Zorn Lab

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. 

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.

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.

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.