Emmanuel Zorn, PhD
- Professor of Medical Sciences (in Medicine)
- Professor of Medical Sciences (in Medicine)
- Director CCTI Biobank and Specimen Processing Core
Credentials & Experience
Education & Training
- PhD, 1999 Immunology, University of Paris, France
Dr. Zorn’s primary research is on B cell immunity with a focus on innate-like B cells and natural antibodies. His lab investigates the development of B cell immunity in human neonates, its evolution across the lifespan and its contribution to different pathological situations such as transplant rejection, autoimmunity and cancer.
B Cell Immunity and Human Transplant Rejection
B cell and plasma cell infiltrates are often observed in solid organ grafts during chronic rejection, yet their function is still unclear. Dr. Zorn’s studies use human cardiac allograft specimens to isolate infiltrating B cells and plasma cells and determine their contribution to the rejection mechanism.
Natural antibodies are broadly reactive serum immunoglobulins implicated in apoptotic cell clearance. Their contribution to inflammatory reactions associated with graft tissue destruction has not been thoroughly examined. Dr. Zorn’s lab is conducting large multi-center studies using samples collected from kidney transplant recipients enrolled at Columbia University as well as at collaborating centers in the USA, Canada and Europe to investigate the clinical significance of natural antibodies in transplant rejection. These studies also examine the function of natural antibodies in mechanisms of chronic graft rejection.
Significance of Plasma Cells in the Human Thymus
In previous studies, using thymus specimens collected from infants to adults, Dr. Zorn’s lab observed the age-dependent recruitment of differentiated antibody-producing plasma cells in the thymic perivascular space. This research also demonstrated that thymic plasma cells included clones specific to common viruses, which likely resulted from past immunizations. In more recent studies, his lab observed the accumulation of plasma cells specific to common dietary antigens present in cow’s milk in the thymus of young children concomitantly with the development of serum antibodies to the same antigens. The significance of these cells in mechanisms of tolerance, especially toward food antigens is now being examined.
Development of Humoral Immunity in Human Newborns
Humans are born with natural antibodies conferring protective innate immunity against endemic pathogens. The source of these natural antibodies is still largely unknown. Ongoing studies in Dr. Zorn’s lab have uncovered the differentiation of B cells into natural antibody-producing cells in the newborn thymus. Remarkably, ~7% of these antibodies cross-reacted to common pathogenic bacterial species such as Staphylococcus aureus or Haemophilus influenzae. Dr. Zorn’s group is now evaluating the functional properties and therapeutic value of these “innate” antibodies.
Antibody Responses to Adducts
Adducts are chemical groups appended to macromolecules through enzymatic or non-enzymatic reactions. An example of adducts are chemical moieties covalently linked to amino acids through post-translational modifications such as phosphorylation, ubiquitination, methylation and citrullination. Adducts are also found on DNA, RNA and lipids. The immunogenicity of adducts has been reported in some diseases . For instance, antibodies to citrullinated proteins are immune markers of rheumatoid arthritis. Yet, the global humoral response to adduct has not been studied. To address this question Dr. Zorn’s lab designed a panel of 93 most common adducts. His team began assessing the baseline repertoire of antibodies reactive to these adducts in healthy donors across lifespan. Further, in collaboration with members of the Herbert Irving Cancer Center, Dr. Zorn started to investigate whether the serological anti-adduct repertoire is perturbed in certain cancer patients as a response to modified proteins and macromolecules in the tumor cells. A first series of experiments revealed distinct serological profiles to adducts in the context of non-small cell lung cancer as well as pancreatic ductal adenocarcinoma.
- See SB, Yang X, Burger C, Lamarthée B, Snanoudj R, Shihab R, Tsapepas DS, Roy P, Larivière-Beaudoin S, Hamelin K, Mendoza Rojas A, van Besouw NM, Bartosic A, Daniel N, Vasilescu ER, Mohan S, Cohen D, Ratner L, Baan CC, Bromberg JS, Cardinal H, Anglicheau D, Sun Y, Zorn E. Natural antibodies are associated with rejection and long-term renal allograft loss in a multi-center international cohort. Transplantation. 2022; In press
- Mantell BS, Cordero H, See SB, Clerkin KJ, Vasilescu R, Marboe CC, Naka Y, Restaino S, Colombo PC, Addonizio LJ, Farr MA, Zorn E. Transcriptomic heterogeneity of antibody mediated rejection after heart transplant with or without donor specific antibodies.J Heart Lung Transplant. 2021. 40(11): 1472-1480.
- Cordero H, King RG, Dogra P, Dufeu C, See SB, Chong AM, Uhlemann AC, Ho SH, Kalfa DM, Bacha EA, Kearney JF, Zorn E. Intrathymic differentiation of natural antibody-producing plasma cells in human neonates. Nature Communications. 2021. 12: 5761
- Melms JC, Biermann J, Huang H, Wang Y, Nair A, Tagore S, Katsyv I, Rendeiro AF, Amin AD, Schapiro D, Frangieh CJ, Luoma AM, Filliol A, Fang Y, Ravichandran H, Clausi MG, Alba GA, Rogava M,. Chen SW, Ho P, Montoro D, Guo X, Kornberg AE, Han AS, Bakhoum M, Anandasabapathy N, Suarez-Farinas M, Bakhoum SF, Lefkowitch JH, Marboe C, Lagana SM, Del Portillo A, Zorn E, Markowitz GS, Schwabe RF, Schwartz RE, Elemento O, Saqi A, Hibshoosh H, Que J, Izar B. A single-cell lung atlas of lethal COVID-19. Nature2021. 595:114-119.
- Yun TJ, Igarashi S, Zhao H, Perez OA, Pereira MR, Zorn E, Shen Y, Goodrum F, Rahman A, Sims PA, Farber DL and Reizis B. Human plasmacytoid dendritic cells mount a distinct antiviral response to virus-infected cells. Science Immunology. 2021. Apr 2; 6(58)
- Habal MV, Miller AM, Rao S, Lin S, Obradovic A, Khosravi-Maharlooei M, See SB, Roy P, Shihab R, Ho SH, Marboe C, Naka Y, Takeda K, Restaino S, Han A, Mancini D, Givertz M, Madsen JC, Sykes M, Addonizio L, Zorn E. T cell repertoire analysis suggest a prominent bystander response in human cardiac allograft vasculopathy. American J. Transplant. 2020. 21: 1465-1476.
- Hidalgo Y, Nuñez S, Fuenzalida MJ, Flores-Santibáñez F, PJ Saez, Dorner J, Lennon-Dumenil AM, Martínez V, Zorn E, Rosemblatt M, Sauma D, Bono MR. Thymic B cells promote germinal center-like structures and the expansion of follicular helper T cells in lupus-prone mice. Frontiers in Immunology. 2020. 11:696
- See SB, Mantell BS, Clerkin KJ, Ray B, Vasilescu ER, Marboe CC, Naka Y, Restaino S, Colombo PC, Addonizio LJ, Farr MA, Zorn E. Profiling non-HLA antibody responses in antibody-mediated rejection following heart transplantation. American J. Transplant. 2020. 20:2571-2580.
- Moore C, Gao B, Roskin KM, Vasilescu R, Addonizio L, Givertz MM, Madsen JC, Zorn E. B cell clonal expansion within immune infiltrates in human cardiac allograft vasculopathy. American J. Transplant. 2020. 20:1431-1438.
- Delville M, Lamarthée B, Pagie S, See SB, Rabant M, Burger C, Gatault P, Giral M, Thaunat O, Arzouk N, Hertig A, Hazzan M, Matignon M, Mariat C, Caillard S, Kamar N, Sayegh J, Westeel PF, Garrouste C, Ladrière M, Vuiblet V, Rivalan J, Merville P, Bertrand D, Le Moine A, Van Huyen JPD, Cesbron A, Cagnard N, Alibeu O, Satchell SC, Legendre C, Zorn E, Taupin JL, Charreau B, Anglicheau D. Early acute microvascular kidney transplant rejection in the absence of anti-HLA antibodies is associated with performed IgG antibodies against diverse glomerular endothelial cell antigens. J. Am. Soc. Nephrol. 2019. 30: 692-709.
- See SB Aubert O, Loupy A, Veras Y, Lebreton X, Gao B, Legendre C, Anglicheau D, Zorn E. Post-Transplant Natural Antibodies Associate with Kidney Allograft Injury and Reduced Long-Term Survival. J. Am. Soc. Nephrol. 2018. 29: 1761-1770.
- Chatterjee D, Moore, C, Gao B, Clerkin KJ, See SB, Shaked D, Rogers K, Nunez S, Veras Y, Addonizio L, Givertz MM, Naka Y, Mancini D, Vasilescu R, Marboe C, Restaino S, Madsen JC, Zorn E. Prevalence of polyreactive innate clones among graft infiltrating B cells in human cardiac allograft vasculopathy. J Heart Lung Transplant. 2018. 37(3):385-393.
- Kennel PJ, Saha A, Maldonado DA, Givens R, Brunjes DL, Castillero E, Zhang X, Ji R, Yahi A, George I, Mancini DM, Koller A, Fine B, Zorn E, Colombo PC, Tatonetti N, Chen EI, Schulze P. Serum exosomal protein profiling for the non-invasive detection of cardiac allograft rejection. C. J Heart Lung Transplant. 2018. 37(3):409-417.
- Clerkin KJ, See SB, Farr MA, Restaino SW, Serban G, Farhana Latif F, Li L, Colombo PC, Vlad G, Ray Bryan, Vasilescu ER and Zorn E. Comparative assessment of anti-HLA antibodies using 2 commercially available Luminex-based assays. Transplantation Direct. 2017. Oct 2;3(11):e218.
- Gao B, Gu Y, Rong C, Moore C, Porcheray F, Wong W, Preffer F, Saidman SL, Fu Y, Cosimi AB, Sachs DH, Kawai T, Sykes M, Zorn E. Dynamics of B cell recovery following kidney/bone marrow transplant recipients. Transplantation. 2017; 101: 2722-2730.
- See SB, Clerkin KJ, Kennel PJ, Zhang F, Weber MP, Rogers K, Chatterjee D, Vasilescu ER, Vlad G, Naka Y, Restaino S, Farr M, Topkara VK, Colombo PC, Mancini DM, Schulze PC, Levin B, Zorn E. Ventricular assist device elicits serum natural IgG that correlate with the development of primary graft dysfunction following heart transplantation. J Heart Lung Transplant. 2017. 36: 862-870.
- Sprangers B, DeWolf S, Savage T, Morokata T, Obradovic A, LoCascio S, Shonts B, Zuber J, Lau SP, Shah R, Morris H, Steshenko V, Zorn E, Preffer F, Olek S, Dombkowski D, Turka L, Colvin R, Winchester R, Kawai T, Sykes M. Origin of enriched regulatory T cells in patients receiving combined kidney/bone marrow transplantation to induce transplantation tolerance. American J. Transplant. 2017. 17: 2020-2032.
- Clerkin KJ, Farr MA, Restaino SW, Zorn E, Latif F, Vasilescu ER, Marboe CC, Colombo PC, Mancini DM. Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation. J Heart Lung Transplant. 2017. 35(5):540-545.
- Nuñez S, Moore C, Gao B, Rogers K, Hidalgo Y, del Nido P, Restaino S, Naka Y, Bhagat G, Madsen JC, Bono MR and Zorn E. The human thymus perivascular space is a functional niche for viral-specific plasma cells. Science Immunology. 2016. Dec; 1(6) eaah4447