Public Health Research Institute Center and
Dept. Medicine, Division of Pulmonary and Critical Care Medicine,
UMDNJ - New Jersey Medical School
225 Warren Street
Newark, New Jersey 07103

Phone: (973) 854-3323
FAX: (973) 854-3101
e-mail: ryanlk@umdnj.edu



Research Summary

Research in my laboratory is centered around pulmonary innate immune and inflammatory responses of the lung to either infectious or toxic agents or the combined effects of drugs and air pollutants on the innate immune processes in the lung, focusing on beta defensins.

The focus of my laboratory is on beta-defensin involvement in the innate immunity against viruses. Enveloped viruses such as influenza virus, an RNA virus, and Herpes Simplex virus (HSV-1), a DNA virus, increase both mRNA and peptide expression of human beta defensin-1 (hBD-1) in monocytes and plasmacytoid dendritic cells (PDC). How hBD-1 is induced and the mechanism of regulation of this antimicrobial peptide is of intense interest.

Several studies center on a mouse model of influenza virus (H3N2). First, the role of beta defensins in influenza virus infection is being studied in a mouse model using mouse adapted influenza A/Hong Kong/1968/passage 18. We have obtained mice on a C57BL6/J background with mouse beta defensin (mBD)-1 and mBD-3 deleted to further understand their role in the pathogenesis and replication of the virus in vivo. The mouse influenza model is also utilized for immunomodulation studies of doxycycline on influenza virus morbidity and mortality in BALB/c mice as well as the behavioral effects of influenza virus infection of pregnant BALB/c mice on their offspring.

In addition, because the role of beta defensins is important in bacterial infections of the lung, particularly gram positive infections that cause pneumonia, my laboratory is examining the effect of particulate matter containing vanadium pentoxide on innate immune responses in the airway epithelium, examining the effects on Streptococcus zooepidemicus and Staphylococcus aureus infections that model pneumonia in mice.




Selected Publications


Articles

1. Ryan LK, Diamond G, Dai J, Megjugorac N, Fitzgerald-Bocarsly PA. Viral Induction of Human Beta Defensin 1 (hBD-1) in Plasmacytoid Dendritic Cells (PDC) and Other Peripheral Blood Mononuclear Cells (PBMC). 2009; J. Immunol. (In Revision).

2. Ryan LK, Dai J, Megjugorac N, Uhlhorn V, Yim S, Schwartz KD, Abrahams JM, Diamond G, Fitzgerald-Bocarsly PA. Modulation of Human Beta-defensin-1 (hBD-1) in Plasmacytoid Dendritic Cells (PDC), Monocytes, and Epithelial Cells by Influenza Virus, Herpes Simplex Virus and Sendai Virus and its Possible Role in Innate Immunity. 2009; J. Leuk. Biol. (In Revision).

3. Klein-Patel ME, Diamond G, Boniotto M, Saad S, Ryan LK. Inhibition of ß-defensin Gene Expression in Airway Epithelial Cells by Low Doses of Residual Oil Fly Ash is Mediated by Vanadium. 2006; Toxicol. Sci. 92:115-125.

4. Ryan LK, Diamond G, Amrute S, Feng Z, Weinberg A, Fitzgerald-Bocarsly PA. Detection of HBD1 Peptide in Peripheral Blood Mononuclear Cell Subpopulations by Intracellular Flow Cytometry 2003; Peptides 24:1785-1794.

5. Ryan LK, Copeland LR, Daniels MJ, Costa ER, Selgrade MJK. Proinflammatory and Th1 cytokine alterations following ultraviolet radiation enhancement of disease due to influenza infection in mice. 2002; Toxicol. Sci. 67:88-97.

6. Suliman H, Ryan LK, Bishop LR, Folz RJ. Overexpression of extracellular superoxide dismutase (ecSOD) in the airways of transgenic mice reduces the resultant lung injury induced by primary infection with influenza virus. 2001; Am. J. Physiol. Lung Cell Mol. Physiol. 280: L69-L78.

7. Ryan LK, Neldon DL, Bishop LR, Gilmour MI, Daniels MJ, Selgrade MJK. Exposure to Ultraviolet Radiation Enhances Mortality and Pathology Associated with Influenza Infection in Mice. 2000; Photochem. Photobiol. 72:497-507.

8. Ryan LK, Rhodes J, Bhat M, Diamond G. Expression of Beta-Defensin Genes in Bovine Alveolar Macrophages. 1998; Infect. Immun. 66:878-881.

9. Ryan LK, Golenbock DT, Wu J, Vermeulen MW. Characterization of Inflammatory Cytokine Production and CD14 in Mouse Alveolar Macrophage Cell Lines. 1997; In Vitro Cell Develop. Biol.-Animal 33:647-653.

10. Ryan LK, Vermeulen MW. Alveolar Macrophages from C3H/HeJ mice Show Sensitivity to Endotoxin. 1995; Am. J. Respir. Cell Mol. Biol. 12:540-546.

11. Ryan LK, Jin R, Boggs SS, Karol MH, Day BW. Mouse Model for Assessing Endotoxin Involvement in the Lung Inflammation and Cytokine Production Resulting from Inhaled Organic Dust. Inhal. Toxicol. 1994; 6: 485-499.

12. Ryan LK, Jin R, Boggs SS, Karol MH, Day BW. Endotoxin Involvement in Cotton Dust Inflammation Assessed Using a Murine Model. In: Jacobs RR, Wakelyn PJ (eds). Proceedings of the Seventeenth Cotton Dust Research Conference, New Orleans, Louisiana, January 13-14, 1993. National Cotton Council, Memphis, TN, pp. 319-321.

13. Ryan LK, Karol MH. Release of Tumor Necrosis Factor in Guinea Pigs upon Inhalation of Cotton Dust. Am. J. Respir. Cell Mol. Biol. 1991; 5: 93-98.

14. Griffiths-Johnson DA, Ryan LK, Karol MH Development of an Animal Model for Organic Dust Toxic Syndrome. Inhal. Toxicol. 1991; 3:405-417.

15. Ryan LK, Karol MH. The Effect of Cotton Dust Exposure on the Release of Tumor Necrosis Factor from Guinea Pig Alveolar Macrophages. In: Jacobs RR,Wakelyn PJ (eds). Proceedings of the Fourteenth Cotton Dust Research Conference, Las Vegas, Nevada, January 12-13, 1990. National Cotton Council, Memphis, TN, pp 146-150.

16. Ryan LK, Karol MH. Acute Respiratory Response of Guinea Pigs to Lipopolysaccharide, Lipid A and Monophosphoryl Lipid A from Salmonella minnesota. Am. Rev. Respir. Dis. 1989; 140: 1429-1435.

17. Griffiths-Johnson DA, Ryan LK, Spear K, Karol MH. Pulmonary Response of Guinea Pigs to a Chemically-Treated Crude Preparation of E. agglomerans Cells. In: Jacobs RR, Wakelyn PJ (eds). Proceedings of the Thirteenth Cotton Dust Research Conference. Nashville, Tennessee, January 5-6, 1989. National Cotton Council, Memphis, TN. pp. 101-104.

18. Ryan LK, Karol MH. Acute Respiratory Response of Guinea Pigs to Monophosphoryl and Diphosphoryl Lipid A from the Salmonella Minnesota Re595 Mutant. In: Jacobs RR, Wakelyn PJ (eds). Proceedings of the Thirteenth Cotton Dust Research Conference. Nashville, Tennessee, January 5-6, 1989; pp. 101-104.

19. Ryan LK, Karol MH. Production of Antibody to Lipopolysaccharides (LPS) Following Immunization with a LPS-Polymyxin B-Agarose Immunogen. J. Appl. Bacteriol. 1988: 64:487-495.

20. Ryan LK, Erdal S, Karol MH. Acute Respiratory Response of Guinea pigs to Lipopolysaccharide from Salmonella minnesota and the Re595 Mutant. In: Jacobs RR, Wakelyn PJ (eds). Proceedings of the Twelfth Cotton Dust Research Conference. New Orleans, Louisiana, January 6-7, 1988. National Cotton Council, Memphis, TN. pp.47-49.

21. Ryan LK, Karol MH. Immune Response to a Lipopolysaccharide Polymyxin-B Complex. In: Jacobs RR, Wakelyn PJ (eds). Proceedings of the Eleventh Cotton Dust Research Conference. Dallas, Texas, January 7-8, 1987. National Cotton Council, Memphis, TN. pp.45-46.

22. Lange JH, Weyel DA, Rosato LM, Tucker D, Malek DE, Mayernik JA, Ryan LK. Preliminary Results on Smoking Patterns for Workers Attending an Asbestos Abatement Course. 1987; Scand. J. Work, Environ. Health 13:459.

Books, Monographs and Chapters

1. Laube DM, Yim S, Ryan LK, Kisich KO, Diamond G. Antimicrobial Peptides in the Airway. In: Shafer, W. (ed.) Antimicrobial Peptides in Human Diseases. Current Topics in Microbiology and Immunology Vol. 306. Springer, NY, NY; 2006 pp.155-184.

2. Ryan LK. Ozone. In: Cohen M, Zelikoff J, Schlesinger R (eds.). Pulmonary Immunotoxicology. Kluwer Publishing Co., NY; 2000 pp. 301-336.

Reviews

1. Diamond G., Legarda D, Ryan LK. The Innate Immune Response of the Respiratory Epithelium. 2000; Immunol. Rev. 173:27-38.

2. Diamond, G., Beckloff, N., Ryan, LK. Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences. 2008; J. Dent. Res. 87:916-928.






Research Funding


NIH-NIEHS (R03) (2009-2011). “Inhibition of Lung Defense by Air Pollutant Particulates”

NIH-NIAID (R21) (2008-2010). “Human Beta Defensin-1 in HSV-1 Innate Immunity”

New Jersey Governor’s Council on Autism (2008-2010, Co-PI with Dr. Steve Zalcman, Department of Psychiatry, New Jersey Medical School). “Treatments for the prevention of autistic-like behavior in offspring of mothers infected with influenza virus during pregnancy: An animal model.”

Research Institute for Fragrance Materials (2009) “Particle Deposition and In Vitro Testing for Respiratory Sensitizing Fragrance Materials”

Antibody Systems, Inc. (2006-2009). “Inhibition of the Influenza-Induced Cytokine Response via Cytokine Receptor Antagonist Induction by Doxycycline”






C.V.


Education:

Ph.D. in Toxicology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, 1992.
M.S. Medical Microbiology, West Virginia University Medical School, Morgantown, West Virginia, 1983
B.S. Microbiology, Penn State University, University Park, Pennsylvania, 1980

Professional experience:

Assistant Professor of Medicine, Division of Pulmonary and Critical Care Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 2008 – present; Assistant Professor of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, 2003 – 2008; Assistant Professor, Department of Pathology and Laboratory Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 2000 – 2003; Research Biologist and Principal Investigator, Immunotoxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 1995-2000; U.S. EPA Office of Research and Development, Office of Science Policy Science Advisor, Region 2 (NY, NJ, PR and VI), New York, New York, 1998-2000; Pulmonary Research Fellow, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 1992-1995; Research Technician, Experimental Therapeutics, Cancer Research Laboratory, Allegheny-Singer Research Institute, Pittsburgh, PA, 1983-1986; Research Technician, Molecular Virology, Department of Microbiology, University of Pittsburgh, Pittsburgh, PA, 1983.