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Anne-Marie Hansen, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Microbiology and Immunology

Location:

HSF I, 373

Phone (Primary):

410 706 3004

Fax:

410 706 6970

Education and Training

Odense University, Denmark, BS, Molecular and Cell Biology, 1997

University of Southern Denmark at Odense, MS, Molecular and Cell Biology, 2000

University of Southern Denmark at Odense and National Institutes of Health, NCI-Bethesda, Maryland, PhD, Molecular Microbiology, 2005

National Institutes of Health, NCI-Frederick, Maryland, Post-doctoral fellow in the laboratory of Dr. Ding J. Jin, 2005-2006

University of Maryland School of Medicine at Baltimore, Post-doctoral fellow in the laboratory of Dr. James B. Kaper, Department of Microbiology and Immunology, 2006-2009

University of Maryland School of Medicine at Baltimore, Research Associate with Dr. James B. Kaper, Department of Microbiology and Immunology, 2009-2015

Biosketch

My research focus is to advance our knowledge of the molecular basis for E. coli pathogenesis with the focus being on enterohemorrhagic E. coli (EHEC). While pursuing my Ph.D. degree in Molecular Microbiology from the University of Southern Denmark, I was fortunate to carry out my thesis work at the NIH/NCI in the laboratory of Dr. Ding J. Jin. During my training at the NIH, I gained extensive experience in various aspects of microbiology, molecular biology and genetics. In particular, my research topics at the NIH focused on two global regulators in E. coli, SspA and H-NS. As part of this research, we showed that SspA up-regulates gene expression of the LEE pathogenicity island by decreasing H-NS levels in EHEC. This experience led me to pursue further research on the molecular pathogenesis of E. coli infections in the laboratory of Dr. James B. Kaper at the University of Maryland at Baltimore (UMB), who has made pioneering discoveries in this field. My initial studies at UMB concerned the regulation of EHEC virulence factors by the RNA chaperone Hfq. More recently, I have focused my research on the role of protein tyrosine phosphorylation in regulating EHEC virulence.

Although protein tyrosine phosphorylation is a well-established regulatory mechanism in eukaryotes, it is a nearly unexplored aspect of global signaling in bacteria. In an interdisciplinary study, we used a mass spectrometry-based proteomics approach to comprehensively identify tyrosine-phosphorylated proteins in E. coli. We demonstrated that phosphotyrosine-modified proteins are far more prevalent in bacteria than previously anticipated. Identified tyrosine-phosphorylated proteins relate to fundamental cell processes and EHEC virulence, suggesting a central role of phosphotyrosine modifications in bacterial cell signaling. Our current research focus is to elucidate how protein tyrosine phosphorylation regulates EHEC virulence. A comprehensive understanding of the regulatory basis for virulence is important for identifying new therapeutic approaches, particularly since the use of antibiotics is contraindicated for treatment of EHEC diseases.

Research/Clinical Keywords

Molecular Microbiology, Genetics, E. coli Pathogens, Enterohemorrhagic E. coli, Regulation of Virulence, Type Three Secretion System, Protein Tyrosine Phosphorylation

Highlighted Publications

Hansen AM, Qiu Y, Yeh N, Blattner FR, Durfee T, Jin DJ. SspA is required for acid resistance in stationary phase by downregulation of H-NS in Escherichia coli. Mol Microbiol. 2005 May;56(3):719-34.

Hansen AM, Kaper JB. Hfq affects the expression of the LEE pathogenicity island in enterohaemorrhagic Escherichia coli. Mol Microbiol. 2009 Aug;73(3):446-65.

Hansen AM, Jin DJ. SspA up-regulates gene expression of the LEE pathogenicity island by decreasing H-NS levels in enterohemorrhagic Escherichia coli. BMC Microbiol. 2012 Oct 11;12:231.

Hansen AM, Chaerkady R, Sharma J, Díaz-Mejía JJ, Tyagi N, Renuse S, Jacob HK, Pinto SM, Sahasrabuddhe NA, Kim MS, Delanghe B, Srinivasan N, Emili A, Kaper JB, Pandey A. The Escherichia coli phosphotyrosine proteome relates to core pathways and virulence. PLoS Pathog. 2013;9(6):e1003403.

Boisen N, Hansen AM, Melton-Celsa AR, Zangari T, Mortensen NP, Kaper JB, O'Brien AD, Nataro JP. The presence of the pAA plasmid in the German O104:H4 Shiga toxin type 2a (Stx2a)-producing enteroaggregative Escherichia coli strain promotes the translocation of Stx2a across an epithelial cell monolayer. J Infect Dis. 2014 Dec 15;210(12):1909-19.

In J, Foulke-Abel J, Zachos NC, Hansen AM, Kaper JB, Bernstein HD, Halushka M, Blutt S, Estes MK, Donowitz M, Kovbasnjuk O. Enterohemorrhagic Escherichia coli reduce mucus and intermicrovillar bridges in human stem cell-derived colonoids. Cell Mol Gastroenterol Hepatol. 2016 Jan 1;2(1):48- 62.e3.

Robertson CD, Hazen TH, Kaper JB, Rasko DA, Hansen AM. Phosphotyrosine-mediated regulation of enterohemorrhagic Escherichia coli virulence. mBio 2018;9(1):e00097-18.

Awards and Affiliations

Awards:

Visiting Fogarty Exchange Scientist Award, National Institutes of Health, 1999

Scholarship in Biotechnology and Biomedical Sciences, Novo Nordisk, 1999

Predoctoral Visiting Fellow Award, National Institutes of Health, 2001

Cancer Research Training Award, National Cancer Institute, 2005

Exceptional Stipend Increase Award for Exceptional Performance, National Cancer Institute, 2005

 Affiliations:

General member, American Society for Microbiology, 2008 - present

Grants and Contracts

R21 AI115217-01A1, NIH/NIAID (Hansen, PI)

06/20/15-05/31/17

Phosphotyrosine-mediated regulation of enterohemorrhagic E. coli virulence

The goal of the NIH-funded project is to elucidate the regulatory role of phosphotyrosine-mediated signaling in EHEC virulence with emphasis on the global regulator of metabolism and virulence genes, Cra.