Researcher’s Profile

Emmanuel Zorn, PhD

Director CCTI Biobank
Body: 

Dr. Zorn is an Associate Professor of Medical Sciences at Columbia University Medical Center in New York City. Dr. Zorn received a Ph.D. in tumor immunology from Paris University in 1999 for his studies on melanoma antigens targeted by tumor infiltrating T cells. He then joined Dana-Farber Cancer Institute where he studied the role of regulatory T cells in chronic graft versus host disease in humans. Dr. Zorn moved to the Transplant Center at Massachusetts General Hospital in 2006 to work on human kidney graft rejection. He then relocated to Columbia University Medical Center in 2014, where he directs a human transplantation immunology research laboratory. He is also the Director of the Columbia Center for Translational Immunology Biobank core. The primary focus of Dr. Zorn’s lab is on B cells and antibodies in mechanisms of rejection or acceptance of kidney and heart transplants.

Lab Projects

Role of B cells infiltrating heart transplants during cardiac allografts vasculopathy: B cell infiltrates are often observed in solid organ grafts during chronic and acute rejection, yet their function is still unclear. Our studies use cardiac al grafts explanted because of rejection to isolate infiltrating B cells and determine their contribution to the rejection mechanism.

Role of Natural Antibodies in solid organ graft rejection: 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 examined. We initiated a large multi-center study using samples collected from kidney transplant recipients at our institution as well as at collaborating centers in the USA, Canada and Europe to investigate the clinical significance of natural antibodies in transplant rejection. We also investigate the function of these natural antibodies in in mechanisms of acute and chronic graft rejection.  

We have recently reported the presence of antibody-secreting plasma cells in the human thymus. These cells accumulate with age in the thymic perivascular space and include clones with specificity to common viruses. Ongoing studies in our lab are investigating the role of these plasma cells in anti-viral protection as well as T cell negative selection.

Research Statement: 

Dr. Zorn’s laboratory investigates host-graft interactions following solid organ transplantation in humans with a primary focus on B cells and antibodies in mechanisms of rejection of heart and kidney transplants.

Role of B cells infiltrating heart transplants during cardiac allografts vasculopathy: B cell infiltrates are often observed in solid organ grafts during chronic and acute rejection, yet their function is still unclear. Our studies use cardiac allografts explanted because of rejection to isolate infiltrating B cells and determine their contribution to the rejection mechanism.

Mechanisms of chronic antibody mediated rejection of kidney allografts: Chronic humoral rejection (CHR) is one of the leading causes of late graft loss. The etiology of CHR is currently unknown. Our multicenter study uses samples collected from kidney transplant recipients at our institution as well as at collaborating centers in the USA and Europe to identify immune markers associated with CHR and piece together the causal chain leading to this complication.

Role of Natural Antibodies in host responses to solid organ grafts: 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 examined. In our studies we investigate the function of these natural antibodies in acute and chronic rejection as well as in mechanisms of ischemia reperfusion injury.

Lab Members: 
Sarah See, Ph.D., Post-doctoral research fellow
Debanjana Chatterjee, Ph.D., Post-doctoral research fellow
Kun Zhang, M.D., Post-doctoral research fellow
April Myung, Research Technician
Publications: 

Recent publications:

1.       Porcheray, F., Wong, W., Saidman, S.L., DeVito, J., Girouard, T.C., Chittenden, M., Shaffer, J., Tolkoff-Rubin, N., Bimalangshu, D.R., Spitzer, T.R., Colvin, R.B., Cosimi, A.B., Kawai, T., Sachs, D.H., Sykes, M., and Zorn, E. B cell immunity in the context of T cell tolerance after combined kidney and bone marrow transplantation in humans. American J. Transplant, 2009; 9:2126-35. PMCID: PMC2837587

2.       Wong, W., Lee, R.A., Saidman, S.L., Smith, R.N. and Zorn, E. Bortezomib in kidney transplant recipients with antibody mediated rejection: three case reports. Clin Transpl, 2009: 401-5. PMID: 20524305.

3.       Porcheray, F., DeVito, J., Yeap, B.Y., Xue, L., Dargon, I., Paine, R., Girouard, T.C., Saidman, S.L., Colvin, R.B., Wong, W. and Zorn, E. Chronic humoral rejection of human kidney allografts associates with broad autoantibody responses. Transplantation, 2010; 89:1239-46. PMCID: PMC3744373

4.       Wong, W., DeVito, J., Nguyen, H., Sarracino, D., Porcheray, F., Dargon, I., Pelle, P.D., Collins, A.B., Tolkoff-Rubin, N., Smith, R.N., Colvin, R.B. and Zorn, E. Chronic humoral rejection of human kidney allografts is associated with MMP-2 accumulation in podocytes and its release in the urine. American J. Transplant, 2010; 10:2463-71. PMCID: PMC3805271.

5.       Porcheray, F., Miklos, D., Floyd, B.H., Sarantopoulos, S., Bellucci, R., Soiffer, R.J., Antin, J.H., Alyea, E.P., Ritz, J. and Zorn, E. Combined CD4 T cell and antibody response to human histocompatibility antigen DBY after allogeneic stem cell transplantation. Transplantation, 2011; 92: 359-65. PMCID: PMC3263512

6.       Porcheray, F., DeVito, J., Helou, Y., Dargon, I., Fraser, J.W., Nobecourt, P., Ferdman, J., Germana, S., Girouard, T.C., Kawai, T., Saidman, S.L., Wong, W., Colvin, R.B., Leguern, C., and Zorn, E.Expansion of polyreactive B cells cross-reactive to HLA and self in the blood of a patient with kidney graft rejection. American J. Transplant, 2012; 12:2088-97. PMCID: PMC3402627.

7.       Porcheray, F, Fraser JW, Gao B, McColl A, DeVito J, Dargon I, Helu Y, Wong W, Girouard TC, Saidman SL, Colvin RB, Palmisano A, Maggiore U, Vaglio A, Smith RN and Zorn E. Polyreactive Antibodies Developing Amidst Humoral Rejection of Human Kidney Grafts Bind Apoptotic Cells and Activate Complement. American J. Transplant. 2013. 10: 2590-600. PMCID: PMC3864117.

8.       Mengel M., Chong A., Rothstein D.M., Zorn E. and Maltzman J.S. AST Cutting Edge of Transplantation 2013 Meeting report: A comprehensive look at B cells and antibodies in transplantation. American J. Transplant. 2014. 3: 524-530. PMCID: PMC4046165

9.       Kawai T., Sachs D.H., Sprangers B., Sptizer T.R., Saidman S.L., Zorn E., Tolkoff-Rubin N., Preffer F., Crisalli K., Gao B., Wong W., Morri H., LoCscio S.A., Sayer P., Shonts B., Williams W.W., Smith R.N., Colvin R.B., Sykes M. and Cosimi A.B. Long-Term Results in Recipients of Combined HLA mismatched Kidney and Bone Marrow Transplantation Without Maintenance Immunosuppression. American J. Transplant. 2014; 14: 1599-611. PMID: 24903438.

10.   Ferdman J., Porcheray F., Gao B., Moore C., DeVito J., Dougherty S., Thomas M.V., Farkash., Elias N., Kawai T., Malek S.K., Tullius S.G., Wong W. and Zorn E. Expansion and somatic hypermutation of B cell clones in rejected human kidney grafts. Transplantation. 2014; 98:766-72. PMID: 24825521

11.    Gao B., Moore C, Porcheray F., Rong C., Abidoglu A., DeVito J., Paine R., Girouard T.C., Saidman S.L., Schoenfeld D., Levin B., Wong W., Elias N., Schuetz C., Rosales I.A., Fu Y and Zorn E. Pre-Transplant IgG Reactivity to Apoptotic Cells Correlates with Late kidney Allograft Loss. American J.