Researcher’s Profile

Adam D. Griesemer, MD

Surgical Director, Pediatric Liver Transplantation
Surgical Director, Living Donor Liver Transplantation-Columbia Campus
Director, Large Animal Xenotransplantation Laboratory, Columbia Center for Translational Immunology
Overview: 

Allogeneic Studies

My laboratory is investigating the ability of ex-vivo expanded Tregs to enhance bone marrow engraftment and extend the duration of mixed chimerism. The induction of durable mixed chimerism without graft-versus-host disease should in turn lead to life-long donor-specific tolerance to any co-transplanted cells (islets) or solid organs (heart, liver, lung) from the donor. We are also collaborating with other investigators at the CCTI to study the ability of amnion-derived multipotent progenitor cells to enhance bone marrow engraftment in translational models as an alternate, and potentially synergistic, strategy to induce durable mixed chimerism.

We are also investigating the ability to translate the induction protocol that induces tolerance to simultaneously co-transplanted bone marrow and kidney grafts (despite only transient mixed chimerism developing) to combined bone marrow and liver grafts. In particular, we are investigating 1) the role of donor and recipient memory cells in mediating host-versus-graft and graft-versus-host responses; and 2) the role that inflammatory cytokines, particularly in the portal system, play in priming inflammatory and tolerogenic cellular responses.

The future goals of the laboratory include collaborating with the Chen lab in testing the ability of durable mixed chimerism to induce tolerance to organs that do not facilitate tolerance with the transient mixed chimerism approach, such as islets. We also plan to test the ability of modulating the T cell memory responses and the inflammatory environment induced after liver transplant to reliably induce rapid tolerance after liver transplants.

Xenogeneic Studies

The development of Gal-knockout swine removed the most significant target of natural antibodies from the surface of pig cells. However, low levels of non-Gal antibodies represent a barrier to long-term solid organ xenograft survival and xenogeneic bone marrow engraftment. Since pharmacological interventions have been unsuccessful in decreasing natural antibody levels, my lab is investigating the efficacy of Treg therapy in reducing anti-swine antibodies and facilitating tolerance induction to xenotransplants.

Current investigations include:

1. Studies on the optimal method of stimulating Tregs during expansion to generate donor-specific Tregs

2. Suppression of xenogeneic natural antibodies by donor-specific Tregs in preclinical models

3. Augmentation of xenogeneic chimerism using donor-specific Tregs

The future goals of the laboratory are to utilize donor-specific Tregs to control the natural anti-swine antibody response in translational swine-to-humanized mice and swine-to-nonhuman primate models. This in turn will facilitate the induction of xenogeneic chimerism that is expected to result in robust tolerance to donor solid organ transplants.

Lab Members: 
Paula Alonso-Guallart, DVM, Postdoctoral Researcher
Karina Bruestle, MD, Postdoctoral Researcher
Hiroshi Sakai, MD, Postdoctoral Researcher
Emily Lopes, Lab Technician
Karl Erik Berglund, MD, Postdoctoral Researcher
Nathaly Llore, MD, Postdoctoral Researcher
Genevieve Pierre, Lab Technician
Publications: 
Samstein B, Griesemer A, Halazun K, Kato T, Guarrera JV, Cherqui D, Emond JC. Pure Laparoscopic Donor Hepatectomies: Ready for Widespread Adoption? Ann Surg. 2018 Aug 10. PMID: 30102634 Chaudhry SG, Bentley-Hibbert S, Stern J, Lobritto S, Martinez M, Vittorio J, Halazun KJ, Lee HT, Emond J, Kato T, Samstein B, Griesemer A. Growth of Liver Allografts Over Time in Pediatric Transplant Recipients. Pediatric Transplantation. 2018 Mar;22(2). PMID: 29334158 Elnaggar AS, Griesemer AD, Bentley-Hibbert S, Brown RS, Martinez M, Lobritto SJ, Kato T, Emond JC. Liver Atrophy and Regeneration in Non-Cirrhotic Portal Vein Thrombosis: Effect of Surgical Shunts. Liver Transplantation. 2018. In Press.  PMID: 29377486 Quillin RC, Bongu A, Kasper v, Vittorio JM, Martinez M, Lobritto SJ, Griesemer AD, Guarrera JG. Roux-en-Y enterolith leading to obstruction and ischemic necrosis after pediatric orthoscopic liver transplantation. Pediatric Transplantation. 2018. In Press. Przybyszewski EM, Verna EC, Lobritto SJ, Martinez M, Vittorio J, Fox AN, Samstein B, Kato T, Griesemer AD, Emond JC. Durable Clinical and Immunologic Advantage of Living Donor Liver Transplantation in Children. Transplantation2018. In Press. PMID: 29369249 Vallabhajosyula P, Hirakata A, Weiss M, Griesemer A, Shimizu A, Hong H, Habertheuer A, Tchipashvili V, Yamada K, Sachs DH. Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet-Kidney Transplantation. Cell Transplant. 2017 Nov;26(11):1755-1762. PMID: 29338381 Rahnemai-Azar AA, Griesemer AD, Velasco ML, Kato T. Ex vivo excision of retroperitoneal soft tissue tumors: A case report. Oncol Lett. 2017 Oct;14(4):4863-4865. PMID: 29085493 Kato Y, Griesemer AD, Wu A, Sondermeijer H, Weiner JI, Duran-Struuck R, Martinez M, Slate A, Romanov A, Lefkowitch JH, Sykes M, and Kato T. Novel H-Shunt Venovenous Bypass for Liver Transplantation in Cynomolgus Macaques. Comparative Medicine. 2017 Oct 1;67(5):436-441. PMID: 28935006 Halazun KJ, Rana AA, Fortune B, Quillan RC, Verna EC, Samstein B, Guarrera JV, Kato T, Griesemer AD, Fox A, Brown RS Jr, Emond JC. No Country for Old Livers? Examining and Optimizing the Utilization of Elderly Liver Grafts. Am J Transplant. 2017 Sep 27.  PMID: 28960723 Carpenter DJ, Granot T, Matsuoka N, Senda T, Kumar BV, Thome JJC, Gordon CL, Miron M, Weiner J, Connors T, Lerner H, Friedman A, Kato T, Griesemer AD,Farber DL. Human immunology studies using organ donors: impact of clinical variations on immune parameters in tissues and circulation. Am J Transplant. 2017 Jul 18. PMID: 28719147 Halazun KJ, Quillin RC, Rosenblatt R, Bongu A, Griesemer AD, Kato T, Smith C, Michelassi F, Guarrera JV, Samstein B, Brown RS Jr, Emond JC. Expanding the Margins: High Volume Utilization of Marginal Liver Grafts Among >2000 Liver Transplants at a Single Institution. Ann Surg. 2017 Jun 27. PMID: 28657945. Griesemer AD, Emond JC. Big improvements for the smallest recipients. Liver Transpl. 2017 Jun 15. PMID: 28618184. Granot T, Senda T, Carpenter DJ, Matsuoka N, Weiner J, Gordon CL, Miron M, Kumar B, Griesemer A, Ho S, Lerner H, Thome J, Connors T, Reizis B, Farber DL. Dendritic cells display subset and tissue-specific maturation dynamics over human life. Immunity. 2017 Mar 21;46(3):504-515.  Duran-Struuck R, Sondermeijer HP, Bühler L, Alonso-Guallart P, Zitsman J, Kato Y, Wu A, McMurchy AN, Woodland D, Griesemer A, Martinez M, Boskovic S, Kawai T, Cosimi AB, Wuu CS, Slate A, Mapara M, Baker S, Tokarz R, Dʼ Agati V, Hammer S, Pereira M, Lipkin WI, Wekerle T, Levings M, Sykes M. Effect of ex vivo Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus Macaques. Transplantation. 2017 Eeb;101(2):274-283. PMID: 27846155 Halazun KJ, Najjar M, Abdelmessih RM, Samstein B, Griesemer AD, Guarrera JV, Kato T, Verna EC, Emond JC, Brown RS Jr. Recurrence After Liver Transplantation for Hepatocellular Carcinoma: A New MORAL to the Story. Ann Surg. 2016 Sep 16. PMID: 27611615 Emond JC, Griesemer AD.Tolerance in clinical liver transplantation: The long road ahead. Hepatology2017 Feb;65(2):411-413.  PMID: 27718261 Zuber J, Shonts B, Lau S, Obradovic A, Fu J, Yang S, Lambert M, Coley S, Weiner J, Thome J, DeWolf S, Farber DL, Shen Y, Caillat-Zucman S, Bhagat G, Griesemer A, Martinez M, Kato T, Sykes M. Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome. Science Immunology. 2016 October 07; 1(4). Halazun KJ, Przybyszewski EM, Griesemer AD, Cherqui D, Michelassi F, Guarrera JV, Kato T, Brown RS Jr, Emond JC, Samstein B. Leaning to the Left: Increasing the Donor Pool by Using the Left Lobe, Outcomes of the Largest Single-center North American Experience of Left Lobe Adult-to-adult Living Donor Liver Transplantation. Ann Surg. 2016 Jul 18. PMID: 27433896 Martinez M, Brodlie S, Griesemer A, Kato T, Harren P, Gordon B, Parker T, Levine D, Tyberg T, Starc T, Cho I, Min J, Elmore K, Lobritto S, Hudgins LC. Effects of Liver Transplantation on Lipids and Cardiovascular Disease in Children With Homozygous Familial Hypercholesterolemia. Am J Cardiol. 2016 May 28. PMID: 27365335 Weiner J, Griesemer A,Island E, Lobritto S, Martinez M, Selvaggi G, Lefkowitch J, Velasco M, Tryphonopoulos P, Emond J, Tzakis A, Kato T. Long term outcomes of auxiliary partial orthotopic liver transplantation in preadolescent children with fulminant hepatic failure. Liver Transpl. 2016 Apr;22(4):485-94 PMID: 26479577 Parekh M, D Kluger M, Griesemer A, Bentley-Hibbert S. Regenerative liver surgeries: the alphabet soup of emerging techniques. Abdom Radiol (NY). 2016 Jan;41(1):162-73. PMID: 26830622 Thome JJ, Bickham KL, Ohmura Y, Kubota M, Matsuoka N, Gordon C, Granot T, Griesemer A, Lerner H, Kato T, Farber DL. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues. Nature Medicine.2016; 22(1):72-7. NIHMSID: NIHMS738060; PMID: 26657141 PMCID: PMC4703455 Soubrane O, de Rougemont O, Kim KH, Samstein B, Mamode N, Boillot O, Troisi RI, Scatton O, Cauchy F, Lee SG, Griesemer A, Ahmed Z, Clavien PA, Cherqui D. Laparoscopic Living Donor Left Lateral Sectionectomy: A New Standard Practice for Donor Hepatectomy. Ann Surg. 2015 Nov;262(5):757-763. PMID: 26583663 Weiner J, Griesemer A, Island E, Lobritto S, Martinez M, Selvaggi G, Lefkowitch J, Velasco M, Tryphonopoulos P, Emond J, Tzakis A, Kato T. Long-Term Outcomes of Auxiliary Partial Orthotopic Liver Transplantation in Pre-Adolescent Children with Fulminant Hepatic Failure. Liver Transpl. 2015 Oct 19. PMID: 26479577 Matsuoka N, Weiner JI, Griesemer AD, Samstein BB, Zhao Y, et al. Ex Vivo Pancreaticoduodenectomy and Liver Autotransplantation for Pancreatic Head Tumor with Extensive Involvement of the Hepatoduodenal Ligament. Liver Transplantation. 2015 Dec;21(12):1553-6; PMID: 26289503 Samstein B, Griesemer A, Cherqui D, Mansour T, Pisa J, et al. Fully laparoscopic left-sided donor hepatectomy is safe and associated with shorter hospital stay and earlier return to work: A comparative study. Liver Transplantation. 2015; 21(6):768-73.PMID: 25789460 Weiner J, Duran-Struuck R, Zitsman J, Buhler L, Sondermeijer H, McMurchy A, Levings MK, Sykes M, Griesemer A. Restimulation after cryopreservation and thawing preserves the phenotype and function of expanded baboon regulatory T cells. Transplantation Direct. 2015 February; 1(1):1-7. Wang H, Griesemer AD, Parsons RF, Graham JA, Emond JC, Samstein B. Delayed Gastric Emptying after Living donor Hepatectomy for Liver Transplantation. Case Reports in Transplantation. 2014. PMID: 25610698 PMCID: PMC4291134 Halazun KJ, Patzer RE, Rana AA, Verna EC, Griesemer AD, Parsons RF, Samstein B, Guarrera JV, Kato T, Brown RS Jr, Emond JC. Standing the test of time: Outcomes of a decade of prioritizing patients with HCC, results of the UNOS natural geographic experiment. Hepatology. 2014 Jun 20. PMID: 24954365  Weiner J, Wu J, Martinez M, Lobritto S, Ovchinsky N, Rohde C, Griesemer A, Kato T. The use of bi-planar tissue expanders to augment abdominal domain in a pediatric intestinal transplant recipient. Pediatr Transplant. 2014 Aug;18(5):E174-9. PMID: 25041331 Griesemer A, Yamada K, Sykes M. Xenotransplantation: immunological hurdles and progress toward tolerance. Immunological Reviews. Immunol Rev. 2014 Mar;258(1):241-58. PMID: 24517437 PMCID: PMC4023346 Samstein B, Cherqui D, Guarrera J, Griesemer A, Halazun KJ, Kato T, Emond JE. Totally laparoscopic full left hepatectomy for living donor liver transplantation in adolescents and adults. Am J Transplant. 2013 Sept:13: 2462–2466. PMID: 24034709 Weiner J, Scalea J, Ishikawa Y, Okumi M, Griesemer A, Hirakata A, Etter J, Gillon B, Moran S, Shimizu A, Yamada K, Sachs DH.  Tolerogenicity of Donor Major Histocompatibility complex-matched Skin Grafts in Previously Tolerant Massachusetts General Hospital Miniature Swine. Transplantation. 2012 Dec 27;94(12):1192-9.  PMID:23269447 PMCID: PMC3531825 Yamada K, Hirakata A, Tchipashvili V, Shimizu A, Iwaki H, Griesemer A, Moran S, Sachs DH Composite Islet-Kidneys From Single Baboon Donors Cure Diabetes Across Fully Allogenic Barriers. Am J Transplant. 2011 Dec;11(12):2603-12.  PMID:21929644 Tena A, Vallabhajosyula P, Hawley RJ, Griesemer A, Yamada K, Sachs DH.  Quantification of Baboon Thymopoiesis in Porcine Thymokidney Xenografts by the Signal-Joining T-Cell Receptor Excision Circle Assay.  Transplantation. 2011 Mar 27;91(6):639-44.  PMID: 21285918PMCID: PMC3255479 Hirakata A, Okumi M, Griesemer AD, Shimizu A, Nobori S, Tena A, Moran S, Arn S, Boyd RL, Sachs DH, Yamada K. Reversal of age-related thymic involution by an LHRH agonist in miniature swine. Transpl Immunol. 2010 Oct;24(1):76-81. PMID: 20692342 PMCID: PMC2988885 Griesemer AD, Sorenson EC, Hardy MA.  The Role of the Thymus in Tolerance. Transplantation.2010 Sep 15;90(5):465-74. PMID: 20555306 Griesemer A, Liang F, Hirakata A, Hirsh E, Lo D, Okumi M, Sykes M, Yamada K, Huang CA, Sachs DH.  Occurrence of specific humoral non-responsiveness to swine antigens following administration of GalT-KO bone marrow to baboons.  Xenotransplantation. 2010 Jul;17(4):300-12. PMID: 20723202 NIHMSID: NIHMS231299 Griesemer A, Widmann W, Forde KA, Hardy MA.  John Jones, MD.  Pioneer, Patriot and Founder of American Surgery.  World J Surg. 2010 Apr;34(4):605-9. PMID: 20012608 PMCID: PMC2860285 IshikawaY, Hirakata A, Griesemer A, Etter J, Moran S, Weiner J, Shimizu A, Yamada K.  Tolerance and long-lasting peripheral