Ashish Sharma, MBBS, PhD
Department of Surgery
Gainesville, FL 32608
- MBBS, MR Medical College, Gulbarga, India (1998)
- PhD, University of Virginia, Charlottesville, VA (2012)
Associate Professor, Department of Surgery, University of Florida, Gainesville, FL (2018-present)
Assistant Professor, Department of Surgery, University of Virginia, Charlottesville, VA (2012-2018)
Instructor, Department of Surgery, University of Virginia, Charlottesville, VA (2008-2012)
Research Associate, Department of Surgery, University of Virginia, Charlottesville, VA (2004-2008)
Post-doctoral fellow, Medical University of South Carolina, Charleston, SC (1999-2004)
1. Mechanisms of aortic aneurysm pathobiology. Dr. Sharma is currently investigating the molecular mechanisms of aortic aneurysm pathogenesis. After initialing describing a critical role of IL-23/IL-17 axis in mediating vascular inflammation and remodeling, he characterized the protective role of human mesenchymal cell (MSC) treatment to attenuate the IL-23/IL-17 axis and NADPH oxidase-dependent HMGB1 production to mitigate inflammation, immune cell infiltration and aortic aneurysm formation. Current studies are focused on MSC-derived extracellular vesicles in the modulation of microRNAs (specifically miR-147, miR-19a, Let-7i and miR-98) for the prevention of aortic smooth muscle cell and immune cell activation during abdominal aortic aneurysm formation. Furthermore, his laboratory is characterizing the role of pannexin channels in smooth muscle cell and endothelial cell activation during aortic aneurysm formation using inducible SMMHC-Panx1 and VE-Cad-Panx1 inducible knockout mice.
- Sharma AK, Lu G, Jester A,Johnston WF,Zhao Y,Hajzus VA,Saadatzadeh MR,Su G, Bhamidipati CM,Mehta GS,Kron IL,Laubach VE,Murphy MP,Ailawadi Gand Upchurch GR Jr. Experimental abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal stem cell treatment. Circulation, 126 (11 Suppl 1):S38-45, 2012 [PMCID: PMC3448933]
- Sharma AK, Salmon MD, Lu G, Su G, Pope NH, Smith JR, Weiss, ML, Upchurch Gr Jr. Mesenchymal stem cells attenuate NADPH oxidase-dependent high mobility group box 1 production and inhibit abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 36(5):908-18, 2016 [PMCID:PMC4861899]
- Spinosa M, Su G, Mehaffey JH, Narahari AK, Isakson BE, Ravichandran KS, Upchurch Gr, Jr., and Sharma AK. Inhibition of pannexin-1 channels attenuates vascular inflammation and aortic aneurysm formation. Circulation, (Abstract; American Heart Association conference, 2018).
- Lu G, Salmon MD, Gehrau R, Su G, Smith JR, Weiss ML, Mas VR, Upchurch GR, Jr.,Sharma AK.Human mesenchymal stem cell-derived extracellular vesicles attenuate aortic aneurysm formation and smooth muscle activation via microRNA-147.FASEB; In Press; doi: 10.1096/fj.201701138RR.
2. Mechanisms and therapeutic strategies for post-lung transplant injury. Another major area of research interest in Dr. Sharma’s laboratory are the studies involving the mechanistic signaling pathway in the initiation of lung ischemia-reperfusion (IR) injury after pulmonary transplantation. Dr. Sharma was the first to demonstrate that alveolar macrophage-produced HMGB1 can activate RAGE on iNKT cells to amplify IL-17 production and mediate neutrophil infiltration in lung tissue to cause injury and inflammation. His research also revealed a paradigm shift in the manner that we understand initiation of lung IR injury which occurs via CD4+ iNKT cell infiltration and subsequent IL-17A production. Further studies have shown a pivotal role of NADPH oxidase-dependent free radicals in modulation of proinflammatory cytokines like IL-17 and mediation of synergistic effect of IL-17 and TNF-a on alveolar type II epithelial cell-produced CXCL1. His studies underline the importance of NADPH oxidase in specific cell populations (i.e. iNKT cells and alveolar type II epithelial cells) for the initiation and progression of lung IR injury.
- Sharma AK, LaPar DJ, Stone ML, Zhao Y, Mehta CK, Kron IL, and Laubach VE. NOX2 activation of NKT cells is blocked by adenosine A2A receptor to inhibit lung reperfusion injury. Am J Respir Crit Care Med., 2016 [PMCID: PMC4872653]
- Sharma AK, LaPar DJ, Zhao Y, Li L, Lau CL, Kron IL, Iwakura Y, Okusa MD, and Laubach VE. Natural killer T cell-derived IL-17 mediates lung ischemia-reperfusion injury. Am J Respir Crit Care Med183(11):1539-49, 2011 [PMCID: PMC3137143]
- Sharma AK, LaPar DJ, Stone, ML, Zhao Y, Kron IL, Laubach VE. Receptor for advanced glycation end products (RAGE) on iNKT cells mediates lung ischemia-reperfusion injury. Am J Transplant,13(9):2255-67, 2013 [PMCID: PMC3776006]
- Sharma AK, Mulloy DP, Le LT and Laubach VE. NADPH oxidase mediates synergistic effects of IL-17 and TNF-α on CXCL1 expression by epithelial cells after lung ischemia-reperfusion.Am J Physiol Lung Cell Mol Physiol, 306(1):L69-79; 2014 [PMCID: PMC3920214]
3. Adenosine and sphingosine receptor biology in lung preservation and attenuation of lung IR injury. A related area of research in Dr. Sharma’s laboratory is the rehabilitation of non-heart beating donor lungs (i.e. DCD or donation after cardiac death) via ex vivo lung perfusion (EVLP) which has the potential to increase the donor lung pool size. Dr. Sharma’s research focuses on the use of stem cells and extracellular vesicles to supplement EVLP as a strategy to rescue marginal donor lungs and to prevent primary graft dysfunction. These projects utilize mouse and pig models of lung transplant & ischemia-reperfusion injury, mouse/pig/human EVLP models and in vitro models. Sharma has previously characterized the role of adenosine and sphingosine receptors in lung IR injury and have demonstrated a potent therapeutic role of pharmacological modalities of these receptors. Specifically, his prior research has exemplified a prominent role of adenosine A2AR receptor agonists as well as combined therapy with sphingosine-1-phosphate and sphingosine kinase inhibitor in improving non-heart beating lung preservation and post-transplant lung IR injury using a murine lung IR model, porcine lung transplant model as well asin vitro studies.
- Sharma AK, Linden J, Kron IL, Laubach VE. Protection from pulmonary ischemia-reperfusion injury by adenosine A2A receptor activation. Respir Res10:58, 2009 [PMCID: PMC2711962]
- Anvari F, Sharma AK, Fernandez LG, Hranjec T, Ravid K, Kron IL and Laubach VE. Tissue-derived pro-inflammatory effect of adenosine A2B receptor in lung ischemia-reperfusion injury. J Thorac Cardiovasc Surg140:871-7, 2010 [PMCID: PMC2943004]
- Sharma AK, Laubach VE, Ramos SI, Zhao Y, Linden J, Kron IL, and Yang Z. Adenosine A2A receptor activation on CD4+ T lymphocytes and neutrophils attenuates lung ischemia-reperfusion injury. J Thorac Cardiovasc Surg 139(2):474-482, 2010 [PMCID: PMC2813368]
- LaPar DJ, Laubach VE, Emaminia A, Crosby IK, Sharma AK, Sumner HM, Webb DV, Lau CL, and Kron IL. Pretreatment strategy with adenosine A2A receptor agonist attenuates reperfusion injury in a preclinical porcine lung transplantation model. J Thorac Cardiovasc Surg142(4):887-94, 2011 [PMCID: PMC3212732]
- Mehaffey JH, Charles, EJ, Narahari AK, Schubert S, Laubach VE, Teman NR, Lynch KR, Kron IL, and Sharma AK.Increasing circulating sphingosine-1-phosphate attenuates lung injury during ex vivo lung perfusion.J Thorac Cardiovasc Surg. 2018 Aug;156(2):910-917
- Stone ML, Zhao Y, Smith JR, Weiss M, Kron IL, Laubach VE, Sharma AK. Mesenchymal stromal cell-derived extracellular vesicles attenuate lung ischemia-reperfusion injury and enhance reconditioning of donor lungs after circulatory death.Respir Res.2017 Dec 21;18(1):212 [PMCID: PMC5740880]
Complete List of Published Work:
Dr. Sharma has received funding from National Institute of Health (NIH) and independent foundations since 2003. He has trained 18 surgical residents and 14 undergraduate students in research techniques and methodologies as well as served on advisory committees for doctoral candidates. His trainees have successfully transitioned to academic medicine and some currently serve as faculty of various colleges of medicine across the country.
Current Research Support:
- NIH R01 138931 (MPI)
‘Pannexin signaling in abdominal aortic aneurysms’
- American Heart Association Grant-in-Aid (PI)
‘Protective role of stem cell-derived microvesicles and microRNAs in aortic aneurysms’
- NIH RO1 HL081629 (Co-Investigator)
‘Gender differences in experimental aortic aneurysms’
- NIH RO1 HL124131 (Co-Investigator)
‘Role of neutrophil extracellular traps in AAA pathogenesis’
- Dean’s Excellence in Team Science Research Award for outstanding contributions in lung transplant research at University of Virginia (2017)
- Conrad Jobst Award for outstanding contributions in vascular research from the Coller Surgical Society at University of Michigan (2016)
- PVD Council Award, Arteriosclerosis, Thrombosis and Vascular Biology (2014)
- Top 10 Abstract Award, American Heart Association (2015)
- Ad Hoc Member, NHLBI, Lung Cellular, Molecular, And Immunobiology Study Section (2016)
- Member, American Thoracic Society (2006-present)
- Member, American Heart Association (2012-present)