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Michelle Dziejman, Ph.D.

Michelle Dziejman, Ph.D.

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Office (585) 273-4459

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About Me

Faculty Appointments

Associate Professor - Department of Microbiology and Immunology (SMD)

Credentials

Post-doctoral Training & Residency

Postdoctoral Research Fellow, Massachusetts General Hospital, Charlestown MA 1996 - 1998

Education

PhD | Univ of Pennsylvania. Microbiology, All Other. 1996

BS | University of Rochester. Microbiology. 1988

Awards

NIH NRSA.

Research

Research Focus
Type Three Secretion System mediated pathogenesis of V. cholerae
Research Overview
Vibrio cholerae is a diverse species found in aquatic environments worldwide, and it is the causative agent of the severe diarrheal disease known as cholera. Epidemic disease in Asia ...
Research Focus
Type Three Secretion System mediated pathogenesis of V. cholerae
Research Overview
Vibrio cholerae is a diverse species found in aquatic environments worldwide, and it is the causative agent of the severe diarrheal disease known as cholera. Epidemic disease in Asia and South America is currently caused only by strains of the O1 or O139 serogroup of V. cholerae. However, a significant amount of world wide, sporadic disease is caused by strains of other serogroups, collectively called non-O1/non-O139 strains. Ribotyping and comparative genomic analyses have shown that these strains are very diverse both phylogenetically and in their genetic content compared to strains of the O1 and O139 serogroups. Unlike epidemic strains, the majority of non-O1/non-O139 strains do not carry the well characterized virulence factors for colonization (toxin co-regulated pilus, TCP) and cholera toxin (CT) production. It is presumed that pathogenic non-O1/non-O139 isolates have acquired novel virulence factors that confer the ability to colonize and cause disease in a TCP/CT independent manner. However, these strains remain largely uncharacterized.
AM-19226 is a clinically isolated, O39 serogroup strain of V. cholerae that does not carry the genes encoding TCP or CT. However, whole genome sequencing of AM-19226 has identified open reading frames (ORFs) having significant similarity to genes encoding the structural components of a Type Three Secretion System (T3SS). These ORFs, named vcs, lie within a ~60kb pathogenicity island that has been found in other non-O1/non-O139 strains. A wide variety of gram-negative, pathogenic bacteria use TTSSs as a conserved mechanism to translocate multiple virulence factors, referred to as T3SS effector proteins, directly into the cytosol of eukaryotic cells. We therefore postulate that the vcs genes represent a previously unidentified mechanism for host cell interaction acquired by V. cholerae. Also within this island are two open reading frames predicted to encode proteins having sequence similarity to ToxR, an important player in the network of regulatory proteins that govern the expression of virulence factors in epidemic O1 and O139 serogroup strains. Although the amino acid sequences of proteins encoding the structural components are highly conserved among T3SSs of different organisms, the sequences of effector proteins typically share limited or no homology. Effector proteins are therefore often unique to a specific T3SS, and their interactions with eukaryotic host cell proteins serve to elicit distinct phenotypes beneficial for the particular bacterial pathogen.
In order to understanding the scope of molecular mechanisms responsible for TTSS mediated disease, we are working to:

1. understand the role of the ToxR paralogs and ToxR itself in T3SS related gene expression.
2. identify in vitro conditions that promote expression of the T3SS genes.
3. identify effector proteins that are required during infection to provide functions critical for colonization and disease.

To accomplish these goals we use several experimental approaches, including genetic and molecular techniques complimented by in vitro mammalian cell culture model systems. In addition, we collaborate with Dr. J. Scott Butler (also in the Dept. of Microbiology & Immunology) in using S. cerevisiae as a model system for the identification of effector proteins and the analyses of their molecular interactions with components of the eukaryotic host machinery.

Publications

Journal Articles

Antagonistic effects of actin-specific toxins on Typhimurium invasion into mammalian cells.

Heisler DB, Kudryashova E, Hitt R, Williams B, Dziejman M, Gunn J, Kudryashov DS

bioRxiv : the preprint server for biology.. 2024 July 2 Epub 07/02/2024.

Genomic Analysis of Clostridioides difficile in 2 Regions of the United States Reveals a Diversity of Strains and Limited Transmission.

Pecora N, Holzbauer S, Wang X, Gu Y, Taffner S, Hatwar T, Hardy D, Dziejman M, D'Heilly P, Pung K, Guh A, Qiu X, Gill S, Dumyati G

The Journal of infectious diseases.. 2022 January 5225 (1):121-129. Epub 1900 01 01.

DksA coordinates bile-mediated regulation of virulence-associated phenotypes in type three secretion system-positive .

Sofia MK, Dziejman M

Microbiology.. 2021 February 167 (2)Epub 1900 01 01.

Vibrio variations on a type three theme.

Miller KA, Tomberlin KF, Dziejman M

Current opinion in microbiology.. 2019 February 47 :66-73. Epub 01/31/2019.

Characterization of V. cholerae T3SS-dependent cytotoxicity in cultured intestinal epithelial cells.

Miller KA, Chaand M, Gregoire S, Yoshida T, Beck L, Ivanov AI, Dziejman M

Cellular microbiology.. 2016 December 18 (12):1857-1870. Epub 07/22/2016.

Regulation by ToxR-Like Proteins Converges on vttRB Expression To Control Type 3 Secretion System-Dependent Caco2-BBE Cytotoxicity in Vibrio cholerae.

Miller KA, Sofia MK, Weaver JW, Seward CH, Dziejman M

Journal of bacteriology.. 2016 June 1198 (11):1675-1682. Epub 05/13/2016.

Using S. cerevisiae as a Model System to Investigate V. cholerae VopX-Host Cell Protein Interactions and Phenotypes.

Seward CH, Manzella A, Alam A, Butler JS, Dziejman M

Toxins.. 2015 October 147 (10):4099-110. Epub 10/14/2015.

Type 3 Secretion System Island Encoded Proteins Required for Colonization by Non-O1/non-O139 Serogroup .

Chaand M, Miller KA, Sofia MK, Schlesener C, Weaver JW, Sood V, Dziejman M

Infection and immunity.. 2015 July 83 (7):2862-2869. Epub 05/04/2015.

Vibrio cholerae VttR(A) and VttR(B) regulatory influences extend beyond the type 3 secretion system genomic island.

Chaand M, Dziejman M

Journal of bacteriology.. 2013 May 195 (10):2424-36. Epub 03/22/2013.

The Vibrio cholerae trh gene is coordinately regulated in vitro with type III secretion system genes by VttR(A)/VttR(B) but does not contribute to Caco2-BBE cell cytotoxicity.

Miller KA, Hamilton E, Dziejman M

Infection and immunity.. 2012 December 80 (12):4444-55. Epub 10/08/2012.

A broadly applicable approach to T cell epitope identification: application to improving tumor associated epitopes and identifying epitopes in complex pathogens.

Valentino MD, Abdul-Alim CS, Maben ZJ, Skrombolas D, Hensley LL, Kawula TH, Dziejman M, Lord EM, Frelinger JA, Frelinger JG

Journal of immunological methods.. 2011 October 28373 (1-2):111-26. Epub 08/18/2011.

Identification of Vibrio cholerae type III secretion system effector proteins.

Alam A, Miller KA, Chaand M, Butler JS, Dziejman M

Infection and immunity.. 2011 April 79 (4):1728-40. Epub 01/31/2011.

vttRA and vttRB Encode ToxR family proteins that mediate bile-induced expression of type three secretion system genes in a non-O1/non-O139 Vibrio cholerae strain.

Alam A, Tam V, Hamilton E, Dziejman M

Infection and immunity.. 2010 June 78 (6):2554-70. Epub 04/12/2010.

A type III secretion system in Vibrio cholerae translocates a formin/spire hybrid-like actin nucleator to promote intestinal colonization.

Tam VC, Serruto D, Dziejman M, Brieher W, Mekalanos JJ

Cell host & microbe.. 2007 April 191 (2):95-107. Epub 1900 01 01.

Genomic analysis of the Mozambique strain of Vibrio cholerae O1 reveals the origin of El Tor strains carrying classical CTX prophage.

Faruque SM, Tam VC, Chowdhury N, Diraphat P, Dziejman M, Heidelberg JF, Clemens JD, Mekalanos JJ, Nair GB

Proceedings of the National Academy of Sciences of the United States of America.. 2007 March 20104 (12):5151-6. Epub 03/12/2007.

Transcriptional profiling of Vibrio cholerae recovered directly from patient specimens during early and late stages of human infection.

Larocque RC, Harris JB, Dziejman M, Li X, Khan AI, Faruque AS, Faruque SM, Nair GB, Ryan ET, Qadri F, Mekalanos JJ, Calderwood SB

Infection and immunity.. 2005 August 73 (8):4488-93. Epub 1900 01 01.

Genomic characterization of non-O1, non-O139 Vibrio cholerae reveals genes for a type III secretion system.

Dziejman M, Serruto D, Tam VC, Sturtevant D, Diraphat P, Faruque SM, Rahman MH, Heidelberg JF, Decker J, Li L, Montgomery KT, Grills G, Kucherlapati R, Mekalanos JJ

Proceedings of the National Academy of Sciences of the United States of America.. 2005 March 1102 (9):3465-70. Epub 02/22/2005.

Genetic diversity and virulence potential of environmental Vibrio cholerae population in a cholera-endemic area.

Faruque SM, Chowdhury N, Kamruzzaman M, Dziejman M, Rahman MH, Sack DA, Nair GB, Mekalanos JJ

Proceedings of the National Academy of Sciences of the United States of America.. 2004 February 17101 (7):2123-8. Epub 02/06/2004.

ToxR regulon of Vibrio cholerae and its expression in vibrios shed by cholera patients.

Bina J, Zhu J, Dziejman M, Faruque S, Calderwood S, Mekalanos J

Proceedings of the National Academy of Sciences of the United States of America.. 2003 March 4100 (5):2801-6. Epub 02/24/2003.

Determination of the transcriptome of Vibrio cholerae during intraintestinal growth and midexponential phase in vitro.

Xu Q, Dziejman M, Mekalanos JJ

Proceedings of the National Academy of Sciences of the United States of America.. 2003 February 4100 (3):1286-91. Epub 01/27/2003.

IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking.

Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD

The Journal of immunology : official journal of the American Association of Immunologists.. 2002 April 1168 (7):3195-204. Epub 1900 01 01.

Quorum-sensing regulators control virulence gene expression in Vibrio cholerae.

Zhu J, Miller MB, Vance RE, Dziejman M, Bassler BL, Mekalanos JJ

Proceedings of the National Academy of Sciences of the United States of America.. 2002 March 599 (5):3129-34. Epub 02/19/2002.

Comparative genomic analysis of Vibrio cholerae: genes that correlate with cholera endemic and pandemic disease.

Dziejman M, Balon E, Boyd D, Fraser CM, Heidelberg JF, Mekalanos JJ

Proceedings of the National Academy of Sciences of the United States of America.. 2002 February 599 (3):1556-61. Epub 01/29/2002.

Enhanced inhibition of human immunodeficiency virus type 1 by Met-stromal-derived factor 1beta correlates with down-modulation of CXCR4.

Yang OO, Swanberg SL, Lu Z, Dziejman M, McCoy J, Luster AD, Walker BD, Herrmann SH

Journal of virology.. 1999 June 73 (6):4582-9. Epub 1900 01 01.

The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells.

Sauty A, Dziejman M, Taha RA, Iarossi AS, Neote K, Garcia-Zepeda EA, Hamid Q, Luster AD

The Journal of immunology : official journal of the American Association of Immunologists.. 1999 March 15162 (6):3549-58. Epub 1900 01 01.

ToxR co-operative interactions are not modulated by environmental conditions or periplasmic domain conformation.

Dziejman M, Kolmar H, Fritz HJ, Mekalanos JJ

Molecular microbiology.. 1999 January 31 (1):305-17. Epub 1900 01 01.

Involvement of the IP-10 chemokine in sarcoid granulomatous reactions.

Agostini C, Cassatella M, Zambello R, Trentin L, Gasperini S, Perin A, Piazza F, Siviero M, Facco M, Dziejman M, Chilosi M, Qin S, Luster AD, Semenzato G

The Journal of immunology : official journal of the American Association of Immunologists.. 1998 December 1161 (11):6413-20. Epub 1900 01 01.

Analysis of membrane protein interaction: ToxR can dimerize the amino terminus of phage lambda repressor.

Dziejman M, Mekalanos JJ

Molecular microbiology.. 1994 August 13 (3):485-94. Epub 1900 01 01.

Expression of glutamine/glutamic acid-rich proteins in rat submandibular glands.

Mirels L, Kopec L, Yagil C, Dickinson DP, Dziejman M, Tabak LA

Archives of oral biology.. 1990 35 (1):1-5. Epub 1900 01 01.