Sarah Clark, PhD

Professional Titles

• Assistant Professor
• Boettcher Investigator

Recognitions

• AAI Young Investigator Award and Invited speaker, Colorado Immunology Conference (2018)
• Translational Research Category Poster Winner, University of Colorado (2016)
• Young Investigator Award and Invited Speaker, American Association of Immunologists (2015)
• Colorado Pilot Program award recipient, CCTSI (2018)
• F32 Postdoctoral Fellowship Award, NIAID of the National Institutes of Health (2014)
• K22 Career Transition Award, NIAID of the National Institutes of Health (2019)
• Featured New Investigator Award, Council of the Central Society for Clinical and Translational Research (2020)
• American Thoracic Society Research Program Award, American Thoracic Society (2021)
• Boettcher Investigator Webb-Warring Biomedical Research Award, Boettcher Foundation (2021)
• American Lung Association Innovation Award, American Lung Association (2021)
• Research Grant, Cystic Fibrosis Foundation (2023)
• NIAID R0101AI172858, NIH (2023)
• NIDCD R21DC019169, NIH (2022)

Research Interests

The Clark lab investigates bacterial-driven immune modulation in the respiratory tract. The upper respiratory tract is home to a diverse microbial community that includes both commensal and opportunistic bacterial pathogens. Research in the lab explores how exposure to these bacteria influences upper and lower respiratory tract inflammation and disease, with a focus on the innate immune response to acute infection. One project area investigates bacterial activation of pathways leading to the secretion of IL-10, the prototypical anti-inflammatory cytokine, and how this response influences inflammation and susceptibility to secondary infections. Another project area investigates how commensal airway bacteria activate immune responses which contribute to protection against bacterial pathogens. We model host-pathogen interactions using Streptococcus pneumoniae, the most common cause of acute otitis media and bacterial pneumonia in children, Haemophilus influenzae, and commensal bacterial species. The long-term goal of this work is to identify new therapeutic approaches for the clinically significant problems of respiratory tract infection and inflammation.

Publications

• Clark SE, Burrack KS, Jameson SC, Hamilton SE, Lenz LL. NK Cell IL-10 Production Requires IL-15 and IL-10 Driven STAT3 Activation. Front Immunol. 2019;10:2087. PubMed PMID: 31552035
• Clark SE, Schmidt RL, McDermott DS, Lenz LL. A Batf3/Nlrp3/IL-18 Axis Promotes Natural Killer Cell IL-10 Production during Listeria monocytogenes Infection. Cell Rep. 2018 May 29;23(9):2582-2594. PubMed PMID: 29847790
• McIntosh D, Cunningham M, Ji B, Fekete FA, Parry EM, Clark SE, Zalinger ZB, Gilg IC, Danner GR, Johnson KA, Beattie M, Ritchie R. Transferable, multiple antibiotic and mercury resistance in Atlantic Canadian isolates of Aeromonas salmonicida subsp. salmonicida is associated with carriage of an IncA/C plasmid similar to the Salmonella enterica plasmid pSN254. J Antimicrob Chemother. 2008 Jun;61(6):1221-8. PubMed PMID: 18375380
• Clark SE, Jude BA, Danner GR, Fekete FA. Identification of a multidrug efflux pump in Flavobacterium johnsoniae. Vet Res. 2009 Nov-Dec;40(6):55. PubMed PMID: 19558960
• Clark SE, Snow J, Li J, Zola TA, Weiser JN. Phosphorylcholine allows for evasion of bactericidal antibody by Haemophilus influenzae. PLoS Pathog. 2012;8(3):e1002521. PubMed PMID: 22396641
• Clark SE, Eichelberger KR, Weiser JN. Evasion of killing by human antibody and complement through multiple variations in the surface oligosaccharide of Haemophilus influenzae. Mol Microbiol. 2013 May;88(3):603-18. PubMed PMID: 23577840
• Clark SE, Filak HC, Guthrie BS, Schmidt RL, Jamieson A, Merkel P, Knight V, Cole CM, Raulet DH, Lenz LL. Bacterial Manipulation of NK Cell Regulatory Activity Increases Susceptibility to Listeria monocytogenes Infection. PLoS Pathog. 2016 Jun;12(6):e1005708. PubMed PMID: 27295349
• Soderborg TK, Clark SE, Mulligan CE, Janssen RC, Babcock L, Ir D, Young B, Krebs N, Lemas DJ, Johnson LK, Weir T, Lenz LL, Frank DN, Hernandez TL, Kuhn KA, D'Alessandro A, Barbour LA, El Kasmi KC, Friedman JE. The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD. Nat Commun. 2018 Oct 26;9(1):4462. PubMed PMID: 30367045
• Clark SE, Weiser JN. Microbial modulation of host immunity with the small molecule phosphorylcholine. Infect Immun. 2013 Feb;81(2):392-401. PubMed PMID: 23230294
• Nakamura S, Shchepetov M, Dalia AB, Clark SE, Murphy TF, Sethi S, Gilsdorf JR, Smith AL, Weiser JN. Molecular basis of increased serum resistance among pulmonary isolates of non-typeable Haemophilus influenzae. PLoS Pathog. 2011 Jan 6;7(1):e1001247. PubMed PMID: 21253576
• Clark SE, Schmidt RL, Aguilera ER, Lenz LL. IL-10-producing NK cells exacerbate sublethal Streptococcus pneumoniae infection in the lung. Transl Res. 2020 Dec;226:70-82. PubMed PMID: 32634590
• Clark SE. Commensal bacteria in the upper respiratory tract regulate susceptibility to infection. Curr Opin Immunol. 2020 May 13;66:42-40. PubMed PMID: 32416468.
• Horn KJ, Jaberi Vivar AC, Arenas V, Andani S, Janoff EN and Clark SE. Corynebacterium species inhibit Streptococcus pneumoniae colonization and infection of the mouse airway. Front. Microbiol. 2022 Jan;12:804935. PubMed PMID: 35082772.
• Horn, K.J., Schopper, M.A., Drigot, Z.G., Clark, S.E. Airway Prevotella promote TLR2-dependent neutrophil activation and rapid clearance of Streptococcus pneumoniae from the lung. Nat Commun 2022; 13:3321. PubMed PMID: 35680890.
• Horn KJ, Fulte S, Yang M, Lorenz BP, Clark SE. Neutrophil responsiveness to IL-10 impairs clearance of Streptococcus pneumoniae from the lungs. J Leukoc Biol. 2023;00:1-12. PubMed PMID: 37381945.
• Fulte S, Atto B, McCarty A, Horn KJ, Redzic JS, Eisenmesser E, Yang M, Marsh RL, Tristram S, Clark SE. Heme sequestration by hemophilin from Haemophilus haemolyticus reduces respiratory tract colonization and infection with non-typeable Haemophilus influenzae. mSphere. 2024 Mar 26;9(3):e0000624. PubMed PMID: 38380941
• Drigot ZG, Clark SE. Insights into the role of the respiratory tract microbiome in defense against bacterial pneumonia. Curr Opin Microbiol. 2024 Feb;77:102428. PubMed PMID: 38277901

Professional Memberships

• American Association of Immunologists, Member
• American Society for Microbiology, Member
• American Thoracic Society, Member
• Society for Leukocyte Biology, Member