Researcher’s Profile

Adam D. Griesemer, MD

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, PhD Candidate
Sulemon Chaudry, MD, Former Lab Member
Jeffery Stern, MD, Former Lab Member
Joshua Weiner, MD, Former Lab Member
Karl Erik Berglund, MD, Postdoctoral Research Fellow
Nathaly Llore, MD, Postdoctoral Research Fellow
Publications: 
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,