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James B Bliska, BS, PhD

Title(s)
Professor of Microbiology and Immunology

Additional Titles/Positions/Affiliations
Distinguished Professor and Senior Lead Faculty Member of the Personalized Treatments for Cystic Fibrosis (CF) Cluster

Department(s)
Microbiology and Immunology

Education
BS, 5/83, Bacteriology, University of Wisconsin-Madison
PhD, 2/88, Molecular Biology, University of California-Berkeley
Postdoctoral, 1/93, Stanford University

Programs
Molecular and Cellular Biology Graduate Programs
Molecular Pathogenesis Program

Websites
https://geiselmed.dartmouth.edu/bliska/

Contact Information

Room 524A
Remsen Building
66 College Street
Hanover NH 03755

Email: James.Bliska@Dartmouth.edu


Professional Interests

RESEARCH
The focus of my research is to understand how bacterial toxins interact with the host immune system to trigger pathogenesis or host protection.
As a postdoc in the laboratory of Stanley Falkow, I carried out pioneering studies on a protein secretion system, now designated “type III”, that is used by numerous Gram-negative bacteria to inject “effectors” into infected host cells. I focused on type III effectors in Yersinia species, which are an important cause of lung, intestinal and systemic infections in humans, are genetically-tractable and can be studied in mice as a natural infection model. I collaborated with Jack Dixon and was the first to demonstrate that a type III effector could enter the host cell to act on a target protein during bacterial infection (Bliska, J. B., Guan, K., Dixon, J. E., and Falkow, S. (1991). Tyrosine phosphate hydrolysis of host proteins by an essential Yersinia virulence determinant. Proc. Natl. Acad. Sci.).
After I became a faculty member at Stony Brook University, I continued to characterize Yersinia effectors and uncovered basic principles of how this class of proteins function to counteract innate immunity. Research in my laboratory also lead to the discovery that effectors can activate immune responses, providing novel insights into the immunology of infection.
The above studies culminated in my discovery of a complex interplay between three Yersinia effectors and a host protein call pyrin inside infected cells (Chung et al. Cell Host Microbe, 2016; see paper listed under selected publications). One significant outcome of this work is that it helped establish the concept of pyrin as a unique immune sensor that “guards” host cells against attack by a specific class of bacterial effectors and toxins. A second significant finding was that Yersinia can counteract the guard function of pyrin in order to bypass immune responses that are protective against systemic infection. In addition to Yersinia, a number of other medically important bacteria produce toxins that are sensed by pyrin.
In January of 2018 I joined the Department of Microbiology and Immunology at the Geisel School of Medicine as the Senior Lead Faculty Member of the Dartmouth Personalized Treatments for Cystic Fibrosis (CF) Cluster. My current research is focused on understanding how pyrin senses toxins and generates immune responses during bacterial infections. I am also exploring the use of synthetic immunology to combat bacterial lung infections in CF patients.

MENTORING, TRAINING AND TEACHING
I have a strong commitment to research training and career development of young scientists from diverse backgrounds at the undergraduate, graduate and post-graduate levels. I have mentored 13 graduate students, 10 to completion of the PhD and 2 remain in training. In addition, I have mentored 7 postdoctoral fellows, several of whom have obtained academic faculty positions. I am committed to increasing the diversity of individuals pursuing research-related careers. As an additional example of my strong commitment to teaching and training of young scientists, I served as Director of the NIH-funded T32 Molecular and Cell Biology of Infectious Disease Training Program for PhD students at Stony Brook University from 2003 to 2018. Since the inception of the Program (1998), and during my directorship, all PhD students appointed to the Program successfully completed it and obtained a PhD (or MD/PhD) or remained in training. In 2015, I was awarded the Dean’s Award for Excellence in Graduate Mentoring at Stony Brook. I have also been active in directing and teaching graduate level courses on topics such as microbiology, molecular biology, genetics, cell biology and immunology.

LEADERSHIP
As the Senior Lead Faculty Member of the Dartmouth Personalized Treatments for CF Cluster, I have developed a vision for its mission which is to strengthen and expand the excellent translational research and training in CF and other lung diseases at Dartmouth. This will be made possible by working with the existing Lung Biology Center, to further increase the outstanding scientific environment, collaborative atmosphere and excellent core facilities for studies of host-pathogen interactions in the lung at Dartmouth.

Grant Information

R01AI099222, Regulation of Host Innate and Adaptive Immunity by Bacterial Type III Effectors, 5/17-4/22

Courses Taught

CF: Bench to Bedside Module, Immunology of the Airway

Biography

1/80-8/83 Undergraduate research with Dr. Oliver Smithies
Laboratory of Genetics, University of Wisconsin-Madison

3/84-2/88 Doctoral research with Dr. Nicholas R. Cozzarelli
Department of Molecular Biology, University of California-Berkeley

3/88-1/93 Postdoctoral research with Dr. Stanley Falkow
Department of Microbiology and Immunology, Stanford University

2/93-1/99 Assistant Professor
Department of Molecular Genetics and Microbiology, Stony Brook University

2/99-4/03 Associate Professor
Department of Molecular Genetics and Microbiology, Stony Brook University

5/03-2/18 Professor
Department of Molecular Genetics and Microbiology, Stony Brook University

1/16-2/18 Director
Center for Infectious Diseases, Stony Brook University

3/18-present Professor Emeritus
Department of Molecular Genetics and Microbiology, Stony Brook University

1/18-present Distinguished Professor
Senior Lead Faculty Member of the Dartmouth Personalized Treatments for Cystic Fibrosis (CF) Cluster
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth


Selected Publications

 

Neutrophil inflammasomes sense the subcellular delivery route of translocated bacterial effectors and toxins.
Oh C, Li L, Verma A, Reuven AD, Miao EA, Bliska JB, Aachoui Y
Cell Rep. 2022 Nov 22;41(8):111688. doi: 10.1016/j.celrep.2022.111688.
PMID: 36417874

Correction: γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans.
Chu TH, Khairallah C, Shieh J, Cho R, Qiu Z, Zhang Y, Eskiocak O, Thanassi DG, Kaplan MH, Beyaz S, Yang VW, Bliska JB, Sheridan BS
PLoS Pathog. 2022 May;18(5):e1010586. doi: 10.1371/journal.ppat.1010586. Epub 2022 May 25.
PMID: 35613102

Role of the Yersinia pseudotuberculosis Virulence Plasmid in Pathogen-Phagocyte Interactions in Mesenteric Lymph Nodes.
Bliska JB, Brodsky IE, Mecsas J
EcoSal Plus. 2021 Dec 15;9(2):eESP00142021. doi: 10.1128/ecosalplus.ESP-0014-2021. Epub 2021 Oct 27.
PMID: 34910573

γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans.
Chu TH, Khairallah C, Shieh J, Cho R, Qiu Z, Zhang Y, Eskiocak O, Thanassi DG, Kaplan MH, Beyaz S, Yang VW, Bliska JB, Sheridan BS
PLoS Pathog. 2021 Dec;17(12):e1010103. doi: 10.1371/journal.ppat.1010103. Epub 2021 Dec 6.
PMID: 34871329

The Burkholderia cenocepacia Type VI Secretion System Effector TecA Is a Virulence Factor in Mouse Models of Lung Infection.
Loeven NA, Perault AI, Cotter PA, Hodges CA, Schwartzman JD, Hampton TH, Bliska JB
mBio. 2021 Oct 26;12(5):e0209821. doi: 10.1128/mBio.02098-21. Epub 2021 Sep 28.
PMID: 34579569

Model Systems to Study the Chronic, Polymicrobial Infections in Cystic Fibrosis: Current Approaches and Exploring Future Directions.
O'Toole GA, Crabbe A, Kummerli R, LiPuma JJ, Bomberger JM, Davies JC, Limoli D, Phelan VV, Bliska JB, DePas WH, Dietrich LE, Hampton TH, Hunter R, Khursigara CM, Price-Whelan A, Ashare A, Cramer RA, Goldberg JB, Harrison F, Hogan DA, Henson MA, Madden DR, Mayers JR, Nadell C, Newman D, Prince A, Rivett DW, Schwartzman JD, Schultz D, Sheppard DC, Smyth AR, Spero MA, Stanton BA, Turner PE, van der Gast C, Whelan FJ, Whitaker R, Whiteson K
mBio. 2021 Oct 26;12(5):e0176321. doi: 10.1128/mBio.01763-21. Epub 2021 Sep 21.
PMID: 34544277

A blend of broadly-reactive and pathogen-selected Vγ4 Vδ1 T cell receptors confer broad bacterial reactivity of resident memory γδ T cells.
Khairallah C, Bettke JA, Gorbatsevych O, Qiu Z, Zhang Y, Cho K, Kim KS, Chu TH, Imperato JN, Hatano S, Romanov G, Yoshikai Y, Puddington L, Surh CD, Bliska JB, van der Velden AWM, Sheridan BS
Mucosal Immunol. 2022 Jan;15(1):176-187. doi: 10.1038/s41385-021-00447-x. Epub 2021 Aug 30.
PMID: 34462572

Precursor Abundance Influences Divergent Antigen-Specific CD8(+) T Cell Responses after Yersinia pseudotuberculosis Foodborne Infection.
Zhang Y, Qiu Z, Sheridan BS, Bliska JB
Infect Immun. 2021 Jul 15;89(8):e0026521. doi: 10.1128/IAI.00265-21. Epub 2021 Jul 15.
PMID: 34031132

The pyrin inflammasome and the Yersinia effector interaction.
Malik HS, Bliska JB
Immunol Rev. 2020 Sep;297(1):96-107. doi: 10.1111/imr.12907. Epub 2020 Jul 28.
PMID: 32721043

Ancient familial Mediterranean fever mutations in human pyrin and resistance to Yersinia pestis.
Park YH, Remmers EF, Lee W, Ombrello AK, Chung LK, Shilei Z, Stone DL, Ivanov MI, Loeven NA, Barron KS, Hoffmann P, Nehrebecky M, Akkaya-Ulum YZ, Sag E, Balci-Peynircioglu B, Aksentijevich I, Gul A, Rotimi CN, Chen H, Bliska JB, Ozen S, Kastner DL, Shriner D, Chae JJ
Nat Immunol. 2020 Aug;21(8):857-867. doi: 10.1038/s41590-020-0705-6. Epub 2020 Jun 29.
PMID: 32601469

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