Vincent T. Lee

Assistant Professor

Ph.D. - University of California - Los Angeles, 2000
Telephone: (301) 405-9397
Fax: (301) 314-9489
E-mail: vtlee@umd.edu

Research Interests: Host-pathogen interactions, Molecular mechanisms of pathogenesis for Pseudomonas aeruginosa, Allosteric regulation of molecular complexes.

Pseudomonas aeruginosa is an important Gram-negative bacterial opportunistic pathogen that causes nosocomial infections of hospitalized patients including burn wound infections, corneal infections, urinary tract infections, pneumonia in cystic fibrosis patients and systemic infection in people with immunocompromised conditions. The large genome of P. aeruginosa encodes a number of virulence factors that allow infection to occur at various sites in the host. Surface located and secreted factors allow the bacteria to manipulate the immune system at the host pathogen interface. Our laboratory is interested in the molecular mechanisms of these virulence factors and the identification of novel virulence factors.

Type III secretion system (TTSS)

TTSS is utilized by a large number of bacterial pathogens to cause a variety of diseases by the direct transport of proteins from the bacteria cytoplasm into the contacting host cell. P. aeruginosa delivers a number of proteins including two cytotoxins, ExoS and ExoU. A cell based screen for small molecule compounds has identified a number of protective inhibitors. We wish to utilize these molecules to dissect the TTSS and understand the mechanism of action on the TTSS.

Biofilm formation/polysaccharide export

Biofilm formation is essential for bacteria to attach to surfaces including host tissues, catheters and implants. The formation of these biofilms prevents eradication of the bacteria from patient resulting in recurring/chronic infections. Bacterial biofilms are comprised of a matrix of protein and/or polysaccharide. In P. aeruginosa, the pel operon encodes a functional polysaccharide export system that is required for biofilm formation. We are interested in understanding the mechanism of the Pel proteins in promoting polysaccharide export.

Novel virulence factors

In addition to causing a large number of infections, P. aeruginosa can be found in a variety of niches in the environment. Using a high throughput genome sequencing technology, we wish to sequence a number of environmental and clinical isolates. Our goal is to utilize the genomic information to identify both shared and disease specific virulence factors.

Selected Publications:

1. Kulasakara, H., Lee, V., Brencic, A., Liberati, N., Urbach, J., Miyata, S., Lee, D.G., Neely, A.N., Hyodo, M., Hayakawa, Y., Ausubel, F.M., and Lory, S. 2006 Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3'-5')-cyclic-GMP in virulence. Proc Natl Acad Sci U S A. 103:2839-44.

2. Lee, V.T., Smith, R.S., Tümmler, B., and Lory, S. 2005. Activities of Pseudomonas aeruginosa effectors secreted by the Type III Secretion system in vitro and during infection. Infect. Immun, 73:1695-705.

3. Wolfgang, M.C., Lee, V.T., Gilmore, M.E. and Lory, S. 2003. Coordinate Regulation of Bacterial Virulence Genes by a Novel Adenylate Cyclase-Dependent Signaling Pathway. Dev. Cell. 4:253-63.

4. Lee, V. T., Mazmanian S. K. and Schneewind, O. 2001.  Multiple host inducers trigger type III secretion by Yersinia enterocolitica. J Bact. 183(17):4970-8.

5. Lee, V. T. and Schneewind, O. 1999. Type III machines of pathogenic yersiniae secrete virulence factors into the extracellular milieu. Mol. Microbiol. 31(6):1619-1629.

6. Lee, V.T. and Schneewind, O. 2001. Protein secretion and the pathogenesis of bacterial infections. Genes Dev. 15(14):1725-52.

7. Lee, V. T., Anderson, D. M. and Schneewind, O. 1998. Targeting of Yersinia Yop proteins into the cytosol of HeLa cells: one-step translocation of YopE across bacterial and eukaryotic membranes is dependent on SycE chaperone. Mol. Micobiol. 28(3):593-601.

8. Desi, J. U., Gordon, J. C., Kraatz, H.-B., Lee, V. T., Owens-Waltermire, B. E., Poli, R. Rheingold, A.L., and White, C. B.  1994. (Pentamethylcyclopentadienyl)molybdenum bromides and iodides. Inorg. Chem. 33(17):3752-3769.

9. Gordon, J. C., Lee, V. T., and Poli, R. 1993. Preparation of CpMoX₃ (Cp = -C₅H₅; X = Cl, Br, I) by thermal decarbonylation of CpMoX₃ (CO) ₂, a previously overlooked phenomenon. Inorg. Chem. 32(20):4460-4463.

Graduate Research Assistantships: My lab has 2-3 new openings for graduate student research assistants and will provide outstanding individual research projects for them. Please contact me for possible lab rotations.