Xunrong Luo, MD, PhD, deals with rejection a little differently than most. For the associate professor in medicine-nephrology, microbiology-immunology and surgery-organ transplantation, it functions as the beginning, not the end, of her scientific approach.
“Understanding mechanisms of rejection, and how to coax the host’s immune system to not reject the transplanted organ or tissue will allow complete avoidance of immunosuppression drugs,” Luo said.
Luo’s research is focused on using donor pancreas organs for islet cell transplantation. The process, an experimental approach to treating type 1 diabetes, involves the cluster of cells in the pancreas that produce insulin. The transplanted cells can then regulate levels of glucose in the blood.
It’s a process Luo, the medical director of the Human Islet Cell Transplantation Programs at Northwestern Memorial Hospital, feels is likely to become standard practice in the near future at centers where processing human islets has been standardized and shown to be highly successful, as is the case here.
“The next set of challenges comes from the need to avoid immunosuppression drugs, hence the need for tolerance strategies, and the need to expand donor sources,” she said.
Luo, who left Beijing in 1991, received MD and PhD degrees from Duke University and completed her clinical medicine residency and transplant nephrology fellowship training at New York-Presbyterian Hospital Weill Medical College in 2005. She started at Feinberg in July 2005.
Having grown up in Shanghai, Luo attended Tsinghua University in Beijing, before leaving China as part of the approximately 20 percent of Chinese graduates who seek higher education abroad. She said that trend was further fueled at the time by the government’s crackdown on student demonstrations in 1989 at Tiananmen Square.
What are your research interests?
Our primary research interest is transplant immune tolerance. In organ and tissue transplantation, the immune responses in the recipient are those of a pro-inflammatory nature with the ultimate goal of rejecting the “non-self.” Consequently, transplant recipients are required to take immunosuppression medications for the rest of their lives in order to suppress such rejection responses. However, lifelong immunosuppression weakens the immune system and predisposes patients to a multitude of medical problems, some of which are life-threatening, such as cancers and opportunistic infections. Therefore, understanding mechanisms of rejection, and how to “coax” the host’s immune system to not reject the transplanted organ or tissue, will allow complete avoidance of immunosuppression and its myriad side effects.
What is the ultimate goal of your research?
Using our innovative tolerance strategies, we have successfully induced transplant tolerance in animal models of allogeneic islet cell, heart, skin, and xenogeneic islet cell transplantation. Our ultimate goal is to identify highly efficient and safe tolerance strategies for testing in human organ (kidney, liver, and heart) and tissue (islet cell, and composite tissue) transplantation recipients for tolerance induction and maintenance.
What types of collaborations are you engaged in?
Across campus, we collaborate with experts in the immunobiology of inflammation, like Stephen Miller, PhD, professor in microbiology-immunology and dermatology; Lonnie Shea, PhD, professor in chemical and biological engineering, William Lowe, MD, professor in medicine-endocrinology; Joseph Leventhal, MD, professor in surgery-organ transplantation; and Anat Roitberg-Tambur, DMD, PhD, research professor in surgery-organ transplantation. Beyond campus, we collaborate with researchers Dr. Bernhard Hering at the University of Minnesota, and Drs. Dixon Kaufman and Luis Fernandez at the University of Wisconsin, all of whom have expertise in large animal models. Each collaborator harbors unique expertise that helps us test new strategies, materials, and models with the ultimate goal of transplanting our research findings to human patients receiving transplantation.
How did you become interested in this area of research?
My interest in this area of research is inspired by the desire to know the unknown. As a student of biology almost 20 years ago at the top university in China, I spent more time studying and understanding the subject of immunology than on seemingly more challenging subjects like biophysics and organic chemistry. It was through the intense learning of this subject that I realized the vast unknowns. Through my medical training, I saw opportunities in the field of transplantation where significant advances in the field of immunology could translate into enormous benefits to our transplant patient population. Advances include increasing their probability of receiving transplantation, decreasing their wait time before receiving transplantation, and improving their quality of life after transplantation.
How is your research funded?
Our current research is largely funded by the National Institutes of Health (NIH) and the Juvenile Diabetes Research Foundation.
Who makes up your team and what role does each individual play in your research?
Our current research team is made up of three post-doctoral fellows and one research technologist. Each post-doctoral fellow focuses on organ/tissue specific rejection and tolerance mechanisms unique to islets (allogeneic and xenogeneic), in heart and kidney transplantation. The research technologist provides support to the entire team in areas such as tissue histology, animal husbandry, cell genotyping, and phenotyping. In addition to our basic science research team, the lab is also the home for the Human Islet Isolation Team. This team is made up of four standing members, including research associates and a research technologist. The primary task of this team is to process the human pancreas from a deceased donor under good manufacturing practices for clinical human islet transplantation at Northwestern Memorial Hospital. Human islet transplantation is currently being performed at Northwestern Memorial Hospital on a clinical trial basis funded by the NIH.
Where have you recently published papers?
Our recent papers have been published in: Proceedings of the National Academy of Sciences; Immunity; the Journal of Experimental Medicine; the Journal of Immunology; the American Journal of Transplantation; Biomaterials; Diabetologia; and Transplantation.