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Lynn Bry, MD, PhD
Associate Pathologist, Brigham and Women's Hospital
Associate Professor of Pathology, Harvard Medical School

Brigham and Women's Hospital
Department of Pathology
75 Francis Street
Boston, MA 02115

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Research Narrative:

Research: Host-pathogen-commensal cross-talk in the gut
My laboratory studies the following aspects of host defense against microbial pathogens (1) host reponses against attaching and effacing pathogens such as Citrobacter rodentium and the enteropathogenic E. coli (EPEC), (2) the molecular basis of mucosal projection from colonization with commensals.

We have defined the effector functions and locations at which protective T cell and B cell responses develop against the murine attaching and effacing pathogen Citrobacter rodentium. This EPEC-like organism produces a primary infection of the apical surface of the gut epithelium. Surprisingly, systemic and CD4+ T cell dependent IgG, and not mucosal IgA, proved the critical adaptive response needed to successfully control mucosal infection. Pathogen-specific IgG acts systemically and in the gut lumen to effect eradication of pathogens from the host. We have subsequently shown that interactions with complement are important for this eradication and for the development of protective IgG responses.
We have further developed this model to elucidate how the commensal flora contributes to host defense of mucosal surfaces through mechanisms including ecological/competitive effects in the gut lumen as well as stimulation of innate and adaptive responses that are recruited early in infection with enteric pathogens. As Director of the HDDC Gnotobiotic Mouse Core, we have devised a number of model systems using genetically tenable pathogens and commensals in conventional and germfree mice to dissect what is otherwise a highly complicated ecosystem. Our microbiomics group includes collaborations with Dr. Colleen Cavanaugh in the Dept. of Evolutionary Biology at Harvard University to perform deep sequencing of microbial communities in enteric environments, and with Anaerobe Research Laboratory run by Dr. Andy Onderdonk at BWH/Channing Laboratory.

Research: Crimson Project - IT infrastructure to support high-through sample collection for discovery pipelines
The Crimson application prospectively matches discarded samples from clinical laboratories per investigator-defined criteria. This feature effectively harnesses the thousands of samples and associated data generated daily in clinical laboratories for productive use in IRB-approved studies. Additional functions of Crimson include management of sample inventories, user workgroups, and auditing capabilities to insure compliance with HIPAA and local IRBs. The application is also capable of receiving forwarded cohorts of potential subjects from multiple Clinical Data Repositories (CDRs) in use within Partners Healthcare, including the Research Patient Data Registry (RPDR) and i2b2CRC repositories that house electronic medical information across Partners Hospitals. This integration allows an investigator to define a cohort of patients on the CDR and forward it to Crimson for collection of discarded samples.

Crimson went live on 2/1/2007 and has since handled >60,000 samples collected for use by IRB-approved studies. The application was developed by myself and Neil Herring in the Pathology IT Division at BWH with software development support for Daedalus Software Inc. in Cambridge MA. Crimson remains a unique an innovative system, one that is being adopted by i2b2 (Informatics for Integrating Biology to the Bedside), an NIH Roadmap initiative. It is also a major component of the Partners-wide Personalized Medicine Biorepository that is obtaining consented patient samples for use in research.


Additional News:

Publications (Pulled from Harvard Catalyst Profiles):

1. Abdel-Gadir A, Stephen-Victor E, Gerber GK, Noval Rivas M, Wang S, Harb H, Wang L, Li N, Crestani E, Spielman S, Secor W, Biehl H, Dibendetto N, Dong X, Umetsu DT, Bry L, Rachid R, Chatila TA. Microbiota therapy acts via a regulatory T cell MyD88/ROR?t pathway to suppress food allergy. Nat Med. 2019 Jul; 25(7):1164-1174.

2. Hsu BB, Gibson TE, Yeliseyev V, Liu Q, Lyon L, Bry L, Silver PA, Gerber GK. Dynamic Modulation of the Gut Microbiota and Metabolome by Bacteriophages in a Mouse Model. Cell Host Microbe. 2019 Jun 12; 25(6):803-814.e5.

3. Tashiro H, Cho Y, Kasahara DI, Brand JD, Bry L, Yeliseyev V, Abu-Ali G, Huttenhower C, Shore SA. Microbiota contribute to obesity-related increases in the pulmonary response to ozone. Am J Respir Cell Mol Biol. 2019 May 30.

4. Pecora N, Zhao X, Nudel K, Hoffmann M, Li N, Onderdonk AB, Yokoe D, Brown E, Allard M, Bry L. Diverse Vectors and Mechanisms Spread New Delhi Metallo-ß-Lactamases among Carbapenem-Resistant Enterobacteriaceae in the Greater Boston Area. Antimicrob Agents Chemother. 2019 Feb; 63(2).

5. Crothers J, Bry L. Gutting TMA to Save the Heart. Cell Host Microbe. 2018 10 10; 24(4):470-471.

6. Pirrone M, Imber DA, Marrazzo F, Pinciroli R, Zhang C, Bry L, Delaney ML, Dubois AM, Thomas JG, Nistico L, Melton-Kreft R, Bittner EA, Kacmarek RM, Berra L. Silver-Coated Endotracheal Tubes Cleaned With a Mechanism for Secretion Removal. Respir Care. 2019 Jan; 64(1):1-9.

7. Kim S, Kerns SJ, Ziesack M, Bry L, Gerber GK, Way JC, Silver PA. Quorum Sensing Can Be Repurposed To Promote Information Transfer between Bacteria in the Mammalian Gut. ACS Synth Biol. 2018 09 21; 7(9):2270-2281.

8. Yao L, Seaton SC, Ndousse-Fetter S, Adhikari AA, DiBenedetto N, Mina AI, Banks AS, Bry L, Devlin AS. A selective gut bacterial bile salt hydrolase alters host metabolism. Elife. 2018 07 17; 7.

9. Lavin R, DiBenedetto N, Yeliseyev V, Delaney M, Bry L. Gnotobiotic and Conventional Mouse Systems to Support Microbiota Based Studies. Curr Protoc Immunol. 2018 04; 121(1).

10. Fujisaka S, Avila-Pacheco J, Soto M, Kostic A, Dreyfuss JM, Pan H, Ussar S, Altindis E, Li N, Bry L, Clish CB, Kahn CR. Diet, Genetics, and the Gut Microbiome Drive Dynamic Changes in Plasma Metabolites. Cell Rep. 2018 03 13; 22(11):3072-3086.