Dr. Alexander Krupnick's Lab
Alexander Krupnick, MD
The Krupnick laboratory was established in 2007 at Washington University in St. Louis and relocated to The University of Maryland in June of 2020. The laboratory focuses its translational research on two clinically relevant areas, namely immunotherapy for thoracic malignancies and lung transplant immunoregulation. In 2007, along with the laboratories of Daniel Kreisel and Andrew Gelman, the Krupnick laboratory developed the world’s first model of physiologic, vascularized, orthotopic lung transplantation in the mouse (https://www.nature.com/articles/nprot.2008.218). This model is now utilized by multiple laboratories around the world to further understand lung transplantation physiology and develop new drugs to treat rejection. The model has been used by our laboratory to unravel lung transplant-specific immune responses, including the role of CD8+ T cells and eosinophils in the establishment and maintenance of tolerance (https://www.jci.org/articles/view/71359) (https://insight.jci.org/articles/view/96455) ( https://insight.jci.org/articles/view/128241) and continues to be used to design better immunosuppression and immunomodulatory strategies for the lung.
Despite the unfortunate fact that lung cancer is the number one cause of cancer-specific death in the United States, limited data is available on how lung cancer evades the immune response as it grows and progresses. To address this problem the Krupnick laboratory began a dedicated research focus to better understand the lung cancer specific immune response in 2010. We discovered several unique features of lung cancer, including the critical role of natural killer cells in controlling lung cancer development and growth (https://pubmed.ncbi.nlm.nih.gov/22751136/), the importance of natural killer cell education, or “licensing” in control of lung cancer (https://pubmed.ncbi.nlm.nih.gov/30381460/) as well as unique genetic differences in natural killer cell physiology that may make some individuals more susceptible to lung cancer (https://pubmed.ncbi.nlm.nih.gov/28123874/). Utilizing this knowledge in 2015 the laboratory developed a first-in-class retargeted cytokine designed to stimulate natural killer cells specifically and precisely for the treatment of lung cancer (https://pubmed.ncbi.nlm.nih.gov/27650575/). The cytokine is currently in GMP phase of production and slated for human clinical trials in early 2022.
Laboratory Members
Yizhan Guo, BM
Yizhan Guo is Assistant Professor of Surgery and world-leading expert in eosinophil immunoregulation of lung allograft specific immune responses. His research focuses on tolerance induction and downregulation of ischemia-reperfusion injury-mediated lung damage.
Dr. Banerjee is an Assistant Professor of Surgery and focuses his research efforts on lung cancer specific immune responses. His work is leading to a better understanding now natural killer cells interact with CD8+ T cells to control the growth of lung cancer.
Dongge Li, MD
Dr. Li is a senior research specialist whose work focuses on general lung-specific immune responses in both cancer and transplant.
Dr. Mei’s work focuses on chronic lung allograft acceptance and mechanisms contributing to maintenance of tolerance.
Dr. Krupnick is a Professor of Surgery at the University of Maryland School of Medicine with clinical and research in thoracic organ transplantation and malignancies.
Grant Support
The lab is fortunate and thankful for continuing grant support from the National Institute of Health and the Veteran’s System for Health Care Administration, industry, as well as greatful patients and benefactors.
Active Funding
Inflammatory Cellular Mechanisms for Establishing and Maintaining Lung Allograft Tolerance
P01 AI116501 Pathways Regulating Lung Transplant Tolerance (https://www.grantome.com/grant/NIH/P01-AI116501-05-6223)
- Funding: NIH, National Institute of Allery and Infectious Diseases
The Role of Eosinophils in the Lung Allograft
R01 AI145108-01 (https://grantome.com/grant/NIH/R01-AI145108-01)
- Funding: NIH, National Institute of Allery and Infectious Diseases
The Role of JAK Inhibition in Chronic Lung Allograft Rejection
(https://www.incyte.com/)
- Funding: Incyte Corporation
Mechanisms of Immunosurveillance for Lung Cancer-the Role of CD8+ T Cells in Tumor Tolerance Induction
- Funding: VA Health System I01 BX002299-05
Completed Grant Support
- 11/01/19 – 10/31/20 UVA Engineering in Medicine Seed Grant: Targeting the Thy-1/Integrin Signaling Axis in Chronic Lung Transplant Rejection
- 04/01/19 - 03/31/20 VA Health System 1 IO1 IBX0104588A High-dose targeted and non-toxic IL-2 cytokine therapy
- 09/01/18 – 08/31/19 NIH NCI R41 CA224520-01A1 NCI Novel Immuno-oncology Strategy for Targeted Cytotoxic Lymphocyte Activation”
- 2018-2019 CIC Collaborative Research Award University of Virginia Cancer Center
- 2013-2017 VA Merit Grant, 1I01BX002299-01 Mechanisms of Immunosurveillance for Lung Cancer2012-2016 NIH 2012-2016 NIAAD R01HL113931Mechanisms of Lung Allograft Acceptance
- 2009-2011 American Thoracic Society Lungevity Foundation Research Grant: The Basis for Immunotherapy of Lung Cancer
- 2009-2011 Mallinkrodt Institute of Radiology Internal Pilot Research Grant
- 2009-2011 NIH National Cancer Institute American Recovery and Reinvestment Act of 2009 Administrative Supplement for KO8CA131097
- 2008-2013 NIH National Cancer Institute, KO8CA131097, The Role of Non-Hematopoietic Cells in Tumor Tolerance Induction
- 2008-2013 Thoracic Surgery Foundation for Research and Education NIH KO8 Matching Funds
- 2008-2010 American Association of Thoracic Surgeons Norman E. Shumway Research Scholarship
- 2007-2008 American Cancer Society Internal Research Grant from the Siteman Cancer Center
- 2005-2007 Career Development Grant Melanoma Research Foundation
- 2004-2006 American Society of Transplant Surgeons Novartis Fellowship in Transplantation
- 2004-2006 NIH National Loan Repayment Program (NLRP)
- 2001-2003 American Society of Transplant Surgeon Thoracic Surg Fellowship
- 1999-2002 NIH National Research Service Award-#F32 HL 10251-01, National Heart, Lung, and Blood Institute Tissue Engineering for Diaphragmatic Reconstruction
Post Doctoral Training Opportunities:
The laboratory is now looking for post-doctoral trainees with an interest in lung transplantation and immune tolerance. Please contact Sasha Krupnick (akrupnick@som.umaryland.edu) .
Laboratory Publications: https://pubmed.ncbi.nlm.nih.gov/?term=krupnick+as&sort=date