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


Selected Publications

Ryan LK, Dai J, Yin Z, Megjugorac N, Uhlhorn V, Yim S, Schwartz KD, Abrahams JM, Diamond G, Fitzgerald-Bocarsly P (2011) 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. J Leukoc Biol 90: 343-356. PMI: 21551252

Ryan LK (2011) In Uversky V, Kretsinger RH, and Permyakov EA (eds.), Encyclopedia of Metalloproteins. Springer, New York, NY, pp. In Press.

Rigo I, McMahon L, Dhawan P, Christakos S, Yim S, Ryan LK, Diamond G (2011) Induction of triggering receptor expressed on myeloid cells (TREM-1) in airway epithelial cells by 1,25(OH)2 vitamin D3. Innate Immun. PMI: 21690199

McMahon L, Schwartz K, Yilmaz O, Brown E, Ryan LK, Diamond G (2011) Vitamin D-mediated induction of innate immunity in gingival epithelial cells. Infect Immun 79: 2250-2256. PMI: 21422187

Diamond G, Ryan LK (2011) Beta-Defensins: What are they REALLY doing in the oral cavity? Oral Diseases 17: 628-635. PMI: 0

Diamond G, Beckloff N, Ryan LK (2008) Host defense peptides in the oral cavity and the lung: similarities and differences. J Dent Res 87: 915-927. PMI: 18809744

Laube DM, Yim S, Ryan LK, Kisich KO, Diamond G (2006) Antimicrobial peptides in the airway. Curr Top Microbiol Immunol 306: 153-182. PMI: 16909921

Klein-Patel ME, Diamond G, Boniotto M, Saad S, Ryan LK (2006) Inhibition of beta-defensin gene expression in airway epithelial cells by low doses of residual oil fly ash is mediated by vanadium. Toxicol Sci 92: 115-125. PMI: 16641320

Ryan LK, Diamond G, Amrute S, Feng Z, Weinberg A, Fitzgerald-Bocarsly P (2003) Detection of HBD1 peptide in peripheral blood mononuclear cell subpopulations by intracellular flow cytometry. Peptides 24: 1785-1794. PMI: 15019211

Ryan LK, Copeland LR, Daniels MJ, Costa ER, Selgrade MJ (2002) Proinflammatory and Th1 cytokine alterations following ultraviolet radiation enhancement of disease due to influenza infection in mice. Toxicol Sci 67: 88-97. PMI: 11961220

Suliman HB, Ryan LK, Bishop L, Folz RJ (2001) Prevention of influenza-induced lung injury in mice overexpressing extracellular superoxide dismutase. Am J Physiol Lung Cell Mol Physiol 280: L69-78. PMI: 11133496

Ryan LK, Neldon DL, Bishop LR, Gilmour MI, Daniels MJ, Sailstad DM, Selgrade MJ (2000) Exposure to ultraviolet radiation enhances mortality and pathology associated with influenza virus infection in mice. Photochem Photobiol 72: 497-507. PMI: 11045721

Ryan LK (2000) In Cohen M, Zelikoff J, and Schlesinger R (eds.), Pulmonary Immunotoxicology. Kluwer Publishing, New York, NY, pp. 301-336.

Diamond G, Legarda D, Ryan LK (2000) The innate immune response of the respiratory epithelium. Immunol Rev 173: 27-38. PMI: 10719665

Ryan LK, Rhodes J, Bhat M, Diamond G (1998) Expression of beta-defensin genes in bovine alveolar macrophages. Infect Immun 66: 878-881. PMI: 9453661

Ryan LK, Golenbock DT, Wu J, Vermeulen MW (1997) Characterization of proinflammatory cytokine production and CD14 expression by murine alveolar macrophage cell lines. In Vitro Cell Dev Biol Anim 33: 647-653. PMI: 9338148

Ryan LK, Vermeulen MW (1995) Alveolar macrophages from C3H/HeJ mice show sensitivity to endotoxin. Am J Respir Cell Mol Biol 12: 540-546. PMI: 7742017

Ryan LK, Jin R, Boggs SS, Karol MH, Day BW (1994) Mouse Model for Assessing Endotoxin Involvement in the Lung Inflammation and Cytokine Production Resulting from Inhaled Organic Dust. Organic dust. Inhal. Toxicol. 6: 485-499. PMI: 0

Ryan LK, Jin R, Boggs SS, Karol MH, Day BW (1993) In Jacobs RR (ed.), Proceedings of the Seventeenth Cotton Dust Research Conference, New Orleans, Louisiana. National Cotton Council, Memphis, TN, pp. 319-321.

Ryan LK, Karol MH (1991) Release of tumor necrosis factor in guinea pigs upon acute inhalation of cotton dust. Am J Respir Cell Mol Biol 5: 93-98. PMI: 1878256

Griffiths-Johnson DA, Ryan LK, Karol MH (1991) Development of an Animal Model for Organic Dust Toxic Syndrome. Inhal. Toxicol. 3: 405-417. PMI: 0

Ryan LK, Karol MH (1989) Acute respiratory response of guinea pigs to lipopolysaccharide, lipid A, and monophosphoryl lipid A from Salmonella minnesota. Am Rev Respir Dis 140: 1429-1435. PMI: 2817607

Ryan LK, Karol MH (1988) Production of antibody to lipopolysaccharide (LPS) after immunization with a LPS-polymyxin B-agarose immunogen. J Appl Bacteriol 64: 487-495. PMI: 3049507

Lange JH, Weyel DA, Rosato LM, Tucker D, Malek DE, Mayernik JA, Ryan LK (1987) Preliminary results on smoking patterns for workers attending an asbestos abatement course. Scand J Work Environ Health 13: 459. PMI: 3433048






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.