Kopecky Lab
PI- Assistant Professor, Medicine-Cardiology |  Sr. Research Instructor, Medicine-Cardiology |
The Kopecky lab focuses on the immune-stromal interactions in heart transplant rejection. Informed by patient samples, we utilize state of the art technologies including RNA sequencing and genetic lineage tracing in murine models to ask how immune and stromal cells (or cellular signaling) can be targeted to prevent heart transplant rejection. As such, we employ a bidirectional approach where our scientific questions arise from clinical knowledge gaps, using novel techniques in our lab we fill these gaps to develop novel therapies for our patients.
We are a growing lab and welcome enthusiastic team members at all levels!
Please reach out to Benjamin.kopecky@cuanschutz.edu to learn more.
Heart transplant rejection is prevalent and current therapies non-specifically target recipient T-cells, making the patient susceptible to infections and cancers. Our lab has recently shown that rather than targeting the RECIPIENT T-Cell, we can effectively target the DONOR MACROPHAGE, proving that we can effectively impact transplant rejection well before our current therapies. Our lab currently is focused on how innate immune cells (such as macrophages) impact both acute and chronic rejection.
A) Acute Rejection: Occurs primarily within the first year after transplant and is T-cell mediated. We have shown that deleting CCR2+ macrophages (pro-inflammatory subset) in the DONOR heart (prior to transplant) improves post-transplant outcomes. Contrarily, deleting CCR2- macrophages (anti-inflammatory subset) in the DONOR heart (prior to transplant) worsens post-transplant survival. Hence, DONOR macrophages represent one of the earliest cells than can be modulated PRIOR to transplant, mitigating side effects of pharmacologic interventions in the recipient. Ongoing studies are investigation how these DONOR macrophages function to effect downstream signaling and transplant rejection.
B) Chronic Rejection: Is nearly ubiquitous and is the primary cause of allograft failure after transplant. Its major form is Cardiac Allograft Vasculopathy (CAV). CAV results when neo-intimal proliferation blocks the coronary artery lumen resulting in allograft failure. Its pathobiology is incompletely understood but we are discovering a strong interplay between immune and stromal cells. Ongoing investigations in our lab using spatial transcriptomics and RNA sequencing of human disease coupled with a novel murine model of heart transplantation aim to uncover where these cells are coming from, what is homing them, and how these signaling pathways can be interrupted.
Lab Members:
a. Benjamin Kopecky MD PhD (PI- Assistant Professor)
b. Hao Dun (Sr. Research Instructor)
| Junedh M. Amrute, Xin Luo, Vinay Penna, Andrea Bredemeyer, Tracy Yamawaki, Gyu Seong Heo, Sally Shi, Andrew Koenig, Steven Yang, Farid Kadyrov, Cameran Jones, Christoph Kuppe, Benjamin J. Kopecky, Sikander Hayat, Pan Ma, Guoshai Feng, Yuriko Terada, Angela Fu, Milena Furtado, Daniel Kreisel, Nathan O. Stitziel, Chi-Ming Li, Rafael Kramann, Yongjian Liu , Brandon Ason , Kory J. Lavine. Targeting the Immune-Fibrosis Axis in Myocardial Infarction and Heart Failure. 2023 bioRxiv. doi: https://doi.org/10.1101/2022.10.17.512579. |
| Owen, Macee C., Kopecky, Benjamin J. Targeting Macrophages in Organ Transplantation: A Step Towards Personalized Medicine. (In Revision- Transplantation). |
| Yun Zhu Bai, Benjamin J. Kopecky, Kory J. Lavine, Daniel Kreisel. Ferroptosis in the Post-Transplantation Inflammatory Response. Cellular Immunology. doi: 10.1016/j.cellimm.2023.104774. |
| Junedh M. Amrute, Lulu Lai, Pan Ma, Andrew Koenig, Kenji Kamimoto, Andrea Bredemeyer, Thirupura S. Shankar, Christoph Kuppe, Farid F. Kadyrov, Linda J. Schulte , Dylan Stoutenburg, Benjamin J. Kopecky , Sutip Navankasattusas, Joe Visker , Samantha A. Morris, Rafael Kramann, Florian Leuschner, Douglas L. Mann , Stavros G. Drakos, and Kory J. Lavine. Defining Cardiac Recovery at Single Cell Resolution. Nature CVR April 2023 DOI: 10.1038/s44161-023-00260-8. |
| Ramzi Abboud, Sena Kim, Karl Staser, Reyka Jayasinghe, Sora Lim, Parmeshwar Amatya, Corbin Frye, Benjamin J. Kopecky, Feng, Gao, Kory Lavine, Daniel Kreisel, John F. DiPersio, Jaebok Choi. Baricitinib with Cyclosporine Eliminates Acute Graft Rejection in Fully Mismatched Skin and Heart Transplant Models (Accepted; Frontiers in Immunology). |
| Kopecky, BJ and Lavine KJ. Cardiac macrophage metabolism in health and disease. Trends in Endocrine and Metabolism 2023. doi: 10.1016/j.tem.2023.10.011 |
| Sirimuvva Tadepalli, Derek R. Clements, Sanjana Saravanan, Anja Lüdtke, Beau Blackmore, Joao A. Paulo, Leslie Chan, Benjamin J. Kopecky, Zhaoyuan Liu, Florent Ginhoux, Kory J. Lavine, J. Patrick Murphy, Matthias Mack, Edward E. Graves, Juliana Idoyag. Rapid Monocyte Recruitment Dictates the Therapeutic Efficacy of Focal Radiotherapy. Science Immunology June 2023 DOI: 10.1126/sciimmunol.add7446. |
| Nicholas Borcherding, Wentong Jia1, Rocky Giwa, Rachael L. Field, John R. Moley, Benjamin J. Kopecky, Mandy M. Chan, Bin Q. Yang, Jessica M. Sabio, Emma C. Walker, Omar Osorio, Andrea Bredemeyer, Terri Pietka, Jennifer Alexander-Brett, Sharon Celeste Morley, Maxim N. Artyomo, Nada A. Abumra, Joel Schilling, Kory Lavine, Clair Crewe, and Jonathan R. Brestoff. Dietary lipids inhibit mitochondria transfer to macrophages to divert adipocyte-derived mitochondria into blood for distribution to distant organs. Cell Metabolism. 2022 Oct 4;34(10):1499-1513.e8. doi: 10.1016/j.cmet.2022.08.010. Epub 2022 Sep 6. |
| Kopecky BJ, Dun H, Amrute J, Lin C, Bredemeyer A, Terada Y, Bayguinov P, Koenig A, Frye C, Fitzpatrick J, Kreisel D, Lavine K. Donor Macrophages Modulate Rejection after Heart Transplantation. Circulation. 2022;0:10.1161/CIRCULATIONAHA.121.057400. ** Featured in “Literature Watch” American Journal of Transplantation. Vol 23, Issue 4, pg 455-456. https://doi.org/10.1016/j.ajt.2023.02.018 ** Featured on “Circulation on the Run” podcast url: https://circulation.libsyn.com/circulation-august-23-2022-issue ** Featured in Natures Reviews Cardiology: Lim, G.B. Donor macrophages influence rejection of transplanted hearts. Nat Rev Cardiol 19, 641 (2022). https://doi.org/10.1038/s41569-022-00764-z |
| Wong NR*, Mohan J*, Kopecky BJ*, Guo S*, Du L, Leid J, Feng G, Lokshina I, Dmytrenko O, Luehmann H, Bajpai G, Ewald L, Bell L, Patel N, Bredemeyer A, Weinheimer CJ, Nigro JM, Kovacs A, Morimoto S, Bayguinov PO, Fisher MR, Stump WT, Greenberg M, Fitzpatrick JAJ, Epelman S, Kreisel D, Sah R, Liu Y, Hu H, Lavine KJ. Resident cardiac macrophages mediate adaptive myocardial remodeling. Immunity. 2021 Sep 14;54(9):2072-2088.e7. doi: 10.1016/j.immuni.2021.07.003. Epub 2021 Jul 27. PubMed PMID: 34320366; PubMed Central PMCID: PMC8446343. *co-first authors. |
| Moreno JD, Verma AK, Kopecky BJ, Dehner C, Kostelecky N, Vader JM, Lin CY, Schilling JD. Angiotensin II Type 1 Receptor Antibody-mediated Rejection Following Orthotopic Heart Transplant: A Single-center Experience. Transplantation. 2022 Feb 1;106(2):373-380. doi: 10.1097/TP.0000000000003712. PubMed PMID: 33988339. |
| Nichols DH, Bouma JE, Kopecky BJ, Jahan I, Beisel KW, He DZZ, Liu H, Fritzsch B. Interaction with ectopic cochlear crista sensory epithelium disrupts basal cochlear sensory epithelium development in Lmx1a mutant mice. Cell Tissue Res. 2020 Jun;380(3):435-448. doi: 10.1007/s00441-019-03163-y. Epub 2020 Jan 13. PubMed PMID: 31932950; PubMed Central PMCID: PMC7393901. |
| Kopecky BJ, Frye C, Terada Y, Balsara KR, Kreisel D, Lavine KJ. Role of donor macrophages after heart and lung transplantation. Am J Transplant. 2020 May;20(5):1225-1235. doi: 10.1111/ajt.15751. Epub 2020 Jan 29. Review. PubMed PMID: 31850651; PubMed Central PMCID: PMC7202685. |
| Heo GS, Kopecky B, Sultan D, Ou M, Feng G, Bajpai G, Zhang X, Luehmann H, Detering L, Su Y, Leuschner F, Combadière C, Kreisel D, Gropler RJ, Brody SL, Liu Y, Lavine KJ. Molecular Imaging Visualizes Recruitment of Inflammatory Monocytes and Macrophages to the Injured Heart. Circ Res. 2019 Mar 15;124(6):881-890. doi: 10.1161/CIRCRESAHA.118.314030. PubMed PMID: 30661445; PubMed Central PMCID: PMC6435034. |
| Lavine KJ, Pinto AR, Epelman S, Kopecky BJ, Clemente-Casares X, Godwin J, Rosenthal N, Kovacic JC. The Macrophage in Cardiac Homeostasis and Disease: JACC Macrophage in CVD Series (Part 4). J Am Coll Cardiol. 2018 Oct 30;72(18):2213-2230. doi: 10.1016/j.jacc.2018.08.2149. Review. PubMed PMID: 30360829; PubMed Central PMCID: PMC6209119. |
| Tang J, Qian Y, Li H, Kopecky BJ, Ding D, Ou HC, DeCook R, Chen X, Sun Z, Kobel M, Bao J. Canertinib induces ototoxicity in three preclinical models. Hear Res. 2015 Oct;328:59-66. doi: 10.1016/j.heares.2015.07.002. Epub 2015 Jul 7. PubMed PMID: 26163095; PubMed Central PMCID: PMC4581429. |
| Kopecky BJ, Liang R, Bao J. T-type calcium channel blockers as neuroprotective agents. Pflugers Arch. 2014 Apr;466(4):757-65. doi: 10.1007/s00424-014-1454-x. Epub 2014 Feb 25. Review. PubMed PMID: 24563219; PubMed Central PMCID: PMC4005039. |
| Fritzsch B, Pan N, Jahan I, Duncan JS, Kopecky BJ, Elliott KL, Kersigo J, Yang T. Evolution and development of the tetrapod auditory system: an organ of Corti-centric perspective. Evol Dev. 2013 Jan;15(1):63-79. doi: 10.1111/ede.12015. Review. PubMed PMID: 23331918; PubMed Central PMCID: PMC3918746. |
| Kopecky BJ, Jahan I, Fritzsch B. Correct timing of proliferation and differentiation is necessary for normal inner ear development and auditory hair cell viability. Dev Dyn. 2013 Feb;242(2):132-47. doi: 10.1002/dvdy.23910. PubMed PMID: 23193000; PubMed Central PMCID: PMC3553268. |
| Kopecky BJ, Duncan JS, Elliott KL, Fritzsch B. Three-dimensional reconstructions from optical sections of thick mouse inner ears using confocal microscopy. J Microsc. 2012 Dec;248(3):292-8. doi: 10.1111/j.1365-2818.2012.03673.x. PubMed PMID: 23140378; PubMed Central PMCID: PMC3625616. |
| Kopecky BJ, Decook R, Fritzsch B. N-Myc and L-Myc are essential for hair cell formation but not maintenance. Brain Res. 2012 Nov 12;1484:1-14. doi: 10.1016/j.brainres.2012.09.027. Epub 2012 Sep 25. PubMed PMID: 23022312; PubMed Central PMCID: PMC3482343. |
| Pan N, Kopecky B, Jahan I, Fritzsch B. Understanding the evolution and development of neurosensory transcription factors of the ear to enhance therapeutic translation. Cell Tissue Res. 2012 Aug;349(2):415-32. doi: 10.1007/s00441-012-1454-0. Epub 2012 Jun 13. Review. PubMed PMID: 22688958; PubMed Central PMCID: PMC3508675. |
| Kopecky B, Decook R, Fritzsch B. Mutational ataxia resulting from abnormal vestibular acquisition and processing is partially compensated for. Behav Neurosci. 2012 Apr;126(2):301-13. doi: 10.1037/a0026896. Epub 2012 Feb 6. PubMed PMID: 22309445; PubMed Central PMCID: PMC3314111. |
| Jahan I, Pan N, Kersigo J, Calisto LE, Morris KA, Kopecky B, Duncan JS, Beisel KW, Fritzsch B. Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival. PLoS One. 2012;7(1):e30853. doi: 10.1371/journal.pone.0030853. Epub 2012 Jan 24. PubMed PMID: 22292060; PubMed Central PMCID: PMC3265522. |
| Pan N, Jahan I, Kersigo J, Duncan JS, Kopecky B, Fritzsch B. A novel Atoh1 "self-terminating" mouse model reveals the necessity of proper Atoh1 level and duration for hair cell differentiation and viability. PLoS One. 2012;7(1):e30358. doi: 10.1371/journal.pone.0030358. Epub 2012 Jan 18. PubMed PMID: 22279587; PubMed Central PMCID: PMC3261193. |
| Kopecky B, Johnson S, Schmitz H, Santi P, Fritzsch B. Scanning thin-sheet laser imaging microscopy elucidates details on mouse ear development. Dev Dyn. 2012 Mar;241(3):465-80. doi: 10.1002/dvdy.23736. Epub 2012 Jan 23. PubMed PMID: 22271591; PubMed Central PMCID: PMC5010664. |
| Kopecky B, Fritzsch B. The myc road to hearing restoration. Cells. 2012 Sep 25;1(4):667-98. doi: 10.3390/cells1040667. PubMed PMID: 24710525; PubMed Central PMCID: PMC3901154. |
| Kopecky B, Fritzsch B. Regeneration of Hair Cells: Making Sense of All the Noise. Pharmaceuticals (Basel). 2011 Jun 1;4(6):848-879. doi: 10.3390/ph4060848. PubMed PMID: 21966254; PubMed Central PMCID: PMC3180915. |
| Pan N, Jahan I, Kersigo J, Kopecky B, Santi P, Johnson S, Schmitz H, Fritzsch B. Conditional deletion of Atoh1 using Pax2-Cre results in viable mice without differentiated cochlear hair cells that have lost most of the organ of Corti. Hear Res. 2011 May;275(1-2):66-80. doi: 10.1016/j.heares.2010.12.002. Epub 2010 Dec 10. PubMed PMID: 21146598; PubMed Central PMCID: PMC3065550. |
| Fritzsch B, Jahan I, Pan N, Kersigo J, Duncan J, Kopecky B. Dissecting the molecular basis of organ of Corti development: Where are we now?. Hear Res. 2011 Jun;276(1-2):16-26. doi: 10.1016/j.heares.2011.01.007. Epub 2011 Jan 21. Review. PubMed PMID: 21256948; PubMed Central PMCID: PMC3097286. |
| Kopecky B, Santi P, Johnson S, Schmitz H, Fritzsch B. Conditional deletion of N-Myc disrupts neurosensory and non-sensory development of the ear. Dev Dyn. 2011 Jun;240(6):1373-90. doi: 10.1002/dvdy.22620. Epub 2011 Mar 29. PubMed PMID: 21448975; PubMed Central PMCID: PMC3092837. |
| Pauley S, Kopecky B, Beisel K, Soukup G, Fritzsch B. Stem cells and molecular strategies to restore hearing. Panminerva Med. 2008 Mar;50(1):41-53. Review. PubMed PMID: 18427387; PubMed Central PMCID: PMC2610336. |