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Manfred Brigl, MD
Associate Pathologist, Brigham and Women's Hospital
Assistant 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:

My research seeks to address fundamental unanswered questions regarding the function of CD1d-restricted Natural Killer T (NKT) cells in the context of antimicrobial immunity.  NKT cells are a specialized subset of lymphocytes recognizing lipids, a novel group of T cell antigens.  Recently, we have described a unique pathway of NKT cell activation during infection, findings that are widely recognized and integrated in the research efforts in the field.  My current work continues this line of investigation, expands the findings into a broad range of infectious agents including fungi, deepens the mechanistic understanding of this pathway, and attempts to identify novel antigenic compounds that are recognized by NKT cells.  I am also contributing experimental data on NKT cells to a collaborative effort mapping the genomic pathways regulating immune cells.  Together, these research efforts have significance for understanding the function of NKT cells and are important for host defense to infection and other diseases. 


Education:
MD

Publications (Pulled from Harvard Catalyst Profiles):

1. Solomon IH, Lin C, Horback KL, Kanjilal S, Rojas-Rudilla V, Brigl M, Laga AC, Lindeman NI, Padera RF. Utility of Histologic and Histochemical Screening for 16S Ribosomal RNA Gene Sequencing of Formalin-Fixed, Paraffin-Embedded Tissue for Bacterial Endocarditis. Am J Clin Pathol. 2019 Jun 07.

2. Wolf BJ, Tatituri RV, Almeida CF, Le Nours J, Bhowruth V, Johnson D, Uldrich AP, Hsu FF, Brigl M, Besra GS, Rossjohn J, Godfrey DI, Brenner MB. Identification of a Potent Microbial Lipid Antigen for Diverse NKT Cells. J Immunol. 2015 Sep 15; 195(6):2540-51.

3. Macho-Fernandez E, Brigl M. The Extended Family of CD1d-Restricted NKT Cells: Sifting through a Mixed Bag of TCRs, Antigens, and Functions. Front Immunol. 2015; 6:362.

4. Brennan PJ, Brigl M, Brenner MB. Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol. 2013 Feb; 13(2):101-17.

5. Tatituri RV, Watts GF, Bhowruth V, Barton N, Rothchild A, Hsu FF, Almeida CF, Cox LR, Eggeling L, Cardell S, Rossjohn J, Godfrey DI, Behar SM, Besra GS, Brenner MB, Brigl M. Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs. Proc Natl Acad Sci U S A. 2013 Jan 29; 110(5):1827-32.

6. Cohen NR, Brennan PJ, Shay T, Watts GF, Brigl M, Kang J, Brenner MB. Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells. Nat Immunol. 2013 Jan; 14(1):90-9.

7. Bedel R, Matsuda JL, Brigl M, White J, Kappler J, Marrack P, Gapin L. Lower TCR repertoire diversity in Traj18-deficient mice. Nat Immunol. 2012 Jul 19; 13(8):705-6.

8. Cohen NR, Tatituri RV, Rivera A, Watts GF, Kim EY, Chiba A, Fuchs BB, Mylonakis E, Besra GS, Levitz SM, Brigl M, Brenner MB. Innate recognition of cell wall ß-glucans drives invariant natural killer T cell responses against fungi. Cell Host Microbe. 2011 Nov 17; 10(5):437-50.

9. Brennan PJ, Tatituri RV, Brigl M, Kim EY, Tuli A, Sanderson JP, Gadola SD, Hsu FF, Besra GS, Brenner MB. Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals. Nat Immunol. 2011 Oct 30; 12(12):1202-11.

10. Brigl M, Tatituri RV, Watts GF, Bhowruth V, Leadbetter EA, Barton N, Cohen NR, Hsu FF, Besra GS, Brenner MB. Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection. J Exp Med. 2011 Jun 06; 208(6):1163-77.