Discovering allergic host responses to pulmonary diseases

Samarasinghe Group Research Interests

Asthma is a disease of the respiratory system that affects approximately 300 million worldwide. In spite of extensive knowledge regarding disease pathogenesis, a cure is still out of reach. Allergic asthma is the most common subtype of asthma, and ubiquitous environmental agents such as pollen, animal dander, and fungi are common allergens. We generated a murine model system that faithfully recapitulates hallmarks of severe asthma with fungal sensitization using native conidia from Aspergillus fumigatus in an airborne inhalation delivery system to study disease pathogenesis. This model system can be used to interrogate pathways by which disease pathogenesis may occur.

Asthma exacerbations can be associated with respiratory infections, and some viruses are known inducers of asthma in predisposed individuals. Influenza is a disease caused by negative sense RNA viruses that can undergo rapid changes in antigens. These changes in the influenza virus genome can lead to the generation of a novel virus to which there is no herd immunity thereby increasing the likelihood of causing disease in pandemic proportions. During the last influenza pandemic in 2009, asthma was identified as a risk factor associated with hospitalization, although the reasons for this increased susceptibility were undetermined.

By combining our fungal asthma model with an established model of influenza, our laboratory created a model system of comorbidity to study the interplay between these two immunologically distinct diseases. Our studies were the first to show that the timing of influenza virus infection in hosts with allergic asthma had a direct impact on disease outcome. Our findings were corroborated by external epidemiologic studies wherein asthmatics were less likely to require intensive care or mechanical ventilation during the 2009 pandemic. Virus infection during an asthma exacerbation (heightened allergic inflammation) protected the host from influenza morbidity, while virus infection that occurs in an allergic lung that has undergone airway wall remodeling makes the host susceptible to severe influenza.

Our ongoing studies are aimed at delineating mechanisms by which this protection may occur. Our research is funded through the American Lung Association, the NIAID, and the Le Bonheur Foundation to investigate the following:

  • The role of eosinophils in antiviral immunity
  • The role of antimicrobial peptides as immunomodulators during influenza
  • The role of a vasoactive intestinal peptide and vitamin D in eosinophilic esophagitis

The Samarasinghe group works tirelessly toward understanding the immunological responses in the allergic host with the unified aim of finding novel targets for therapeutics.

Amali Samarasinghe, PhD.

Education

  • PostDoc, St. Jude Children’s Research Hospital, Infectious Diseases
  • Ph.D., North Dakota State University, Molecular Pathogenesis
  • M.S., California State University, Northridge, Neuroimmunology
  • B.S., California State University, Northridge, Biotechnology

Principal Awards

  • Outstanding Researcher Award, Department of Pediatrics, UTHSC 2017
  • Junior-Level Peer Recognition Award, MTPI Assembly, ATS 2017
  • Rising Stars of Research Award, American Thoracic Society, MTPI Assembly 2016
  • Young Investigator Award, Le Bonheur Associate Board and Foundation 2015
  • Presidential Doctoral Fellowship, training and stipend, NDSU 2006 –2010

Current Funding

  • NIH, NIAID R01 High Priority Immunology Grant 2017 – 2022
    Title: Eosinophils as Regulators of Host Immunity against Influenza Infections
    Role: Principal Investigator

In the News

 

Amali left her home country Sri Lanka in 1998 for higher studies in the US. She graduated with an Associate Degree from Los Angeles Pierce College and transferred to California State University, Northridge where she earned a Bachelors Degree in Biotechnology with a Chemistry minor in 2003. Amali returned to Sri Lanka having achieved her primary goal but soon realized that she wanted to earn a higher degree and returned to California State University Northridge in 2004 to pursue a Masters degree. It was during this time period that her passions for bench science and teaching were kindled. She was co-mentored by Dr. Randy Cohen, a neurophysiologist and Dr. Lisa Banner, an immunologist during her Masters tenure. Her cross disciplinary research was focused on delineating the roles of IL-6 and LIF in the degenerating hippocampus and cerebellum in a rat model of glutamate excitatoxicity. She also engaged in formal teaching both at CSUN and as an adjunct faculty member at Moorpark College teaching didactic courses in general biology and human biology among several laboratory courses. After graduating with honors from CSUN in 2006, Amali moved to North Dakota to join her husband. She was awarded a Presidential Fellowship from North Dakota State University to pursue her doctoral degree in the field of Pulmonary Immunology in the laboratory of Dr. Jane Schuh. During this time, Amali worked closely with laboratory manager, Mr. Scott Hoselton, to perfect an inhalation based model system of severe asthma with fungal sensitization which she then used to investigate the role of vasoactive intestinal peptide in disease pathogenesis. She graduated with honors in 2010 and moved to the Department of Infectious Diseases at St. Jude Children’s Research Hospital as a postdoctoral fellow in the laboratory of Dr. Jon McCullers. During this time, Amali’s studies pioneered investigations into the immunological impact of influenza virus infections in hosts with established asthma highlighting that the timing of the virus infection directly relates to the outcome. Her independent laboratory was established in August 2012 in the Department of Pediatrics at the University of Tennessee Health Science Center with a focus on understanding host-pathogen interactions during respiratory infections in hosts with fungal asthma.

Meet the team

Kim LeMessurier, Ph.D.
Lab Manager
Kim completed her PhD in microbiology with Dr. James Paton at the University of Adelaide, Australia, and a post-doctoral fellowship with Dr. Elaine Tuomanen at St. Jude Children’s Research Hospital. During these appointments, she examined niche-specific pneumococcal gene expression changes during the progression of infection from asymptomatic colonization of the nasopharynx to sepsis, and also how CD4 T-cells and type-1 interferon contribute to the development of invasive pneumococcal disease. Kim joined the Samarasinghe group as the Lab Manager in 2012. Although influenza A virus infection is typically cleared by individuals, a co-current S. pneumoniae infection can synergistically augment pathogenesis and morbidity, culminating in death. Kim currently studies the severity of influenza A virus/pneumococcal co-infection in mice with fungal allergic asthma, the immune responses, proteins, and alterations to the lung microbiome within the model.
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Maneesha Palipane, B.S.
Senior Research Assistant
Maneesha earned a Baccalaureate degree from Christian Brothers University, TN, majoring in Natural Sciences with minors in Biology and Chemistry. She joined the Samarasinghe group in 2015 as a Research Assistant and was promoted to Senior Research Assistant less than a year later. She has expertise in animal modeling and tissue harvest for downstream analyses, in addition to routine maintenance of cell lines for studies. Her research project is aimed at understanding the effect of resistin-like molecules in fungal allergic asthma.
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Jennifer Armbruster-Lee, M.D.
Clinical Fellow
Jenn earned a medical degree from West Virginia University and completed a Residency in Pediatrics at the University of Tennessee Health Science Center in 2015. She was the Chief Resident from 2014-2015. She is currently in a Fellowship program at our institute focusing on Pediatric Gastroenterology. She joined the Samarasinghe group in 2016 to complete her Research training for her Fellowship. Her research interests include eosinophilic esophagitis, vitamin D deficiency, and obesity.
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Meenakshi Tiwary, Ph.D.
Postdoctoral Research Associate
Meenakshi graduated with the doctoral degree in Biotechnology from the University of Delhi in 2017 wherein she isolated heavy metal-tolerant, pesticide-degrading bacteria from contaminated sites and investigated the molecular mechanisms of action in these strains. She joined the Samarasinghe group in the Summer of 2017 as a Postdoctoral Research Associate and is involved in studies that investigate the pathogenesis of respiratory infectious agents in allergic asthma with a focus on immunomodulators of disease.
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John Snyder, B.S.
Graduate Student
John graduated with Honors from Blue Mountain College in MS with a Bachelor's Degree in Biology. He started his pre-doctoral training at the University in August 2017 and joined the Samarasinghe group in January 2018. His project is aimed at delineating the function of IGF-1 in the pathogenesis of respiratory diseases, including asthma and influenza.
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Hannah Buser
Summer Intern
Hannah is an undergraduate student at Colgate University, New York, majoring in Psychology. She is interested in neurology and the study of learning and memory. Hannah joined the Samarasinghe group in 2015 as a Summer Intern. Her research goals are to determine how cytokines are regulated in the hippocampus and cerebellum in a model of glutamate excitatoxicity and to determine the impact of lung inflammation on the brain during allergic asthma.
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Funding

Current Funding

  • NIH, NIAID R01 High Priority Immunology Grant, 2017 – 2022: Principal Investigator
  • UTHSC, Pediatrics Clinical Fellowship (Lee, J), 2016 – 2018: Mentor

Past Funding

  1. American Lung Association, Biomedical Research Grant, 2015 – 2017: PI
  2. NIH, NIAID R56 High Priority Project Award (Smith, A), 2016 – 2017: Co-Investigator
  3. Le Bonheur Associate Board, Young Investigator Award, 2015 – 2016: PI
  4. Le Bonheur Children’s Foundation, Junior Faculty Grant, 2013 – 2015 (Competitive Renewal): PI
  5. University of Tennessee Health Science Center, iRISE Pilot Project Grant, 2015: PI

Publications

  1. Armbruster-Lee J, Cavender CP, Lierberman JA, and Samarasinghe AE. Understanding fibrosis in eosinophilic esophagitis: Are we there yet? Journal of Leukocyte Biology, 2018. PMID: 29377264
  2. Lew DB, LeMessurier KS, Palipane M, Lin Y, and Samarasinghe AE. Saccharomyces cerevisiae-Derived Mannan does not Alter Immune Responses to Aspergillus allergens. BioMed Research International, 2018; 3298378, 9 pages.
  3. Doorley LA, LeMessurier KS, Iverson AR, Palipane M, and Samarasinghe AE. Humoral immune responses during asthma and influenza co-morbidity in mice. Immunobiology, 2017, Immunobiology, 222; 1064-1073. PMID: 28889999
  4. Michael CF, Waters CM, LeMessurier KS, Samarasinghe AE, Song C, Malin K, and Lew DB. Airway epithelial repair by a prebiotic mannan derived from Saccharomyces cerevisiae. Journal of Immunology Research, 2017; 8903982, 7 pages. PMID: 28770233
  5. Lew DB, Michael CF, Overbeck T, Robinson WS, Rohman EL, Lehman JM, Patel JK, Eiseman B, LeMessurier KS, Samarasinghe AE, and Gaber MW. Beneficial effects of a prebiotic Saccharomyces cerevisiae mannan in allergic asthma mouse models. Journal of Immunology Research, 2017; 3432701, 10 pages. PMID: 28835901
  6. Apiwattanakul N, Palipane M, and Samarasinghe AE. Immune responses to fungal aeroallergen in Heligmosomoides polygyrus-infected mice vary by age. Cellular Immunology, 2017; 317: 26-36. PMID: 28476343
  7. Samarasinghe AE, Melo RCN, Duan S, LeMessurier KS, Liedmann S, Surman S, Lee JJ, Hurwitz J, Thomas PG, and McCullers JA. Eosinophils enhance antiviral immunity against influenza A virus infection. Journal of Immunology, 2017; 198(8), 3214-3226. PMID: 28283567
  8. LeMessurier KS, Lin Y, McCullers JA, and Samarasinghe AE. Antimicrobial peptides alter early immune response to influenza A virus infection in C57BL/6 mice. Antiviral Research, 2016; 133: 208-217. PMID: 27531368
  9. Samarasinghe AE, Hoselton SA, Schuh JM, McCullers JA. Modeling Asthma and Influenza Co-morbidity in C57BL/6 Mice. JoVE, 2015, In Press.
  10. Hrincius ER, Liedmann S, Finkelstein D, Vogel P, Gansebom S, Samarasinghe AE, You D, Cormier SA, McCullers JA. Acute lung injury results from innate sensing of viruses by an ER stress pathway. Cell Reports, 2015; 11(10): 1591-1603. PMID: 26051937
  11. Ghosh S, Samarasinghe AE, Hoselton SA, Dorsam GP, and Schuh JM. Hyaluronan deposition and co-localization with inflammatory cells and collagen in a murine model of fungal allergic asthma. Inflammation Research, 2014; 63(6):475-84. PMID: 24519432
  12. Samarasinghe AE, Woolard SN, Boyd KL, Hoselton SA, Schuh JM, and McCullers JA. The immune profile associated with acute allergic asthma accelerates clearance of influenza virus. Immunology and Cell Biology, 2014; 92: 449-459. PMID: 24469764                        News and Commentary Featured Article: Asthma and the Flu: a tricky two-step. Richard M Locksley and John V Fahy. ICB, 2014; 92: 381-391
  13. Alymova IV, Samarasinghe A, Vogel P, Green AM, Weinlich R, and McCullers JA. A novel cytotoxic sequence contributes to influenza A viral protein PB1-F2 pathogenicity and predisposition to secondary bacterial infection. Journal of Virology, 2014; 88(1): 503-15. PMID: 24173220
  14. Samarasinghe AE, Hoselton SA, and Schuh JM. A comparison between intratracheal and inhalation delivery of Aspergillus fumigatus conidia in the development of fungal allergic airways disease in C57BL/6 mice. Fungal Biology, 2011; 115(1) 21-29. PMID: 21215951
  15. Samarasinghe AE, Hoselton SA, and Schuh JM. The absence of VPAC2 receptor deficiency leads to aberrant antibody production in a murine model of fungal allergic asthma. Peptides, 2011; 32(1): 131-137. PMID: 20923692
  16. Samarasinghe AE, Hoselton SA, and Schuh JM. Spatio-temporal localization of vasoactive intestinal peptide and neutral endopeptidase in allergic murine lungs. Regulatory Peptides, 2010; 164: 151-157. PMID: 20566347
  17. Hoselton SA, Samarasinghe AE, Seydel JM, and Schuh JM. An inhalation model of airway allergic response to inhalation of environmental Aspergillus fumigatus conidia in sensitized BALB/c mice. Medical Mycology, 2010; 48(8): 1056-65. PMID: 20482452
  18. Samarasinghe AE, Hoselton SA, and Schuh JM. The absence of the VPAC2 receptor does not protect mice from Aspergillus induced allergic asthma. Peptides, 2010; 31(6): 1068-1075. PMID: 20226823
  19. Dorsam GP, Hoselton SA, Sandy AR, Samarasinghe AE, Dorsam ST, Vomhof-Dekrey EE, Schuh JM. Gene expression profiling and network analysis of peripheral blood monocytes in a chronic model of allergic asthma. Microbiology and Immunology, 2010; 54: 558-563. PMID: 20840155
  20. Hoselton SA, Samarasinghe AE, Seydel JL, Serie KM, Schuh JM. Creation and characterization of an IgG1-type monoclonal antibody against intact Aspergillus fumigatus conidia. Hybridoma, 2007; 26(4): 251-254. PMID: 17725387