A porcine model of acute rejection for cardiac transplantation.
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2025-01
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Ex vivo machine perfusion has been growing in utility for preserving donor organs prior to transplantation. This modality has tremendous potential for bioengineering and conditioning organs prior to transplantation using small molecule or advanced therapeutics. To safely translate potential interventions, well characterized models of disease are crucial for testing the therapeutic and possible side effects that could manifest from the interventions. Acute cellular rejection remains a significant complication in organ transplantation that affects transplant recipients with significant morbidity and mortality. This disease could potentially be mitigated with therapeutic intervention during ex vivo machine perfusion. A porcine animal model of acute rejection could be characterized in order to translate human biological processes with high fidelity. The Yucatan pig breed has been increasingly used in both biomedical research and xenotransplantation applications given its similarity to the human heart. A challenge with utilizing this pig breed for designing a model of acute rejection is its highly conserved ancestral lineage, which could make it difficult to induce acute rejection in a timely and consistent manner. We present a detailed characterization of a porcine model of acute rejection based on swine leukocyte antigen mismatching paired with a limited period of clinically relevant immunosuppression. The result is a robust and consistent protocol that results in fulminant acute rejection of an intra-abdominally transplanted heart.
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Mendiola Pla, Michelle, Yuting Chiang, Carolyn Glass, David C Wendell, Devjanee Swain-Lenz, Sam Ho, Marat Fudim, Franklin H Lee, et al. (2025). A porcine model of acute rejection for cardiac transplantation. Frontiers in cardiovascular medicine, 12. p. 1549377. 10.3389/fcvm.2025.1549377 Retrieved from https://hdl.handle.net/10161/34186.
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Carolyn Glass
Division Chief, Cardiovascular Pathology
Co-Director, Division of Artificial Intelligence and Computational Pathology
Associate Director, Residency Program
Dr. Glass completed medical residency in Anatomic Pathology at the Brigham and Women’s Hospital/Harvard Medical School followed by fellowships in Cardiothoracic Pathology also at Brigham and Women’s Hospital/Harvard Medical School and Pulmonary/Cardiac Transplant Pathology at the University of Texas Southwestern Medical Center. Dr. Glass initially trained as a vascular surgeon with a focus on endovascular/interventional procedures through the 0+5 Integrated Vascular Surgery Program at the University of Rochester Medical Center from 2007-2011. As a recipient of the NIH National Lung Blood Institute T32 Ruth Kirschstein National Service Research Award, she completed a Ph.D with a concentration in Genomics and Epigenetics in 2014. Dr. Glass serves as P.I. of multiple NIH grants, including U54 and SBIR.
As a thoracic surgical pathologist, Dr. Glass diagnoses complex heart transplant rejection and thoracic malignancies. She works closely with the Duke Thoracic Oncology Group, DCI Center for Cancer Immunotherapy, Duke Division of Cardiovascular Medicine and Cardiothoracic Surgery and Pratt School of Biomedical Engineering.
Dr. Glass is the recipient of the Society of Cardiovascular Pathology (SCVP) Young Investigator’s Award, the William von Liebig Vascular Biology Research Fellowship at the Harvard Institutes of Medicine, the Duke Pathology Salvatore V. Pizzo Faculty Research Mentor Award, the Duke Department of Pathology Early Career Research Achievement Award and is author of over 100 publications (including book chapters in the recent W.H.O. Classification Tumours of the Lung, Pleura, Thymus and Heart) and 50 national presentations in cardiovascular disease, thoracic malignancies, surgery and machine learning.
In addition to her clinical and research activities, Dr. Glass has served on the Executive/National Committees for the Society of Cardiovascular Pathology, College of American Pathology Artificial Intelligence Committee and the Duke School of Medicine Executive Admissions Committee.
Devi Swain Lenz
Devjanee (Devi) Swain Lenz, PhD, is the Director of the Duke Sequencing and Genomics Technologies Core Facility (SGT) and has over 15 years of experimental and computational experience in genomics research. She earned her PhD in Molecular Genetics and Genomics at Washington University in St. Louis and completed her postdoctoral research at Duke University. Her research interests focus on understanding how cis-regulatory variation contributes to phenotypic differences between and within species. She has also held multiple leadership roles for nonprofit organizations whose emphasis is on increasing and maintaining diversity, equity, and inclusion in STEM-related fields.
If you are interested in working with the SGT, you can find more information on our website or schedule a consultation.
Marat Fudim
Laura Pope Hale
The Hale laboratory employs techniques of cellular and molecular biology to study mechanisms responsible for the generation of both normal immune responses and immune-mediated diseases. Research in the laboratory is mainly focused on inflammatory bowel disease (IBD), an immune-mediated disorder that is hypothesized to result from the abnormal immune response of a genetically susceptible host to the antigens derived from enteric bacteria. Development of optimal treatments for disease requires a detailed understanding of mechanisms of disease pathogenesis. Thus current work in the laboratory is aimed at understanding triggers of intestinal inflammation and mechanisms of inflammation-associated neoplasia, in addition to developing novel therapies for IBD treatment. Ongoing research also includes investigating mechanisms that determine the immunogenicity of oral antigens, to develop novel adjuvants for oral vaccines. This work has relevance for pathogenesis and treatment of infectious diseases affecting the gastrointestinal tract, as well as for inflammatory bowel disease.
Dr. Hale is an expert in pathologic evaluation of colitis and immunodeficiency in both humans and mice and is board-certified in Anatomic and Clinical Pathology.
Dawn Elizabeth Bowles
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