James Cassat
Last active: 4/15/2019

Profile

The major focus of my research is to understand the interaction between host and pathogen during invasive bacterial infections. Specifically, we seek to define the bacterial virulence mechanisms and host defenses employed during osteomyelitis, an invasive infection of bone common in both children and adults. Risk factors and protective immune responses for osteomyelitis are poorly defined, and bone infections are notoriously recalcitrant to antimicrobial therapy due to both pathogen-induced bone destruction and the emergence of multi-drug resistant pathogens. Therefore, we have created new tools to investigate the host-pathogen interface during osteomyelitis. As Staphylococcus aureus is by far the most common cause of osteomyelitis, we have focused our efforts on identifying the mechanisms by which S. aureus causes bone infection and resulting bone destruction, as well as the host defenses that protect against staphylococcal infection. Using a combination of bone cell culture models, proteomic analyses of bacterial virulence factors, and a new quantitative in vivo model of staphylococcal osteomyelitis, we have uncovered specific bacterial factors that contribute to the pathogenesis of osteomyelitis by triggering osteoblast cell death and bone destruction in vivo. We have also identified staphylococcal genes necessary for survival within the bone. By further defining the mechanisms by which S. aureus survives within bone and ultimately triggers bone destruction, we hope to identify new therapeutic targets to treat osteomyelitis and to limit the morbidity associated with this invasive infection. Moreover, by characterizing the host responses to bacterial pathogens in the bone, we seek to define protective correlates of innate immunity in bone and potentially uncover risk factors for the development of osteomyelitis in otherwise healthy children. Finally, by investigating how bacterial pathogens perturb bone cell physiology, we wish to enhance an understanding of changes in bone remodeling in the face of infectious and inflammatory insults.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. MyD88 and IL-1R signaling drive antibacterial immunity and osteoclast-driven bone loss during Staphylococcus aureus osteomyelitis. Putnam NE, Fulbright LE, Curry JM, Ford CA, Petronglo JR, Hendrix AS, Cassat JE (2019) PLoS Pathog 15(4): e1007744
    › Primary publication · 30978245 (PubMed) · PMC6481883 (PubMed Central)
  2. Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions. Cassat JE, Moore JL, Wilson KJ, Stark Z, Prentice BM, Van de Plas R, Perry WJ, Zhang Y, Virostko J, Colvin DC, Rose KL, Judd AM, Reyzer ML, Spraggins JM, Grunenwald CM, Gore JC, Caprioli RM, Skaar EP (2018) Sci Transl Med 10(432)
    › Primary publication · 29540616 (PubMed) · PMC6005374 (PubMed Central)
  3. An Unusual Source of Sepsis in Two Previously Healthy Children. Frazier SB, Katz S, Wood JB, Cassat JE (2018) Clin Pediatr (Phila) 57(9): 1120-1122
    › Primary publication · 29084446 (PubMed) · PMC5878989 (PubMed Central)
  4. Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis. Ford CA, Cassat JE (2017) Expert Rev Anti Infect Ther 15(9): 851-860
    › Primary publication · 28837368 (PubMed) · PMC5870900 (PubMed Central)
  5. Monoclonal Antibodies Against the Staphylococcus aureus Bicomponent Leukotoxin AB Isolated Following Invasive Human Infection Reveal Diverse Binding and Modes of Action. Thomsen IP, Sapparapu G, James DBA, Cassat JE, Nagarsheth M, Kose N, Putnam N, Boguslawski KM, Jones LS, Wood JB, Creech CB, Torres VJ, Crowe JE (2017) J Infect Dis 215(7): 1124-1131
    › Primary publication · 28186295 (PubMed) · PMC5426380 (PubMed Central)
  6. Staphylococcus aureus protein A enhances osteoclastogenesis via TNFR1 and EGFR signaling. Mendoza Bertelli A, Delpino MV, Lattar S, Giai C, Llana MN, Sanjuan N, Cassat JE, Sordelli D, Gómez MI (2016) Biochim Biophys Acta 1862(10): 1975-83
    › Primary publication · 27475257 (PubMed)
  7. Impact of sarA and Phenol-Soluble Modulins on the Pathogenesis of Osteomyelitis in Diverse Clinical Isolates of Staphylococcus aureus. Loughran AJ, Gaddy D, Beenken KE, Meeker DG, Morello R, Zhao H, Byrum SD, Tackett AJ, Cassat JE, Smeltzer MS (2016) Infect Immun 84(9): 2586-94
    › Primary publication · 27354444 (PubMed) · PMC4995912 (PubMed Central)
  8. Repurposing the Nonsteroidal Anti-inflammatory Drug Diflunisal as an Osteoprotective, Antivirulence Therapy for Staphylococcus aureus Osteomyelitis. Hendrix AS, Spoonmore TJ, Wilde AD, Putnam NE, Hammer ND, Snyder DJ, Guelcher SA, Skaar EP, Cassat JE (2016) Antimicrob Agents Chemother 60(9): 5322-30
    › Primary publication · 27324764 (PubMed) · PMC4997817 (PubMed Central)
  9. Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host-Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection. Wilde AD, Snyder DJ, Putnam NE, Valentino MD, Hammer ND, Lonergan ZR, Hinger SA, Aysanoa EE, Blanchard C, Dunman PM, Wasserman GA, Chen J, Shopsin B, Gilmore MS, Skaar EP, Cassat JE (2015) PLoS Pathog 11(12): e1005341
    › Primary publication · 26684646 (PubMed) · PMC4684308 (PubMed Central)
  10. Inter- and intraspecies metabolite exchange promotes virulence of antibiotic-resistant Staphylococcus aureus. Hammer ND, Cassat JE, Noto MJ, Lojek LJ, Chadha AD, Schmitz JE, Creech CB, Skaar EP (2014) Cell Host Microbe 16(4): 531-7
    › Primary publication · 25299336 (PubMed) · PMC4197139 (PubMed Central)
  11. Validation of two vancomycin nomograms in patients 10 years of age and older. Gillon JE, Cassat JE, Di Pentima MC (2014) J Clin Pharmacol 54(1): 35-8
    › Primary publication · 24249098 (PubMed)
  12. Recent advances in experimental models of osteomyelitis. Cassat JE, Skaar EP (2013) Expert Rev Anti Infect Ther 11(12): 1263-5
    › Primary publication · 24215241 (PubMed)
  13. Investigation of biofilm formation in clinical isolates of Staphylococcus aureus. Cassat JE, Smeltzer MS, Lee CY (2014) Methods Mol Biol : 195-211
    › Primary publication · 24085698 (PubMed)
  14. Two heme-dependent terminal oxidases power Staphylococcus aureus organ-specific colonization of the vertebrate host. Hammer ND, Reniere ML, Cassat JE, Zhang Y, Hirsch AO, Indriati Hood M, Skaar EP (2013) MBio 4(4)
    › Primary publication · 23900169 (PubMed) · PMC3735196 (PubMed Central)
  15. Analysis of the Staphylococcus aureus abscess proteome identifies antimicrobial host proteins and bacterial stress responses at the host-pathogen interface. Attia AS, Cassat JE, Aranmolate SO, Zimmerman LJ, Boyd KL, Skaar EP (2013) Pathog Dis 69(1): 36-48
    › Primary publication · 23847107 (PubMed) · PMC3877740 (PubMed Central)
  16. A secreted bacterial protease tailors the Staphylococcus aureus virulence repertoire to modulate bone remodeling during osteomyelitis. Cassat JE, Hammer ND, Campbell JP, Benson MA, Perrien DS, Mrak LN, Smeltzer MS, Torres VJ, Skaar EP (2013) Cell Host Microbe 13(6): 759-72
    › Primary publication · 23768499 (PubMed) · PMC3721972 (PubMed Central)
  17. Iron in infection and immunity. Cassat JE, Skaar EP (2013) Cell Host Microbe 13(5): 509-519
    › Primary publication · 23684303 (PubMed) · PMC3676888 (PubMed Central)
  18. Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity. Cassat JE, Skaar EP (2012) Semin Immunopathol 34(2): 215-35
    › Primary publication · 22048835 (PubMed) · PMC3796439 (PubMed Central)
  19. Factors contributing to the biofilm-deficient phenotype of Staphylococcus aureus sarA mutants. Tsang LH, Cassat JE, Shaw LN, Beenken KE, Smeltzer MS (2008) PLoS One 3(10): e3361
    › Primary publication · 18846215 (PubMed) · PMC2556392 (PubMed Central)
  20. Impact of oleic acid (cis-9-octadecenoic acid) on bacterial viability and biofilm production in Staphylococcus aureus. Stenz L, François P, Fischer A, Huyghe A, Tangomo M, Hernandez D, Cassat J, Linder P, Schrenzel J (2008) FEMS Microbiol Lett 287(2): 149-55
    › Primary publication · 18754790 (PubMed)
  21. Investigation of biofilm formation in clinical isolates of Staphylococcus aureus. Cassat JE, Lee CY, Smeltzer MS (2007) Methods Mol Biol : 127-44
    › Primary publication · 18025674 (PubMed) · PMC4098860 (PubMed Central)
  22. The cidA murein hydrolase regulator contributes to DNA release and biofilm development in Staphylococcus aureus. Rice KC, Mann EE, Endres JL, Weiss EC, Cassat JE, Smeltzer MS, Bayles KW (2007) Proc Natl Acad Sci U S A 104(19): 8113-8
    › Primary publication · 17452642 (PubMed) · PMC1876580 (PubMed Central)
  23. Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390. Cassat J, Dunman PM, Murphy E, Projan SJ, Beenken KE, Palm KJ, Yang SJ, Rice KC, Bayles KW, Smeltzer MS (2006) Microbiology 152(Pt 10): 3075-90
    › Primary publication · 17005987 (PubMed)
  24. Comparative genomics of Staphylococcus aureus musculoskeletal isolates. Cassat JE, Dunman PM, McAleese F, Murphy E, Projan SJ, Smeltzer MS (2005) J Bacteriol 187(2): 576-92
    › Primary publication · 15629929 (PubMed) · PMC543526 (PubMed Central)
  25. Should antibiotics be discontinued at 48 hours for negative late-onset sepsis evaluations in the neonatal intensive care unit? Kaiser JR, Cassat JE, Lewno MJ (2002) J Perinatol 22(6): 445-7
    › Primary publication · 12168120 (PubMed)