Edit Entry

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:

 

Characterization of pyrin dephosphorylation and inflammasome activation in macrophages as triggered by the <i>Yersinia</i> effectors YopE and YopT.
Medici NP, Rashid M, Bliska JB
Infect Immun. 2019 Jan 2; pii: IAI.00822-18. doi: 10.1128/IAI.00822-18. Epub 2019 Jan 2.
PMID: 30602502

A Single Amino Acid Change in the Response Regulator PhoP, Acquired during Yersinia pestis Evolution, Affects PhoP Target Gene Transcription and Polymyxin B Susceptibility.
Fukuto HS, Vadyvaloo V, McPhee JB, Poinar HN, Holmes EC, Bliska JB
J Bacteriol. 2018 May 1;200(9) pii: e00050-18. doi: 10.1128/JB.00050-18. Epub 2018 Apr 9.
PMID: 29440252

CCR2<sup>+</sup> Inflammatory Monocytes Are Recruited to Yersinia pseudotuberculosis Pyogranulomas and Dictate Adaptive Responses at the Expense of Innate Immunity during Oral Infection.
Zhang Y, Khairallah C, Sheridan BS, van der Velden AWM, Bliska JB
Infect Immun. 2018 Mar;86(3) pii: e00782-17. doi: 10.1128/IAI.00782-17. Epub 2018 Feb 20.
PMID: 29263104

White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection.
Han SJ, Glatman Zaretsky A, Andrade-Oliveira V, Collins N, Dzutsev A, Shaik J, Morais da Fonseca D, Harrison OJ, Tamoutounour S, Byrd AL, Smelkinson M, Bouladoux N, Bliska JB, Brenchley JM, Brodsky IE, Belkaid Y
Immunity. 2017 Dec 19;47(6):1154-1168.e6. doi: 10.1016/j.immuni.2017.11.009. Epub 2017 Dec 5.
PMID: 29221731

Effects of host cell sterol composition upon internalization of <i>Yersinia pseudotuberculosis</i> and clustered β1 integrin.
Kim J, Fukuto HS, Brown DA, Bliska JB, London E
J Biol Chem. 2018 Jan 26;293(4):1466-1479. doi: 10.1074/jbc.M117.811224. Epub 2017 Dec 2.
PMID: 29197826

Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components.
Zwack EE, Feeley EM, Burton AR, Hu B, Yamamoto M, Kanneganti TD, Bliska JB, Coers J, Brodsky IE
Infect Immun. 2017 Oct;85(10) pii: e00778-16. doi: 10.1128/IAI.00778-16. Epub 2017 Sep 20.
PMID: 28784930

The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome.
Chung LK, Park YH, Zheng Y, Brodsky IE, Hearing P, Kastner DL, Chae JJ, Bliska JB
Cell Host Microbe. 2016 Sep 14;20(3):296-306. doi: 10.1016/j.chom.2016.07.018. Epub 2016 Aug 25.
PMID: 27569559

Gut Check: IFNγ Delays Mucosal Recovery during Antibiotic Therapy.
Chung LK, Bliska JB
Cell Host Microbe. 2016 Aug 10;20(2):128-9. doi: 10.1016/j.chom.2016.07.016.
PMID: 27512899

The Importance of Role Models in Research.
Bliska JB
PLoS Pathog. 2016 Jun;12(6):e1005426. doi: 10.1371/journal.ppat.1005426. Epub 2016 Jun 2.
PMID: 27254648

Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence.
Schoberle TJ, Chung LK, McPhee JB, Bogin B, Bliska JB
Infect Immun. 2016 Apr;84(4):1062-1072. doi: 10.1128/IAI.00843-15. Epub 2016 Mar 24.
PMID: 26810037