2023/2024
Machine Learning Enabled Optimization of Perioperative Hemodynamics in Renal Transplantations in Humans
Making kidney transplants last as long as possible is a goal shared by everyone. In order to get a kidney transplant the patient needs to have major surgery. This research project is geared towards making an artificial intelligence model for the operating room that can take all the data from the kidney donor, the kidney itself and the kidney recipient and make the best plan for how to optimize the many drugs and IV fluids used in the OR and afterwards to make the kidney work right away. This artificial intelligence will be able to make personalized plans for each patient having an operation, no matter how sick they are, or what quality of donor kidney they receive. Before this research, these types of calculations could not be done because there are too many factors to keep track of, but with artificial intelligence, the computer can be trained to help doctors improve kidney transplant survival for the long term.
Principal investigator Dr. Christopher Nguan
Co-investigators: Dr. Matthew Kadatz, Rohit Malyala, Dr. Adeera Levin, and Dr. Andrew Meikle
Patient Partner: Skully White and Teresa Atkinson
For an up-to-date list of publications by Dr. Christopher Nguan, please see ResearchGate
Characterizing the cerebrovascular physiology of circulatory death during withdrawal of life sustaining therapies in humans
Organ donation may proceed only after the brain’s function / blood flow are lost and death is declared. It can occur after withdrawal of life support machines while waiting for the heart to stop delivering blood flow and oxygen to the brain. This process is called donation after circulatory death (DCD). In DCD, death is determined when the pulse pressure (generated by the heart beat) is less than 5mmHg for a period of 5 minutes. However, owing to the disease characteristics of eligible organ donation patients (i.e. increased pressure inside the skull from a swollen brain), the brain is likely to lose its function and blood flow before the loss of heart function results in this very low blood pressure in the body. This delay in declaring death leads to a prolonged period of waiting during which the eligible organs become increasingly dysfunctional. This may lead to missed opportunities to donate organs or to worse outcomes when the organs are transplanted into patients who need them.
The research team will conduct a prospective feasibility study to characterize the moment of loss of brain blood flow with microcatheters that have been inserted into the brain during the management of the patient. By doing so, the team will identify the moment and pulse pressure at which the brain’s blood flow has ceased. They will also use a brain ultrasound to compare its accuracy in non-invasively determining the moment and pulse pressure at which the brain loses blood flow. By doing so, this study will provide the foundation to conduct a larger multisite study to definitively determine the moment that brain blood flow stops using brain monitoring devices and expedite the process of DCD.
Principal investigator Dr. Mypinder Sekhon
Co-investigators: Dr. Donald Griesdale, Dr. George Isac, Dr. Ryan Hoiland, Dr. Sam Shemie, Dr. Sonny Dhanani, and Dr. Peter Kim
Patient Partner: Ms. Carmen Choi and Mr. and Mrs. Peeler
For an up-to-date list of publications by Dr. Mypinder Sekhon, please see ResearchGate
A unique reciprocity-based strategy to improve living kidney donations in British Columbia: Focus Group Consultations
Despite the tremendous benefits of kidney transplantation, the demand for transplantation far exceeds the availability of organ donors in Canada, meaning patients have to wait years on dialysis before receiving a deceased donor kidney transplant (DDKT). Deceased donor rates have not changed since 2020. Further, there are limited living kidney donors in Canada and the numbers continue to stagnate. One of the things that limits potential living donors is the concern that someone they know, or love may need a kidney in the future and if they donate now they won’t be able to help other family members.
This project will explore the acceptability of policy in which living kidney donors would be able to identify someone who could receive a priority for a DDKT if they need it. As this would have important implications it is important to understand whether such a policy is acceptable to key stakeholders.
The research team will conduct focus group consultations with patients that are on the waitlist and those that have already been transplanted, living kidney donors, and general community members to explore the acceptability of reciprocity-based strategy. The results will be analyzed and reviewed with the key knowledge users and stakeholders, and policy briefs and reports will be developed to directly inform the development and implementation of reciprocity-based strategy in British Columbia.
Principal investigator Dr. Jagbir Gill
Co-investigators: Dr. Fuchsia Howard, Dr. John Gill, Dr. Justin Gill, and Reetinder Kaur
Patient Partner: Gurjit Pawar, Shakti Pawar, and Craig Setee
For an up-to-date list of publications by Dr. Jagbir Gill, please see ResearchGate
Accelerating the Translation of a Novel Luminex Anti-ABO Antibody Detection Technology to Expand the Use of ABO-Incompatible Transplantation in Canada
Although kidney transplantation offers better patient survival and quality of life over dialysis treatment, many patients on the transplant wait-list have a hard time finding a match due to their blood type. The ABO blood group of a patient is one of the most important factors that determines their ability to find a match. In Canada, patients that are blood group B and O experience much longer transplant wait-times compared to patients with other blood groups (A and AB).
To overcome this problem, doctors can perform transplantation across blood groups (ABO incompatible transplantation) to help difficult to match patients. However, this approach is not used widely as it can increase the risk of rejection. This is because doctors cannot reliably tell based on the current lab test which patients are safe to transplant across the ABO blood group. In a breakthrough development, Lan’s research group developed a new lab test (Luminex method) which can better assess the risk of rejection in patients that choose to receive an ABO-incompatible transplant.
The research team will apply the Luminex test to understand why some patients develop rejection when they receive an ABO-incompatible transplant while others don’t. In addition, they will test blood samples from patients on the current transplant wait-list to advise clinicians whether ABO-incompatible transplantation is a good treatment option. This research is innovative as it has the potential to safely allow for transplants that would previously not occur and greatly expand the transplant opportunities for patients awaiting a kidney transplant.
Principal investigator Dr. James Lan
Co-investigators: Dr. Jenny Tran, Dr. Paul Keown, Dr. Karen Sherwood, Dr. Melin Bissonnette, Dr. Azim Gangji, Dr. Lakshman Gunaratnam, Dr. Robert Liwski, Dr. Anne Haplin, and Dr. Lori West
Patient Partner: Kuljit Grewal, Kristi Coldwell and Teresa Atkinson
For an up-to-date list of publications by Dr. James Lan, please see ResearchGate
2022/2023
Virtual Reality and Gameplay as a Model for Exercise Rehabilitation in Pediatric Solid Organ Transplant Patients. A Patient and Family Led Initiative
Physical activity provides important health benefits for all children. Unfortunately, children undergoing solid organ transplantation (SOT) face many barriers preventing them from participating in regular physical activity including end-stage organ failure, prolonged hospitalization, chronic illness, other comorbidities and personal or parental concerns about the safety of exercise. While some recipients return to age-appropriate activities and lead healthy active lives, others need more support. Traditional hospital-based exercise rehabilitation can be effective at providing this support, but are also expensive to run, only accessible to patients who live close to the transplant centre and do not necessarily engage patients in activity outside of the structured program. Home-based programs can also be successful but prior experience by the study team suggests patient uptake is limited.
The idea for this project was initiated by a transplant recipient and his father based on the patient’s experience using immersive virtual reality (iVR) gameplay to increase physical activity levels following his transplant. In collaboration with patient and family partners the project team will employ a prospective, randomized, crossover cohort study to assess whether 8 weeks of iVR will increase cardiorespiratory fitness and strength in SOT patients.
It is anticipated that 8-weeks of iVR gameplay will not only improve cardiorespiratory fitness
and strength but will also improve patient compliance, engagement, and limit attrition in our program. Regular physical activity is essential for every SOT patient to be able to enjoy a long, healthy, and productive life. The project team believes that this patient and family partner-initiated project is key to helping achieve these goals.
Principal investigator Dr. Kathryn Armstrong
Co-investigators: Astrid De Souza, Julie Fairbairn, Dr. Tom Blydt-Hansen, Dr. Orlee Guttman, Dr. Mark Chilvers, John Jacob, and Dr. Jim Potts
Patient Partner: Sam Needham
For an up-to-date list of publications by Dr. Kathryn Armstrong, please see ResearchGate
2021/2022
Urine Microbiome Profiling in Kidney Transplant Recipients in Health and Disease
Kidney transplant represents the best treatment for those with end stage renal disease, however transplant recipients have weakened immune systems secondary to anti-rejection medications that are necessary to prevent organ rejection with subsequent failure. Recently, specific bacterial communities have been found to reside in the urinary tract which may influence the immune system, the so-called urinary microbiome. The urinary microbiome has not been extensively investigated in kidney transplant patients. The goal of this project is to understand the role urinary bacteria play in renal transplant patients and their associated influence on the transplanted kidney and the immune system. This work will explore if urinary bacteria directly influence the transplanted kidney, potentially maintaining or exacerbating the health of that kidney. Adult and pediatric renal transplant recipient urine, with associated clinical information, will be examined to determine bacterial compositions that live in the urine in both healthy post-transplant states and during kidney transplant rejection using state of the art laboratory techniques (16S rRNA sequencing).
Furthermore, the urine bacterial environments of male and female patients will be examined as there have been reported differences in the urinary microbiome based on gender related to hormonal and anatomic considerations in non-transplant patients. If successful, this study will pave the way for future projects aimed at developing tools to identify and halt kidney transplant injury so that transplant recipients can maintain their health for as long as possible.
Principal investigator Dr. David Harriman
Co-investigators: Dr. Olwyn Johnston and Dr. Dirk Lange
Patient Partner: Paul Albrighton
For an up-to-date list of publications by Dr. David Harriman, please see ResearchGate
Evaluation of propyl gallate for limitation of cold ischemic injury in organ preservation
Organ transplantation starts from a surgical procedure – removing an organ from a donor body and then implanting it into a recipient. However, cells of the donor organ die immediately after the blood supply is disrupted; thus, the donor organ must be perfused and stored in a cold preservation solution to control its damage. There are several preservation solutions available, but none of them performs ideally, particularly in the preservation of the deceased donors because a large number (up to 50%) of them don’t not work properly after transplantation. As a result, it increases the health care cost of transplant patients, shortens implanted organ survival and limits use of those deceased donors. This project seeks to develop a better cold preservation solution based on a novel hyperbranched polyglycerol and propyl gallate. Preliminary studies show that the HPG-based preservation solution protects the organs to be transplanted superior to any of the current methods available. Addition of propyl gallate to this HPG solution or standard University of Wisconsin (UW) solution further prevents cell death in three different human cells. In this proposal, a preclinical model will be used to confirm the increased prevention of donor kidney injury by addition of propyl gallate to the organ preservation solution. It is anticipated that the success of this project will have a significant impact: on patient’s recovery after surgery; increasing the donor pool to benefit more Canadians who need a transplant to save their life; and will translate to significant savings to the Canadian health care system.
Principal investigator Dr. Caigan Du
Co-investigators: Dr. Christopher Nguan
Patient Partner: Teresa Atkinson
For an up-to-date list of publications by Dr. Caigan Du, please see ResearchGate
2020/2021
An 8-week Virtual Exercise and Texting Program for Pediatric Solid Organ Transplant Patients
Being active is important for the health of children. Technology is now changing how children can be active. Children who have had a solid organ transplant have low activity levels. This is especially true for those with disabilities. Finding ways to increase activity levels in all children with a solid organ transplant is vital for their long-term health and development.
To date, exercise programs have been tried both in hospital and at home. Hospital-based programs are expensive to run and only allow access for local patients. Home-based programs are cheaper to run, more children are able to join in, but interest in these programs is varied.
Using our expertise in exercise and technology, we have developed a new online program that will be live streamed to provide 1-on-1 coaching to participants. Exercise classes can be done at home, are designed with input from participants, and are specific to their needs. This project builds on our previous work that used text messaging for solid organ transplant patients to communicate with their health care team. We will use the same platform to deliver the exercise program.
Principal investigator Dr. Kathryn Armstrong
Co-investigators: Astrid De Souza, Dr. Tom Blydt-Hansen, Dr. Anita Cote, and Dr. Jim Potts
For an up-to-date list of publications by Dr. Kathryn Armstrong, please see ResearchGate
Exploring ethical considerations in relation to direct contact between pediatric transplant recipient and donor families
BC Transplant has recently implemented a direct contact policy between transplant donor families and recipients in the adult population. The move to allow direct contact follows years of facilitated anonymous correspondence in the adult population and was prompted by self-advocacy on the part of donor families and recipients. Concerns related to privacy, boundary setting, consent and the autonomy of individuals, beneficence and non-maleficence, as well as legislative parameters were considered in the development of this policy.
While these ethical and other considerations have been explored in the adult context, there is very limited discussion of this topic in the pediatric context. Research in this area is therefore necessary as the situation in pediatrics is complicated due to pediatric recipients developing autonomy and capacity to consent, as well as other pediatric specific concerns. To examine this issue further, this research will investigate the unique considerations, risks, and benefits of direct contact in the pediatric context.
Through a two-step exploratory interview process, starting with those who have graduated into the adult program and then transitioning to those still in the pediatric program, we will examine the views of recipients, their families, and of donor families in relation to pediatric direct contact. Interviews will explore whether there are perceived differences between severable contact (eg. facilitated anonymous contact through BCT) and more final direct contact (eg. the exchange of personal information). These interviews will also analyze what supports pediatric transplant participants may want moving forward.
Principal investigator Dr. Alice Virani
Co-investigators: Jordy Hermiston, Dr. Tom Blydt-Hansen, and Jordan Joseph Wadden
Patient Partner: Shelby Gielen and Ranjeet Dhaliwal
For an up-to-date list of publications by Dr. Alice Virani, please see ResearchGate
2019/2020
The role of IL-17 receptor A in transplant rejection
Organ transplantation is the only treatment for end-stage organ failure. As such, it is a potentially curative procedure for devastating conditions such as kidney, heart and liver disease. The success of organ transplantation is limited by the rejection of grafts by the immune system of recipients.
Activation of the immune response that causes rejection depends on the actions of proteins that signal between cells, termed cytokines. IL-17 is a cytokine that has been implicated in transplant rejection but little is known about how it does this. Also, one of the main types of rejection that is particularly difficult to manage is caused by the production of antibodies that target transplanted organs. Dr. Choy’s laboratory has preliminary evidence that IL-17 may contribute to immune-mediated rejection of transplanted organs by supporting the development of antibodies that target the graft. The proposed studies will examine how IL-17 contributes to transplant rejection through supporting the production of antibodies. The findings have the potential to identify new therapeutic targets for the prevention of organ transplant rejection.
Principal investigator Dr. Jonathan Choy
Co-investigators: Winnie Enns and Kevin Rey
For an up-to-date list of publications by Dr. Jonathan Choy, please see ResearchGate
Investigating serum immuno metabolomic profiles associated with kidney transplant alloimmune outcomes
Transplantation is the leading treatment for people with end-stage kidney failure. But beyond the first year after transplant, we know some people will develop chronic forms of rejection that limits the transplant survival. We know that some people’s immune systems adapt better or become more “tolerant” to the transplant, but we don’t know all of the reasons why. While medications are an important part, we also know a person’s metabolism can play a role. That includes things like nutrition and disease, which can influence how a person’s immune system will respond. Under the right conditions, the immune system may be more likely to “adapt” to the transplant and avoid chronic rejection.
This study will look at samples that have been collected before transplant, to see if there are changes we can measure in metabolism that predict who will have a positive (tolerant) or negative (rejection) response to the transplant. We will use blood samples collected from people before transplant and test for hundreds of small molecules (called metabolites). We will look for patterns of these metabolites that might predict who is more likely to develop chronic rejection and also early rejection. We will use this information to develop a test that could be used before transplant to tell people about their risk of rejection. It may also help to identify why that risk is higher, and ways to reduce the risk.
We hope that this research will help us understand and predict who is at high-risk for chronic rejection, and give us clues about how we can change them before transplant to improve chances for long-term transplant survival.
Principal investigator Dr. Tom Blydt-Hansen
Co-investigators: Dr. Paul Keown, Dr. Atul Sharma, Dr. David Wishart, Dr. Graham Sinclair
For an up-to-date list of publications by Dr. Tom Blydt-Hansen, please see ResearchGate
2018/2019
“Let’s Talk Teenage Transplant”: Using Text Messaging to Engage with Adolescent Solid Organ Transplant Patients
Adolescence is a crucial time in the transplant journey. During this time patients experiment with not taking their medications and are resistant to attending medical appointments. Choosing not to take medications or follow medical advice can have significant consequences and can lead to serious and life-threatening illness. The reasons for these choices are not well understood and likely depend on several factors, but may be partly attributed to the ongoing development of executive function which occurs throughout adolescence. Executive function (EF) refers to a set of skills that are required to plan and perform complex tasks.
Establishing better communication between adolescents and their health care providers (HCP) may help adolescents gain the skills to plan and perform complex tasks related to their health (ie. taking medications or filling a prescription). This fosters independence and teaches the adolescent how to manage their own health. Currently, parents are the primary communicators with HCP. Improved communication methods between HCP and adolescent patients are needed.
Text messaging is a preferred way for adolescents to communicate. Due to hospital policies, HCP are unable to text message their patients. Using a short messaging service (SMS) platform allows for communication via text messaging in accordance with hospital policies. The goal of this project is to implement a SMS platform to communicate with adolescent transplant patients and to determine its effect on health outcomes.
Principal investigator Dr. Kathryn Armstrong
Co-investigators: Astrid De Souza, Dr. Tom Blydt-Hansen, Dr. Anita Cote, Dr. Derek Human, Dr. Orlee Guttman, Dr. Shu Sanatani, Dr. Tim Oberlander, and Dr. Jim Potts
For an up-to-date list of publications by Dr. Kathryn Armstrong, please see ResearchGate
Examining the Impact of Overdose Deaths on Solid Organ Transplantation
Canada is facing a worsening opioid overdose crisis. This has resulted in a dramatic increase in the number of overdose related deaths, now surpassing all other causes of unnatural deaths. On average four people die every day in BC as a result of overdose; the majority of these are relatively young adults (aged 18-50). In parallel, the number of people dying as a result of organ failure is increasing. Many of these patient’s lives can be saved or improved with organ transplantation. Unfortunately, the number of organs available for transplantation is too small to help all people who could benefit. People dying from opioid overdose can become organ donors. In fact, 25% of transplantation in BC is currently a result of organ donation from people dying of overdose. However, when someone dies of overdose there is concern that they are at higher risk of having viruses such as HIV and Hepatitis B and C, and that they may transmit these viruses to organ failure patients via transplantation. This theoretical concern may lead to non-utilization of these potential donors or their organs for transplantation, despite the otherwise good health of organs from these donors. This project will determine the safety of organ transplantation from overdose donors (i.e. disease transmission and survival), and examine patterns of non-utilization of donors and their organs.
Principal investigator Dr. Caren Rose
Co-investigators: Dr. Mustafa Toma, Dr. Sean Keenan, and Dr. Mel Krajden
For an up-to-date list of publications by Dr. Caren Rose, please see PubMed
The Impact of Slow Efficiency Hemodialysis on the Duration of Delayed Graft Function: A Feasibility Pilot
Kidney transplantation is the preferred treatment for patients with kidney failure. Unfortunately, the number of kidneys available for transplantation is insufficient to the meet the need for transplantation and patients wait up to eight years to receive a transplant from a deceased donor. To help meet this need, it is necessary to use kidneys from older deceased donors and other donors at risk for post transplant complications. These kidneys can be successfully transplanted but are at increased risk of complications after transplantation that can compromise transplant survival and success. One of the most important complications is failure of the kidney to immediately function after transplantation known as delayed graft function (DGF). During DGF patients must be supported by dialysis, which itself can prolong the duration DGF by causing low blood pressure and increasing inflammation. Remarkably no studies have addressed the optimal way to provide dialysis in patients with DGF. We hypothesize that long intermittent dialysis, which minimizes the adverse effects of dialysis, will reduce the duration of DGF compared to conventional dialysis treatment. The proposed study will inform the feasibility of a definitive randomized controlled trial to determine whether long intermittent dialysis will reduce the duration of DGF leading to better short- and long-term transplant outcomes.
Principal investigator Dr. Mercedeh Kiaii
Co-investigators: Dr. Clair Harris, Dr. Jagbir Gill, Dr. James Lan, Dr. John Gill, Dr. Mathew Kadatz, and Dr. Olwyn Johnston
For an up-to-date list of publications by Dr. Mercedeh Kiaii, please see ResearchGate
2016/2017
Granzyme K in Allograft Vasculopathy and Expression in Cardiac Tissue
Heart Failure is a common disease affecting at least 23 million people world-wide. Heart transplantation is the gold-standard treatment in patients with end stage heart failure. Transplant rejection is the major limiting factor in long term survival of transplant patients. There are 2 types of immune rejection; early (acute) and late (chronic). Late rejection is dominated by immune damage to the blood vessels that feed the transplanted heart. As a result, scar tissue narrows these blood vessels and the heart muscle is deprived of oxygen and nutrients and the heart ultimately fails.
Immune cell infiltration is one of the earliest steps in late rejection. Immune cells can cause damage to the transplanted heart by secreting protein-degrading enzymes known as Granzymes. These so-called proteases damage the inner layer of the blood vessels of the transplanted heart causing them to die.
Granzyme K (GzmK) has been shown to be highly elevated in patients with late rejection and causes significant inflammation in blood vessels. Using a mouse model of human transplant rejection and mice that genetically lack GzmK, we will test whether GzmK deficiency results in reduced late rejection and inflammation. This project will provide key proof of concept data as to whether to pursue GzmK as a future drug target for attenuating chronic transplant rejection. Ultimately our goal is to reduce the impact of late rejection and increase transplant patient survival.
Principal investigator Dr. David Granville
Co-investigators: Dr. Jonathan Choy
For an up-to-date list of publications by Dr. David Granville, please see ResearchGate
The Donor Heart After Withdrawal of Life Support
The biggest problem in heart transplantation is the shortage of donor hearts. This shortage results in the death of significant numbers of patients with end-stage heart failure who would have been eligible to receive a new heart. To boost the number of hearts available for transplantation, researchers have been investigating alternative pathways for heart donation. One solution that has significantly increased the number of organs available for lung, liver, and kidney transplantation is referred to as donation after circulatory death (DCD).
The main objective of this proposal is to study human DCD hearts on a machine, to find ways of identifying when a heart is too injured, and therefore unsafe to use for a recipient. This approach would allow surgeons to make decisions about a heart’s suitability before committing a recipient to a heart with an uncertain outcome. In most of the world (including British Columbia), DCD hearts are not currently used for transplantation. In fact, these hearts are simply discarded. This represents a lost opportunity for researchers who could put the heart to good use, and make valuable discoveries that would benefit heart failure patients and society.
Principal investigator Dr. John Boyd
Co-investigators: Dr. Mark Kearns
For an up-to-date list of publications by Dr. John Boyd, please see PubMed
2015/2016
Quality of Life and Mental Health Needs of Children After Solid Organ Transplantation in BC
Severe kidney, heart or liver failure that is life threatening can be rescued by organ transplantation. Children and families who have survived these critical illnesses often carry mental scars related to their experiences with organ failure. As a result, children and their parents experience intense and chronic stress, isolation, family disruption and restriction in their ability to participate in “normal” childhood activities.
We expect that children with this lived experience may suffer symptoms related to anxiety, post-traumatic stress, depression and impaired tolerance of medical procedures. Quality of life is perhaps the most important outcome for solid organ transplant recipients, given that the goal of transplantation is rehabilitation with restoration of organ function.
We have previously initiated mental health and quality of life screening in the transplant clinic at BC Children’s Hospital. This research proposal will review the results from screening to learn what types of mental health symptoms are most common, their severity and to understand how they impact quality of life. We hope to develop better interventions that holistically enhance rehabilitation of children after transplantation and improve their long-term quality of life.
For an up-to-date list of publications by Dr. Tom Blydt-Hansen, please see ResearchGate
Early Detection of Artery Thickening in Pediatric Heart Transplant Recipients
Children who have had a heart transplant are at risk for developing a disease called cardiac allograft vasculopathy (CAV) where their coronary artery walls thicken over time. Sadly, CAV is responsible for 1 in 4 patient deaths. The current way to look for CAV is to use a technique called angiography where dye is injected directly into the coronary arteries and imaged. However, the limitation of angiography is that it can only detect late-stage disease and therefore treatment is less likely to work.
For this project, Dr. Harris will use a new imaging technique called optical coherence tomograph (OCT) to detect problems developing in children’s heart transplant grafts early enough to treat the problem. OCT is an imaging technique designed for use in adults that is beginning to be used in children. Dr. Harris has already performed a preliminary OCT study and found that OCT detects artery thickening earlier than angiography in children heart transplant recipients. He will now use OCT to follow these children over time to establish this technique for reliable, routine use.
For an up-to-date list of publications by Dr. Kevin Harris, please see ResearchGate
Treating Multidrug Resistant Infections in Transplant Recipients with Fecal Microbiota Transplants
Organ transplant patients are at increased risk of developing highly antibiotic resistant infections as a result of their transplant surgery, lengthy hospitalization and repeated use of antibiotics during their medical care. The source of these multidrug-resistant bacteria is the patient’s own gut. In this study, Dr. Manges will test whether fecal microbiota transplantation (FMT) can remove highly drug-resistant bacteria from the gut of kidney transplant patients. FMT is a therapy that involves the infusion by enema of a well screened, healthy donor stool into a patient’s gut. FMT can replace the gut microbial community containing these drug-resistant bacteria, with a microbial community characterized by more beneficial organisms with lower levels of antibiotic resistance, thereby lowering a kidney transplant patients’ risk of hard to treat, post-transplant infections. The goals of this study are to confirm that FMT can eliminate drug resistant bacteria from the gut of transplant recipients, and to determine how long the patient remains free of these drug resistant organisms.
For an up-to-date list of publications by Dr. Amee Manges, please see ResearchGate
Transplantation of Thyroids Enclosed in Protective Pouches
The thyroid gland makes hormones which control how quickly the body uses energy, makes protein and controls the body’s sensitivity to other hormone. The thyroid is often removed because of cancer or benign disease (several hundred thousand per year in N America), and loss of thyroid function leads to severe illness and disease, so these people take thyroid hormone (thyroxine) replacement therapy. But people receiving thyroxine still experience side effects (weight gain, depression, headaches, cardiovascular disease) because taking thyroxine is not the same as having a functional thyroid gland that can monitor the body’s metabolism and produce hormones in real time as it is needed. Transplantation of thyroid gland back into these people would give better metabolic control.
Dr. Wiseman will test whether thyroid glands obtained from deceased donors can be placed inside a special pouch and implanted into a recipient. The pouch will protect the thyroid gland from attack by the immune system so the recipient can live a normal life with a functioning thyroid gland without having to take anti-rejection drugs.
For an up-to-date list of publications by Dr. Sam Wiseman, please see ResearchGate
2014/2015
Integrating Registration for Organ Donation into Routine Health Care Encounters
Canadians have made it overwhelmingly clear they support organ donation, yet this does not translate into eventual donation. Our deceased organ donor rate is around 15 per million people. This ranks us 23rd in the world behind countries such as Croatia, Puerto Rico and Latvia. Dr. Gill and his team propose eliminating one potential barrier by getting health care providers to discuss organ donation with patients during routine health encounters. His project will establish protocols and quantify their effect on the rate of organ donation. By “normalizing” the conversation around organ donation, much as the medical system in BC has done with routine HIV testing, Dr. Gill believes we can greatly enhance organ donation rates.
For an up-to-date list of publications by Dr. John Gill, please see ResearchGate
Development of Multi Allograft Kidney Organ (MAKO) Units from Nephrectomy Specimens for Meeting Kidney Transplant Donor Supply
With kidney transplant waitlists in BC up to ten years long, one of the province’s leading urologic surgeons is hoping to find a potential new source of kidneys. Dr. Nugan believes a potential new source of kidneys could be those that are removed for reasons such as kidney stones, obstruction and small tumors. Even though only part of the kidney is damaged, the entire organ is usually discarded. Initial research has shown some of these discarded kidneys can be successfully repaired and transplanted. Dr. Nguan and his team want to go one step further by taking smaller portions of disease-free discarded kidneys and devising surgical techniques to reassemble them into a whole functioning organ. These reassembled kidneys can then be used for transplantation.
For an up-to-date list of publications by Dr. Christopher Nguan, please see ResearchGate
2013/2014
A novel flush/preservation solution for cold preservation of donor organs for transplantation
Cold preservation of donor organs is a crucial aspect of organ transplantation, not only to keep the organ viable but also to prevent as much cellular damage as possible during the time the organ is out of the body. Several organ-preservation solutions are available, but they are not satisfactory and as a result organ damage still occurs. Thus, a new cold storage solution that can prevent cellular edema and tissue destruction is needed for the safe preservation of donor organs before they are transplanted into recipients. Dr. Du has developed a novel cold storage solution that has the potential to minimize cold ischemia-related injuries in donor organs. Preliminary studies have demonstrated the novel polymer-based solution significantly increased cell survival of cultured human endothelial cells at 4oC, and reduced tissue damage of murine hearts during cold storage. However, more preclinical studies are needed to prove the hypothesis and test the efficacy in animal models. Dr. Du and his team will further evaluate the beneficial effect of this polymer-based solution on cold organ preservation using transplantation models.
For an up-to-date list of publications by Dr. Caigan Du, please see ResearchGate
Use of Topical Immunosuppressive Drugs for the Induction of Tolerance to Allogeneic Skin Transplantation
Solid organ transplantation may be a life-saving treatment in individuals with illnesses that have caused organ failure. However, a challenge remains in preventing graft rejection and eventual graft loss. Current strategies to minimize organ rejection include matching recipients with donors according to their genes and by controlling the patient’s immune system with immunosuppressive drugs. Although current immunosuppressive drug therapy has dramatically improved early transplant outcomes, the long-term rate of organ rejection has not decreased substantially, and the use of immunosuppressive drugs can induce serious side effects. Therefore, we need a better method of educating the immune system to tolerate a foreign organ.
Dr. Dutz’s team believes expanding the number of regulatory T cells in transplant patients will help them accept the foreign organ, minimizing the need for life-long immunosuppressive drug therapy. Corticosteroids and Vitamin D are two immunosuppressive drugs that can direct our bodies to make regulatory T cells. Dr. Du’s laboratory has shown that topical application (rubbing onto the skin) of Vitamin D and corticosteroids generates regulatory T cells, and it is less toxic than the traditional oral method of delivering the drugs. This project seeks to optimize the method of drug delivery through the skin to make regulatory T cells and evaluate its efficacy to prevent organ rejection in laboratory animals.
For an up-to-date list of publications by Dr. Jan Dutz, please see ResearchGate
2012/2013
A Novel Tolerance Induction Strategy for Allotransplantation
Within the immune system, there is a subgroup of immune cells, called T-regulatory cells. The function of these cells is to control and regulate other immune cells and prevent destruction of transplanted organs. One very promising solution to the problem of rejection is to generate tolerance. This can be done by increasing the number of special T regulatory immune cells in transplant recipients’ bodies. Dr. Ghahary’s research seeks to find a novel and effective way to protect transplanted organs without putting the patient’s health in danger by avoiding the use of immune suppressing medications.
For an up-to-date list of publications by Dr. Aziz Ghahary, please see ResearchGate
2011/2012
Use of Naturally Immune Privileged Cells in Islet Transplantation
Parts of hair follicles exhibit “immune privilege” due to the secretion of immuno-regulatory factors and a lack of expression of the human leukocyte antigen (HLA proteins) on their cell surface. It is the HLA antigens that are recognized by the immune system and lead to organ transplant rejection. Because these unusual hair follicle cells do not have HLA antigens on their surface, they are not “seen” by the immune system. Unlike most cells and organs, the hair follicle cells are not rejected when transplanted from one person to another. These hair follicle cells also actively secrete factors that suppress local immune system activity. The team proposes to use these cells, with their natural non- or low immunity, to locally protect transplanted islets. We will “coat” islets with the hair follicle cells to provide a protective shield for the islets against rejection by the transplant recipient’s immune system. After transplantation, the hair follicle cells will hide the islet cells from the immune system but allow them to function and control blood sugar levels. If this approach is successful, it will provide a simple way to transplant islets to people who have type I diabetes and avoid the need for using immunosuppressive drugs.
For an up-to-date list of publications by Dr. Garth Warnock, please see ResearchGate
2010/2011
Quality of Life After Living Kidney Donation: No-directed Versus Directed Donor
There has been an expansion of living kidney donation in Canada with the National Living Donor Kidney Exchange Program. However, the quality of life after non-directed living kidney donation (paired exchange or anonymous kidney donation) is not well established. The team hypothesizes that quality of life after non-directed is equivalent to that after directed living kidney donation. It is expected that there will be no quality-of-life differences between directed and non-directed giving additional evidence to support further expansion of non-directed living kidney donation. In turn would potentially reduce the prolonged waiting time for deceased donor kidney transplantation in British Columbia.
For an up-to-date list of publications by Dr. Olwyn Johnston, please see PubMed
Granzymes in allograft vasculopathy
Dr. Granville has detected an increase in enzymes in patients experiencing chronic rejection following heart transplantation. The researchers will investigate the consequences of these increased enzymes in the context of inflammation and wound repair. It is hypothesized that increased enzymes lead to impaired wound healing.
For an up-to-date list of publications by Dr. David Granville, please see ResearchGate
Tailoring Tregs: A Novel Approach to Generate Alloantigen Specific T Cells
Dr. Levings and team are studying how a type of white blood cell, known as a T regulatory cell, or Treg, can be used as a new way to control how the patient’s immune system responds to a foreign organ. It is thought that by increasing the numbers of Tregs in transplanted patients, there will be a new way to prevent organ rejection that will not come with the side effects of the immunosuppressive drugs that are currently used. The team aims to develop a new way to make Tregs that will specifically control immunity to transplanted organs without impacting any other aspects of the patient’s immune system. If successful, this approach would represent a major step towards implementing the use of Tregs as a novel cell-based therapy to improve the long-term success of organ transplantation.
For an up-to-date list of publications by Dr. Megan Levings, please see ResearchGate