close-up of man looking through microscope
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Expanding the reach of transplant techniques, ​​​​​organs and knowledge as a model to treat diseases wider than transplant.

For years, the scientific community has been studying models rather than people. We plan to study human tissue and human diseases directly.

For example, the liver is the largest solid organ in the body with amazing regenerative abilities. We know shockingly little about the cells that make up the human liver and in particular, the hepatic immune microenvironment. The liver is a critical organ for all metabolic processes, and when it fails due to disease, the only current treatment is transplantation, which is a high-risk surgery that requires lifelong immuno-suppression. Our research investigates how human liver diseases, such as liver cancer (hepatocellular carcinoma), change the immune cells in that organ by looking directly at the human liver and diseased human liver, and how we can modify the liver immune microenvironment with nanoparticle-mediated targeted drug delivery. We are applying similar questions to all of the other solid organs in the body, including lungs, heart, kidney, pancreas and intestine.

The goal of this pillar is to use transplant techniques, organs and knowledge as a model to treat diseases wider than transplant. Furthermore, in this area of research we want to expand the concept of Transplant Oncology for all organs. The wide aim of this pillar is to treat and prevent diseases that lead to transplant, thereby reducing the transplant burden. We aim to slow or reverse ongoing liver damage and promote its regeneration which will prevent the need for transplantation.

We employ many techniques to study human tissues: these include single-cell RNA sequencing (scRNA-seq), flow cytometry, confocal and 2-photon intravital microscopy. Our goals are to accomplish the following:

  • Healthy Organ Modelling: We will model healthy organs as a reference to examine the cellular drivers of organ failure.
  • Disease Modelling: We will characterize and model organ disease to identify targets for therapeutic modifiers to be delivered prior to transplant to prevent rejection, or during chronic disease to prevent the need for transplantation.
  • Transplant Oncolology: We are examining the cellular drivers of cancers that lead to transplantation. This will serve as the basis for clinical trials for non-resectable cancers. We are working on clinical trials to surpass traditional indications for transplant for cancer as well as studying the way to select the best candidates for such procedures.

Our current studies include:

  • Living Donor Liver Transplantation for Non-Resectable Liver Metastases from Colorectal Cancer
    Approximately every second patient with colorectal cancer develops metastases, often to the lung or liver. Although liver resection is a curative surgery for the liver metastases, only 20-40% of patients are candidates for this procedure. In this study, we will offer live liver donor transplantation to select patients who can’t undergo liver resection and who have a living donor willing to take part in the evaluation. Find more information.
  • Liver Transplantation for early stages of Intrahepatic Cholangiocarcinoma
    Intrahepatic cholangiocarcinoma (iCCA), a malignant tumour of the liver, is increasingly being diagnosed in patients with liver cirrhosis. Because of poor rates of survival and high probability of disease recurrence, most transplant centres don’t offer liver transplantation to patients with iCCA. In this study, we will evaluate how effective liver transplantation is in cirrhotic patients with a very early diagnosis of iCCA. Candidates will undergo a strict selection process and an in-depth transplant assessment and will be followed for 5 years from the time of procedure. Find more information.
  • Describing human organs in health and disease at the single cell level
    We are identifying all of the component cells in human organs, in both health and disease, using single cell RNA sequencing. These studies will identify cellular targets for treatment.
  • Creating models of disease using human cells
    We are designing ways to model human disease using small models that are based on human tissue. For example, we are creating a “kidney on a chip” that is based on human cells, and similar studies are underway in other organs. These models will be used for screening drugs and creating models of disease.​

Dr. Sonya MacParland
Email: sonya.macparland@uhnresearch.ca

Dr. Gonzalo Sapisochin
Email: gonzalo.sapisochin@uhn.ca

We are presently looking for trainees in clinical and basic science research. Please contact Sonya MacParland and Gonzalo Sapisochin. ​​