Michelle Dziejman, Ph.D.
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Michelle Dziejman, Ph.D.
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
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 ...
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
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.
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.
Sofia MK, Dziejman M
Microbiology.. 2021 February 167 (2)Epub 1900 01 01.
Miller KA, Tomberlin KF, Dziejman M
Current opinion in microbiology.. 2019 February 47 :66-73. Epub 01/31/2019.
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.
Miller KA, Sofia MK, Weaver JW, Seward CH, Dziejman M
Journal of bacteriology.. 2016 June 1198 (11):1675-1682. Epub 05/13/2016.
Seward CH, Manzella A, Alam A, Butler JS, Dziejman M
Toxins.. 2015 October 147 (10):4099-110. Epub 10/14/2015.
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.
Chaand M, Dziejman M
Journal of bacteriology.. 2013 May 195 (10):2424-36. Epub 03/22/2013.
Miller KA, Hamilton E, Dziejman M
Infection and immunity.. 2012 December 80 (12):4444-55. Epub 10/08/2012.
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.
Alam A, Miller KA, Chaand M, Butler JS, Dziejman M
Infection and immunity.. 2011 April 79 (4):1728-40. Epub 01/31/2011.
Alam A, Tam V, Hamilton E, Dziejman M
Infection and immunity.. 2010 June 78 (6):2554-70. Epub 04/12/2010.
Tam VC, Serruto D, Dziejman M, Brieher W, Mekalanos JJ
Cell host & microbe.. 2007 April 191 (2):95-107. Epub 1900 01 01.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dziejman M, Kolmar H, Fritz HJ, Mekalanos JJ
Molecular microbiology.. 1999 January 31 (1):305-17. Epub 1900 01 01.
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.
Dziejman M, Mekalanos JJ
Molecular microbiology.. 1994 August 13 (3):485-94. Epub 1900 01 01.
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.