2016 International Transplantation Science Mentee-Mentor Awards

The Transplantation Society (TTS) along with the collaboration of its Affiliated Societies celebrates the contributions of basic science to the field of transplantation by recognizing the efforts of basic scientists who have advanced our understanding of transplant science/immunobiology and/or treatment of transplant recipients, and the young investigators who will be the future leaders in transplantation.

This award was made possible with the joint contribution of the Canadian Society of Transplantation (CST) and TTS.

Prospective Treatment and Novel Biomarkers of BK Polyomavirus Associated Nephropathy

Minal Borkar received Mentee-Mentor Award for her work “Prospective treatment and novel biomarkers of BK polyomavirus associated nephropathy”. This project gave significant piece of information about the mechanisms by which BK polyoma virus causes these changes eventually leading to graft loss and patient morbidity. It will also help in the identification of novel biomarkers of cell death and Epithelial Mesenchymal Transition which will eventually lead to better diagnosis and prognosis of BK nephropathy. The more research on understanding the mechanism will help in establishing clinically proven effective antiviral treatment for BK PVAN.

Minal Borkar is a postdoctoral research fellow with Dr. Lee Anne Tibbles at University of Calgary since November 2012. She has received Canadian National Transplant Research Program (CNTRP) fellowship in 2014 and cleared another CNTRP- Alberta Transplant Institute Fellowship in 2015. Minal worked as a Postdoctoral Fellow in Spain and Scientist in Department of Medical Genetics at Sir Ganga Ram Hospital, India. She is the recipient of various awards like Mentee-Mentor Award BSM 2013 Paris, AST-IDCOP Travel Award in American Transplant Congress 2016, CNTRP Travel Award for World Transplant Congress 2014 and twice Nick Norgan award for the best paper of the Journal in 2010 and 2012

These awards were made possible with the joint contribution of the Deutsche Transplantationsgesellschaft (DTG) and TTS.

Metabolites Associated with Bariatric Surgery Reverse Accelerated Rejection and Augmented Alloimmunity in Obese Allograft Recipients

Dr. Markus Quante received the International Transplantation Science Mentee-Mentor Travel Award in for his work on the impact of obesity on alloimmune responses in a mouse transplant model. He showed that obesity accelerated allograft rejection linked to a more pronounced pro-inflammatory immune response. Weight loss subsequent to bariatric surgery, in contrast, prolonged allograft survival and skewed the immune response towards Th2 dominated conditions. Metabolic changes that were linked to bariatric surgery modified alloimmune responses and prolonged graft survival. These results will serve as a basis for a future detailed mechanistic analysis.

Dr. Quante received his MD from the Hannover Medical School, Germany, completed his surgical residency at the University Hospital Leipzig, and afterwards a member of the IFB Integrated Research and Treatment Centre Adiposity Diseases. In July 2013, Dr. Quante joined the Transplant Surgery Research Laboratory at Brigham and Women´s Hospital in Boston as a postdoctoral research fellow. Dr. Quante is currently at the Department of General-, Visceral-, and Transplantation Surgery in Tuebingen, Germany.

Cell-free Mitochondrial DNA Activates DCs in an Age-dependent Fashion and Compromises the Survival of Older Grafts

In 2016 Sebastian Stead was awarded the International Transplantation Science Mentee-Mentor Travel Award in recognition for his abstract entitled: Dendritic cell phenotype and function modification with targeted porous silicon nanoparticles. His work is focused on identifying novel treatments within the field of nanomedicine, providing alternative methods for delivering immunosuppressive medications in an acute, localised fashion. Functionalisation of the nanoparticles has shown the ability to provide enriched delivery to myeloid dendritic cells, one of the least abundant cells within the body. The composition of the nanoparticles allows them to be tailored for specific therapy, capable of being loaded with a myriad of drugs or coated with different antibodies, permitting cell specific targeting.

Sebastian is currently a PhD candidate in Medicine, at the University of Adelaide in Australia, under the supervision of Professor P. Toby Coates. His research is focused on utilising nanoparticles to induce antigen specific tolerance within type 1 diabetics, and if successful, it may have the potential to improve the lives of millions of sufferers. The clinical applications could also be tailored to help deliver drugs to treat cancers more specifically than current chemotherapeutic methods, or have positive ramifications in the manufacture of more effective vaccines.

These awards were made possible with the joint contribution of the Indian Society of Organ Transplantation (ISOT) and TTS.

Peripheral NK-cell Repertoire Distribution in Chronic Allograft Dysfunction after Renal Transplantation

Sailaja Kesiraju completed her Post-doctoral fellowship at Bhagwan Mahavir Medical Research Centre, Hyderabad. Her current on-going five year research project has the rubric “Non Invasive Diagnosis of Acute Rejection and Methods to Monitor Graft Survival in Renal Transplant Patients”; the work is being carried out in the Immunology department at the Bhagwan Mahavir Medical Research Centre. Dr.Sailaja received her Doctor of Philosophy award from Osmania University and her thesis was on the topic “Oxidant-Antioxidant Status of Serum and Roncho-alveolar Lavage in Common Respiratory Disorders”.

Dr. Kesiraju’s primary research goal is to find a non-invasive, accurate, sensitive and rapid diagnostic test for the early detection of rejection, chronic allograft dysfunction as well as tolerance of the allograft. A sensitive non-invasive test that is able to detect acute and chronic injuries in the transplant will be a very useful adjunct in clinical practice to monitor the graft function.

Impact of Single Centre Kidney Paired Donation Transplantation to Increase Donor Pool in India

Vivek Kute received the International Transplantation Science Mentee-Mentor Award 2016 recognizing his work on “Impact of Single Center Kidney Paired Donation Transplantation to Increase Donor Pool in India” under mentorship of Prof HL Trivedi and Prof PR Shah.

Vivek Kute is Associate Professor of Nephrology and Transplantation at Institute of Kidney Diseases and Research Center and Dr. HL Trivedi Institute of Transplantation Sciences, (IKDRC-ITS) and the Gujarat University of Transplantation Sciences (GUTS) Ahmedabad, India. He has received various awards for his major contributions in the field of transplantation, including a Young Investigator award 2012 in Berlin, Bansal Oration and Janseen-Cilag award by Indian Society of Nephrology, and Udupa Memorial Lecture 2015 by ISOT. He is a mentor for the Young Nephrologist Mentoring Program for ISN. He has published over 100 research papers in peer reviewed journals and made oral presentations in various national and international conferences. His research involves expanding donor pool with kidney-paired donation transplantation.

Development of De-novo Donor Specific Antibody (DSA) and Vitamin D Status after Renal Transplantation

Ultra-high Resolution Non-contrast Imaging for Chronic Rejection Monitoring and Procedural Planning in Reconstructive Transplantation

Shailesh B. Raval received a Mentor-Mentee Award for the developmental work on the non-invasive, non-radiation, contrast-free, ultra-high resolution (UHR), 3D nerve and vascular MRI imaging method in conjunction with RF imaging system. Our approach is renal-toxic-contrast and radiation-free, increasing its safety in Reconstructive transplantation (Craniofacial or Upper Extremity) or even Solid Organ transplantation (especially renal transplant) applications for sequential non-invasive graft monitoring of Chronic Rejection (CR). These could include intimal, luminal and flow parameters reflective of CR related vascular changes that may result in ischemic graft attrition or loss in RT or in SOT. In addition, Nervetractography can monitor neuroregeneration after transection, repair or transplant related nerve outcomes.

Shailesh is completing his PhD in Bioengineering (in collaboration with Radiology and Plastic Surgery) from the University of Pittsburgh. His current work includes development of unique RF imaging systems and exploring cutting edge medical imaging applications in various body organs.

Imbalance of T Helper 17 Cells and T Regulatory Cells is Associated with Chronic Active Antibody Mediated Rejection in Renal Allograft Recipients

Brijesh Yadav is a final year PhD student under Prof. Narayan Prasad in the Department of Nephrology and Renal Transplantation at Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. His PhD thesis is on “Regulatory, effector and cytotoxic T cell profiles in chronic renal allograft dysfunction”, profiling regulatory, effectors and cytotoxic T cell subsets frequency by Flowcytometry, Serum and PBMC culture supernatant cytokines by ELISA, intragraft infiltrations of above T cell subsets by quantitative real time PCR and Immunohistochemistry in biopsy proven renal allograft recipient patients of chronic active antibody mediated rejection, calcineurin inhibitor toxicity and idiopathic transplant glomerulopathy. He has been awarded with Newton-Bhabha Fellowship for research training at Cambridge University by the British Council, Best Abstract award by the Asian Society of Transplantation Singapore (CAST-2015), Young Scientist awards by Invertis University India, Abstract of Distinction award by Gujarat University of Transplantation Science, and the DST-INSPIRE Senior Research Fellowship by DST, Govt. of India.

These awards were made possible with the joint contribution of the Japan Society for Transplantation (JST) and TTS.

Systemic Therapy of Regulatory Dendritic Cells Derived Form Induced Pluripotent Stem Cells allows Allogeneic Cardiac Grafts Acceptance

Songjie Cai received a Mentee-Mentor Award for her work with systemic therapy of regulatory dendritic cells. In collaboration with Dr. Xiao-Kang Li’s lab at National Research Institute for Child Health and Development (Tokyo), dendritic cells (DCs) were generated and characterized from murine induced pluripotent stem cells (iPSCs). Dr. Cai identified that donor-type iPSCs derived DCregs (iPS-DCregs) could lead to permanent acceptance of fully MHC-mismatched murine allogeneic cardiac grafts, but rejected third-party allografts. She also found that preconditioning of donor-type iPS-DCregs to recipients generated antigen-specific regulatory T cells (Tregs), which is in association with TGFβ.

Dr. Cai got her MD in clinical medicine from Shanghai Jiaotong University (China), completed her Surgery residency at Shanghai East Hospital, and her PhD on medicine science from Osaka University (Japan). Her research interests are immunobiology of dendritic cells during immune response to transplantation alloantigen. Under Dr. Shiro Takahara’s mentorship, Dr. Cai’s research focused on understanding the basic processes that control dendritic cells maturation, activation and migration with the ultimate goal of enabling clinicians to cell therapy and immunosuppression monitoring.

Various Pathogenic Microbes Induce CNI-resistance in B-cells Responding to Blood Group Antigens through TLR–MyD88 Pathway

Hiroshi Sakai received a Mentor-Mentee award for his work with pathogenic microbes. He focused on the influence of toll-like receptor signaling, through the binding of bacterial-derived ligands, on B cell activation in response to blood group carbohydrate-antigens, because bacterial infection following ABO-incompatible organ transplantation has been reported to be associated with refractory antibody-mediated rejection. This study provides the first evidence that B-cells responding to blood type A carbohydrate, in the presence of toll-like receptor-MyD88 signaling, show the sIgM+CD5dim/-B-1b phenotype, and lose susceptibility to inhibition by CsA, following ABO-incompatible transplantation.

Dr. Sakai received his MD from Hirosaki University, and is now a PhD student in Gastroenterological and Transplant Surgery at Hiroshima University. Under Dr. Hideki Ohdan and Dr. Yuka Tanaka’s mentorship, Dr. Sakai’s research is aimed at regulating B cells responding to carbohydrate antigens in allo- and xeno-transplantation.

Clinical and Immunological Significance of Controlling Portal Vein Pressure in Living Donor Liver Transplantation

This award was made possible with the joint contribution of the Nederlandse Transplantatie Vereniging (NTV) and TTS.

Belatacept Fails to Inhibit Donor-reactive Tfh-B Cell Interaction but Favors a Regulatory Transitional B Cell Profile Over Tacrolimus

Gretchen de Graav received a Mentee-Mentor award for her research on the effects of belatacept on follicular T helper-B cell interaction in kidney transplantation. Under supervision of Dr. Carla Baan at the Transplantation Laboratory at Erasmus University Rotterdam, the donor-antigen driven formation of plasmablasts was compared between cultures spiked with belatacept and tacrolimus. Cells were obtained from 40 kidney transplant patients randomized to a belatacept-based or tacrolimus-based immunosuppressive regimen. Unlike in animal studies, plasmablast formation was not inhibited by belatacept, but only by tacrolimus. The survival of regulatory IL10+ transitional B cells was, however, favored in the presence of belatacept, but diminished by tacrolimus. The question remains which patients can benefit from and which patients are burdened with the attenuated inhibitory effects of belatacept on Tfh-B cell interaction.

Dr. de Graav received her MD from the Erasmus Medical Center University. Currently, she is finishing her PhD project and she will start her Internal Medicine Residency at the Maasstad Hospital, Rotterdam.

This award was made possible with the joint contribution of the Société Française de Transplantation (SFT) and TTS.

Interleukin-34 is a Treg-specific Cytokine and Mediates Transplant Tolerance

Dr. Séverine Bézie received a Mentee-Mentor Award for her work on Interleukin-34, a Treg-specific ucytokine that mediates transplant tolerance, Under the mentorship of Dr. carole Guillonneau. In a translational study from rat to human, she showed that IL-34 has immunoregulatory properties, inducing tolerance to the allograft and delaying GVHD. Moreover, it was shown that this cytokine is specifically expressed by Foxp3+Tregs and involved in their suppressive function, but also modulated macrophages polarization to expand Tregs in a feedback loop. These properties make it a promising candidate as tolerance inducer treatment.

Dr Bézie got her PhD from the Université de Nantes, France, focused on the identification of new immunoregulatory molecules in a rat model of transplantation. She currently works at the INSERM 1064 Center of Research in Transplantation and Immunology in Nantes, with interests in new therapies promoting allo-specific Tregs.

This award was made possible with the joint contribution of the Sociedad Mexicana de Trasplantes (SMT) and TTS.

Pre-transplant AT1Rabs are Associated with Acute Rejection in 2-Haplotypes Kidney Transplant Recipients

These awards were made possible with the joint contribution of the Transplantation Society of Australia and New Zealand (TSANZ) and TTS.

Surface Modification of Porcine Aortic Endothelial Cells with Corline Heparin Conjugate (CHC) Protects Against Xenogeneic Thrombosis and Inflammation

Anjan K. Bongoni received a Mentee-Mentor Award for his work on the surface modification of porcine aortic endothelial cells. In this study, the feasibility of using CHC to protect pig vascular endothelial cells against xenogenic coagulation and inflammation was tested in an in vitro pig-to-human xenotransplantation setting using a whole blood coagulation assay that closely mimics the in vivo small vessel endothelial surface-to-blood volume ratio. Results demonstrated that surface immobilization of the multi-arm heparin conjugate CHC has the potential to prevent the establishment of pro-coagulant and pro-inflammatory environment induced by xenotransplantation and thus may support the survival and function of porcine xenografts. Therefore, this strategy provides a possible therapeutic option to attenuate thromboinflammation in xenotransplantation.

Dr. Anjan Bongoni received his PhD in immunology from the University of Bern, mainly focused on the functional evaluation of multi-transgenes in genetically modified pigs for xenotransplantation. Currently, he is working as a post-doc fellow in the Immunology Research Centre (IRC) at St. Vincent’s Hospital Melbourne. His research interests are: identifying and testing novel reagents and regulators of the intravascular innate immune system (complement, coagulation and inflammation) in mouse models of renal ischemia-reperfusion injury and heart allotransplantation. He received Young Investigator Awards in the past from the International Xenotransplantation Association and The Transplantation Society.

Disruption of CD8-coreceptor Cinding Abrogates Tolerance Induction via Liver-directed Expression of Donor MHC Class I

Dendritic Cell Phenotype and Function Modification with Targeted Porous Silicon Nanoparticles

In 2016 Sebastian Stead was awarded a Mentee-Mentor Award in recognition for his work with dendritic cell phenotype and function modification. His work is focused on identifying novel treatments within the field of nanomedicine, providing alternative methods for delivering immunosuppressive medications in an acute, localised fashion. Functionalisation of the nanoparticles has shown the ability to provide enriched delivery to myeloid dendritic cells, one of the least abundant cells within the body. The composition of the nanoparticles allows them to be tailored for specific therapy.

Sebastian is currently a PhD candidate in Medicine at the University of Adelaide, under the supervision of Professor P. Toby Coates. His research is focused on utilising nanoparticles to induce antigen specific tolerance within type 1 diabetics.

Risky Organs: Trends in Comorbidities among Potential and Actual Australian Organ Donors in New South Wales 2010-2015

Imogen Thomson received a TTS/TSANZ Mentee-Mentor Award in conjunction with her supervisor, Associate Professor Angela Webster, for her abstract 'Risky Organs: Trends in Comorbidities among Potential and Actual Australian Organ Donors in New South Wales 2010-2015’. Ms Thomson’s research centred on characterising disease burden among organ donor referrals, and the impact that this has on the likelihood of a potential donor proceeding to donate.

Ms Thomson is currently in her second year of the Doctor of Medicine Program at the University of Sydney, and completed her undergraduate studies in Biomedical Science at Bond University, Australia. Under the mentorship of Associate Professor Webster, she is also undertaking a Master of Philosophy (Medicine) alongside her medical studies, with a focus on identifying opportunities to increase organ donation rates in New South Wales. She hopes to pursue a career in the field of transplantation in the future.

These awards were made possible with the contribution of The Transplantation Society (TTS).

Effect of Epigenetic Modifications in Graft Kidneys Progressing to Chronic Allograft Dysfunction

Dr. Sai Vineela Bontha received a Mentee-Mentor award for her work with epigenetic modifications in grafts. Mentored by Dr. Valeria Mas, this work evaluates the differences in DNA methylation patterns between renal allografts with histologic evidence of interstitial fibrosis and tubular atrophy which progress to chronic allograft dysfunction and those with normal histology and function. Differential DNA methylation patterns were studied in association with changes in gene expression patterns downstream using an integrative approach. Future studies are planned to identify the timeline associated with the changes in DNA methylation patterns and to delineate a cause-effect relationship between DNA methylation and allograft dysfunction.

Dr. Bontha received her PhD from Leibniz Graduate School on Aging and Jena University Hospital in Germany. She is currently a post-doctoral research associate at the Translational Genomics Transplant Laboratory at the University of Virginia. Her research interests include the identification of noninvasive biomarkers that predict short- and long-term graft outcomes, as well as furthering understanding of the underlying mechanisms leading to chronic renal allograft dysfunction.

Human Anti Thrombotic Genes do not Obviate the Need for Anticoagulation in Aiding Long-term Xenograft Survival

Joshua Chan was awarded a Mentee-Mentor Award for his work on the use of multi-transgene expression for prevention of cardiac xenotransplantation-associated consumptive coagulopathy. The novel use of six-gene modified cardiac xenografts, particularly the inclusion of humanized factors TFPI, DAF, and EPCR, was found to be associated with improved levels of multiple factors in the coagulation-fibrinolysis cascade. Prevention of post-xenotransplant critical consumptive coagulopathy may have significant implications for the potential clinical application of cardiac xenotransplantation.

Dr. Chan is a research fellow in the Cardiothoracic Surgery Research Program at the National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH). His primary interest is in cardiac xenotransplantation, specifically in xenoimmunology, transgenic engineering, and transplant rejection. He received his Bachelors of Arts degree in Biology at New York University (NYU) and subsequently earned his medical degree from the University of Southern California Keck School of Medicine (USC). He went on to complete his internship at Cedars-Sinai Medical Center where he matriculated from his 3rd year general surgery resident prior to his current research sabbatical.

Vascular Sequestration of Donor-specific Antibodies Protects Allogeneic Islets from Humoral Rejection

Chien-Chia Chen was granted a Mentee-Mentor Award for a translational research project in which he combined the analysis of clinical samples with the use of murine models to explore the mechanisms of resistance of allogenic islets to antibody-mediated rejection. His work led to the conclusion that endothelial chimerism combined with vascular sequestration of alloantibodies explains why the rate of attrition of islet graft was not accelerated in the presence of alloantibodies. These results suggests that the alloantibodies should be seen as 'marker' of rejection rather then 'maker' in islet great recipients.

Dr. Chen received his MD and completed his surgical residency at the National Taiwan University. He is currently a PhD student under the supervision of Prof. Thaunat in INSERM U1111, Lyon, France. His researches focus mainly on deciphering pathophysiology of antibody-mediated rejection.

CD45RA Identifies TSDR Demethylated Regulatory T Cells with a Stable Phenotype and Suppressive Cytokine Profile

Rebeca Arroyo-Hornero was granted a Mentee-Mentor Award for her research paper “CD45RA Identifies TSDR Demethylated Regulatory T Cells with a Stable Phenotype and Suppressive Cytokine Profile”. Regulatory T cells are currently being tested as a cellular therapy in transplant patients aiming at promoting transplant tolerance and reducing levels of immunosuppression chemotherapy. Stable bona fide regulatory T cells can be accurately identified by the demethylated status of a specific DNA region called TSDR. However, for cellular therapy is crucial to identify cell surface markers sufficient to isolate cells that remain stable and potent after expansion and in the presence of immunosuppressive drugs. In comparison with CD45RA- regulatory T cells, CD45RA+ regulatory T cells retained more stable suppressive properties after in vitro expansion, also in the presence of low levels of calcineurin inhibitors. All suggests that CD45RA+ regulatory T cell population is a promising candidate for cell therapy and should be studied further.

Ms. Arroyo-Hornero received her Bachelor Degree in Biotechnology from the University of Murcia in Spain. Currently, she is a PhD student at the University of Oxford, studying cellular therapies for transplantation. She is interested in discerning how regulatory T cells suppress the immune response and the possibility of genetically modified regulatory T cells to potentiate and stabilize their suppressive activity.

AMP-activated Protein Kinase Attenuated Marginal Liver Graft Injury via Promoting Mitochondrial Biogenesis and Respiratory Function

Liu Jiang received a Mentee-Mentor Award for his work on the AMP-activated protein kinase attenuates marginal liver graft injury via promoting mitochondrial biogenesis and respiratory function. The specific gene favoring improving marginal graft survival was studied using hundreds of clinical liver transplant samples, rat model with small-for-size orthotopic liver transplantation and AMPK transgenic mice received I/R injury plus major hepatectomy. The key findings provide a possible way to ameliorate fatty graft injury by increasing activity of the kinase. Further study applying activators for activating this kinase is needed for clinical application.

Dr. Liu received his bachelor and master degrees in clinical medicine from Medical School of Nankai University in China. He is a current PhD student in the University of Hong Kong. His research interests are: mitochondrial function and marginal graft injury after liver transplantation, metabolism alternation during fatty graft injury, and surgical treatment for late phase liver diseases. He received a Young Investigator Award in the past from the International Liver Transplantation Society.

The Clinical Significance and Potential Therapeutic Role of GPx3 in Tumor Recurrence after Liver Transplantation

Qi Xiang received Mentee/Mentor Award as mentee for his research paper “The Clinical Significance and Potential Therapeutic Role of GPx3 in Tumor Recurrence after Liver Transplantation”. Under the instruction of Prof. Man, the research team identified that the down-regulation of GPx3 in small-for-size liver graft was significantly associated with HCC invasiveness in a rat model and lower plasma GPx3 was an independent predictor for poor overall survival of HCC patients after liver transplantation. Moreover, they found that GPx3 was not only a predictor for prognosis, but also suppressed HCC invasiveness through JNK-cJun-MMP2 signalling pathway. Therefore, in addition to prognostic value, GPx3 may possess the therapeutic potential targeting at HCC recurrence after liver transplantation.

Dr. Qi earned his MD in clinical medicine from mainland China and PhD on surgery from The University of Hong Kong. Currently, he works as post-doctoral fellow in Department of Surgery, The University of Hong Kong. His research interests are: explore the role of functional biomarker for tumor recurrence after liver transplantation. He received Mentee-Mentor Awards twice in the past from The Transplantation Society and is a 2-time recipient of a Young Investigator Award from The Liver Transplantation Society.