Explore Research Innovation at the David Geffen School of Medicine
Elaine Reed, PhDDirector, UCLA Immunogenetics Center
Professor, Department of Pathology & Laboratory Medicine, David Geffen School of Medicine at UCLA
Dr. Elaine Reed redirected the path of transplant rejection research when she established that chronic rejection results from an antibody-mediated immune response—not the cell-mediated immune response most researchers were studying.
Faced with chronic rejection, patients must receive a new organ or return to dialysis. In some cases, chronic rejection leads to death.
Dr. Reed hopes for a future where patients have functional transplants for life. She is working toward that future by trying to stop the humoral rejection pathway at its origin.
After a transplantation, patient antibodies sometimes attack the mismatched human leukocyte antigens (HLA) of the donor organ. Once the attack begins, it is nearly impossible to turn off with drug-based treatments. That's why Dr. Reed's lab wants to stop immune initiation at its most proximate point.
"By targeting these interactions most proximately, at the top of the pyramid, we can block all the negative downstream events triggered by the early immune response," says Dr. Reed.
By studying antibody-mediated immune responses in vitro, in animal models, and in human tissue, Dr. Reed’s team has defined several critical mechanisms of chronic rejection.
Discovery: An antibody-mediated response is focused in the endothelium.
Antibodies activate the endothelia and cause alterations in their function. Once endothelia become dysfunctional, the transplant can experience inflammation and chronic injury. Read more in Induction of High Affinity Fibroblast Growth Factor Receptor Expression and Proliferation in Human Endothelial Cells by Anti-HLA Antibodies: A Possible Mechanism for Transplant Atherosclerosis, published in the Journal of Immunology.
Implication: Knowing the immune activation point, the team could better focus their studies and achieve the next big breakthrough.
Discovery: A specific molecular partnership triggers an immune response against a transplant.
Focusing on the endothelium, Dr. Reed and her team uncovered a signaling pathway triggered by mismatched human leukocyte antigens on the donor organ. The pathway enables endothelial cell activation and proliferation, leading to organ injury and rejection. Read more in HLA Class I Molecules Partner with Integrin β4 to Stimulate Endothelial Cell Proliferation and Migration, published in Science Signaling.
Implication: The finding gave researchers a pathway they might block to protect transplants from immune attack.
Dr. Reed and her team are testing drugs to block immune effector functions while continuing to explore additional immune initiation pathways contributing to transplant rejection.
In addition to researching ways to stop rejection, Dr. Reed is also developing ways to better diagnose and treat the chronic rejection we cannot stop.
Dr. Reed patented a biomarker panel that allows physicians to determine if a patient is suffering from rejection without taking biopsies, which can be painful, costly, and sometimes deadly. If commercialized, the panel could soon be available to facilities everywhere. Read more in Phosphorylated S6 Kinase and S6 Ribosomal Protein are Diagnostic Markers of Antibody-Mediated Rejection in Heart Allografts, published in Journal of Heart and Lung Transplantation.
Dr. Reed is also on a research team using precision medicine techniques to study cytomegalovirus (CMV), a common herpes virus that can damage transplants and devastate immunocompromised patients. Backed by $8 million from the National Institute of Allergy and Infectious Diseases, the team plans to map the molecular processes of CMV infection to better assess patient risks and develop optimal treatments.
Dr. Reed believes we can improve patient health by constantly testing novel interventions to tame the most damaging aspects of transplant rejection. That doesn’t stop her from dreaming of a future without rejection.
"Imagine telling a child transplant recipient that she'll have her new organ for a lifetime. That would be the most important thing we could do in transplant," says Dr. Reed.
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UCLA Pathology & Laboratory Medicine