Academic & Research Interests
Dr. Deshane is committed to an academic career combining basic and translational research with an emphasis on inflammatory diseases of the airway. Research in Dr. Deshane’s laboratory is focused on myeloid-derived regulatory cells (MDRCs) and their immunoregulatory roles in chronic inflammatory lung diseases. Dr. Deshane is particularly interested in delineating mechanisms underlying the differentiation, activation, metabolism and function of MDRCs. Her group recently reported that a subset of reactive oxygen species (ROS)-producing MDRCs exacerbate T cell responses and airway hyper-reactivity in mice. They recently characterized human MDRC subsets in bronchoalveolar lavage of asthmatics.
Dr. Deshane’s current research interests are to study effects of MDRCs on post-translational oxidative and nitrative modifications of self-peptides. This study is based the hypothesis that these modified self-proteins are recognized as non-tolerized neo-antigens and stimulate Th responses that underlie the immunopathology of asthma. Furthermore, her lab investigates how environmental pollutants such as tobacco smoke would impact MDRC function and contribute to exacerbation of inflammation in asthmatic smokers. These studies will provide insight into the role of MDRC in tobacco related pathology of the lung.
Dr. Deshane’s group also studies the function of these myeloid-lineage cells in anti-tumor immunity. They have developed novel therapeutic strategies to target these immunoregulatory cells to enhance anti-tumor immunity for lung cancer; in parallel, they seek to understand molecular signatures of the tumor microenvironment (TME). Their innovative therapeutic strategy targets Indoleamine 2, 3- dioxygenase (IDO), an enzyme that regulates tryptophan metabolism in the TME and suppresses the function of these regulatory myeloid cells. This novel strategy has distinct advantages over existing immunotherapy strategies targeting CTLA-4 and PD-1/PDL-1 in that it overrides the IDO resistance associated with current immunotherapy strategies. Dr. Deshane’s group investigates the mechanisms by which this therapeutic strategy induces metabolic reprogramming in the TME involving IDO and the nutrient sensing metabolic signaling pathways. They also seek to translate these findings in human studies to investigate efficacy of combination chemotherapy strategies in targeting these cells and amino acid metabolism pathways in lung cancer patients.
Srivastava RK, Li C, Wang Y, Weng Z, Elmets CA, Harrod KS, Deshane JS, Athar M. Activating transcription factor 4 underlies the pathogenesis of arsenic-mediated impairment of macrophage innate immune functions.Toxicol Appl Pharmacol.2016 Jul 23. pii: S0041-008X(16)30199-5. doi: 10.1016/j.taap.2016.07.015. PubMed PMID: 27461142
Larson-Casey JL,Deshane JS, Ryan AL, Thannickal VJ and A B Carter. Macrophage Akt1-mediated mitophagy modulates apoptosis resistance and pulmonary fibrosis. Immunity. 2016 Feb 22. pii: S1074-7613(16)00002-9. doi: 10.1016/j.immuni.2016.01.001. [Epub ahead of print]. PubMedPMID: 26921108
Walker MM, Novak L, Widener R, Grubbs JA, King J, Hale JY, Ochs MM, Myers LE, Briles DE, Deshane J. PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia. J Immunol. 2016 Feb 1. pii: 1402518. [Epub ahead of print] PubMed PMID: 26829988. PMCID in progress
Liu RM, Eldridge S, Watanabe N, Deshane JS, Kuo HC, Jiang C, Wang Y, Liu G, Schwiebert LM, Miyata T, Thannickal VJ. Therapeutic potential of an orally effective small molecule inhibitor of plasminogen activator inhibitor for asthma. Am J Physiol Lung Cell Mol Physiol. 2015 Dec 23:ajplung.00217.2015. doi: 10.1152/ajplung.00217.2015. [Epub ahead of print]. PubMed PMID: 26702150. PMCID in progress.
Liu Z, Bone N, Jiang S, Park DW, Tadie JM, Deshane J, Rodriguez CA, Pittet JF, Abraham E, Zmijewski JW. AMP-activated protein kinase and Glycogen Synthase Kinase 3β modulate the severity of sepsis-induced lung injury. Molecular Medicine. 2015 Mol Med. 2015 Nov 30. doi: 10.2119/ molmed.2015. 00198. [Epub ahead of print]. PubMed PMID: 26650187 PMCID in progress.
Yu H, Liu Y, McFarland BC, Deshane JS, Hurst DR, Ponnazhagan S, Benveniste EN, Qin H. SOCS3 Deficiency in Myeloid Cells promotes Tumor Development: Involvement of STAT3 Activation and Myeloid-Derived Suppressor Cells. Cancer Immunol Res. 2015 Feb; pii: canimm.0004.2015. [Epub ahead of print]. PubMed PMID: 25649351 PMCID in progress.
*Deshane JS, Redden DT, Zeng M, Spell MT, Zmijewski JW, Anderson JT, Deshane RJ, Gaggar A, Siegal GP, Abraham EA, Dransfield MT, DD Chaplin. Subsets of airway myeloid-derived regulatory cells distinguish mild asthma from chronic obstructive pulmonary disease. J. Allergy and Clinical Immunology. 2015 Feb;135(2):413-424.e15 doi: 10.1016/j.jaci.2014. PubMed PMID: 25420684 PMCID: PMC 4323991 (Available on 2016-02-01).
Wang Y, Jin TH, Farhana A, Freeman J, Estell K, Zmijewski JW, Gaggar A, Thannickal V, Schwiebert L, Steyn AJC, Deshane JS. Exposure to cigarette smoke impacts myeloid-derived regulatory cell function and exacerbates airway hyper-responsiveness. Laboratory Investigation. 2014 Dec;94(12):1312-1325. doi:10.1038/labinvest.2014.126. PubMed PMID:25365203 PMCID: PMC 4245361(Available on 2015/6/1).
Trevor JL & Deshane JS. Refractory Asthma: mechanisms, targets and therapy. Allergy 2014 Jul ;69(7):817-27, doi: 10.1111/all.12412. PubMed PMID: 24773466 PMCID: PMC 4279947.
Sawant A, Schafer CC, Jin TH, Zmijewski J, Tse HM, Roth J, Sun Z, Siegal GP, Thannickal VJ, Grant SC, Ponnazhagan S, Deshane J. Enhancement of antitumor immunity in lung cancer by targeting myeloid-derived suppressor cell pathways. Cancer Res 2013 Nov 15;73:6609-20. doi: 10.1158/0008-5472. PubMed PMID: 24085788 PMCID:PMC3854493.
Sawant A, Deshane J, Jules J, Lee CM, Harris BA, Feng X, Ponnazhagan S. Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer. Cancer Res. 2013 Jan 15;73(2):672-82. doi: 10.1158/0008-5472.CAN-12-2202. Epub 2012 Dec 14. PubMed PMID: 23243021; PubMed Central PMCID: PMC3548966.
Sawant A, Schafer CC, Ponnazhagan S, Deshane J. The dual targeting of immunosuppressive cells and oxidants promotes effector and memory T-cell functions against lung cancer. Oncoimmunology 2014 Jan 1;3(1):e27401,doi:10.4161/onci.27401. PubMed PMID: 24711958 PMCID: PMC 3976979.
Jiang S, Park DW, Tadie JM, Gregoire M, Deshane J, Pittet JF, Abraham E, Zmijewski JW. Human resistin promotes neutrophil proinflammatory activation and neutrophil extracellular trap formation and increases severity of acute lung injury. J Immunol. 2014 May 15;192(10):4795-803. doi: 10.4049/jimmunol.1302764. PubMed PMID: 24719460 PMCID: PMC4018664.
Bae HB, Zmijewski JW, Deshane JS, Zhi D, Thompson LC, Peterson CB, Chaplin DD, Abraham E. Vitronectin inhibits neutrophil apoptosis through activation of integrin-associated signaling pathways. Am J Respir Cell Mol Biol. 2012 Jun;46(6):790-6. doi: 10.1165/rcmb.2011-0187OC. Epub 2012 Jan 26. PubMed PMID: 22281987; PubMed Central PMCID: PMC3380283.
Tadie JM, Bae HB, Deshane JS, Bell CP, Lazarowski ER, Chaplin DD, Thannickal VJ, Abraham E, Zmijewski JW. Toll-like receptor 4 engagement inhibits adenosine 5'-monophosphate-activated protein kinase activation through a high mobility group box 1 protein-dependent mechanism. Mol Med. 2012 May 9;18:659-68. doi: 10.2119/molmed.2011.00401. PubMed PMID: 22396017; PubMed Central PMCID: PMC3388138.
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