Research Overview
Dr. Silbart's laboratory research program focuses on the development of mucosal vaccines and understanding the correlates of immune protection associated with specific pathogens. Specific projects are outlined below:

Project 1: Mucosal vaccines to protect livestock from foot-and-mouth disease virus (FMDV).
We are working collaboratively with scientists at the USDA's Plum Island Animal Disease Center (PIADC) to develop vaccines to protect livestock from FMDV. This work involves the development of peptide vaccines, mucosal adjuvants and novel delivery systems to elicit protective mucosal and systemic immune responses. We are currently using a porcine model, and perform vaccination studies followed by immune assessments that include ELISA, ELISPOT, flow cytometry and immunohistochemistry. More recent work focuses on designing vaccines that are structurally similar to secondary structures found in the viral VP1 G-H loop. Roger Barrett, Rupa Challa and Debra Rood are actively involved on these projects.

Project 2: Determining the correlates of immune protection of a live attenuated Mycoplasma gallisepticum vaccine for poultry.
In collaboration with Dr. Steven Geary's laboratory, we have participated in the development of live-attenuated M. gallisepticum vaccines that confer protection to chickens. This protection appears to be mediated by mucosal antibodies, and involves a rapid memory response by antibody secreting cells (IgG and IgA) present in the respiratory mucosa. We are currently characterizing the mediators responsible for mucosal leukocyte infiltration (cytokine, chemokine etc.) and identifying the mechanisms responsible for aberrant responses in unvaccinated animals exposed to wild-type organisms. We are using techniques such as ELISA, ELISPOT, flow cytometry, immunohistochemistry, microarray and RT-PCR to address these questions. Mohammed Javed and Debra Rood are actively involved in this project, as well as several students from Dr. Geary and Dr. Frasca's lab (PVS).

Project 3: Understanding the role of alveolar macrophages in pulmonary inflammatory leukocyte infiltration, especially eosinophils, in allergic asthma.
In the commonly used mouse model of allergy/asthma, the harmless egg protein known as ovalbumin is used as an allergen. We and others have observed large numbers of eosinophils infiltrating the allergic lung of sensitized mice, but little is known about what cells play a role in eosinophilic infiltration. Using microarray, RT-PCR and immunohistochemistry, we are investigating the role of alveolar macrophages in initiating these events by secreting key chemokines (e.g. eotaxin 1 and eotaxin 2). Shafiuddin Siddiqui, Debra Rood and Naomi Avery are actively involved in this project.

Project 4: Immuno-intervention in oral carcinogenesis using transgenic tobacco expressing anti-carcinogen recombinant binding sites.
We are working to develop a transgenic tobacco plant expressing a recombinant single chain antibody that will bind to an important tobacco specific nitrosamine that is, in part, responsible for initiating cancer in the oral cavity. We hope to test the hypothesis that by intercepting the carcinogen prior to its interaction with the oral epithelial surface, the bioactivation and subsequent DNA damage in epithelial cells can be reduced or prevented. Debra Rood and Dr. Michael Lynes (MCB) are collaborating on this project.

Education
Undergraduate:
University of Michigan, Ann Arbor, B.G.S. (Biochemistry conc.), 1976- 80
Graduate:        
University of Michigan (Ann Arbor), Toxicology/Industrial Health
(double concentration), 1980-83, M.P.H. University of Michigan (Ann Arbor), Toxicology, 1983-87, Ph.D.

Featured Publications
Wilkinson, J., Rood, D., Minor, D., Guillard, K., Darre, M. and Silbart, L.K. (2003) Immune Response to a Mucosally Administered Aflatoxin B1 Vaccine. Poultry Science 82:1565-1572.
Zinckgraf, J.W. and L.K. Silbart (2003) Modulating gene expression using DNA vaccines with different 3'-UTRs influences antibody titer, seroconversion and cytokine profiles. Vaccine 21:1640-1649.
Fischer, D, Rood, D., Barette, R., Zuwallack, A., Kramer, E., Brown, F., and L.K. Silbart. (2003) Intranasal immunization of guinea pigs with an immunodominant FMDV peptide conjugate induces mucosal and humoral antibodies and protection upon challenge.  J. Virology 77:7486-7491.
Javed M.A., Frasca, S. Jr., Rood, D., Cecchini K., Gladd, M., Geary, S.J., Silbart, L.K. (2005) Correlates of Immune Protection in Chickens Vaccinated with Mycoplasma gallisepticum Strain GT5 following Challenged with Pathogenic M. gallisepticum Strain Rlow  Infection and Immunity 73:5410-5419.

Silbart, L.K. (2006) Incorporating Problem-Based Learning Exercises into an Environmental Health Curriculum. Feature Aritcle: J. Environ. Health 68(9):43-47.

C. Srinivasan, J. Lee, F. Papadimitrakopoulos, L.K. Silbart, M. H. Zhao, and D.J. Burgess.   Labeling and intracellular tracking of functionally active plasmid DNA with semiconductor quantum dots. Mol Ther. 2006 Aug;14(2):192-201. Epub 2006 May 12.
Barrette, R.W., Urbonas, J., Silbart, L.K., (2006) Quantifying Specific Antibody Concentrations by ELISA using Slope Correction. Clinical and Vaccine Immunology 13(7): 802-805.
Challa S., Barrette R., Rood .D, Zinckgraf J., French R., Silbart L. (2007) Non-toxic Pseudomonas aeruginosa exotoxin A expressing the FMDV VP1 G-H loop for mucosal vaccination of swine against foot and mouth disease virus. Vaccine. Apr 30;25(17):3328-37. Epub 2007 Jan 12.
Mohammed J, Frasca S Jr, Cecchini K, Rood D, Nyaoke AC, Geary SJ, Silbart LK. (2007) Chemokine and cytokine gene expression profiles in chickens inoculated with Mycoplasma gallisepticum strains Rlow or GT5. Vaccine. Dec 12;25(51):8611-21. Epub 2007 Oct 16.
Rezamand P, Hoagland TA, Moyes KM, Silbart LK, Andrew SM. (2007) Energy status, lipid-soluble vitamins, and acute phase proteins in periparturient Holstein and Jersey dairy cows with or without subclinical mastitis. J Dairy Sci. 2007 Nov;90(11):5097-107.

Yang H, Knapp J, Koirala P, Rajagopal D, Peer WA, Silbart LK, Murphy A, Gaxiola RA. (2007) Enhanced phosphorus nutrition in monocots and dicots over-expressing a phosphorus-responsive type I H+-pyrophosphatase. Plant Biotechnol J. Nov;5(6):735-45. Epub 2007 Aug 16.

Siddiqui, S., Rood. D., Morris, J.,  Wyand S., Silbart, L.K., (2008)  Allergen deposition in the lower respiratory tract correlates with eosinophilia in the airways of  BALB/c mice. In revision.

Gates A.E., S. Frasca, S. Jr,  Nyaoke, A., Gorton, T.S., Silbart, L.K., Geary, S.J., (2008) Comparative Assessment of a Metabolically Attenuated Mycoplasma gallisepticum Mutant as a Live Vaccine for the Prevention of Avian Respiratory Mycoplasmosis. Vaccine (in press).

Nair, M.K.M, Venkitanarayanan, K., Silbart, L.K. and Kim, K.S., (2008) Outer membrane protein A (OmpA) of Enterobacter sakazakii binds fibronectin and contributes to invasion of human brain microvascular endothelial cells. (Submitted)

Barrette, R., Rood, D. and Silbart, L.K. (2008) Refocusing the immune response toward an immunodominant, hypervariable region within the FMDV VP1 G-H loop to a more highly conserved epitope via xenoepitope substitution. For submission 2/08