true

Pierson Lab

The Pierson Laboratory in the Center for Transplantation Sciences at MGH is focused on translational research to improve results with heart and lung transplantation, and to develop clinical Xenotransplantation as a safe, effective therapeutic alternative.
tertiary
email
Email: rpierson@mgh.harvard.edu
rpierson@mgh.harvard.edu
tertiary
email
Email: spratts@mgh.harvard.edu

Lab manager:  Shannon Pratts

spratts@mgh.harvard.edu
style
palette-white

Overview

The Pierson laboratory explores clinically important questions in transplantation. Working primarily in a cynomolgus monkey heterotopic heart allograft model, we study the pathogenesis of chronic rejection, and investigate costimulation and chemokine pathway modulation as approaches to induce operational tolerance. Barriers to successful application of pig-to-human xenotransplantation are studied in lung, liver, heart, kidney, and thymosternal composite tissue models, focusing on coagulation pathway regulation, costimulation pathway blockade, and cell adhesion mechanisms. Extensive international collaborative interactions support these “translational” research projects.

Research Projects

Preclinical Translation of Kidney, Heart, and Lung Xenotransplantation

Supported by U19 AI191384 (RN Pierson, III, PI). Using genetically engineered pigs designed for clinical use, this grant will test four working hypotheses regarding the reasons for preclinical and, in the case of heart xenografts, clinical organ xenograft failures. The role of xenoantigens, NK cells and tissue resident macrophages, von Willebrand’s factor-mediated coagulation pathway dysregulation, ischemia/reperfusion injury, and complement activation will be explored in the context of novel costimulation pathway blockade-based immunosuppression.

New Approaches to Inducing Cardiac Allograft Tolerance   7/21-6/26

Supported by P01 HL158504 (JC Madsen PI; RN Pierson, III, Project 3 PI). Extending work previously performed, we will (Aim 1) achieve tolerance of isolated hearts by combining a clinically relevant αCD2 mAb (αLoCD2bR1) to block effector TEMs with a novel αCD28 mAb (FR104) to promote Tregs; and (Aim 2) use a Bcl-2 inhibitor (ABT-199) and/or combined αCD117- and αCD45-Amanitin antibody-drug conjugates (ADC) to reduce/eliminate total body irradiation (TBI) and achieve a less toxic mixed chimerism conditioning regimen.

Achieving Long-Term, Survival of Cardiac Allografts in NHPs without Calcineurin Inhibitors

Planned for 8/26-7/31. U19 application submitted (Madsen PI; Pierson Project 2 PI).

Takemoto S, Burdorf L , Pierson RN 3rd. Pig Lung Xenotransplantation: Barriers on the Road to Clinical Translation. Transpl Int 2026 Jan 9:38:15542. PMID: 41583874 PMCID: PMC12827209 doi: 10.3389/ti.2025.15542. eCollection 2025.

This review summarizes why lung xenotransplantation remains uniquely difficult, highlighting early vascular barrier failure as a major obstacle to durable graft function and describing how it reflects a complex interplay of inflammatory, coagulation, and innate immune dysregulation. It also highlights recent progress in donor genetic engineering and peri-transplant therapeutic strategies, and identifies key future directions needed to move the field closer to clinical translation.

Kinoshita K, Maenaka A, Terashita M, Rosales IA, Hidaka Y, Lavalla GE, Ma M, Habibabady Z, Ayares D, Lederman S, Colvin RB, Pierson RN 3rd, Kawai T, Cooper DKC. Proteinuria Remains a Significant Hurdle to Successful Pig Kidney Xenotransplantation Despite an Effective Immunosuppressive Regimen. Transplantation. 2026 Jan 1;110(1):e141-e153. doi: 10.1097/TP.0000000000005508. Epub 2025 Oct 7. PMID: 41053932

Using ‘induction’ T- and B-cell depletion, IL-6R blockade, and a CD154- and rapamycin-based IS regimen, this study using 10-GE pig kidneys achieved the longest renal xenograft survivals yet reported in baboons. While adaptive immunity was well controlled, proteinuria and thrombotic microangiopathy were consistently observed in long-term follow-up.

Chaban R, Ileka I, McGrath G, Kinoshita K, Habibabady Z, Ma M, Diaz V, Maenaka A, Calhoun A, Dufault M, Rosales I, Laguerre CM, Sanatkar SA, Burdorf L, Ayares DL, Eyestone W, Sardana P, Kuravi K, Sorrells L, Lederman S, Lucas CG, Prather RS, Wells KD, Whitworth KM, Cooper DKC, Pierson RN 3rd. Extended survival of 9- and 10-gene-edited pig heart xenografts with ischemia minimization and CD154 costimulation blockade-based immunosuppression. J Heart Lung Transplant. 2024 Dec;43(12):1932-1944. doi: 10.1016/j.healun.2024.07.022. Epub 2024 Aug 7. PMID: 39097214

Using multiply genetically modified pig hearts in baboons, ischemia minimization, and a CD154-based immunosuppressive regimen, we show that inclusion of the CMAH carbohydrate gene KO may be associated with enhanced immune injury in the baboon heterotopic heart xenograft model. This result has important implications regarding preferential use of pigs lacking the CMAH gene KO in NHP models to more accurately predict clinical results.

Chaban R, Ileka I, Kinoshita K, McGrath G, Habibabady Z, Ma M, Diaz V, Maenaka A, Rosales I, Lederman S, Tkachev V, Madsen JC, Pierson RN 3rd. Enhanced Costimulation Blockade With αCD154, αCD2, and αCD28 to Promote Heart Allograft Tolerance in Nonhuman Primates. Transplantation. 2025 Jun 1;109(6):e287-e296. doi: 10.1097/TP.0000000000005315. Epub 2025 Jan 9. PMID: 39792548

A new ‘enhanced’ costimulation pathway blocking strategy, based on CD154, CD28, and CD2 blockade, induced robust and relatively durable chimerism after delayed bone marrow transplantation in a mixed-chimerism tolerance induction protocol. Heart allograft function and histology were well-preserved in this cynomolgus monkey model, but at the cost of high morbidity due to impaired host defense and PTLD.

Burdorf L, Laird CT, Harris DG, Connolly MR, Habibabady Z, Redding E, O'Neill NA, Cimeno A, Parsell D, Phelps C, Ayares D, Azimzadeh AM, Pierson RN 3rd. Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments. Am J Transplant. 2022 Jan;22(1):28-45. doi: 10.1111/ajt.16809. Epub 2021 Sep 20. PMID: 34424601

This study demonstrated extended survival of pig lung xenografts in baboons using targeted donor genetic modifications and co-stimulation blockade-based pharmacologic treatment. At the time of publication, it reported the longest survival in pig-to-baboon lung xenotransplantation, reaching 31 days with a DKO-based (CMAH-intact) donor, a finding consistent with the possibility that CMAH-intact donors may be better suited to the baboon model.

Chaban R, et al. Increased human complement pathway regulatory protein gene dose is associated with increased endothelial expression and prolonged survival during ex-vivo perfusion of GTKO pig lungs with human blood. Xenotransplantation. 2023 Jul-Aug;30(4):e12812. doi: 10.1111/xen.12812. Epub 2023 Jul 28. PMID: 37504492

This study demonstrates that increased expression of human complement regulatory proteins, particularly CD46, is associated with reduced platelet activation and modulation of coagulation pathways and with improved survival of GTKO pig lung xenografts during ex vivo perfusion with human blood.

Habibabady ZA, et al. Human erythrocyte fragmentation during ex-vivo pig organ perfusion. Xenotransplantation. 2022 Mar;29(2):e12729. doi: 10.1111/xen.12729. Epub 2022 Feb 2. PMID: 35112383

Human red blood cell fragmentation during pig organ perfusion generates platelet-like particles that confound standard platelet measurements. Using flow cytometry, we demonstrate a more accurate method to quantify platelets, and reveal underlying hemolytic RBC injury. This platform allows us to better understand and prevent erythrocyte sequestration and damage during the initial interaction between human blood and pig endothelium.

Petitpas K, et al Genetic modifications designed for xenotransplantation attenuate sialoadhesin-dependent binding of human erythrocytes to porcine macrophages. Xenotransplantation. 2022 Nov;29(6):e12780. doi: 10.1111/xen.12780. Epub 2022 Sep 20. PMID: 36125388

This study identifies sialic acid-dependent binding of human red blood cells to porcine macrophages as a key mechanism driving erythrocyte sequestration and damage observed during ex vivo perfusion of pig lung, liver, and other organs with human blood. Xeno-directed genetic modifications (carbohydrate gene knock-outs; human thromboregulatory and complement regulatory gene expression; expression of self-recognition receptors) and sialoadhesin blockade significantly reduce this interaction, suggesting strategies to mitigate anemia and erythrocyte injury in xenotransplantation models, and clinically.

Connolly MR, et al. Humanized von Willebrand factor reduces platelet sequestration in ex vivo and in vivo xenotransplant models. Xenotransplantation. 2021 Nov;28(6):e12712. doi: 10.1111/xen.12712. Epub 2021 Oct 17. PMID: 34657336

Expression of humanized porcine von Willebrand factor (h*pvWF) by GTKO.hCD46 lung and liver prevented non-physiologic platelet aggregation in vitro and significantly decreased platelet sequestration during ex vivo perfusion with human blood and after lung xenotransplantation in baboons. The results support h*pvWF as a promising genetic strategy to reduce platelet dysregulation and improve performance of organ xenografts in preclinical models, and clinically.

style
palette-white

Research Team

Zahra Habib Abbady
Instructor in Surgery, HMS, Postdoctoral Research Scientist
Jesse Akaa
Research Technician
Gweneth Lavalla
Research Technician, Veterinary Technologist
Syed Fahad Mohsin
Predoctoral Research Fellow
Shannon Pratts
Lab Manager
Sho Takemoto
Postdoctoral Research Fellow
Victor Tkachev
Assistant Professor in Surgery, HMS, Collaborating Scientist
Publications
  1. Kurlansky PA, Dresdale AR, Pierson RN III, McManus RP, Michler RE, Sachs H, Thomas WG, Lau H, Hardy, MA, Marboe C, Reemtsma K, Rose EA: Prolongation of canine cardiac allograft survival using donor-specific buffy coat pretransfusions. Transplantation 1986; 42(1): 98-101.
  2. Pierson RN III, Winn HJ, Russell PS, Auchincloss H Jr: CD-4 positive lymphocytes play a dominant role in murine xenograft rejection. Transplant Proc 1989; 21(1): 519.
  3. Pierson RN III, Winn HJ, Russell PS, Auchincloss H Jr: Xenogeneic skin graft rejection is especially dependent on CD4+ T cells. J Experimental Medicine 1989; 170: 991-6.
  4. Sanda MG, Pierson RN III, Smith C, Reemtsma K, Rose EA: Serum Dipeptidyl Peptidase IV in cardiac transplant recipients. Transplant Proc 1989; 21(1): 2525-6.
  5. Fuzesi L, Pepino P, Berger CL, Panza A, Chiang YC, Marboe CC, Pierson RN III, Smith CR, Reemtsma K, Rose EA: Immunomanipulation of the response to cardiac allo- and xenoreactive leukocytes. Transplant Proc 1989; 21(1): 537-9.
  6. Moses RD, Pierson RN III, Winn HJ, Auchincloss H Jr: Xenogeneic proliferation and lymphokine production are dependent on CD4+ helper T cells and self antigen-presenting cells in the mouse. J Exp Med 1990; 172(2): 567-75.
  7. Pierson RN III, Tew DF, Konig WK, White DJG, Wallwork J: Profound pulmonary hypertension, characteristic of pig lung rejection by human blood, is mediated by xenoreactive antibody independent of complement. Transplant Proc 1995; 27(1): 274.
  8. Young VK, Pierson RN III, Kasper-Konig W, Kellow N, Chavez G, White DJG, Wallwork J: Pig hearts transgenic for human decay accelerating factor are protected from hyperacute rejection. J Heart and Lung Transplant 1995; 14(1) Pt 2.
  9. Robson SC, Young VK, Cook NS, Metternich R, Kasper-Konig W, Lesnikoski BA, Pierson RN III, Hancock WW, White DJG, Bach FH: Thrombin inhibition in an ex vivo model of porcine heart xenograft hyperacute rejection. Transplantation 1996; 61(6):862-8.
  10. Pierson RN III, Kasper-Konig W, Tew DN, Young VK, Dunning JJ, Horsley J, Carey NRB, Wallwork J, White DJG: Hyperacute lung rejection in a pig-to-human transplant model. 1) The role of anti-species antibody and complement. Transplantation 1997; 63(4): 594-603.
  11. Pierson RN III, Pino-Chavez G, Young VK, Kasper-Konig W, White DJG, Wallwork J: Expression of human decay accelerating factor may protect pig lung from hyperacute rejection by human blood. J Heart and Lung Transplant 1997; 16(2): 231-239.
  12. Skepper JN, Pierson RN III, Tew DN, Boa Y-P, Williamson G, Wallwork J, White D, Davies MJ, Jones JG, Menon DK. Cytochemical demonstration of sites of hydrogen peroxide generation and increased vascular permeability in isolated pig hearts after ischemia and reperfusion. Microscopy Research and Techniques 1998; 42(5): 369-385.
  13. Chang AC, Blum MG, Blair KSA, Zhang J, Scott MA, Brock JE, Thomas DW, Burkly LC, Miller GG, Pierson RN III. Modulation of interleukin-12 gene expression in primate cardiac allografts during anti-CD40 Ligand monoclonal antibody treatment. Surgical Forum 1998; XLIX: 363-364.
  14. Pierson RN III, Chang AC, Blum MG, Blair KSA, Scott MA, Atkinson JB, Collins BJ, Zhang J-P, Thomas DW, Burkly LC, Miller GG. Prolongation of primate cardiac allograft survival by treatment with anti-CD 40L (CD154) antibody. Transplantation 1999; (68): 1800-1822.
  15. Miller GG, Davis SF, Atkinson JB, Chomsky DB, Pedroso P, Reddy VS, Drinkwater DC, Zhao XM, Pierson RN III. Longitudinal analysis of fibroblast growth factor (aFGF) expression after transplantation and association with severity of cardiac allograft vasculopathy. Circulation 1999; 100:2396-2399.
  16. Zhang JP, Blum MG, Chang AC, Shyr Y, Blair KSA, Awwad M, Pierson RN III. Immunohistologic evaluation of mechanisms mediating hyperacute lung rejection, and the effect of treatment with K76 COOH, FUT 175, and anti Gal column immunoadsorption. Xenotransplantation 1999; 6: 249-261.
  17. Zorn GL III, Pfeiffer S, Azimzadeh A, Pierson RN III. Thrombin inhibition protects the pulmonary xenograft from hyperacute rejection. Surgical Forum 2000; LI: 338-40.
  18. Collins BJ, Blum MJ, Parker RE, Chang AC, Blair KSA, Christman BW, Pierson RN III. Thromboxane mediates pulmonary hypertension and contributes to microvascular injury during hyperacute lung rejection. J Applied Physiology 2001; 90: 2257-2268.
  19. Pierson RN III, Crowe JE Jr., Pfeiffer S, Atkinson J, Azimzadeh A, Miller GG. CD40-Ligand in Primate Cardiac Allograft and Viral Immunity. Immunologic Research 2001; 23(2-3): 253-62.
  20. Pfeiffer S, Zorn GL III, Kelishadi S, Oriol R, Wolf P, Pierson RN III, Azimzadeh AM. Role of anti-Gal α1,3Gal and anti-platelet antibodies in hyperacute rejection of pig lung by human blood. Ann Thorac Surg 2001; 72(5): 1681-9; discussion 1690.
  21. Azimzadeh A, Zorn GL III, Blair KSA, Zhang JP, Pfeiffer S, Harrison RA, Cozzi E, White DJG, Pierson RN III. Hyperacute Lung Rejection in the Pig-to-Human Model. 2. Synergy between soluble and membrane complement inhibition. Xenotransplantation 2003; 10: 120-131.
  22. Crowe JE Jr, Sannella EC, Pfeiffer S, Zorn GL III, Azimzadeh A, Newman R, Miller GG, Pierson RN III. CD154 blockade following cardiac allotransplantation inhibits the humoral immune response to influenza vaccine. Am J Transplant 2003; 3(6): 680-8.
  23. Pfeiffer S, Zorn GL III, Zhang J-P, Farley SM, Giorgio TD, Robson SC, Azimzadeh AM, Pierson RN III. Hyperacute Lung Rejection in the Pig-to-Human Model. 3. Platelet Receptor Inhibitors Synergistically Modulate Complement Activation and Lung Injury. Transplantation 2003; 75(7): 953-9.
  24. Schröder C, Azimzadeh AM, Wu G, Price JO, Atkinson JB, Pierson RN III. Anti-CD20 treatment depletes B-cells in blood and lymphatic tissue of cynomolgus monkeys. Transplant Immunology 2003; 12(1): 19-28.
  25. Pfeiffer S , Zorn GL III, Blair KSA, Farley SM, Wu G, Schuurman H-J, White DJG, Azimzadeh AM, Pierson RN III. Hyperacute Lung Rejection in the Pig-to-Human Model. 4. Evidence for complement- and antibody independent mechanisms. Transplantation 2005; 79(6): 662-71.
  26. Wu G, Pfeiffer S, Schröder C, Zhang T, Nguyen BN, Kelishadi S, Atkinson JB, Schuurman H-J, White DJG, Azimzadeh AM, Pierson RN III. Co-stimulation blockade targeting CD154 and CD28/B7 modulates the induced antibody response after a pig-to-baboon cardiac xenograft. Xenotransplantation 2005; 12(3): 197-208.
  27. Azimzadeh AM, Pfeiffer S, Wu GS, Schröder C, Zorn GL III, Kehry M, Miller GG, Rose ML, Pierson RN III. Humoral immunity to vimentin is associated with cardiac allograft injury in nonhuman primates. Am J Transplant 2005; 5(10): 2349-59.
  28. Azimzadeh A, Pfeiffer S, Wu G, Schröder C, Zorn G III, Ozkaynak E, Kehry M, Atkinson J, Miller G, Pierson RN III. Alloimmunity in primate heart recipients with CD154 blockade: evidence for alternative costimulation mechanisms. Transplantation 2006; 81(2): 255-64.
  29. Wu G, Pfeiffer S, Schröder C, Zhang T, Nguyen BN, Kelishadi S, Atkinson JB, Schuurman H-J, White DJG, Azimzadeh AM, Pierson RN III. Coagulation cascade activation triggers early failure of pig hearts expressing human complement regulatory proteins. Xenotransplantation 2007; 14(1): 34-47.
  30. Schröder C*, Pierson RN III *, Nguyen BN, Kawka DW, Peterson LB, Wu G, Zhang T, Springer MS, Siciliano SJ, Iliff S, Ayala JM, Lu M, Mudgett JS, Lyons K, Mills S, Miller GG, Singer II, Azimzadeh AM, DeMartino JA. CCR5 blockade modulates inflammation and alloimmunity in primates. J Immunol 2007; 179(4): 2289-99.
  31. Nguyen BN, Azimzadeh AM, Zhang T, Wu G, Shuurman H-J, Sachs DH, Ayares D, Allan JS, Pierson RN III. Life-Supporting Function of Genetically Modified Swine Lungs in Baboons. J Thorac CV Surg 2007; 133(5): 1354-63.
  32. Ezzelarab M, Garcia B, Azimzadeh A, Sun F, Hara H, Kelishadi S, Zhang T, Lin JY, Tai H-C, Long C, Wagner R, Thacker J, Murase N, McCurry K, Barth RN, Ayares D, Pierson RN III *, Cooper DKC*. The Innate Immune Response and Activation of Coagulation in α1,3-Galactosyltransferase Gene-Knockout Xenograft Recipients. Transplantation 2009; 87(6): 805-12.
  33. Poirier N, Azimzadeh AM, Zhang T, Dilek N, Mary C, Nguyen B, Tillou X, Wu G, Reneaudin K, Hervouet J, Martinet B, Coulon F, Allain-Launay E, Karam G, Soulillou J-P, Pierson RN III*, Blancho G*, Vanhove B*. Inducing CTLA-4–Dependent Immune Regulation by Selective CD28 Blockade Promotes Regulatory T Cells in Organ Transplantation. Science Translational Medicine 2010; 2 (17): 17ra10. PMID: 20371478.
  34. Kelishadi SK, Azimzadeh AM, Zhang T, Stoddard T, Welty E, Avon C, Higuchi M, Laaris A, Cheng X-F , McMahon C, Pierson RN III. Preemptive CD20+ B cell depletion attenuates cardiac allograft vasculopathy in cyclosporine-treated monkeys. J Clin Invest 2010; 120(4): 1275-84.
  35. Nguyen BN, Azimzadeh AM, Schroeder C, Buddensick T, Zhang T, Laaris A, Cochrane M, Schuurman H-J, Sachs DH, Allan JS, Pierson RN III. Absence Of Gal Epitope Prolongs Survival Of Swine Lungs In An Ex Vivo Model Of Hyperacute Rejection. Xenotransplantation 2011; 18(2): 94-107.
  36. Burdorf L, Stoddard T, Zhang T, Rybak E, Riner A, Avon C, Laaris A, Cheng X, Sievert E, Braileanu G, Newton A, Phelps CJ, Ayares D, Azimzadeh AM, Pierson RN III. Expression of human CD46 modulates inflammation associated with GalTKO lung xenograft injury. Am J Transplant 2014; 14(5): 1084-95. PMID: 24698431.
  37. Ezzelarab MB, Ekser B, Azimzadeh A, Lin CC, Zhao Y, Rodriguez R, Echeverri GJ, Iwase H, Long C, Hara H, Ayares D, Pierson RN III, Thomson AW, Cooper DK. Systemic inflammation in xenograft recipients precedes activation of coagulation. Xenotransplantation 2015; 22(1): 32-47. PMID: 25209710.
  38. Harris DG, Quinn KJ, French BM, Schwartz E, Kang E, Dahi S, Phelps CJ, Ayares DL, Burdorf L, Azimzadeh AM, Pierson RN III. Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood. Xenotransplantation 2015; 22(2): 102-11. PMID: 25470239.
  39. Harris DG, Benipal PK, Cheng X, Burdorf L, Azimzadeh AM, Pierson RN III. Four-dimensional characterization of thrombosis in a live-cell, shear-flow assay: development and application to xenotransplantation. PLoS One 2015; 10(4): e0123015. PMID: 25830912.
  40. Azimzadeh AM, Kelishadi SS, Ezzelarab MB, Singh AK, Stoddard T, Iwase H, Zhang T, Burdorf L, Sievert E, Avon C, Cheng X, Ayares D, Horvath KA, Corcoran PC, Mohiuddin MM, Barth RN, Cooper DK, Pierson RN III. Early graft failure of GalTKO pig organs in baboons is reduced by expression of a human complement pathway-regulatory protein. Xenotransplantation 2015; 22(4): 310-6. PMID: 26174749.
  41. Mohiuddin M, Singh AK, Corcoran PC, Thomas ML III, Clark T, Lewis B, Hoyt R, Eckhaus M, Pierson RN III, Belli AJ, Wolf E, Klymiuk N, Phelps C, Reimann K, Ayares D, Horvath KA. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenografts. Nature Communications 2016; 7:11138. PMID: 27045379.
  42. Burdorf L, Riner A, Rybak E, Salles II, De Meyer SF, Shah A, Quinn KJ, Harris D, Zhang T, Parsell D, Ali F, Schwartz E, Kang E, Cheng X, Sievert E, Zhao Y, Braileanu G, Phelps CJ, Ayares DL, Deckmyn H, Pierson RN III, Azimzadeh AM. Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor. Xenotransplantation 2016; 23(3): 222-36. doi: 10.1111/xen.12236. PMID: 27188532.
  43. Azimzadeh AM,* Zhang T,* Wu G, Kelishadi SS, Stoddard T, O’Neill N, Nguyen B-N, Welty E, Avon C, Higuchi M, Mitchell SL, Hershfeld A, Cheng XF, Kronfli A, Rybak E, Burdorf L, Pierson RN III. Preemptive CD20+ B cell depletion attenuates cardiac allograft vasculopathy in CD154-treated monkeys. Transplantation 2017; 101(1): 63-73. PMID: 27362307.
  44. Laird C, Burdorf L, French B, Kubicki N, Zhang T, Cheng S, O’Neill N, Cimeno A, Parsell D, Braileanu G, Sun W, So E, Bähr A, Klymiuk N, Phelps C, Ayares D, Azimzadeh AM, Pierson RN III. Transgenic Expression of Human Leukocyte Antigen-E Attenuates GalTKO.hCD46 Porcine Lung Xenograft Injury. Xenotransplantation 2017: 24(2). Doi:10.1111/xen.12294, PMID 28258595.
  45. OʼNeill NA, Zhang T, Braileanu G, Sun W, Cheng X, Hershfeld A, Laird CT, Kronfli A, Hock LA, Dahi S, Kubicki N, Sievert E, Hassanein W, Cimeno A, Pierson RN 3rd, Azimzadeh AM. Comparative Evaluation of αCD40 (2C10R4) and αCD154 (5C8H1 and IDEC-131) in a Nonhuman Primate Cardiac Allotransplant Model. Transplantation 2017; 101(9): 2038-2047. PMID: 28557955.
  46. Cimeno A, Hassanein W, French BM, Powell JM, Burdorf L, Goloubeva O, Cheng X, Parsell DM, Ramsoondar J, Kuravi K, Vaught T, Uluer MC, Redding E, O'Neill N, Laird C, Hershfeld A, Tatarov I, Thomas K, Ayares D, Azimzadeh AM, Pierson RN 3rd, Barth RN, LaMattina JC. N-glycolylneuraminic acid knockout reduces erythrocyte sequestration and thromboxane elaboration in an ex vivo pig-to-human xenoperfusion model. Xenotransplantation 2017; 24(6). doi: 10.1111/xen.12339. PMID: 28940313.
  47. Sendil S, Diaconu SC, O'Neill NA, Burdorf L, Tatarov I, Parsell DM, Azimzadeh AM, Pierson RN 3rd, Nam AJ. Vascularized Thymosternal Composite Tissue Allo- and Xenotransplantation in Nonhuman Primates: Initial Experience. Plast Reconstr Surg Glob Open. 2017 Dec 22; 5(12): e1538. doi: 10.1097/GOX.0000000000001538. PMID: 29632759.
  48. Zhang T, Azimzadeh AM, Sun W, O'Neill NA, Sievert E, Bergbower E, Braileanu G, Burdorf L, Cheng X, Monahan T, Dahi S, Harris DG, Rybak E, Welty E, Kronfli A, Avon C, Pierson RN 3rd. Selective CD28 Inhibition Modulates Alloimmunity and Cardiac Allograft Vasculopathy in Anti-CD154-Treated Monkeys. Transplantation 2018; 102(3): e90-e100. PMID: 29319621.
  49. Laird CT, Hassanein W, O'Neill NA, French BM, Cheng X, Fogler WE, Magnani JL, Parsell D, Cimeno A, Phelps CJ, Ayares D, Burdorf L, Azimzadeh AM, Pierson RN 3rd. P- and E-selectin receptor antagonism prevents human leukocyte adhesion to activated porcine endothelial monolayers and attenuates porcine endothelial damage. Xenotransplantation 2018 Jan 23. doi: 10.1111/xen.12381. PMID: 29359469.
  50. French BM, Sendil S, Sepuru KM, Ranek J, Burdorf L, Harris D, Redding E, Cheng X, Laird CT, Zhao Y, Cerel B, Rajarathnam K, Pierson RN 3rd, Azimzadeh AM. Interleukin-8 mediates neutrophil-endothelial interactions in pig-to-human xenogeneic models. Xenotransplantation 2018 Feb 9. doi: 10.1111/xen.12385. PMID: 29427404.
  51. O'Neill NA, Zhang T, Braileanu G, Cheng X, Hershfeld A, Sun W, Reimann KA, Dahi S, Kubicki N, Hassanein W, Laird C, Cimeno A, Azimzadeh AM, Pierson RN 3rd. Pilot Study of Delayed ICOS/ICOS-L Blockade With αCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac Allograft Model. Transplant Direct. 2018 Feb 2; 4(2): e344. doi: 10.1097. PMID: 29464205.
  52. Burdorf L, Harris D, Dahi S, Laird C, Zhang T, Ali F, Shah A, Thompson M, Braileanu G, Cheng X, Sievert E, Schwartz E, Sendil S, Parsell DM, Redding E, Phelps CJ, Ayares DL, Azimzadeh AM, Pierson RN 3rd. Thromboxane and histamine mediate PVR elevation during xenogeneic pig lung perfusion with human blood. Xenotransplantation 2019: e12458. PMID: 30175863.
  53. Pierson RN 3rd, Burdorf L, Madsen JC, Lewis GD, D'Alessandro DA. Pig-to-human heart transplantation: Who goes first? Am J Transplant 2020; 20(10): 2669-2674. doi: 10.1111/ajt.15916. Epub 2020 May 25. PMID: 32301262.
  54. Pierson RN 3rd, Fishman JA, Lewis GD, D'Alessandro DA, Connolly MR, Burdorf L, Madsen JC, Azimzadeh AM. Progress Toward Cardiac Xenotransplantation. Circulation. 2020 Oct 6;142(14):1389-1398. doi: 10.1161/CIRCULATIONAHA.120.048186. Epub 2020 Oct 5. PMID: 33017208.
  55. Patel PM, Connolly MR, Coe TM, Calhoun A, Pollok F, Markmann JF, Burdorf L, Azimzadeh A, Madsen JC, Pierson RN 3rd. Minimizing Ischemia Reperfusion Injury in Xenotransplantation. Front Immunol. 2021 Sep 9; 12:681504. doi: 10.3389/fimmu.2021. 681504. eCollection 2021. PMID: 34566955.
  56. Burdorf L, Laird CT, Harris DG, Connolly MR, Habibabady Z, Redding E, O’Neill NA, Cimeno A, Parsell D, Phelps C, Ayares D, Azimzadeh AM, Pierson RN III. In vivo lung Pig-to-Baboon Lung Xenotransplantation: Extended Survival with targeted genetic modifications and pharmacologic treatments. Am J Transplant 2022 Jan; 22(1): 28-45. doi: 10.1111/ajt.16809. Epub 2021 Sep 20. PMID: 34424601.
  57. Connolly MR, Kuravi K, Burdorf L, Sorrells L, Morrill B, Cimeno A, Vaught T, Dandro A, Sendil S, Habibadady Z, Monahan J, Li T, LaMattina J, Eyestone W, Ayares D, Phelps C, Azimzadeh AM, Pierson RN III. Humanized von Willebrand factor reduces platelet sequestration in ex vivo and in vivo xenotransplant models. Xenotransplantation 2021; 28(6): e12712. doi: 10.1111/xen.12712. Epub 2021 Oct 17. PMID: 34657336.
  58. Habibabady ZA, Sendil S, Ellett F, Pollok F, Lias GF, French BM, Sun W, Braileanu G, Burdorf L, Irima D, Pierson RN III, Azimzadeh AM. Human erythrocyte fragmentation during ex‐vivo pig organ perfusion. Xenotransplantation 02 February 2022 https://doi.org/ 10.1111/ xen.12729 PMID: 35112383.
  59. Cimeno A, Kuravi K, Sorrells L, Dandro A, Sendil S, Burdorf L, Parsell DM, Eyesonte W, Phelps C, Ayares D, Azimzadeh AM, Pierson RN III, Barth RN, LaMattina JC. hEPCR.hTBM.hCD47.hHO‐1 with donor clodronate and DDAVP treatment improves perfusion and function of GalTKO.hCD46 porcine livers perfused with human blood. Xenotransplantation 15 February 2022 https://doi.org/10.1111/xen.12731 PMID: 35166407.
  60. Miura S, Habibabady ZA, Pollok F, Connolly M, Pratts S, Dandro A, Sorrells L, Karavi K, Phelps C, Eyestone W, Ayares D, Burdorf L, Azimzadeh A, Pierson RN 3rd. Effects of human TFPI and CD47 expression and selectin and integrin inhibition during GalTKO.hCD46 pig lung perfusion with human blood. Xenotransplantation. 2022 Mar;29(2):e12725. doi: 10.1111/xen.12725. Epub 2022 Mar 2. PMID: 35234315.
  61. Chaban R, Habibabady Z, Hassanein W, Connolly MR, Burdorf L, Redding E, Laird C, Ranek J, Braileanu G, Sendil S, Cheng X, Sun W, O'Neill NA, Kuravi K, Hurh S, Ayares DL, Azimzadeh AM, Pierson RN 3rd. Knock-out of N-glycolylneuraminic acid attenuates antibody-mediated rejection in xenogenically perfused porcine lungs. Xenotransplantation. 2022 Nov;29(6):e12784. doi: 10.1111/xen.12784. Epub 2022 Oct 17. PMID: 3625056.
  62. Petitpas K, Habibabady Z, Ritchie V, Connolly MR, Burdorf L, Qin W, Kan Y, Layer JV, Crabtree JN, Youd ME, Westlin WF, Magnani DM, Pierson RN 3rd, Azimzadeh AM. Genetic modifications designed for xenotransplantation attenuate sialoadhesin-dependent binding of human erythrocytes to porcine macrophages. Xenotransplantation. 2022 Nov;29(6):e12780. doi: 10.1111/xen.12780. Epub 2022 Sep 20. PMID: 36125388.
  63. Miura S, Habibabady ZA, Pollok F, Ma M, Rosales IA, Kinoshita K, Pratts S, McGrath G, Chaban R, Fogarty S, Meibohm B, Daugherty B, Lederman SM, Pierson RN III. TNX-1500, an Fc-modified Anti-CD154 Antibody, Prolongs Nonhuman Primate Cardiac Allograft Survival. Am J Transplant 2023 Apr 6: S1600-6135(23)00396-9. doi: 10.1016/ j.ajt.2023.03.025. Online ahead of print. PMID: 37030662.
  64. Lassiter G, Otsuka R, Hirose T, Rosales I, Karadagi A, Tomosugi T, Dehnadi A, Lee H, Colvin RB, Baardsnes J, Moraitis A, Smith EE, Ali Z, Berhe P, Mulder A, Meibohm B, Daugherty B, Fogarty S, Pierson RN, Lederman S, Kawai T. TNX-1500, an Fc-modified Anti-CD154 Antibody, Prolongs Nonhuman Primate Renal Allograft Survival. Am J Transplant. 2023 Apr 3:S1600-6135(23)00371-4. doi: 10.1016/j.ajt.2023.03.022. Online ahead of print. PMID: 37019335.
  65. Hulsmans M, Schloss MJ, Lee IH, Bapat A, Iwamoto Y, Vinegoni C, Paccalet A, Yamazoe M, Grune J, Pabel S, Momin N, Seung H, Kumowski N, Pulous FE, Keller D, Bening C, Green U, Lennerz JK, Mitchell RN, Lewis A, Casadei B, Iborra-Egea O, Bayes-Genis A, Sossalla S, Ong CS, Pierson RN, Aster JC, Rohde D, Wojtkiewicz GR, Weissleder R, Swirski FK, Tellides G, Tolis G Jr, Melnitchouk S, Milan DJ, Ellinor PT, Naxerova K, Nahrendorf M. Recruited macrophages elicit atrial fibrillation. Science. 2023 Jul 14;381(6654):231-239. doi: 10.1126/science.abq3061. Epub 2023 Jul 13. PMID: 37440641.
  66. Chaban R, McGrath G, Habibabady Z, Rosales I, Burdorf L, Ayares DL, Rybak E, Zhang T, Harris DG, Dahi S, Ali F, Parsell DM, Braileanu G, Cheng X, Sievert E, Phelps C, Azimzadeh AM, Pierson RN 3rd. Increased human complement pathway regulatory protein gene dose is associated with increased endothelial expression and prolonged survival during ex-vivo perfusion of GTKO pig lungs with human blood. Xenotransplantation. 2023 Jul-Aug;30(4):e12812. doi: 10.1111/xen.12812. Epub 2023 Jul 28. PMID: 37504492
  67. Burdorf L, Gao Z, Riner A, Sievert E, Harris DG, Kuravi KV, Morrill BH, Habibabady Z, Rybak E, Dahi S, Zhang T, Schwartz E, Kang E, Cheng X, Esmon CT, Phelps CJ, Ayares DL, Iii RNP, Azimzadeh AM. Expression of human thrombomodulin by GalTKO.hCD46 pigs modulates coagulation cascade activation by endothelial cells and during ex vivo lung perfusion with human blood. Xenotransplantation. 2023 Nov-Dec;30(6):e12828. doi: 10.1111/xen.12828. Epub 2023 Sep 28. PMID: 37767640.
  68. Chaban R, Ileka I, McGrath G, Kinoshita K, Habibabady Z, Ma M, Diaz V, Maenaka A, Calhoun A, Dufault M, Rosales I, Laguerre CM, Sanatkar SA, Burdorf L, Ayares DL, Eyestone W, Sardana P, Kuravi K, Sorrells L, Lederman S, Lucas CG, Prather RS, Wells KD, Whitworth KM, Cooper DKC, Pierson RN 3rd. Extended survival of 9- and 10-gene-edited pig heart xenografts with ischemia minimization and CD154 costimulation blockade-based immunosuppression. J Heart Lung Transplant. 2024 Aug 7:S1053-2498(24)01777-7. doi: 10.1016/j.healun.2024.07.022. Online ahead of print. PMID: 39097214.
  69. Chaban R, Ileka I, Kinoshita K, McGrath G, Habibabady Z, Ma M, Diaz V, Maenaka A, Rosales I, Lederman S, Tkachev V, Madsen JC, Pierson RN 3rd. Enhanced Costimulation Blockade With αCD154, αCD2, and αCD28 to Promote Heart Allograft Tolerance in Nonhuman Primates. Transplantation. 2025 Jan 9. doi: 10.1097/TP.0000000000005315. Online ahead of print. PMID: 39792548.
style
palette-white

How to reach us

Please contact us with inquiries about ongoing studies, training or collaboration opportunities, or access to lab resources
tertiary
email
Email: rpierson@mgh.harvard.edu
rpierson@mgh.harvard.edu
tertiary
email
Email: spratts@mgh.harvard.edu

Lab manager: Shannon Pratts

spratts@mgh.harvard.edu
secondary
phone
Call: 617-726-8029
6177268029
style
palette-light-teal