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Alexander S. Krupnick, MD

Academic Title:

Professor

Primary Appointment:

Surgery

Secondary Appointment(s):

Microbiology and Immunology

Administrative Title:

Vice Chief, Thoracic Surgery - Department of Surgery, Division of Thoracic Surgery; Director, Lung Transplant Program - Department of Surgery

Additional Title:

Professor, Vice Chair of Academic Affairs, Department of Surgery

Location:

Baltimore, MD

Phone (Primary):

410-328-6366

Fax:

410-328-0693

Education and Training

Education

1988 - 1992: BS, University of Michigan Honors College, Ann Arbor, Michigan with Highest Honors

1992 - 1996: MD, University of Michigan Medical School, Ann Arbor, Michigan Cum Laude

Biosketch

Sasha Krupnick is a general thoracic surgeon who specializes in the treatment of lung cancer, esophageal cancer, lung transplantation as well as benign thoracic disorders. He immigrated with his family to the United States in 1979 from the former USSR and grew up in the Midwest, receiving his undergraduate and medical degrees from the University of Michigan. He then pursued general surgery training at the Hospital of the University of Pennsylvania in Philadelphia followed by a lung transplantation and thoracic surgery fellowship in Washington University in St Louis. He remained on faculty at Barnes-Jewish Hospital in Washington University after completing training and joined the University of Maryland in 2020..

  1. Krupnick has dedicated his career to both advancing the field of lung transplantation and care of patients with thoracic malignancies. His lung transplantation training and experience under Joel Cooper and Alec Patterson, credited with first successful human lung transplant, puts him at the forefront of the field. He has performed hundreds of lung transplants and was thus recruited in 2020 as the surgical director of the University of Maryland lung transplant program. In addition he has advanced the field of minimally invasive oncologic surgery and is an expert at minimally invasive pulmonary and esophageal resections.
  2. Krupnick will be providing the full range of thoracic surgery services, including minimally invasive lung and esophageal resections, on the University of Maryland Medical School main campus, the VA Medical center as well as St. Joe’s.

In addition to clinical work Dr. Krupnick runs an NIH funded laboratory which he started after finishing his training in 2007. His laboratory mirrors his clinical interests and focuses on the development of new and novel mechanisms of immunosuppression for the lung allograft and well as cancer immunotherapy. He, along with his colleagues, developed the world’s first mouse model of vascularized lung transplantation that mirrors human physiology. This model has allowed for multiple avenues of investigation into both tolerance induction and rejection and has facilitated the development of novel immunosuppression therapies.   His laboratory has made several seminal discoveries regarding the role of the gut microbiome in chronic rejection, the role of previously unrecognized cell types (such as the eosinophil) in tolerance induction as well as mechanisms of early immunologic intervention that can induce long-term graft survival.

In addition to transplantation the Krupnick laboratory also has an interest in lung cancer immunotherapy. He has specifically made the discovery that immunologic control of lung cancer depends on the inherent function of a cell population known as the natural killer cell. His laboratory went on to describe biologic reasons why individuals with poor natural killer cell function are susceptible and those with robust natural killer cell function are resistant to the development of lung cancer. In addition Dr. Krupnick’s laboratory has developed a drug specially designed to improve natural killer cell function (called OMCPmutIL-2 or OPL101) which is expected to begin human clinical trials as early as 2022 in partnership with Valo Health.

Highlighted Publications

Krupnick AS, Gelman AE, Barchet W, Richardson S, Kreisel FH, Turka LA, Colonna M, Patterson GA,Kreisel D. Cutting Edge: Murine Vascular Endothelium Activates and Induces the Generation of Allogeneic CD4+25+Foxp3+ Regulatory T Cells. Journal of Immunology 175: 6265-6270   (2005) *Nominated to Faculty of 1000

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 Am J Respir Cell Mol Biol. 2010.  PMC3135837     

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. J Immunol. 2010 Oct 1;185(7):3809-13. PMC3897247 *Nominated to Faculty of 1000

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.  Journal of Clinical Investigation 2014  Mar  3;124(3):1130-43.    PMC3938255

Christopher B. Medina, Parul Mehrotra, Sanja Arandjelovic, Justin S. A. Perry, Yizhan Guo, Sho Morioka, Brady Barron, Scott F. Walk, Bart Ghesquière, Alexander S. Krupnick, Ulrike Lorenz & Kodi S. Ravichandran. Metabolites released from apoptotic cells act as tissue messengers.  Nature 2020 Mar 18;  580, pp130–135

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. JCI Insight. 2017 Dec 21;2(24). pii: 96455. doi: 10.1172/jci.insight.96455. PMID:29263310

Dr. Krupnick's publications on PubMed

Additional Publication Citations

Dr. Krupnick's publications on PubMed

Onyema OO, Guo Y, Mahgoub B, Wang Q, Manafi A, Mei Z, Banerjee A, Li D, Stoler MH, Zaidi MT, Schrum AG, Kreisel D, Gelman AE, Jacobsen EA, Krupnick AS. Eosinophils Downregulate Lung Alloimmunity by Decreasing TCR Signal Transduction.  JCI Insight. 2019 Jun 6;4(11). pii: 128241. doi: 10.1172/jci.insight.128241. eCollection 2019 Jun 6. PMID: 31167966

Kreisel D, Gelman AE, Higashikubo R, Lin X, Vikis HG, White JM, Toth KA, Deshpande C, Carreno BM, You M, Taffner SM, Yokoyama W, Bui JD, Schreiber RD, Krupnick AS.  Strain-Specific Variation in Murine Natural Killer Gene Complex Contributes to Differences in Immunosurveillance for Urethane-Induced Lung Cancer.  Cancer Research 2012 Sep 1;72(17):4311-4317 PMID: 22751136; PMCID: PMC3432713

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.   Nature Communications   Sep 21;7:12878. doi: 10.1038/ncomms12878. PMID:27650575  PMCID:PMC5036003 DOI:10.1038/ncomms12878

Arefanian S, Schäll D, Chang S, Ghasemi R, Higashikubo R, Zheleznyak A, Guo Y, Yu 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.  Oncoimmunology, Sep 27;5(12):e1238543. doi: 10.1080/2162402X.2016.1238543. (2016) PMID:28123874

Shi L, Li K, Guo Y, Banerjee A, Wang Q, Lorenz U, Parlak M, Sullivan LC, Onyema OO, Arefanian S, Stelow EB, Brautigan DL, Bullock TN, Brown MG, Krupnick AS.  Modulation of NKG2D, NKp46 and Ly49C/I Facilitates Natural Killer Cell-Mediated Control of Lung Cancer. Proceedings of the National Academy of Science 2018 Nov 13;115(46):11808-11813. doi: 10.1073/pnas.1804931115. Epub 2018 Oct 31. PMID:303814604.

Guo Y, Wang Q, Li D, Onyema OO, Mei Z, Manafi A, Banerjee A, Mahgoub B, Stoler MH, Barker TH, Wilkes DS, Gelman AE, Kreisel D, Krupnick AS.  Vendor-Specific Microbiome Controls both Acute and Chronic Murine Lung Allograft Rejection by Altering CD4+Foxp3+ Regulatory T Cell Levels   American Journal of Transplantation.  2019 Jul 6. doi: 10.1111/ajt.15523. PMID: 31278849, PMC7919421

Clinical Specialty Details

Lung Transplant Surgery, Thoracic Surgery

Grants and Contracts

Active Grants:

05/01/20 - 04/30/25
(Krupnick PI Project #2: 15%)
(NIAID) Pathways Regulating Lung Transplant Tolerance

Project #2: Inflammatory Cellular Mechanisms for Establishing and Maintaining Lung Allograft Tolerance
National Institute of Allery and Infectious Diseases P01 AI116501

01/02/19 – 12/31/24
(Krupnick/Jacobsen MPI grant: 15%)
The Role of Eosinophils in the Lung Allograft
NIAAD R01 AI145108-01

10/01/20-09/30/21
Krupnick PI
The Role of JAK Inhibition in Chronic Lung Allograft Rejection
Incyte Corporation

04/01/20-3/31/24
(PI: 31% (2.5/8th)
Mechanisms of Immunosurveillance for Lung Cancer-the Role of CD8+ T Cells in Tumor Tolerance Induction
VA Health System I01 BX002299-05

Completed Grants:

1999-2002
(PI, 75%)
Tissue Engineering for Diaphragmatic Reconstruction        
NIH National Research Service Award-#F32 HL 10251-01,
National Heart, Lung, and Blood Institute

2001-2003
(PI, 25%)
American Society of Transplant Surgeon Thoracic Surg Fellowship

2004-2006
(PI, 0%)
NIH National Loan Repayment Program (NLRP)

2004-2006
(PI, 30%)
American Society of Transplant Surgeons Novartis Fellowship in Transplantation

2005-2007
(PI, 20%)
Career Development Grant Melanoma Research Foundation

2005-2006
(Co-Inv 5%) PI: Patterson
Diaphragmatic Transplantation for Muscular Dystrophy
NIH NHLBI R21HL081240

2007-2008
(PI, 20 %)
American Cancer Society Internal Research Grant from the Siteman Cancer Center

2008-2010
(PI, 20%)
American Association of Thoracic Surgeons Norman E. Shumway Research Scholarship

2008-2013
(PI, 75%)
Thoracic Surgery Foundation for Research and Education NIH KO8 Matching Funds

2008-2013
(PI, 75%)
The Role of Non-Hematopoietic Cells in Tumor Tolerance Induction
NIH National Cancer Institute, KO8CA131097

2009-2011
(PI, 75%)
NIH National Cancer Institute American Recovery and Reinvestment Act of 2009 Administrative Supplement for KO8CA131097

2009-2010
(PI, 5%)
Mallinkrodt Institute of Radiology Internal Pilot Research Grant

2009-2011
(PI, 10%)
American Thoracic Society Lungevity Foundation Research Grant: The Basis for Immunotherapy of Lung Cancer

2012-2016
(Co-Inv 1%)
PI: Benzo
Pulmonary Rehabilitation before Lung Cancer Resection
R01CA163293

2012-2016
(PI 15%) PI: Kreisel (multi PI grant)
Mechanisms of Lung Allograft Acceptance
R01HL113931

2013-2017
(PI, 2.5/8th%)
Mechanisms of Immunosurveillance for Lung Cancer
VA Merit Grant, 1I01BX002299-01

2018-2019
(Brown/Krupnick/Bullock)
CIC Collaborative Research Award

09/01/18 – 08/31/19
(PI: 10%)
NCI Novel Immuno-oncology Strategy for Targeted Cytotoxic Lymphocyte Activation”
NCI R41 CA224520-01A1

04/01/19 - 03/31/23
(PI: 31% (2.5/8th)
(High-dose targeted and non-toxic IL-2 cytokine therapy
VA Health System 1 IO1 IBX0104588A

04/15/19 – 03/31/24
(Co-Inv 1%) PI: Sonkusare
CAV1.TRPV4  Regulation of Endothelial Function in Small Pulmonary Arteries
(NHLBI) 1R01HL146914-01

11/01/19 – 10/31/20
(Krupnick/Barker MPI grant: 5%)
Targeting the Thy-1/Integrin Signaling Axis in Chronic Lung Transplant Rejection
UVA Engineering in Med

Links of Interest