Lawrence Silbart, PhD, MPH
|Vice Provost for Strategic Initiatives & Professor|
|Address||352 Mansfield Rd
Storrs, CT 06269-1101
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 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. Dr. Steven Szczepanek (post-doctoral fellow), Diana Alejo (doctoral student) and Debra Rood (Lab Technician/Manager) 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. Sanjukta Majumder (doctoral student), Bridget Teevan (undergraduate honors student) and Debra Rood (Lab technician/manager) are actively involved in this project as a collaboration with Dr. Geary's lab in 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). Eric Secor (doctoral student) is following up on the work of Dr. Shafiuddin Siddiqui (now a post-doctoral fellow at Harvard). Eric's current work is conducted primarily in Dr. Roger Thrall's laboratory, and focuses on understanding and assessing the role of bromelain, an anti-inflammatory nutraceutical from pineapple that ameliorates airway hyper-reactivity in a mouse model of asthma.
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. Heather Wanczyk (M.S. student) and Debra Rood are working on the project, with Dr. Michael Lynes (MCB) collaborating on this project.
University of Michigan, Ann Arbor, B.G.S. (Biochemistry conc.), 1976- 80
University of Michigan (Ann Arbor), Toxicology/Industrial Health (double concentration), 1980-83, MPH
University of Michigan (Ann Arbor), Toxicology, 1983-87, Ph.D.
Professional Training and Positions Held
1981-84 Clinical Laboratory Tech., Department of Pathology, The University of Michigan Hospital.
1983-84 Staff Scientist, National Wildlife Federation-Great Lakes Natural Resource Center, Ann Arbor,
1985-87 Research Assistant, Department of Pathology, University of Michigan Medical School.
1986-87 Research Assistant, Department of Pharmacology, University of Michigan Medical School.
1988-89 Postdoctoral Research Fellow, Department of Pathology, University of Michigan.
1989-91 Research Investigator, Department of Pathology, University of Michigan.
1991-1996 Assistant Professor of Animal Science, University of Connecticut, Storrs, CT.
1991-97 Joint Appointment - Assistant Professor of Molecular and Cell Biology, UCONN, Storrs, CT
1991-Present Assistant Director, Center for Environmental Health, University of Connecticut, Storrs, CT.
1997-2005 Associate Professor of Animal Science, The University of Connecticut, Storrs, CT
1997-Present Joint Appointment - Associate Professor of Molecular and Cell Biology, UCONN, Storrs, CT
1998-Present Joint Appointment - Associate Professor of Pathobiology, UCONN, Storrs, CT
1997-Present Visiting Scholar, Harvard University School of Public Health, Boston, MA
1997-Present P.I., Center for Excellence in Vaccine Research
1998-Present Co-Facility Head, Flow Cytometry and Confocal Microscopy, UCONN Storrs, CT
1999 Visiting Associate Professor, Children's Hospital, Harvard University, Boston, MA
2001-Present Associate Director, Center of Excellence for Vaccine Research, UCONN
2002-2006 Adjunct Associate Professor of Veterinary Medicine, Tufts School of Veterinary Medicine
2006-Present Adjunct Professor of Veterinary Medicine, Tufts School of Veterinary Medicine
2005-Present Adjunct Professor of Animal Science, University of Connecticut, Storrs, CT
2006-Present Center for Environmental Science and Engineering Advisory Committee
2006-2008 Director, Hawley Armory Fitness Programs
2006-Present Director, Center for Environmental Health
2006-Present Professor and Department Head, Department of Allied Health Sciences, CANR, UCONN Storrs
2010 - Chair-Elect, Division G, American Society of Microbiology
2010 - Harvard Education Resource Center (ERC) Advisory Committee
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.
Pires, G., Pumerantz, A., Silbart, L.K., Pescatello, L.S. (2008) The influence of a pilot nutrition education program on dietary practices among undergraduate college students. Cal. J. Health Promotion 6(2):12-25.
Srinivasan C, Siddiqui S, Silbart LK, Papadimitrakopoulos F, Burgess DJ. (2009) Dual Fluorescent Labeling Method to Visualize Plasmid DNA Degradation. Bioconjug Chem. 20(1):163-9
Nair MK, Venkitanarayanan K, Silbart LK, Kim KS. (2009) Outer membrane protein A (OmpA) of Cronobacter sakazakii binds fibronectin and contributes to invasion of human brain microvascular endothelial cells. Foodborne Pathog Dis.; 6(4):495-501.
G. Marusov, A. Sweatt, E. Guigno, S.J. Geary, L.K. Silbart, Sreerupa Challa, Jacqueline Lagoy, M.A. Lynes (2009) A Microarray Biosensor for Multiplexed Detection of Pathogens Using GCSPRI. Biosensors and Bioelectronics (Submitted).
Siddiqui, S., E. Secor and L.K. Silbart (2011) Alternatively Activated Macrophages secrete chemokines associated with recruitment of pulmonary eosinophils in a mouse model of asthma. (In preparation).
Challa, S., S. Szczepanek, Barrette, R.W., Rood, D. and L.K. Silbart (2011). FMDV O1 VP1 G-H loop fusion proteins elicit mucosal immunity when administered intranasally to guinea pigs. (In Revision).
Barrette, R.W., S. Szczepanek, Rood, D., Challa, R., Avery, N. Vajdy, M., Kramer, E., Rodriguez, L., and L.K. Silbart (2011) Non-toxic Heat Labile Enterotoxin of E. coli Effectively Adjuvant the Mucosal Immune Response to Intranasally Administered FMDV Synthetic Peptides in Pigs. (In revision).
Silbart, L.K., Barker, T., Rood, D., Zapata, D., Howell, A., Johnson, R.I., Richardson, S., Zinckgraf, J., and M. Lynes (2011) Isolation of a hybridoma secreting a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-specific monoclonal antibody (In Preparation).