Megan T. Baldridge, M.D., Ph.D.
Molecular Genetics and Genomics Program
Molecular Microbiology and Microbial Pathogenesis Program
Computational and Systems Biology Program
Room 4204, McKinley Research Building, 4515 McKinley McKinley Ave, St. Louis, MO 63110
microbiota, infection, pathogen, microbiome, virus, interferon, immunity
Defining the mechanisms behind and effects of the interactions between commensal bacteria, pathogens and innate immunity
The Baldridge lab is broadly interested in the complicated interplay between three important factors: commensal microbes, the host immune system, and viral and bacterial pathogens. Previous work has involved characterization of the intestinal commensal microbiota and interrogation of its role in regulation of both enteric viral infection and the host immune system. The coordination of next-generation sequencing efforts with in vivo infections and treatments in mouse models makes the exploration of transkingdom interactions possible. Moving forward, there are several main areas the Baldridge lab will be pursuing:
1. Determine the cellular source of the inflammatory cytokine interferon-lambda (IFN-λ) in the intestine induced by commensal bacteria and by pathogens, and the signaling pathways and transcription factors that regulate its expression.
2. Define specific commensal bacteria necessary and sufficient to enhance and regulate viral infection in the intestine.
3. Explore viral adaptation strategies to take advantage of commensal microbes and to infect at alternate host sites.
Josefsdottir KS, Baldridge MT, Kadmon CS, King KY (2016). Antibiotics impair murine hematopoiesis by depleting intestinal microbiota. Blood. pii: blood-2016-03-708594.
Orchard RC, Wilen CB, Doench JG, Baldridge MT, McCune BT, Lee YJ, Lee S, Pruett-Miller SM, Nelson CA, Fremont DH, Virgin HW (2016). Discovery of a proteinaceous cellular receptor for a norovirus. Science, 353(6302):933-6..
Liu T, Gurram B, Baldridge MT, Head R, Lam V, Luo C, Cao Y, Simpson P, Hayward M, Holtz ML, Bousounis P, Noe J, Lerner D, Cabrera J, Biank V, Stephens M, Huttenhower C, McGovern DPB, Xavier RJ, Stappenbeck TS, and Salzman NH (2016). Paneth cell defects in Crohn’s disease patients promote dysbiosis. JCI Insight, 1(8):e86907.
Moon C*, Baldridge MT*, Wallace MA, Burnham CD, Virgin HW, Stappenbeck TS. (2015). Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation. Nature, 521(7550):90-3. * equal contribution
Baldridge MT, Nice TJ, McCune BT, Yokoyama C, Kambal A, Wheadon M, Lazear HM, Diamond MS, Ivanova Y, Artyomov M, Virgin HW. (2015). Commensal microbes and interferon-λ determine persistence off enteric murine norovirus infection. Science, 347(6219):266-9.
Nice TJ, Baldridge MT, McCune BT, Norman JM, Lazear HM, Artyomov M, Diamond MS, Virgin HW. (2015). Interferon λ cures persistent murine norovirus infection in the absence of adaptive immunity. Science, 347(6219):269-73.
Norman JM*, Handley SA*, Baldridge MT, Droit L, Liu CY, Keller BC, Kambal A, Monaco CL, Zhao G, Fleshner P, Stappenbeck TS, McGovern DP, Keshavarzian A, Mutlu EA, Sauk J, Gevers D, Xavier RJ, Wang D, Parkes M, Virgin HW. (2015). Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease. Cell, 160(3):447-60. * denotes equal contribution
Nelson AM, Elftman MD, Pinto AK, Baldridge M, Hooper P, Kuczynski J, Petrosino JF, Young VB and Wobus CE. (2013). Murine norovirus infection does not cause major disruptions in the murine intestinal microbiota. Microbiome; 1:7.
King KY*, Baldridge MT*, Weksberg DC, Chambers SM, Lukov GL, Wu S, Boles NC, Jung SY, Qin J, Liu D, Songyang Z, Eissa NT, Taylor GA, and Goodell MA. (2011). IRGM1 protects hematopoietic stem cells by negative regulation of interferon signaling. Blood, 118(6):1525-33. * denotes equal contribution
Baldridge MT*, King KY*, Boles NC, Weksberg DC, and Goodell MA. Quiescent hematopoietic stem cells are activated by IFN-gamma in response to chronic infection. (2010). Nature, 465: 793-797. * denotes equal contribution
Last Updated: 1/5/2017 11:46:03 AM