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Associate Professor

Specialty Areas:

Genetics and genomics of allergic airway disease

Chronology:

BS Biochemistry, University of Michigan, 1997; MPH Environmental Health, University of Michigan School of Public Health, 2000; PhD Environmental Health-Toxicology, University of Washington, 2006;Post-doctoral Fellowship, National Human Genome Research Institute, National Institutes of Health, 2006-2012; Assistant Professor of Genetics, 2012-2018; Associate Professor of Genetics, 2018-present.

Research Focus:

We use unbiased, genome-wide approaches to identify the contributions of genetic variation, environmental exposures, and their interactions in airway diseases. To identify these interactions, we utilize powerful mouse genetic reference populations and unique exposure paradigms in concert with genomic and bioinformatic methods. We are particularly focused on using airway gene expression as a way to link genetic variation to disease phenotypes.

Our current projects are designed to identify genes and pathways that mediate:

  1. the development of allergic airway disease in response to exposure to allergens and air pollution
  2. pulmonary innate immune responses to pathogens and injurious agents

Selected Bibliography:

  1. Donoghue LJ, Markovetz MR, Morrison CB, Chen G, McFadden KM, Sadritabrizi T, Gutay MI, Kato T, Rogers TD, Snead JY, Livraghi-Butrico A, Button B, Ehre C, Grubb BR, Hill DB, Kelada SNP. BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance. Am J Physiol Lung Cell Mol Physiol. 2023 Dec 1;325(6):L765-L775. doi: 10.1152/ajplung.00390.2022. [PMID: 37847709]
  2. Tibbs TN, Donoghue LJ, Buzzelli AA, Misumi I, DeMonia M, Ferris MT, Kelada SNP, Whitmire JK. Mice with FVB-derived sequence on chromosome 17 succumb to disseminated virus infection due to aberrant NK cell and T cell responses. iScience. 2023 Oct 28;26(11):108348. doi: 10.1016/j.isci.2023.108348. [PMID: 38026197; PMCID: PMC10665959]
  3. Van Buren E, Radicioni G, Lester S, O’Neal WK, Dang H, Kasela S, Garudadri S, Curtis JL, Han MK, Krishnan JA, Wan ES, Silverman EK, Hastie A, Ortega VE, Lappalainen T, Nawijn MC, Berge MVD, Christenson SA, Li Y, Cho MH, Kesimer M, Kelada SNP. Genetic regulators of sputum mucin concentration and their associations with COPD phenotypes. PLoS Genet. 2023 Jun 23;19(6):e1010445. doi: 10.1371/journal.pgen.1010445. [PMID: 37352370; PMCID: PMC10325042]
  4. Donoghue LJ, McFadden KM, Vargas D, Smith GJ, Immormino RM, Moran TP, Kelada SNP. Collaborative cross strain CC011/UncJ as a novel mouse model of T2-high, severe asthma. Respir Res. 2023 Jun 9;24(1):153. doi: 10.1186/s12931-023-02453-y. [PMID: 37296458; PMCID: PMC10251525]
  5. Tovar A, Smith GJ, Nalesnik MB, Thomas JM, McFadden KM, Harkema JR, Kelada SNPA Locus on Chromosome 15 Contributes to Acute Ozone-Induced Lung Injury in Collaborative Cross Mice. Am J Respir Cell Mol Biol.2022 Nov;67(5):528-538. doi: 10.1165/rcmb.2021-0326OC. [PMID: 35816602; PMCID: PMC9651200]
  6. Virk R, Buddenbaum N, Al-Shaer A, Armstrong M, Manke J, Reisdorph N, Sergin S, Fenton JI, Wallace ED, Ehrmann BM, Lovins HB, Gowdy KM, Smith MR, Smith GJ, Kelada SNP, Shaikh SR. Obesity reprograms the pulmonary polyunsaturated fatty acid-derived lipidome, transcriptome, and gene-oxylipin networks. J Lipid Res. 2022 Oct;63(10):100267. doi: 10.1016/j.jlr.2022.100267. [PMID: 36028048; PMCID: PMC9508350]
  7. Rogers TD, Button B, Kelada SNP, Ostrowski LE, Livraghi-Butrico A, Gutay MI, Esther CR Jr, Grubb BR. Regional Differences in Mucociliary Clearance in the Upper and Lower Airways. Front Physiol. 2022 Mar 9;13:842592. doi: 10.3389/fphys.2022.842592. [PMID: 35356083; PMCID: PMC8959816]
  8. Tovar A, Crouse WL, Smith GJ, Thomas JM, Keith BP, McFadden KM, Moran TP, Furey TS, Kelada SNPIntegrative analysis reveals mouse strain-dependent responses to acute ozone exposure associated with airway macrophage transcriptional activity. Am J Physiol Lung Cell Mol Physiol. 2022 Jan 1;322(1):L33-L49. [PMID: 34755540; PMCID: PMC8721896]
  9. Smith GJ, Tovar A, McFadden K, Moran TP, Wagner JG, Harkema JR, Kelada SNP. A Murine Model of Ozone-induced Nonatopic Asthma from the Collaborative Cross. Am J Respir Cell Mol Biol. 2021 Dec;65(6):672-674. [PMID: 34851239; PMCID: PMC8641798]
  10. Smith GJ, Tovar A, Kanke M, Wang Y, Deshane JS, Sethupathy P, Kelada SNP. Ozone-induced changes in the murine lung extracellular vesicle small RNA landscape. Physiol Rep. 2021 Sep;9(18):e15054. [PMID: 34558223; PMCID: PMC8461034]
  11. Crouse WL, Kelada SNP, Valdar W. Inferring the Allelic Series at QTL in Multiparental Populations. Genetics. 2020 Dec;216(4):957-983. [PMID: 33082282; PMCID: PMC7768242]
  12. Laudermilk LT, Tovar A, Homstad AK, Thomas JM, McFadden KM, Tune MK, Cowley DO, Mock JR, Ideraabdullah F, Kelada SNP. Baseline and innate immune response characterization of a Zfp30 knockout mouse strain. Mamm Genome. 2020 Aug;31(7-8):205-214. [PMID: 32860515; PMCID: PMC7486244]
  13. Tovar A, Smith GJ, Thomas JM, Crouse WL, Harkema JR, Kelada SNP. Transcriptional profiling of the murine airway response to acute ozone exposure. Toxicol Sci. 2020 Jan 1;173(1):114-130. [PMID: 31626304; PMCID: PMC6944221]
  14. Keele GR, Crouse WL, Kelada SNP, Valdar W. Determinants of QTL Mapping Power in the Realized Collaborative Cross. G3 (Bethesda). 2019 May 7;9(5):1707-1727. [PMID: 30914424; PMCID: PMC6505132]
  15. Smith GJ, Walsh L, Higuchi M, Kelada SNP. Development of a large-scale computer-controlled ozone inhalation exposure system for rodents. Inhal Toxicol. 2019 Feb;31(2):61-72. PMID: 31021248 [PMID: 31021248; PMCID: PMC7055063]
  16. Tsai YH, Parker JS, Yang IV, Kelada SNP. Meta-analysis of airway epithelium gene expression in asthma. Eur Respir J. 2018 May 17;51(5). [PMID: 29650561; PMCID: PMC7395676]
  17. Laudermilk LT, Thomas JM, Kelada SN. Differential regulation of Zfp30 expression in murine airway epithelia through altered binding of ZFP148 to rs51434084. G3 (Bethesda). 2018 Feb 2;8(2):687-693. [PMID: 29242385; PMCID: PMC5919737]
  18. Donoghue LJ*, Livraghi-Butrico A*, McFadden KM, Thomas JM, Chen G, Grubb BR, O’Neal WK, Boucher RC, Kelada SNP. Identification of trans protein QTL for secreted airway mucins in mice and a causal role for Bpifb1. Genetics. 2017 Oct; 207(2):801-812. [PMID: 28851744; PMCID: PMC5629340]
  19. Gomez JC, Dang H, Kanke M, Hagan RS, Mock JR, Kelada SNP, Sethupathy P, Doerschuk CM. Predicted effects of observed changes in the mRNA and microRNA transcriptome of lung neutrophils during S. pneumoniae pneumonia in mice. Sci Rep. 2017 Sep 12;7(1):11258. [PMID: 28900269; PMCID: PMC5595893]
  20. Kelada SN. Plethysmography phenotype QTL in mice before and after allergen sensitization and challenge. G3 (Bethesda). 2016 Sep 8;6(9):2857-65. [PMID: 27449512; PMCID: PMC5015943]
  21. Rutledge H, Baran-Gale J, Chessler EJ, Churchill GA, Pardo-Manuel de Villena F, Sethupathy P*, Kelada SN*. Identification of microRNAs Associated with Allergic Airway Disease Using a Genetically Diverse Mouse Population. BMC Genomics 2015; 16:633. [PMID: 26303911; PMCID: PMC4548451]
  22. Kelada SN, Carpenter DE, Aylor DL, Chines P, Rutledge H, Chessler EJ, Churchill GA, Pardo-Manuel de Villena F, Schwartz DA, Collins FS. Integrative Genetic Analysis of Allergic Inflammation in the Murine Lung. Am J Respir Cell Mol Biol 2014; 51(3):436-445. [PMCID: PMC4189492]
  23. Rutledge H, Aylor DL, Carpenter DE, Peck BCE, Chines P, Ostrowski LE, Chessler EJ, Churchill GA, Pardo-Manuel de Villena F, Kelada SN. Genetic Regulation of Zfp30, CXCL1, and Neutrophilic in Mouse Lung. Genetics 2014; 198(2):735-745. [PMID: 25114278; PMCID: PMC4196624]
  24. Kelada SN*, Sethupathy P*, Okoye IS*, Kistasis E, Czieso S, White S.D., Chou D, Martens C, Ricklefs SM, Virtaneva K, Sturdevant DE, Porcella SF, Belkaid Y, Wynn TA, Wilson MS. miR-182 and miR-10a Are Key Regulators of Treg Function during Th2 and Th1-Associated Inflammation. PLoS Pathog 2013; 9(6):e1003451. [PMID: 23825948; PMCID: PMC3695057]
  25. Kelada SN, Wilson MS, Tavarez U, Borate B, Kubalanza K, Carpenter DE, Whitehead G, Maruoka S,Brass D, Wynn TA, Cook DN, Evans CM, Schwartz DA, Collins FS. Strain-Dependent Genomic Factors Affect Allergen-Induced Airway Hyper-responsiveness in Mice. Am J Respir Cell Mol Biol 2011; 45(4):817-824. [PMID: 21378263; PMCID: PMC3208613]
Samir Kelada