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TTS Education Committee’s Precision Medicine Webinar Series

The pre-recorded series, applies current perspectives on precision medicine and the role of translational research and scientists/physician’s engagement to the field of transplantation, illustrating how these approaches have led to significant advancements in the field. It provides further justification for deliberate, targeted efforts to cross-in translational transplant research.

Each month a new webinar will be released. TTS members are invited to submit comments and questions about each webinar for two weeks after the video is released on the site. The questions will be sent to the speaker and moderator to respond and we will post the responses.

Organizers:

Medhat Askar, MD, PhD, MSHPE, FRCPath, D(ABHI), D(ABMLI), HCLD(ABB)

Director, Transplant Immunology
Assistant Director, Cell Processing Lab
Baylor University Medical Center
Professor, Department of Pathology and Laboratory Medicine,
Texas A&M Health Science Center College of Medicine
President, The American Board of Histocompatibility and Immunogenetics (ABHI)
President-Elect, The American Society for Histocompatibility and Immunogenetics (ASHI)
Member of Board of Directors, United Network for Organ Sharing (UNOS)
Councilor (North America), The Transplantation Society (TTS)
Co-Chair, TTS Education Committee

Valeria Mas, M.S., Ph.D., FAST

Endowed Professor of Transplant Research
Professor of Surgery
Professor of Genetics, Genomics, and Informatics
Director, Transplant Research Institute
Methodist University Transplant Institute
University of Tennessee Health Science Center

Bruce Kaplan and Mark Stegall
Moderated by Medhat Askar

Principals of evidence based medicine as it applies to biomarkers and clinical trial design

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Bruce Kaplan's Bio:

Bruce Kaplan, MD is Vice President at Baylor Scott and White. Before coming to Baylor Scott and White, Dr. Kaplan held the Kathy and Harry Jentsch Chair at the University of Arizona. Prior to that, Dr. Kaplan was awarded the highest achievement at the University of Florida and given the rare honor of Eminent Scholar in kidney research for his work on pharmacology and immunology as it relates to kidney failure. He was also awarded the Harvard University Visiting Lectureship in 2005.

Dr. Kaplan received his Medical Degree from the College of Physicians and Surgeons at Columbia University in New York, New York.

Dr. Kaplan’s research interests include kidney transplantation, complex systems and immune pharmacology, he is internationally recognized in immunosuppressive pharmacology and outcomes in transplantation. Dr. Kaplan has published more than 300 peer-reviewed papers (some of the most cited in the field), 30 book chapters and is author of a new textbook on Immunopharmacology.

His articles have been published in various journals, including American Journal of Transplantation, Transplantation, Nature, Clinical Pharmacology and Therapeutics and Journal of Clinical Investigation. Dr. Kaplan was Deputy Editor for American Journal of Transplantation and is now Executive Editor of Transplantation.

He has mentored numerous fellows and faculty. Three of his fellows were winners of young investigator awards by the major transplant society. Six of his trainees are now Medical Directors of renal transplant at major programs.

Mark Stegall's Bio:

The major research goals of Mark D. Stegall, M.D., are to: Improve the long-term outcomes of kidney transplant recipients and develop new therapies to block the body from forming antibodies against the transplanted kidney. Dr. Stegall's research applies to all patients with kidney disease, including those with diabetes, polycystic kidney disease and high blood pressure. His basic science studies might also apply to patients with diseases of the immune system, including autoimmune disorders such as lupus. These studies apply to children and adults of all ethnic groups, but especially those with high rates of kidney disease, such as African-Americans and Native Americans. Dr. Stegall’s focus areas are: Late loss of kidney transplants. Kidney transplantation has become extremely successful over the past decade. However, the long-term survival of kidney transplants — five years and beyond — has not improved. Dr. Stegall's group has led the way in improving the understanding of late kidney transplant loss.

Using sensitive genomic techniques, Dr. Stegall's laboratory has shown that many transplanted kidneys have evidence of rejection that is not seen by conventional microscopic techniques. He and his team now believe that they can predict which kidney transplants are likely to fail, and they are developing clinical trials to determine if changes in immunosuppression can prevent failure. Antibody barriers to kidney transplantation. Many renal transplant candidates — approximately 1 in 3 — have antibodies in their bloodstream that react against kidney transplants. These antibodies can severely damage or even destroy a kidney transplant. Dr. Stegall's laboratory tries to understand how these antibodies are made and has developed novel and sophisticated methods of testing the actual cells that make antibody in humans. They also have developed several new agents that prevent the antibody formation and antibody damage.

The research of Dr. Stegall and his colleagues is significant because their two areas of focus are two of the major unsolved problems in transplantation. Improving long-term kidney graft survival would mean that patients would be less likely to need a second transplant during their lifetime and would lead healthier lives.Overcoming antibody barriers to transplantation would mean that successful kidney transplants could be provided to more people who need them. Today, many patients with antibodies never receive a transplant because they can never find a kidney against which they have no antibodies. Their lives are shortened because they remain on dialysis, and they have a very poor quality of life. Dr. Stegall's hope is that every patient with kidney disease who requires a transplant will be able to receive a successful transplant that will last his or her entire life.

Medhat Askar's Bio:

Medhat Askar, MD, PhD, MSHPE, FRCPath, D(ABHI), D(ABMLI), HCLD(ABB) is a Clinical Professor (Affiliated) in the Department of Pathology and Laboratory Medicine (affiliated) at Texas A&M Health Science Center College of Medicine and the director of the Transplant Immunology and facility director of the Cell Processing Laboratories at Baylor University Medical Center in Dallas, TX, USA. He is the President of The American Society for Histocompatibility and Immunogenetics (ASHI), the Immediate Past President of The American Board of Histocompatibility and Immunogenetics (ABHI). Dr. Askar is a Councilor (North America) and Co-Chair of the TTS Education Committee of The Transplantation Society (TTS). He is also a Member of Board of Directors of United Network for Organ Sharing (UNOS), Organ Procurement and Transplantation Network (OPTN) and a Member of The Joint Commission Pathology Technical Advisory Panel (JC-TAP).

Peter Nickerson
Moderated by Patricia Campbell

Smart Matching: Applying new concepts for improving long-term outcomes

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Peter Nickerson's Bio:

Dr. Peter Nickerson is a Distinguished Professor of Internal Medicine and Immunology and the Vice-Dean Research, Rady Faculty of Health Sciences at the University of Manitoba. He is the Medical Director of Transplant Manitoba and the Medical Advisor, Organ Donation and Transplantation Division, Canadian Blood Services (CBS).

Patricia Campbell's Bio:

Dr. Patricia Campbell is a Transplant Nephrologist and a profesor at the University of Alberta Division of Nephrology and Transplant Immunology. She is the Medical Director of Histocompatibility Laboratory at the University of Alberta Hospitals since 2002. She is the chair if the Canadian Blood services National HLA advisory Committee and the Immediate Past President of ASHI. Her main Interests are Sensitization post transplantation and Antibody mediated rejection.

Maria Kaisar and Rutger Ploeg
Moderated by Göran Klintmalm

Bridging the gap between basic and translational transplant research; the role of transplant biobanks

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Maria Kaisar's Bio:

Dr Maria Kaisar obtained her DPhil in Transplantation Science from the University of Oxford under the supervision of Prof Ploeg. Her interests lie in basic and translational research to better understand the biological mechanisms that lead to organ injury or repair. Her collaborative work, within the National Health Service Blood and Transplant and the University of Oxford, focuses on the development of novel diagnostics of donor organ quality. Her research has the potential to increase utilization of deceased donor organs and improve long term transplantation outcomes for organ recipients. She is currently the Translational Research Coordinator for the UK Consortium of Quality in Organ Donation (QUOD) and she is a Board Member of the Basic Science Committee of the European Society of Organ Transplantation (ESOT) and a member of the TTS Educational Committee.

Rutger Ploeg's Bio:

Rutger Ploeg is Professor of Transplant Biology, Director of Clinical & Translational Research and Consultant Transplant Surgeon at the Nuffield Department of Surgical Sciences, University of Oxford.He undertakes clinical, translational and experimental research in organ donation and transplantation. He focuses on mechanisms of injury and repair to enhance donor organ quality and allow regeneration after transplantation to increase allograft function and survival. Currently, he coordinates a national consortium in the UK to investigate QUality in Organ Donation (QUOD) and a European consortium to study preservation (COPE).

Göran Klintmalm's Bio:

Dr. Goran Klintmalm is chairman and chief of the Annette C. and Harold C. Simmons Transplant Institute at Baylor University Medical Center in the Dal1as, Texas. He is past President of (ASTS) American Society of Transplant Surgeons and during that presidency; he established the Business Practice Committee of ASTS and expanded the Board from six to eight Councilors. Dr. Klintmalm has been involved with UNOS since its creation. On MPSC 1992-94, Board 1994-96. ILTS – Chair Basic Science Committee; International Society of Uterus Transplant – Vice President; DHHS – Transplant Applications Reviewer; American Surgical Association –Membership Committee.

Dr. Klintmalm received his medical degree and PhD from the Karolinska Institute in Stockholm, Sweden. He did his surgical residency in Sweden, then studied transplantation as a Fellow at the University of Colorado Health Science Center, and moved to the University of Pittsburgh Medical School with Dr. Thomas Starzl. He subsequently completed a fellowship in transplantation at the Karolinska Institute in 1983 under Dr. Carl Groth and was named acting associate professor of surgery.

Dr. Klintmalm was recruited to come to Baylor in 1984 to begin a multi-organ transplant program. The program performed its first liver transplant in December 1984 and has performed over 4,300 liver transplants and over 4,600 kidney transplants to date.

From 1995 through 2010, Dr. Klintmalm directed the Dallas Liver Transplant Program in partnership with Children’s Medical Center of Dallas. In 1997, he and his transplant team performed the world’s first extracorporeal perfusion (bridge to transplant) using a genetically altered pig liver, which allowed the patient to successfully undergo liver transplantation. In 1999, he performed the first split liver transplant in North Texas and the first adult living donor transplant in Texas in 2001. He has trained 49 transplant surgery fellows.

Dr. Klintmalm is the author of more than 450 peer-reviewed and over 80 non-peer-reviewed publications, editor of 45 textbooks chapters and 250 published abstracts. Editor of five textbooks. Together with Dr. Ronald Busuttil, he published the textbook “Transplantation of the Liver,” now in its third edition, which is the standard textbook in liver transplantation worldwide. Editorial Boards / Associate Editor/Reviewer – American Journal of Gastroenterology, Annals of Surgery, American Journal of Transplantation, New England Journal of Medicine, Liver Transplantation. Transplantation to mention a few. His research interests include liver, kidney, pancreas and small bowel transplantation, hepatobiliary surgery, immunosuppression and organ preservation. He established and has maintained the Baylor Biorepository and prospective Clinical Research Database in liver transplantation since 1985. The repository collects patients’ blood samples on protocol for life.

Philip F. Halloran
Moderated by Jon Kobashigawa

Molecular Microscope: Unmet need for precision pathological diagnosis; Introduction to molecular microscopy; Advances and insights from standardized molecular measurements

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Philip F. Halloran's Bio:

Dr. Halloran is a clinician-scientist with a focus on organ transplantation and organ diseases, at both the clinical and basic levels. He received his MD and nephrology training from the University of Toronto and his PhD from the University of London. He served on the faculty of the University of Toronto before joining the University of Alberta where he holds the title of Distinguished University Professor.

His research interests are focused on the mechanisms of organ transplant rejection and the effects of immunosuppressive drugs. He has explored the mechanisms of T cell-mediated rejection, and described antibody-mediated kidney rejection, now recognized as the leading cause of late kidney transplant loss (1;2). He has also explored the mechanisms of acute and chronic organ injury and their relationships to disease progression (3;4). He studied the mechanism of action of immunosuppressive drugs and has been an investigator in many of the clinical trials that shaped immunosuppressive drug strategies in organ transplantation (5).  Dr. Halloran is an author of over 300 peer reviewed publications.

Dr. Halloran developed the Alberta Transplant Applied Genomics Centre (ATAGC) into the world’s leading center for molecular studies of organ transplants and organ diseases, based on biopsies (http://atagc.med.ualberta.ca/). He has recently developed the Molecular Microscope Diagnostic System (MMDxTM), a system for reading organ transplant biopsies using microarrays that is now being licensed commercially (6).

Dr Halloran currently leads four ongoing international clinical trials are at various stages of completion towards the organ-specific MMDx test: kidney transplants - INTERCOMEX ClinicalTrials.gov NCT01299168; heart transplants - INTERHEART ClinicalTrials.gov NCT02670408; lung transplants - INTERLUNG ClinicalTrials.gov: NCT02812290; liver transplants - INTERLIVER ClinicalTrials.gov NCT03193151. All are directed at changing care in organ transplantation: new understanding and new tests to support decisions.

He was the founding Editor-in-Chief of the world’s leading transplantation journal, the American Journal of Transplantation, with the editorial office at the University of Alberta from 2000 to 2010. He is also the Chairman of the Board of Trustees of the Roche Organ Transplant Research Foundation, a Swiss-based charity. He is an Officer of the Order of Canada, a Fellow of the Royal Society of Canada, and an elected member of the American Society of Clinical Investigation. He is the first recipient of the Paul Terasaki Award from the American Society for Histocompatibility and Immunogenetics. Other awards include the 2016 medical research Prix Galien for Canada; an honorary degree from the University of Paris (Sorbonne); and the 2018 J. Gordin Kaplan Award for Excellence in Research by the University of Alberta.

Jon Kobashigawa's Bio:

Jon Kobashigawa, MD serves as the Director of the Advanced Heart Disease Section, Director of the Heart Transplant Program and the Associate Director of the Cedars-Sinai Smidt Heart Institute. He is the DSL/Thomas D. Gordon Distinguished Professor of Medicine at the Cedars-Sinai Medical Center and is also Clinical Professor of Medicine at the David Geffen School of Medicine at UCLA. Dr. Kobashigawa is recognized nationally and internationally as a leader in the heart transplant field. He is a past President of the International Society of Heart and Lung Transplantation, a past chair of the American College of Cardiology Committee on Heart Failure and Transplantation, and a past member of the National Thoracic Committee of the United Network of Organ Sharing. He has served on the Executive Program Committee for the World Transplant Congress in 2014. He is the immediate past Chair of the Thoracic Committee and a former member of the Board of Directors of the American Society of Transplantation. Dr. Kobashigawa is a productive writer and has published over 400 peer-reviewed articles, chapters and monographs in the field of heart transplantation and has chaired several multi-center heart transplant studies. He has published in prestigious journals including the New England Journal of Medicine, Circulation and the Journal of the American College of Cardiology. He has also organized and chaired ten International and National Consensus Conferences to discuss pertinent questions in the field of heart failure and heart transplantation. In addition, he has served on several editorial boards including the Journal of Heart and Lung Transplantation, the American Journal of Transplantation, the European Heart Journal and Cardiology today. Dr Kobashigawa lectures at universities around the world and has mentored several young physicians who have ascended to important academic positions throughout the country.

Maarten Naesens
Moderated by Valeria Mas

System Biology and Precision Transplantation Medicine: The Complexity of the human and transplant model and the different layers of biological information; Current applications; Composite scores: clinical applications

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Maarten Naesens' Bio:

Prof. Dr. Maarten Naesens is Clinical Director of the Nephrology and Renal Transplantation unit of the University Hospitals Leuven. He is co-directing the kidney transplant program, with special focus on renal allograft histology, antibody-mediated rejection, HLA sensitization, living donation and ABO-incompatible transplantation. He directs the protocol biopsy program of the University Hospitals Leuven and the “Biobank Renal Transplantation” at this same institution. He is appointed Associate Professor in the Department of Microbiology and Immunology at the University of Leuven. In his translational research performed at this institution, he integrates clinical, histological, pharmacokinetic, pharmacogenetic and gene expression data, to get an integrated view on the determinants of histological damage progression of renal allografts and late graft loss. Prof. Dr. Maarten Naesens is principal investigator of the FP7 project “Biomargin” of the European Commission, focusing on biomarker research for kidney transplantation by using omics strategies and systems medicine, and of the FWO TEMPLATE project for epitope matching in kidney transplantation. He has published more than 120 peer-reviewed manuscripts in international journals, amongst others in New Engl J Med, J Exp Med, Sci Transl Med, Nature Comm, J Am Soc Nephrol, Transplantation, Am J Transplant and Kidney Int. He has established collaborative projects and networks with several European and American research centers. He has received investigator awards from the European Society of Organ Transplantation, from the American Transplant Society and from The Transplantation Society. He is appointed Young Key Opinion Leader of The Transplantation Society and elected Councillor of the European Society of Organ Transplantation (ESOT).

Valeria Mas' Bio:

Valeria Mas has a broad background in transplant immunology and molecular biology. She is currently the Director of the Transplant Research Institute that is part of the Methodist University Transplant Institute associated with University of Tennessee Health Science Center. Until few months ago, she was the Director of the Molecular Transplant Research Laboratory at University of Virginia, and previously, she was the Director of the Transplant Genomics Laboratory at Virginia Commonwealth University. She has been conducting studies in genomics and proteomics related to kidney and liver transplant recipients during the last 18 years. Her research projects are mainly focused to: (1) evaluate the molecular pathways that associate with graft fibrosis development and loss of function post-kidney transplantation, (2) test the effects of organ donor biology in short-and long-term outcomes post-transplantation, and (3) identify early biomarkers that distinguish those organs at high risk of post-transplant dysfunction. She uses integrative approaches (proteomics, epigenetics, transcriptomics, and bioinformatics) for understanding the role of immunological and non-immunological factors in transplantation outcomes as well as the effect of the genome collision from the donor and recipient as determinant of final phenotype post-transplantation. As the PI, co-PI, and co-Investigator of multiple federal and non-federal grants, she established a unique biorepository linked to a detailed data base that constitute the foundation of our research initiatives. She has extensive experience using different high-throughput technologies and strategies (SNP detection, non-coding RNA, gene expression, DNA methylation, proteomics, gene editing, flow cytometer, among others) for executing translational research in transplant recipients.

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