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Krupnick, Alexander

Alexander Krupnick

Primary Appointment

Surgery

Contact Information

PO Box 800679
Charlottesville, VA 22908
Telephone: (434) 924-8746
Fax: (434) 244-9429
Email: ak2yf@virginia.edu
Website: https://surgery.virginia.edu/lung-immuno-biology-lab/

Research Interests

Pulmonary Immunoregulation

Research Description

Lungs are more immunogenic than other organ and tissue grafts. In the clinical setting, combined heart lung transplants have demonstrated the rapid onset of lung rejection. Recent work in our laboratory has demonstrated that immunoregulation of the lungs is unique compared to other solid organs. Unlike the case for other organs CD8+ T cells potentiate graft acceptance rather than rejection. Other ?pro-inflammatory cells? normal considered deleterious for organ grafts act to facilitate lung acceptance. We are currently working to unravel such details in order to design unique tolerance protocols specific for the lung. Our laboratory is also performing mechanistic studies to elucidate the requirements for T cell activation following lung transplantation in an attempt to develop modulatory strategies to downregulate immune responses to lung grafts. In addition we have demonstrated that the immune response to pulmonary malignancies is unique. Our laboratory also evaluates novel immunomodulatory cytokines for the treatment of pulmonary malignancies.

Selected Publications

Gauthier JM, Li W, Hsiao HM, Takahashi T, Arefanian S, Krupnick AS, Gelman AE, Kreisel D, Mechanisms of Graft Rejection and Immune Regulation after Lung Transplant., 2017; Annals of the American Thoracic Society. 14(0) S216-S219 PMID: 28945475 |

Aguilar PR, Bemiss BC, Witt C, Byers DE, Kreisel D, Puri V, Meyers B, Patterson GA, Krupnick AS, Yusen RD, Trulock EP, Hachem RR, Impact of Delayed Chest Closure on Surgical Site Infection After Lung Transplantation., 2017; The Annals of thoracic surgery. 104(4) 1208-1214 PMID: 28821338 |

Takahashi T, Hsiao HM, Tanaka S, Li W, Higashikubo R, Scozzi D, Bharat A, Ritter JH, Krupnick AS, Gelman AE, Kreisel D, PD-1 expression on CD8(+) T cells regulates their differentiation within lung allografts and is critical for tolerance induction., 2017; American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. () PMID: 28730633 |

Rove JY, Krupnick AS, Baciewicz FA, Meyers BF, Gastric conduit revision postesophagectomy: Management for a rare complication., 2017; The Journal of thoracic and cardiovascular surgery. 154(4) 1450-1458 PMID: 28526499 |

Lazear E, Ghasemi R, Hein SM, Westwick J, Watkins D, Fremont DH, Krupnick AS, Targeting of IL-2 to cytotoxic lymphocytes as an improved method of cytokine-driven immunotherapy., 2017; Oncoimmunology. 6(2) e1265721 PMID: 28344875 | PMCID: PMC5353927

Onyema OO, Guo Y, Wang Q, Stoler MH, Lau C, Li K, Nazaroff CD, Wang X, Li W, Kreisel D, Gelman AE, Lee JJ, Jacobsen EA, Krupnick AS, Eosinophils promote inducible NOS-mediated lung allograft acceptance., 2017; JCI insight. 2(24) PMID: 29263310 | PMCID: PMC5752306

Arefanian S, Sch?ll D, Chang S, Ghasemi R, Higashikubo R, Zheleznyak A, Guo Y, Yu J, Asgharian H, Li W, Gelman AE, Kreisel D, French AR, Zaher H, Plougastel-Douglas B, Maggi L, Yokoyama W, Beer-Hammer S, Krupnick AS, Deficiency of the adaptor protein SLy1 results in a natural killer cell ribosomopathy affecting tumor clearance., 2017; Oncoimmunology. 5(12) e1238543 PMID: 28123874 | PMCID: PMC5215235

Guo Y, Krupnick AS, To bleed or not to bleed? That is the question., 2017; The Journal of thoracic and cardiovascular surgery. () PMID: 28992966 |

Ghasemi R, Lazear E, Wang X, Arefanian S, Zheleznyak A, Carreno BM, Higashikubo R, Gelman AE, Kreisel D, Fremont DH, Krupnick AS, Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy., 2016; Nature communications. 7() 12878 PMID: 27650575 | PMCID: PMC5036003

Bharat A, Cunningham SA, Scott Budinger GR, Kreisel D, DeWet CJ, Gelman AE, Waites K, Crabb D, Xiao L, Bhorade S, Ambalavanan N, Dilling DF, Lowery EM, Astor T, Hachem R, Krupnick AS, DeCamp MM, Ison MG, Patel R, Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans., 2015; Science translational medicine. 7(284) 284re3 PMID: 25904745 | PMCID: PMC4677674

Krupnick AS, Lin X, Li W, Higashikubo R, Zinselmeyer BH, Hartzler H, Toth K, Ritter JH, Berezin MY, Wang ST, Miller MJ, Gelman AE, Kreisel D, Central memory CD8+ T lymphocytes mediate lung allograft acceptance., 2014; The Journal of clinical investigation. 124(3) 1130-43 PMID: 24569377 | PMCID: PMC3938255

Chang S, Lin X, Higashikubo R, Toth K, Gelman AE, Kreisel D, Krupnick AS, Unique pulmonary antigen presentation may call for an alternative approach toward lung cancer immunotherapy., 2013; Oncoimmunology. 2(3) e23563 PMID: 23802088 | PMCID: PMC3661173

Hesker PR, Krupnick AS, The role of natural killer cells in pulmonary immunosurveillance., 2013; Frontiers in bioscience (Scholar edition). 5() 575-87 PMID: 23277070 | PMCID: PMC4413461

Lin X, Li W, Lai J, Okazaki M, Sugimoto S, Yamamoto S, Wang X, Gelman AE, Kreisel D, Krupnick AS, Five-year update on the mouse model of orthotopic lung transplantation: Scientific uses, tricks of the trade, and tips for success., 2012; Journal of thoracic disease. 4(3) 247-58 PMID: 22754663 | PMCID: PMC3378197

Krupnick AS, Tidwell VK, Engelbach JA, Alli VV, Nehorai A, You M, Vikis HG, Gelman AE, Kreisel D, Garbow JR, Quantitative monitoring of mouse lung tumors by magnetic resonance imaging., 2012; Nature protocols. 7(1) 128-42 PMID: 22222788 | PMCID: PMC3870466

Kreisel D, Lai J, Richardson SB, Ibricevic A, Nava RG, Lin X, Li W, Kornfeld CG, Miller MJ, Brody SL, Gelman AE, Krupnick AS, Polarized alloantigen presentation by airway epithelial cells contributes to direct CD8+ T cell activation in the airway., 2011; American journal of respiratory cell and molecular biology. 44(6) 749-54 PMID: 21653906 | PMCID: PMC3135837

Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, Bricker TL, Jarman SD, Kreisel D, Krupnick AS, Srivastava A, Swanson PE, Green JM, Hotchkiss RS, Immunosuppression in patients who die of sepsis and multiple organ failure., 2011; JAMA. 306(23) 2594-605 PMID: 22187279 | PMCID: PMC3361243

Vikis HG, Gelman AE, Franklin A, Stein L, Rymaszewski A, Zhu J, Liu P, Tichelaar JW, Krupnick AS, You M, Neutrophils are required for 3-methylcholanthrene-initiated, butylated hydroxytoluene-promoted lung carcinogenesis., 2011; Molecular carcinogenesis. 51(12) 993-1002 PMID: 22006501 | PMCID: PMC3389580

Kreisel D, Richardson SB, Li W, Lin X, Kornfeld CG, Sugimoto S, Hsieh CS, Gelman AE, Krupnick AS, Cutting edge: MHC class II expression by pulmonary nonhematopoietic cells plays a critical role in controlling local inflammatory responses., 2010; Journal of immunology (Baltimore, Md. : 1950). 185(7) 3809-13 PMID: 20810992 | PMCID: PMC3897247

Krupnick AS, Gelman AE, Barchet W, Richardson S, Kreisel FH, Turka LA, Colonna M, Patterson GA, Kreisel D, Murine vascular endothelium activates and induces the generation of allogeneic CD4+25+Foxp3+ regulatory T cells., 2005; Journal of immunology (Baltimore, Md. : 1950). 175(10) 6265-70 PMID: 16272276 |