Kobayashi SD, Ayeras AA, Ashraf M, Graves SF, Ragasa W, Humbird T, Greaver JL, Cantu C, Swain JL, Jenkins L, Blasdel T, Cagle PT, Gardner DJ, DeLeo FR, Musser JM. Lack of a major role of Staphylococcus aureus Panton-Valentine leukocidin in lower respiratory tract infection in nonhuman primates. Am J Pathol. 2010 Mar;176(3):1346-54.
Musser JM, Shelburne SA 3rd. A decade of molecular pathogenomic analysis of group A Streptococcus. J Clin Invest. 2009 Sep;119(9):2455-63. doi: 10.1172/JCI38095. Review.
Shelburne SA 3rd, Keith D, Horstmann N, Sumby P, Davenport MT, Graviss EA, Brennan RG, Musser JM. A direct link between carbohydrate utilization and virulence in the major human pathogen group A Streptococcus. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1698-703.
Kennedy AD, Otto M, Braughton KR, Whitney AR, Chen L, Mathema B, Mediavilla JR, Byrne KA, Parkins LD, Tenover FC, Kreiswirth BN, Musser JM, DeLeo FR. Epidemic community-associated methicillin-resistant Staphylococcus aureus: recent clonal expansion and diversification. Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1327-32.