2016 TTS Young Investigator Scientific Awards

The recipients of the TTS Young Investigator Scientific Awards submitted abstracts to the Hong Kong transplantation Congress and received the highest scores from an international panel of reviewers.

Penelope Allen received a TTS Young Investigator Award for her research on Glomerulonephritis recurrence in kidney transplant recipients. Using data collected over 30 years (1985-2014) from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), the study determined the incidence, risk factors, and outcomes of recurrent glomerulonephritis in kidney transplant recipients. The project was conducted under the supervision of Associate Professor Germaine Wong at the Centre for Kidney Research, Westmead in conjunction with the Sydney University School of Public Health.

Ms. Allen is currently studying postgraduate medicine at The Australian National University in Canberra, and will complete her MChD in 2018. She looks forward to being involved in ongoing research in the field of kidney transplantation. Penelope is a recipient of the Sydney University Summer Research Scholarship and the Transplant Society of Australia and New Zealand Young Investigator Award.

Vaishnavi Calisa received a Young Investigator Award for her work on the relative costs and health benefits of an age-matched deceased donor allocation algorithm compared to current practice, under the supervision of A/Prof Germaine Wong. A probabilistic Markov model was used to determine whether restricting the donor-recipient age-mismatch would improve graft and patient outcomes in different age groups. It was found that age-matching would provide small health benefits across the population, benefitting those between 30 and 60 but slightly disadvantaging those under 30 and over 60.

Ms. Calisa is currently in her second year of Bachelor of Science (Advanced) and Doctor of Medicine at The University of Sydney. Her current research interest is in using mathematical and statistical modelling in medical applications, particularly kidney transplantation. In April 2016 she received the Astellas Clinical Presentation Award and Young Investigator Award at the Transplant Society of Australia and New Zealand Annual Scientific Meeting.

Aravind Cherukuri received a Young Scientific Investigator Award for his work analysing de novo DSA and its relationship with the development of early T cell mediated rejection and chronic allograft histological changes. The study revealed that de novo DSA is associated with the development of early T cell rejection (TCR) and that the combination of DSA and TCR is associated with significantly worse renal function and chronic allograft injury than DSA alone. Further, in patients with DSA, a pro-inflammatory B lymphocyte cytokine profile predicted those at risk of TCR with a specificity of 100% and a sensitivity of 78%. Thus de novo DSA is a marker for a heightened cellular alloresponse and the study of B lymphocytes may potentially help to risk stratify patients allowing for early therapeutic intervention.
Dr. Cherukuri received ­­his MBBS from Guntur Medical College and completed his residency and fellowship training in Nephrology at St. James’s University Hospital. He has an interest in transplant immunology and has taken up translational research in human kidney transplantation centred on cytokine expressing B lymphocytes. He received a PhD from the University of Leeds, and was a post-doctoral fellow at the Thomas E. Starzl Transplantation Institute. Dr. Cherukuri’s research is aimed at understanding the biology of cytokine expressing B cells in the context of immunological tolerance and developing predictive biomarkers for renal transplant rejection.

Jason Davis received a Young Investigator Award for his work on the Changes in Liver Allograft Steatosis and its Impact on Early Graft Function and Long Term Survival. Jason completed his work under the supervision of Dr. Richard S Mangus, the Surgical Director of Small Bowel and Multivisceral Transplantation at the Indiana University School of Medicine (IUSM). Results of the study confirm that there is a marked post-transplant decrease in liver steatosis. Overall, allografts with moderate to severe steatosis have worse early injury, delayed graft function, more substantial acute decrease in renal function, and worse survival. The subgroup analysis showed that transplant recipients who are younger, male, obese, or have fatty liver disease are more able to clear steatosis in the early post-transplant period compared to others.

Jason Davis is currently completing his M.D. from the Indiana University School of Medicine. He has completed multiple projects, receiving various awards and a fellowship in recognition for his work, most recently first place at the 2016 Association for Academic Surgery (AAS) Outstanding Medical Student Presentation. Also the 2015 Carolyn L. Kuckein Student Research Fellowship from the Alpha Omega Alpha (AOA) Honor Medical Society, which has helped him to expand on his other research endeavors in the transplant lab at the IUSM.

Denis Efimov was granted a Young Investigator Award for his research paper on DAMP-associated preservation injury and complications after liver transplantation. The results of the study showed that more severe DAMP-associated ischemia reperfusion liver graft injury was associated with higher incidence of severe early allograft dysfunction and lower incidence of acute rejection. Also it was revealed that donor polymorphism of TLR-4 gene in SNP rs913930 was associated with severe EAD occurrence after DBD LTx in Eastern European (Belarus) patients. This fact may help to stratify donors' grafts on high/low risk of EAD incidence based on genetically proved predictors.

Denis Efimov earned his MD on clinical medicine from Belorussian State Medical University in 2011. Currently, he works at the Republican Scientific and Practical Center for Organ and Tissue Transplantation (Minsk, Belarus). His research interests are: ishemia reperfusion injury, biomarkers, EAD prophylaxis after liver transplantation. He received the best presentation award at EFTW in 2014 (ESOT, Prague).

Shaimaa Elkholy received a Young Investigator Award at for her research on the predictors of mortality in living donor of liver transplantation (LDLT). This work represented a retrospective analysis for LDLT in Cairo University, which is the only source of donation in Egypt. This Unique experience was based only on living donation for which a risk index had been provided for prediction of early mortality. This risk index included MELD score, duration of ICU stay, and intra-operative blood transfusion with cut off values of 20, 9 and 8, respectively.

Dr. Elkholy graduated from Cairo University and she is now a lecturer at the Internal Medicine Department (Hepatogastroenterology Unit) Faculty of Medicine, Cairo University. She earned her phD in infections post liver transplantation, also from Cairo University. Her main interest is in Liver transplantation and GI endoscopy. She also received the Best Abstract award at the Pan Arab Liver Transplantation Society(PALTS) in 2013 for her research into nutrition in liver cirrhosis.

Jianing Fu was granted a Young Investigator Award for her research paper into naïve donor-derived lymphocytes from graft-resident lymphoid progenitors. Mixed lymphocyte reaction and high throughput TCRb CDR3 DNA sequencing were used to identify alloreactive T cell clones, and they were further tracked in blood or allograft post-transplant. The data demonstrated that donor graft-versus-host-reactive T cells and hematopoietic stem cells and progenitor cells carried within the graft play a key role in promoting and maintaining donor chimerism in the peripheral blood, which correlates with better clinical outcomes. This study provides new insights into the underlying mechanism of blood mixed chimerism and paves the way to develop new strategies to reduce graft rejection and achieve tolerance.

Dr. Fu received her MS on Chemical Biology from Peking University in China, and PhD on Cancer Biology and Immunology from University of South Florida. She is now a fellow at the Columbia Center for Translational Immunology at Columbia University. Under Dr. Megan Sykes’s mentorship, Dr. Fu’s research is aimed at decoding the bidirectional alloreactivity after intestinal transplantation and investigating the phenotype and function of gut hematopoietic stem cells and progenitors, with the ultimate goal of eliminating graft rejection by inducing long persistent blood mixed chimerism.

Dr. Barbara Kern received a TTS Young Investigator Award for her work on “Nonalcoholic steatohepatitis (NASH) as indication for Liver Transplantation in Europe - Clinical Analysis of over 37.000 patients”. This study investigates all adult patients with NASH, who underwent LT in Europe between 2002 and 2012 in collaboration with the ELTR registry in order to define risk factors and recommendation for this new epidemic.

Dr. Kern received her medical degree from the Medical University of Vienna. She is now a permanent resident at the Department of Visceral-, Transplant- and Thoracic Surgery at the Innsbruck Medical University, where she is also actively enrolled in the PhD program. To finish part of her thesis, she also spent one year abroad as a research fellow at the Johns Hopkins University, School of Medicine, in Baltimore, USA. Her research interests are in the field of liver, small bowel, and reconstructive transplantation.

Qiang Liu was granted a Young Investigator Award for his research on triglyceride exportation and lipid metabolism in the preservation of discarded steatotic human livers using 24 hours ex vivo normothermic machine perfusion. The study was the first to determine the lipid profile of the perfusate in ex vivo human liver normorthermic perfusion, and indicate that active triglyceride metabolism and exportation occur ex vivo regardless of transaminase release and bile production. It is the basis to reduce steatosis in human donor liver prior to transplantation by using prolonged perfusion and/or proper pharmacological intervention for eventually expanding donor criteria.

Dr. Liu earned his MD in China, mastering in medical imaging; and his PhD in biomedical science at the University of Leuven in Belgium. He also has a MSc in applied statistics. After working in Massachusetts General Hospital, Harvard University, he is currently doing research at the Cleveland Clinic with interest on ex vivo organ perfusion, assessment, and resuscitation prior to transplantation

David Nasralla was awarded a Young Investigator Scientific Award for his presentation of the results from a multinational randomised controlled trial comparing normothermic machine perfusion (NMP) with static cold storage (SCS) in human liver transplantation. This is one of several trials being conducted by the Consortium for Organ Preservation in Europe (COPE) and required 220 livers to be transplanted in 7 transplant centres in 4 EU countries. NMP was shown to substantially improve early graft function as measured by the peak-AST (primary outcome, p<0.01) and early allograft dysfunction rates (p<0.01) despite better organ utilisation and longer preservation times in the NMP group.

David graduated from the Oxford University Medical School in 2005 and is currently completing his surgical training in the Oxford Transplant Centre whilst writing up his DPhil under the supervision of Prof. Peter Friend. In parallel to this, he is collecting the longer-term follow-up data from the trial and remains actively involved with further NMP studies including planning the next phase of clinical trials. Other aspects of his research have been concerned with the uptake of bile salts during ex-vivo liver perfusion and using NMP to immunologically modify an organ.

Kevin Tak-Pan Ng was granted a Young Investigator Award for his research paper: Up-regulation of GSTA2 at early-phase after liver transplantation increases the risk of late-phase hepatocellular carcinoma recurrence. The study has demonstrated that up-regulation of hepatic and plasma GSTA2 at early-phase after liver transplantation indicates not only an increased early-phase hepatic injury and but also a higher risk of late-phase HCC recurrence after liver transplantation. GSTA2 played important roles in liver cancer cells to adapt the dynamic change of ROS condition during the course of liver transplantation. Targeting suppression of GSTA2 is possibly a novel strategy to reduce the likelihood of HCC recurrence after liver transplantation.

Dr. Ng received his PhD degree in the Department of Surgery, at the University of Hong Kong. Currently, he is working on identifying biomarkers and therapeutic targets that can predict and overcome liver cancer recurrence after liver transplantation. He is also a 2-time recipient of a Young Investigator Award from the International Liver Transplantation Society.

Thomas Schachtner was granted a Young Investigator Award for his research paper: Kinetics of CMV-specific T-cells from pre- to posttransplantation predict outcomes in CMV-seronegative kidney transplant recipients. His work suggests that monitoring CMV-specific T-cell kinetics from pre- to post-transplantation offers superior risk stratification of CMV-seronegative kidney transplant recipients from CMV-seropositive donors. He proposed that patients with stable/increasing CMV-specific T-cells are suspected to have protective immunity against CMV, and qualify for safe discontinuation of CMV prophylaxis. In contrast, patients with undetectable/decreasing CMV-specific T-cells are at increased risk of CMV-infection and should continue CMV prophylaxis and monitoring of CMV-specific cellular immunity.

Dr. Schachtner received his M.D. from the Charité University Medicine in Berlin, Germany. Currently, he is focused on the final year of his specialist training in nephrology and the completion of the habilitation procedure. His research interests are: characterization of virus-specific immunity in kidney transplant recipients with CMV- and BKV-infection, characterization of alloreactive cellular immunity in kidney transplant recipients, infectious complications after solid organ transplantation, and long-term outcomes of living kidney donors.

Dr. Oscar K. Serrano received a Young Investigator Award for his research project titled: Defining the Tipping Point in Surgical Performance for Laparoscopic Donor Nephrectomy Among Transplant Surgery Fellows: a Risk-Adjusted Cumulative Summation Learning Curve Analysis. Along with his colleagues at the University of Minnesota, Dr. Serrano performed a retrospective intraoperative case analysis to assess the learning curve of transplant surgery fellows performing laparoscopic donor nephrectomies (LDN). Based on their estimates, transplant surgery fellows require between 35 and 38 cases to become proficient with LDN but demonstrate a tipping point of learning the procedure by approximately 24 to 28 cases. This project is significant for setting standards for the training of transplant surgery trainees and defining a benchmark on the number of LDN operations needed to become proficient.

Dr. Serrano received his MD from Stanford University and his MBA from the Johns Hopkins University. He completed his General Surgery residency at the Albert Einstein College of Medicine and is now a fellow in Transplant Surgery at the University of Minnesota. Clinically, he is interested in all facets of abdominal organ transplantation and hepatobiliary surgery and his research interests integrate practice improvement with biomedical research innovation to improve patient care. He also takes great interest in the education and training of surgical trainees in the modern era.

Rashmi Shingde received a Young Investigator Scientific Award for her systematic review of unexpected donor-derived infectious transmissions in kidney transplants. Under the supervision of Associate Professor Germaine Wong at the Centre for Kidney Research, Westmead, Australia, her work showed that unexpected donor transmissions can have significant patient morbidity and mortality. Whilst rare, the true incidence of such events is unknown due to the lack of a standardised global reporting framework.

Ms. Shingde is currently studying Medicine at the University of New South Wales and has an interest in renal and endocrine medical research.

Umang G. Thakkar was granted a Young Investigator Award for his research paper on Stem cell therapy for post-traumatic paraplegia and for renal parenchymal diseases. Autologous/ allogeneic mesenchymal stem cells (MSCs) can be generated in vitro from adipose tissue. MSCs have no HLA markers, are tolerogenic and immunomodulatory. Hence they can be used in immune disorders/ transplantation/ regenerative medicine. Neuronal differentiated autologous adipose tissue derived mesenchymal stem cells (Ad-MSCs) along with hematopoietic stem cells (HSCs) infused into cerebrospinal fluid for post traumatic paraplegia. Allogenic Ad-MSCs and HSCs were infused into portal, thymic and renal circulation for remission of renal parenchymal diseases. Post traumatic paraplegia which has no hope of recovery, can be treated with neuronal differentiated autologous Ad-MSCs and HSCs. Progression of RPD to ESRD can be arrested/ halted by Ad-MSCs and HSCs.

Mr. Thakkar earned his DCH (Paediatrics) from India and is experienced in the field of regenerative medicine. Currently he is working at the G.R. Doshi and K.M. Mehta Institute of Kidney Diseases & Research Centre (IKDRC) - Dr. H.L. Trivedi Institute of Transplantation Sciences (ITS), Ahmedabad, India. His research interests are stem cell therapy for treatment of various neurological disorders, cardiac disorders, autoimmune diseases like type-1 diabetes mellitus, systemic lupus erythematous etc.

Mirjam Tielen received a Young Investigator Award for her work on medication adherence after kidney transplantation. In collaboration with Emma Massey, Assistant Professor Health Psychologyof the Erasmus Medical Centre of Rotterdam, she has performed several studies on adherence of kidney transplant patients. In this particular study it was found that patients who reported being non-adherent to immunosupressive medication had a lower 4-year graft survival compared to adherent patients.

Ms. Tielen is a nurse practitioner with more than 10 years’ experience in the field of adult kidney transplantation at the Erasmus University Medical Center in Rotterdam. In her work as a nurse practitioner she works mainly at the outpatient clinic, evaluating transplant candidates and their living donors as well as providing post-transplant care. She obtained a PhD degree on 6th April 2016. She is an active member of several nursing organizations and was, for example, the President of the Dutch Workgroup of Transplant Nurses for 5 years. Currently, she is a board member of the Nurse Practitioner Society in the Erasmus Medical Center of Rotterdam and has also been board member of the foundation of OWVS (supporting scientific research among nurse practitioners) since 2013. In the future she will continue her work on medication adherence after kidney transplantation and she will focus on interventions to promote adherence to improve clinical outcomes.

Thomas Vanhove received a Young Investigator Award for his research related to connective tissue growth factor (CTGF). CTGF expression in 3-month renal allograft protocol biopsies was predictive of the progression of interstitial fibrosis on repeat 5-year biopsies, together with donor age. This indicates that, in a cohort of low-risk renal recipients with favorable histology at 3 months, significant differences may exist in the activation of profibrotic pathways, with implications for the development of long-term fibrosis. These findings are largely in agreement with previous microarray data that suggest important profibrotic and inflammatory activity, even in allografts with benign histology.

Thomas Vanhove received his MD from the Catholic University of Leuven, Belgium. He completed a residency in Internal Medicine at the University Hospitals Leuven and currently works as a research fellow at the Department of Nephrology and Renal Transplantation. His research focuses on tacrolimus pharmacology and identifying predictors of long-term renal allograft histology.

Georgios Vrakas received a Young Investigator Award for his work on the immunological impact of simultaneous intestinal and vascularized composite allograft transplantation at the Oxford Transplant Centre. The development of de novo donor specific antibodies (DSAs) after an intestinal transplant, in line with other organ types, is detrimental to the long-term outcome of the graft. So far, the Oxford data suggests that combining an abdominal wall vascularised composite allograft with an intestinal transplant does not increase the incidence of de novo DSAs. Dr. Vrakas received his MD from the

University of Crete, Heraklion, Greece, his M.Sc. from the Dimokrition University, Alexandroupolis, Greece and his Ph.D. from the Aristotle University, Thessaloniki, Greece. He was a resident for General Surgery at Drama and Papanikolaou General Hospitals, Greece. After his board certification as a Specialist for General Surgery, he completed transplant fellowships at Guy’s Hospital, London, UK and Churchill Hospital, Oxford, UK. Currently he is a Consultant Transplant Surgeon at Oxford University Hospitals. Clinically he is interested in intestinal and multivisceral transplantation and in renal autotransplantation following ex vivo resection of conventionally unresectable renal neoplasias. His research interests are: determining sentinel markers tracing status of the transplanted organ and remote, patient led, monitoring.

Johannes Wedel received a Young Investigator Award for his work on the identification of DEPTOR as a novel regulatory molecule in the alloactivation of CD4+ T cells. DEPTOR is a first-in-kind cell intrinsic modulator of mTOR, which Dr. Wedel demonstrated is expressed in T cell subsets and serves to enhance immunoregulation in vitro in cell culture models and in vivo in a fully MHC mismatched model of cardiac allograft rejection. The survival of wild type grafts in DEPTOR transgenic (overexpressors) is significantly prolonged (p<0.05). His studies provide for the intriguing possibility that targeting the regulation of DEPTOR in T cells has promise as a future therapeutic.

Dr. Wedel received his MD from Heidelberg University, Germany, and his PhD from the University of Groningen, The Netherlands. He is currently training as a research fellow in the Briscoe Laboratory and the Transplant Research Program at Boston Children’s Hospital, USA. He is interested further developing his career as a physician scientist in transplantation, and wishes to develop a research effort focused on alloimmunity and the identification of intracellular signals pathways pertinent to T regulatory cell survival and function post-transplantation.

Dr. Cheng Yang received a Young Investigator Award for his work on the cyclic helix B peptide inhibition ischemia reperfusion-induced renal fibrosis via the PI3K/Akt/FoxO3a pathway. In collaboration with Prof. Yaqiu Long in SIMM, Chinese Academy of Sciences, they recently synthesized a novel proteolysis-resistant cyclic helix B peptide (CHBP) that exhibits promising renoprotective effects. In this study, Dr. Yang evaluated the effect of CHBP on renal fibrosis in an in vivo ischemia reperfusion injury (IRI) model and in vitro TGF-β-stimulated tubular epithelial cells (TCMK-1 and HK-2) model. Their findings demonstrate that CHBP attenuates renal fibrosis and the epithelial-mesenchymal transition of tubular cells, through suppression of the PI3K/Akt pathway and thereby the inhibition FoxO3a activity. CHBP may become a promising new drug for the treatment of renal fibrosis.

Dr. Yang received his MD and PhD from the Fudan University in Shanghai. He then completed his surgical residency at Zhongshan Hospital, Fudan University. During the PhD training, he visited University Leicester and collaborated with Prof. Bin Yang on the research of acute kidney injury. He is now a resident in the Department of Urology at Zhongshan Hospital. In addition to TTS, Dr. Yang is a member of AST and ESOT. His research interests include acute kidney injury, rejection and tolerance, immune regulation in transplantation and cell apoptosis/necroptosis.

Oscar Yeung received a Young Investigator Award for his work with the topic "Transforming growth factor beta receptor III (TGFβR3) induced tumor promoting macrophages via complement component C5a in liver cancer". Following his previous study on the identification of M2 macrophages as one of the critical mediators in hepatocellular carcinoma (HCC) development, Dr. Yeung shifted his research focus to the mechanisms of tumor cells used for recruiting and stimulating the macrophage populations in the tumor microenvironment. In the study, he showed that that loss of the TGFβR3 contributed to the increased M2 macrophages in HCC through activating the complement component systems.

Dr. Yeung received his PhD from the University of Hong Kong and currently a post-doctoral fellow in the Department of Surgery. His research projects focus on the innate immunology particularly macrophages in liver transplantation and HCC.