Faculty active in this area of research are listed below. For a brief description of their research interests, click on their name in the list. Clicking on the name at the beginning of the brief description links to their detailed personal website.

R. Pat Bucy, MD, PhD, Department of Pathology
James F. George, PhD, Department of Surgery
Judith A. Kapp, PhD, Department of Ophthalmology
Jayme E. Locke, MD, MPH, FACS, FAST, Director, UAB Comprehensive Transplant Institute
Paige M. Porrett, MD, Department of Surgery

R. Pat Bucy, MD, PhD I am interested in the regulation of immune responses by T cells, particularly the forms of regulation that develop in vivo in situations with chronic antigen presence. Conventional experimental systems have used model antigens given in discreet inoculations so that the clearance of antigen is the dominant overall control mechanism. In physiological situations such as solid organ transplantation, chronic viral diseases, and organ specific autoimmune diseases, antigen is usually not cleared, but the immune system develops various control mechanisms that limit immune damage. In addition to my role as the Director of the UAB Medical Scientist Training Program (joint MD/PhD training), my lab is engaged in a wide range of projects with a translational focus, that span the gamut of basic mechanistic studies in mice to active design of human clinical trials. Active current projects include use of TCR transgenic mice to study murine heart transplant tolerance, analysis of T cell population dynamics in response to various forms of immunization, studies of viral and cellular dynamics in SHIV infected Rhesus Macaques, and a substantial series of studies focused on therapeutic immunization of HIV infected people and assessment of changes in immune function in these people. In all of these systems, multiple techniques are used including flow cytometry, immunohistochemistry, cell culture techniques, production of novel transgenic mice, real-time RT-PCR,. and in situ hybridization analysis of viral and cellular RNA species.

James F. George, PhD Dr. George’s research focuses on the mechanisms of transplantation tolerance induction and immunologic mechanisms of vascular disease in solid organ transplant patients. He and his colleagues perform clinical studies using patient data as well as basic molecular studies using a mouse heart and kidney transplantation models. They study the role of T cell mediated innate immune responses in the development of intimal proliferative lesions of the type that are typically found in over 30% of heart transplantation patients after the first three years post-transplantation. They use induced mutant mice to study the role of Interferon-g and other cytokines in the initiation and progression of vascular lesions. Other interests include the mechanisms by which extracorporeal photopheresis results in downregulation of anti-donor responses in vivo, both in animal models and clinical heart transplant patients.

Judith A. Kapp, PhD Dr. Kapp's research focuses on identifying mechanisms of inducing and abrogating immunological tolerance. Our long-term goal is to translate our findings into novel therapies for preventing graft rejection and augmenting tumor immunity.

A long-term goal is to use knowledge gained from tumor studies and the induction of tolerance to develop methods to prolong graft survival. We have studied two transplantation models. This first involves transplantation of retinal pigment epithelial (RPE) cells as a treatment for age-related macular degeneration (AMD), which is the leading cause of blindness in people over the age of 65 in this country. This disease ultimately results from the loss of light sensing (photoreceptor) cells. However, the loss of photoreceptor cells is preceded by loss of the underlying RPE. Replacement of dead or damaged cells with healthy retinal cells is a very promising approach to the treatment of this, and other, retinal diseases that we are investigating. Although the eye is an immunologically privileged site, we have shown that retinal pigment epithelial cells transplanted into the subretinal space of allogeneic mice are rejected within 4 weeks, whereas they are not rejected in syngeneic mice or immunodeficient Rag-1 knockout allogeneic mice (Kapp, J.A., J. Wen, H.P.Langston, and B.C. Barron in preparation). Our goal is to develop methods to prevent rejection by inducing tolerance. To this end, we have produced transgenic mice expressing OVA in the retinal cells, which will be transplanted into syngeneic mice that have been adoptively transferred with OVA-specific TCR transgenic T cells to track specific cellular interactions in vivo. Experiments are currently underway to determine whether RPE expressing OVA are rejected by OVA-specific T cells and whether rejection can be abrogated by induction of tolerance to OVA. We have developed a novel method to track antigen-presenting dendritic cells (Sanjay G., A. Oran, C. A. Maris, J. Wajchman, S. Sasaki, J.A. Kapp, and J. Jacob. Nat. Immunol.. 4:907-912, 2003), which will be used to determine which APC in the eye induce tolerance.

The second transplant model is for the treatment of insulin dependent diabetes mellitus (IDDM). Because human islets are scarce, th laboratory has studied porcine islet xenograft rejection in spontaneously diabetic NOD mice. Islet microencapsulation plus treatment with immunomodulatory agents (CTLA4Ig, MR1 and/or GK1.5) have been shown to prolong graft function significantly but not prevent rejection (Safley, S.A., J.A. Kapp, and C.J. Weber. Cell Transplant. 11:695-705, 2002). The group is clarifying the mechanisms responsible for enhanced survival and identifying the causes of xenograft failure in this system. Because continuous immunosuppressive therapy is currently required to overcome the autoimmune and transplantation barriers of islet recipients, we have begun exploring the delivery of a modified insulin gene to autologous cells as an alternative transplantation strategy. The development an insulin expression construct, which is transcriptionally up-regulated by glucose and down-regulated by insulin in hepatocytes, serves as the basis for this approach. The insulin gene will be delivered by viral vectors to test the hypothesis that autologous non-islet cells, engineered to express insulin, can circumvent both the autoimmune and graft rejection problems of islet transplantation thereby reducing the need for immunosuppressive drugs.

Jayme E. Locke, MD, MPH, FACS, FAST I am currently in my 8th year as a transplant surgeon at the University of Alabama at Birmingham (UAB), where I am a tenured Professor of Surgery, Director of Transplant Outcomes Research Center (ORC), Director of Transplant Analytics, Informatics & Quality, Chief of the Division of Abdominal Transplantation, and Director of the Comprehensive Transplant Institute (CTI). In addition to my surgical training, I have formal training in biostatistics, epidemiology, and clinical investigation. This multidisciplinary training allows me to identify relevant problems from my clinical practice and apply advanced mathematical techniques to solve them, and I have had several years of experience using mathematical models derived from national registry data to guide policy and clinical decision making. I am the founder and director of the ORC, a multidisciplinary collaboration between the School of Medicine (Transplant Surgery and Medicine), the School of Public Health (Epidemiology and Health Services), UAB Center For AIDS Research (CFAR), UAB Minority Health & Health Disparities Research Center (MHRC), UAB Nephrology Research Training Center, UAB Nutrition and Obesity Research Center (NORC), as well as, Johns Hopkins University, Vanderbilt University, The University of Pennsylvania, the Scientific Registry of Transplant Recipients (SRTR), and the European Consortium. The ORC now employs 3 full-time master’s level and 4 full-time Ph.D. level biostatisticians/epidemiologists and collaborates with more than 30 investigators across UAB and in the broader national academic community. Since its inception, I have acquired and currently maintain data from multiple national registries and longitudinal cohort studies including SRTR, United Network for Organ Sharing (UNOS), CMS claims data (including IMS pharmacy claims), United States Renal Data System, Coronary Artery Risk Development in Young Adults (CARDIA), Atherosclerotic Risk in Communities (ARIC), National Health and Nutrition Examination Survey (NHANES), North American AIDS Cohort Collaboration on Research and Design. These data are stored on a secure and redundant computing cluster (SAS, STATA, and R capable) that can be remotely accessed by investigators within the CTI.

Paige Porrett, MD   Dr. Porrett is a transplant immunologist and surgeon who became interested in the intersection between reproductive and transplant immunology some years ago while caring for women who could not gain access to transplantation because of pregnancy sensitization. In her first faculty years at the University of Pennsylvania, she became fascinated by the immunologic paradox of pregnancy and wanted to understand how the maternal immune system could tolerate paternal alloantigens expressed by the fetus yet also develop antibody responses that were unlikely to be driven by “tolerant” maternal T cells. She thus committed her bench laboratory efforts to the study of maternal immune responses to the fetus. In her initial work, she learned in a mouse model of pregnancy and transplantation that maternal fetal-specific CD8 T cells differentiate into a long-lived dysfunctional population that adopts the phenotypic and transcriptomic characteristics of T cell exhaustion. More recently, her group has expanded its investigations to include maternal macrophages and uterine NK cell populations at the maternal fetal interface. While the group uses mouse models for many of these studies, they are leveraging their unique access to human uterus transplant recipients to understand the origins of these immune populations in the human. They expect significant expansion in this domain as they are currently building what is projected to be the largest uterus transplant program in the United States at UAB. Finally, they have invested significant effort into using another unique resource at UAB – the Donor Recovery Center – to answer a variety of immunologic questions in organ transplantation. This resource will allow Dr. Porrett to longitudinally study immune responses in transplanted organs across the entirety of the transplant episode (i.e. from donor to recipient over time) and help improve our understanding of the molecular mechanisms underlying ischemia-reperfusion injury and organ recovery. This is a critical area of development given the significant organ shortage and pressing need to maximize the number of organs transplanted and optimize their outcomes.