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Susan Lynch, PhD

Susan Lynch, PhD
Associate Professor, Department of Medicine, Gastroenterology
Director, Colitis and Crohn's Disease Microbiome Research Core
Research Summary:
Human Microbiome, Chronic Inflammatory Disease

Background.

The human superorganism represents a coalition of man and microbes, with the greatest diversity and burden of these species concentrated in the lower gastrointestinal (GI) tract. Recent studies in this emerging field have demonstrated relationships between the composition of these communities and diverse aspects of host physiology, including metabolism and immunological function. Our research focuses on microbial communities associated with chronic inflammatory diseases of the gastrointestinal and respiratory tracts. Using clinical samples to inform studies using murine models, we examine relationships between microbial community composition and function in an effort to better understand microbial-host interplay in the context of chronic inflammatory disease.

Major goals. Research in the Lynch laboratory addresses key areas of human microbiome research:

• Early-life microbiome assembly
• Community perturbation and reassembly
• Relationships between microbiome composition, function and chronic immune activation
• Development of rationally designed novel microbiome-based therapeutics
• The gut-airway axis

On-going research.

Inflammatory Bowel Disease. Current efforts are aimed at understanding relationships between host genetics, diet and the gastrointestinal microbiome of patients with ulcerative colitis as well as improving our understanding of the central tenets underlying the process of gut microbiome perturbation and reassembly.

Cystic fibrosis (CF). Airway and gastrointestinal microbiome studies are aimed at improving our understanding of the subsets of species that contribute to chronic pulmonary function decline and susceptibility to pulmonary infection in this patient population.

Asthma. Current research efforts are focused on examining the influence of the household microbial environment on childhood atopic asthma development. Studies involve examination of both upper respiratory and gastrointestinal microbiome and the relationship between community composition and function on clinical and immunological markers of disease. In addition we are engaged in studies determining the impact of very early-life microbiome supplementation with a single Lactobacillus species on gastrointestinal microbial community structure and function and propensity to develop childhood allergic disease. Murine studies are also on-going to identify species and mechanisms of microbial protection against allergen and viral airway infection.

Sinusitus. Upper airway infections, particularly chronic sinus infection impacts more than 30 million Americans and incurs an annual multi-billion dollar health care burden. We are currently engaged in studies examining the role of the sinus microbiome in either mediating or protecting against both acute and chronic sinusitis. We are also examining in pediatric populations, how perturbation to microbial communities in this niche may lead to aberrant community reassembly and chronic disease development.

HIV. Opportunistic pneumonias remain a leading cause of morbidity and mortality in HIV-infected persons worldwide. Our current research efforts focus on cross-sectional and longitudinal studies to characterize the bacterial, viral, and fungal microbiome present in the lungs of patients with acute and early HIV infection, chronic HIV infection, and opportunistic pneumonia. We are also engaged in studies examining the gastrointestinal microbiome of HIV-infected patients to examine relationships between microbiome composition, the degree of immune activation and the microbial community members involved in diseases processes that contribute to reduced life expectancy in this population.

Selected Publications

1.     Caffrey, P, Lynch, S.V., Flood, L., Finnan, S. and Oliynyk, M. Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of polyketide synthase and late genes. Chemistry and Biology. 2001. 8:713-723. PMID: 11451671

2.     Barak, Y., Thorne, S., Ackerley, D.F., Lynch, S.V., Contag, C. and Matin A.C. New enzyme for reductive cancer chemotherapy, YieF, and its improvement by directed evolution. Molecular Cancer Therapeutics. 2006. 5(1):97-103. PMID: 16432167

3.     Lynch, S. V., Dixon, L., Brodie, E.L., Keyhan, M., Hu, P., Ackerley, D.F., Andersen, G.A. and Matin, A.C. Role of rapA Gene in Controlling Antibiotic Resistance of Uropathogenic Escherichia coli Biofilms. Antimicrobial Agents and Chemotherapy. 2007, 51(10):3650-8. PMID: 17664315

4.     Augustin, D.A., Song, Y., Baek, M.S., Sawa, Y., Singh, G., Taylor, B., Rubio-Mills, A., Flanagan, J.L., Wiener-Kronish, J.P. and Lynch, S.V. The Effect of Lipopolysaccharide O-antigen Serotype on Type III Secretion of Pseudomonas aeruginosa. J. Bacteriol. 2007. 189:2203-2209. PMID: 17209027

5.     Flanagan, J.L., Brodie, E.L., Weng, L., Lynch, S.V., Garcia, O., Brown, R., Hugenholtz, P., DeSantis, T.Z, Andersen, G.L., Wiener-Kronish, J.P. and Bristow, J. Loss of Bacterial Diversity During Antibiotic Treatment of Intubated Patients Colonized with Pseudomonas aeruginosa. Journal of Clinical Microbiology. 2007, 45(6):1954-1962. PMID: 17409203

6.     El Solh, A.A., Amsterdam, D. Alhajhusain, A., Akinnusi, M., Saliba, R., Lynch, S.V., Wiener-Kronish, J., and Szarpa, K. Matrix Metalloproteins in Bronchoalveolar lavage fluid of patients with type III Pseudomonas aeruginosa Pneumonia. European Respiratory Journal. 2008 Sep 1;178(5):513-9. PMID: 19535150

7.     El Solh AA, Akinnusi ME, Wiener-Kronish JP, Lynch SV, Pineda LA, Szarpa K. Persistent Infection with Pseudomonas aeruginosa in Ventilator Associated Pneumonia. American Journal of Respiratory and Critical Care Medicine 2008 Sep1;178(5):513-9. PMID: 18467510

8.     Ivanov, I.I., Atarashi, K., Manel, N., Brodie, E.L., Shima, T., Karaoz, U. Wei, D., Goldfarb, K.C., Santee, C.A., Lynch, S.V., Imaoka, A. Itoh, K., Takeda, K., Umesaki, Y., Honda, K., and Littman, D.R. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009 Oct 30;139(3):485-98. PMID: 19836068

9.     Montor WR, Huang J, Hu Y, Hainsworth E, Lynch S.V., Kronish JW, Ordonez CL, Logvinenko T, Lory S, LaBaer J. Genome-wide study of Pseudomonas aeruginosa outer membrane protein immunogenicity using self-assembling protein microarrays. Infection and Immunity. 2009 Nov;77(11):4877-86. PMID: 19737893

10.    Fujimura, K.E., Johnson, C.C., Ownby, D.R., Cox, M.J., Brodie, E.L., Havstad, S.L., Zoratti, E.M., Woodcroft, K.J., Bobbitt, K.R., Wegienka, G., Boushey, H.A. and Lynch, S.V. Man's best friend? The effect of pet ownership on house dust microbial communities. J. Allergy Clin. Immunol. 2010 126(2):410-2. PMID: 20633927

11.    Rauch, M. and Lynch, S.V. Probiotic manipulation of the gastrointestinal microbiota. Gut Microbes. 2010. 1(5):1-4.

12.    Lemon, K.P., Klepac-Ceraj, V., Schiffer, H.K., Brodie, E.L., Lynch, S.V. and Kolter, R. Comparative Analyses of the Bacterial Microbiota of the Human Nostril and Oropharynx. MBIO. 2010. 22;1(3). PMID: 20802827

13.   Cox, M.J., Allgaier, M., Taylor, B., Baek, M.S., Huang, Y.J., Daly, R.A., Karaoz, U., Andersen, G.L., Brown, R., Fujimura, K.E., Wu, B., Tran, D., Kofff, J., Kleinhenz, M.E., Nielson, D., Brodie, E.L. and Lynch, S.V. Airway Microbiota and Pathogen Abundance in Age-Stratified Cystic Fibrosis Patients. (PLoS One PLoS One. 2010 Jun 23;5(6):e11044). PMID: 20585638

14.    Singh, G., Wu, B., Baek, M.S., Camargo, A., Nguyen, A., Slusher, N.A., Srinivasan, R., Wiener-Kronish, J.P. and Lynch, S.V. Secretion of Pseudomonas aeruginosa Type III Cytotoxins is Dependent on Pseudomonas Quinolone Signal Concentration. Microbial Pathogenesis. 2010. 49(4):196-203. PMID: 20570614

15.    Lynch SV, Flanagan JL, Sawa T, Fang A, Baek MS, Rubio-Mills A, Ajayi T, Yanagihara K, Hirakata Y, Kohno S, Misset B, Nguyen JC, Wiener-Kronish JP. Polymorphisms in the Pseudomonas aeruginosa type III secretion protein, PcrV - Implications for anti-PcrV immunotherapy. Microb Pathog. 2010 48(6):197-204. PMID: 20211240

16.    Vanja Klepac-Ceraj, Katherine P. Lemon, Thomas R. Martin, Martin Allgaier, Steven W. Kembel, Alixandra A. Knapp, Stephen Lory, Eoin L. Brodie, Susan V. Lynch, Brendan J.M. Bohannan, Jessica Green, Brian A. Maurer and Roberto Kolter. Cystic fibrosis lung disease severity markers correlate with bacterial community structure. Environ Microbiol. 2010. 12(5):1293-303. PMID: 20192960

17.    Cox, M., Huang, Y.J., Fujimura, K., Liu, J., McKean, M., Brodie, E.L., Boushey, H., Cabana, M. and Lynch, S.V. Lactobacillus casei Abundance is Associated with Profound Shifts in the Infant Gut Microbiome. PLoS One. 2010 Jan 18;5(1). PMID: 20090909

18.    Huang Y.J., Kim E., Cox M.J., Brown R., Wiener-Kronish J.P., Lynch S.V. A Persistent and Diverse Airway Microbiome in Chronic Obstructive Pulmonary Disease. OMICS - a Journal of Integrative Biology. 2010 Feb;14(1):9-59. PMID: 20141328

19.    Huang, Y.J., Nelson, C.E., Brodie, E.L., DeSantis, T.Z., Baek, M.S., Liu, J., Woyke, T., Allgaier, M., Bristow, J., Wiener-Kronish, J.P., Sutherland, R., King, T.S., Icitovic, N., Martin, R.J., Asthma Clinical Research Network Investigators, Boushey, H.A., and Lynch, S.V. Airway Microbiota and Bronchial Hyperresponsiveness in Patients with Sub-optimally Controlled Asthma. J Allergy Clin. Immunol. J Allergy Clin Immunol. 2011 Feb;127(2):372-381.e1-3. Epub 2010 Dec 30. PMID: 21194740

20.    Fricks-Lima, J., Hendrickson, C.M., Allgaier, M., Zhuo, H., Wiener-Kronish, J.P., Lynch, S.V., Yang, K. Differences in Biofilm Formation and Antimicrobial Resistance of Pseudomonas aeruginosa Isolated from Airways of Mechanically Ventilated Patients and Cystic Fibrosis Patients. Int. J. Antimicrob. Agents. 2011 Mar 5. PMID: 21382698

21.    Saulnier DM, Riehle K, Mistretta TA, Diaz MA, Mandal D, Raza S, Weidler EM, Qin X, Coarfa C, Milosavljevic A, Petrosino JF, Highlander S, Gibbs R, Lynch SV, Shulman RJ, Versalovic J Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology. 2011 Nov;141(5):1782-91.

22.    Havstad S, Wegienka G, Zoratti EM, Lynch SV, Boushey HA, Nicholas C, Ownby DR, Johnson CC. Effect of prenatal indoor pet exposure on the trajectory of total IgE levels in early childhood. J Allergy Clin Immunol. 2011 Aug 4.

23.    Song Y, Baer M, Srinivasan R, Lima J, Yarranton G, Bebbington C, Lynch SV. PcrV antibody-antibiotic combination improves survival in Pseudomonas aeruginosa-infected mice. Eur J Clin Microbiol Infect Dis. 2011 Dec 21. PMID: 22187351

24.    Huang YJ, Lynch SV. The emerging relationship between the airway microbiota and chronic respiratory disease: clinical implications. Expert Rev Respir Med. 2011 Dec;5(6):809-21. PMID: 22082166

25.    Nagalingam NA, Lynch SV. Role of the microbiota in inflammatory bowel diseases. Inflamm Bowel Dis. 2011 Sep 20. doi: 10.1002/ibd.21866. PMID: 21936031

26.    Xu X, Zhang H, Song Y, Lynch SV, Lowell CA, Wiener-Kronish JP, Caughey GH. Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa. Leukoc Biol. 2011 Nov 10. PMID: 22075928

27.    Rauch M, Lynch SV. The potential for probiotic manipulation of the gastrointestinal microbiome. Curr Opin Biotechnol. 2011 Nov 30. PMID: 22137452.

28.    Huang, Y. Lynch, S.V., Wiener-Kronish, J.P. From Microbe to Microbiota – Considering Microbial Community Composition in Infections and Airway Diseases. Am J Respir Crit Care Med. 2012 Apr 1;185(7):691-2. No abstract available. PMID: 22467799

29.    Ramsey BW, Banks-Schlegel S, Accurso FJ, Boucher RC, Cutting GR, Engelhardt JF, Guggino WB, Karp CL, Knowles MR, Kolls JK, LiPuma JJ, Lynch S, McCray PB Jr, Rubenstein RC, Singh PK, Sorscher E, Welsh M. Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report. Am J Respir Crit Care Med. 2012 Apr 15;185(8):887-92. Epub 2012 Feb 3. PMID: 22312017

30.    Scanlan PD, Buckling A, Kong W, Wild Y, Lynch SV, Harrison F. Gut dysbiosis in cystic fibrosis. J Cyst Fibros. 2012 Apr 24. PMID: 22538067

31.    Schwarzer C, Fu Z, Patanwala M, Hum L, Lopez-Guzman M, Illek B, Kong W, Lynch SV, Machen TE. Pseudomonas aeruginosabiofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia. Cell Microbiol. 2012 Jan 10. doi: 10.1111/j.1462-5822.2012.01753.x.

32.    Gonzalez CF, Tchigvintsev A, Brown G, Flick R, Evdokimova E, Xu X, Osipiuk J, Cuff ME, Lynch S, Joachimiak A, Savchenko A, Yakunin AF. Structure and activity of the Pseudomonas aeruginosa hotdog-fold thioesterases PA5202 and PA2801. Biochem J. 2012 Jun 15;444(3):445-55. PMID: 22439787

33.    Iwai S, Fei M, Huang D, Fong S, Subramanian A, Grieco K, Lynch SV, Huang L. Oral and Airway Microbiota in HIV-Infected Pneumonia Patients. J Clin Microbiol. 2012 Sep;50(9):2995-3002. PMID: 22760045

34.    Han MK, Huang YJ, Lipuma JJ, Boushey HA, Boucher RC, Cookson WO, Curtis JL, Erb-Downward J, Lynch SV, Sethi S, Toews GB, Young VB, Wolfgang MC, Huffnagle GB, Martinez FJ. Significance of the microbiome in obstructive lung disease. Thorax. 2012 May;67(5):456-63. PMID: 22318161

35.    Nagalingam NA, Lynch SV. Role of the microbiota in inflammatory bowel diseases. Inflamm Bowel Dis. 2012 May;18(5):968-84. doi: 10.1002/ibd.21866. Epub 2011 Sep 20. PMID: 21936031

36.    Abreu, N.A., Song, Y., Mandal, D., Roediger, F.C., Pletcher, S.D., Goldberg, A.N. and Lynch, S.V. Coincident Sinus Microbiota Depletion and Corynebacterium tuberculostearicum Outgrowth Represent a Novel Etiology for Chronic Rhinosinusitis. Sci Transl Med. 2012 Sep 12;4(151):151ra124.

37.    Fujimura KE, Rauch M, Matsui E, Iwai S, Calatroni A, Lynn H, Mitchell H, Johnson CC, Gern JE, Togias A, Boushey HA, Kennedy S, Lynch SV. Development of a standardized approach for environmental microbiota investigations related to asthma development in children. J. Microbiol. Methods. 2012 Sep 4. [Epub ahead of print]

38.    Lynch, S.V., Goldfarb, K.C., Wild, Y., Kong, W., De Lisle, R.C., Brodie, E.L. Cystic Fibrosis Transmembrane gene Knockout in Mice Dramatically Impacts Gastrointestinal Microbiota Composition. (In press, Gut Microbes).

39.    Schwarzer C, Fu Z, Patanwala M, Hum L, Lopez-Guzman M, Illek B, Kong W, Lynch SV, Machen TE. Pseudomonas aeruginosabiofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia.Cell Microbiol. 2012 Jan 10. doi: 10.1111/j.1462-5822.2012.01753.x.

40.    Lynch SV, Bruce KD. The cystic fibrosis airway microbiome. Cold Spring Harb Perspect Med. 2013; 3(3). PMID: 2345729357.

41.    Lozupone C, Cota-Gomez A, Palmer BE, Linderman DJ, Charlson ES, Sodergren E, Mitreva M, Abubucker S, Martin J, Yao G, Campbell TB, Flores SC, Ackerman G, Stombaugh J, Ursell L, Beck JM, Curtis JL, Young VB, Lynch SV, Huang L, Weinstock GM, Knox KS, Twigg H, Morris A, Ghedin E, Bushman FD, Collman RG, Knight R, Fontenot AP; for the Lung HIV Microbiome Project. Widespread Colonization of the Lung by Tropheryma whipplei in HIV Infection. Am J Respir Crit Care Med. 2013 Feb 7.

42.    Nagalingam NA, Cope EK, Lynch SV. Probiotic strategies for treatment of respiratory diseases. Trends Microbiol. 2013 May 23. doi:pii: S0966-842X(13)00082-6. 10.1016/j.tim.2013.04.008. PMID: 23707554

43.    Morris A, Beck JM, Schloss PD, Campbell TB, Crothers K, Curtis JL, Flores SC, Fontenot AP, Ghedin E, Huang L, Jablonski K, Kleerup E, Lynch SV, Sodergren E, Twigg H, Young VB, Bassis CM, Venkataraman A, Schmidt TM, Weinstock GM; Lung HIV Microbiome Project. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med. 2013 May 15;187(10):1067-75. doi: 10.1164/rccm.201210-1913OC. PMID: 23491408

44.    Ivan Vujkovic-Cvijin, Richard M. Dunham, Shoko Iwai, Michael C. Maher, Rebecca G. Albright, Mara J. Broadhurst, Ryan D. Hernandez, Michael M. Lederman, Yong Huang, Ma Somsouk, Steven G. Deeks, Peter W. Hunt, Susan V. Lynch and Joseph M. McCune. Dysbiosis of the Gut Microbiota Is Associated with HIV Disease Progression and Tryptophan Catabolism. Sci. Transl. med. Vol. 5, Issue 193, p. 193ra91