Zorn Lab

Location and Contact Information

650 West 168th Street, 15th Floor
New York, NY 10032
United States

Principal Investigator

The Zorn Lab's primary research interest is on B cell immunity from B cell ontogeny to the development of antibody response in health and disease. An important area of focus is the study of "innate" B cells, also named B1 B cells in mice. These understudied cells are thought to constitute either a separate lineage of B cells or at least a separate subset with distinct properties. Innate B cells are mostly known for the secretion of "natural" antibodies with a polyreactive profile. We have accumulated solid evidence implicating these cells in various pathological situations.


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.


Lab Members

  • Poulomi Roy, BSc

    • Clinical Research Coordinator
  • Talita Ferreira Marques Aguiar, PhD

    • Postdoctoral Researcher
  • Katharina Frank

    • MD, PhD Student

Select Publications

  • Zorn E. and See SB. Antibody Responses to Minor Histocompatibility Antigens After Solid Organ Transplantation. Transplantation. 2021. 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. In press

  • 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

  • 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.

  • 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.

  • Zorn E. and See SB. Is there a role for natural antibodies in rejection following transplantation? Transplantation. 2019. 103(8):1612-1619

  • Zorn E. New insights on innate B cell immunity in transplantation. Xenotransplantation. 2018. 25(3):e12417.

  • 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. 

  • 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.

  • Zorn E. and See SB. Polyreactive natural antibodies in transplantation. Curr. Opin. Organ Transplant. 2017. 22(1):8-13

  • 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.

  • 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

  • Cordero H, Hess J, Nitschki E, Kanshin E, Roy P, Shihab R, Kalfa DM, Bacha EM, Ueberheide B, Zorn E. Antibody responses to dietary antigens are accompanied by specific plasma cells in the infant thymus. J. Allergy Clin. Immunology. In press.

  • Mashiko S, Shihab RR, See SB, Schahadat LGZ, Aguiar TFM, Roy P, Porcheray F, Zorn E. Broad responses to chemical adducts shape the natural antibody repertoire in early infancy. Science Advances. 2023; In press

  • 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. 2023. 107:1580-1592.