Research Summary
The Suresh Lab is interested in several basic science and translational projects. Its primary research focus is the study of microvascular endothelial cell (MVEC) dysfunction in various lung diseases including acute lung injury (ALI) and pulmonary arterial hypertension (PAH).
The lab is specifically interested in the role of mitochondria-derived reactive oxygen species (mtROS) and calcium signaling in promoting MVEC dysfunction in ALI and PAH; using animal models of these diseases as well as cells isolated from animal and humans. The lab studies the links between mtROS, calcium levels and mitochondrial structure/function with the goal of understanding the mechanisms driving mitochondrial and cellular dysfunction in lung MVECs.
Related to this project, in collaboration with the Izumchenko lab in Otolaryngology, the lab also employs computational approaches to discover somatic mutations in mitochondrial DNA with a goal of studying the effects of oxidant stress on induction of somatic mtDNA mutations in non-cancerous pathologies such as PAH.
Lastly, in collaboration with members across the Department of Oncology and the D’Alessio Lab in the Pulmonary/Critical Care division, our lab is conducting translational studies exploring mechanisms of lung injury in patients who develop pneumonitis after receiving immunotherapy. Using human samples and mouse models, we study the biological mechanisms underpinning lung injury in patients who develop pneumonitis after checkpoint immunotherapy.
Clinical Trial Keywords
ROS signaling, calcium signaling, microvascular endothelial cell physiology, mitochondrial structure/function, mechanisms of immunotherapy toxicity
Clinical Trials
Optimization of steroid-refractory immune checkpoint inhibitors; Therapeutic options for autoimmune-associated interstitial lung disease
Selected Publications
View all on PubMed
Suresh K, Servinsky L, Jiang H, Bigham Z, Huetsch J, Kliment C, Damarla M, Shimoda LA. ROS-induced Ca2+ via TRPV4 and microvascular endothelial dysfunction in the SU5416/Hypoxia model of pulmonary arterial hypertension, Am J Physiol Lung Cell Mol Physiol. 2018; 314(5): L893-L907, 2018 (APSselect, April 2018)
Suresh K, Servinsky L, Jiang H, Bigham Z, Zaldumbide J, Huetsch J, Kliment C, Acoba M, Kirsch B, Claypool S, Le, A Damarla M, Shimoda LA. Regulation of mitochondrial fragmentation in microvascular endothelial cells isolated from the SU5416/hypoxia model of pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2019; 317(5): L639-L652
Suresh K, Zhong Q, Voong R, Ettinger D, Marrone K, Kelly R, Hahn C, Levy B, Feliciano J, Brahmer J, Forde P, Feller-Kopman D, Lerner A, Lee H, Yarmus L, D’Alessio F, Danoff S, Naidoo J. Pneumonitis in non-small cell lung cancer patients receiving immune checkpoint immunotherapy: incidence and risk factors. J. Thoracic Onc. 2018; 13: 1930-1939. Editorial by Tay, et al: “Checkpoint Inhibitor Pneumonitis – Real World Incidence and Risk”
Suresh K, Psoter K, Shankar B, Voong R, Ettinger D, Marrone K, Kelly R, Hahn C, Levy B, Feliciano J, Brahmer J, Forde P, Feller-Kopman D, Lerner A, Lee H, Yarmus L, D’Alessio F, Danoff S, Naidoo J. Impact of checkpoint inhibitor pneumonitis on survival in non-small cell lung cancer patients receiving immune checkpoint immunotherapy, J. Thoracic Onc. 2019; 14: 494-502. Editor’s Choice – JTO, March 2019; Editorial by Le et al: “Checkpoint inhibitor pneumonitis: Too clinically serious for benefit?”
Suresh K*, Naidoo J*, Zhong, Q, Xiong Y, Mammen J, Villegas de Flores M, Cappelli L, Balaji A, Palmer T, Anagnastou V, Ettinger D, Marrone K, Kelly R, Hahn C, Levy B, Feliciano J, Forde P, Feller-Kopman D, Lerner A, Lee H, Yarmus L, Shafiq M, Lipson E, Soloski M, Brahmer J, Danoff S, D’Alessio F. The alveolar immune cell landscape is dysregulated in checkpoint inhibitor pneumonitis, J. Clin. Investig. 2019; 129(10):4305-4315. Editor’s Pick – JCI This Month, October 2019. * contributed equally.
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