Charbonneau trainees awarded 2025 CIHR Doctoral and Postdoctoral Awards

Dr. Fatemeh Mashayekhi

Supervisors: Dr. Nicola Wright, Dr. Douglas Mahoney

Building the First Made-in-Canada Base Editing Pipeline for Inborn Errors of Immunity: Proof-of-Concept in ADA-SCID Q3X

Inborn errors of immunity are inherited diseases caused by mutations, which can be thought of as typos, in DNA that weaken the immune system and lead to serious infections. One of the most severe and relatively common in Canada is adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID). The current best treatment is a bone-marrow transplant from a closely matched donor, but many patients don't have a match, the procedure is costly, and it can cause life-threatening complications from using someone else's cells. My research aims to fix the DNA mutation directly in a patient's own blood stem cells. Read more

Dr. Enoch Tin

Supervisors: Dr. Jongbok Lee, Dr. Sorana Morrissy

Developing novel chimeric antigen receptor double-negative T-cell therapy for acute myeloid leukemia

Adoptive cellular therapy (ACT) is a treatment method that involves infusing human immune cells into patients to fight diseases like cancer. One form of ACT uses genetically engineered (GE)-T cells, a major type of white blood cell, to kill cancer cells based on a selected molecule found on the cancer cell surface. While successful with certain blood cancers, its application to acute myeloid leukemia (AML), the most common form of adult acute leukemia, has been challenging due to the inability to find safe and effective target molecules on all AML cells. AML cells are very similar to normal stem cells, essential cells that develop into all types of blood cells, and have different characteristics between patients or within the same patient. This project focuses on a rare subtype of T cells called double-negative T cells (DNTs), which can kill AML while sparing healthy cells without any modifications. However, some AML cells cannot be killed by DNTs. The objective is to develop GE-DNTs to better target AML cells and understand their anti-cancer mechanisms. Read more

Jada Curry

Supervisor: Dr. Pierre Billon

Repurposing a clinically approved safety switch to engineer exhaustion resistant CAR-T cells

The ability to retrain the immune system to detect and eliminate cancer has revolutionized cancer treatment, particularly through CAR-T cell immunotherapy. CAR-T therapy reprograms a patient's own T cells, the killer cell of the immune system, to recognize and precisely eliminate cancer cells. While revolutionary for some patients, this approach suffers from variable response rates. Gene editing can significantly improve CAR-T cell function; however, low editing efficiencies currently limit its therapeutic applications. We hypothesize that repurposing inducible caspase 9 (iC9), a safety switch used for cellular therapies, as a selection system for edited cells will achieve therapeutically relevant editing efficiencies (>80%) to enable engineering of superior CAR-T therapies. Read more

Rachelle Drummond

Supervisors: Dr. Tavis Campbell, Dr. Fiona Schulte

Evaluating a Behavioural Intervention to Improve Long-Term Follow-Up Care Among Survivors of Childhood Cancer Survivors: A Phase II Proof-of-Concept Study.

Surviving childhood cancer is a remarkable achievement of a long and hard journey, but the journey doesn't end when treatment does. Most survivors will develop health problems later in life due to their treatments, called late effects. These can include, but are not limited to, secondary cancers, mental health challenges and fertility complications, often showing up years after treatment ends. Specialized, long-term follow-up (LTFU) care is one of the most successful ways to identify and manage these problems early, improving quality of life and health outcomes for survivors. Despite this, fewer than half of childhood cancer survivors in Canada attend LTFU care. To better understand why many young adult survivors never engage with LTFU care or stop engaging with care, and how we can help them re-engage, we are currently conducting interviews with survivors who are "lost-to-follow-up" (i.e., they have not been to a survivor clinic in two or more years or have never attended). Read more

John Hutchinson

Supervisor: Dr. Darren Brenner

Development of a Risk-Prediction Model for Early Onset Colorectal Cancer

Colorectal cancer has become increasingly common in people younger than 50 years old in Canada. Given this increase, there is motivation to expand colorectal cancer screening tests to cover people between 45 and 50 years of age. However, this change will not allow for detection of cancers below 45 years of age. Therefore, rather than relying only on age, it is essential to assess an individual's risk before inclusion in future screening. The goal of this study is to study various colorectal cancer risk factors and construct a risk prediction model to determine which people below 50 years old would benefit most from screening. Read more

Jethro Langley

Supervisors: Dr. Pierre Billon, Dr. Douglas Mahoney

VIVO-EDIT: In Vivo Engineering of Multiplex-Edited CAR-T Cells Using Virus-Like Particles for Cancer Immunotherapy

This research aims to demonstrate the anti-tumor efficacy of VIVO-EDIT (Aim 1) by testing its ability to eliminate cancer in humanized mouse models of leukemia, directly comparing it to conventional CAR-T cell therapy. We will also establish its safety profile (Aim 2) using mouse models by measuring immune responses to VIVO-EDIT, identifying potential off-target effects and assessing inflammation and toxicity. By eliminating complex manufacturing requirements while enhancing treatment durability, this approach would fundamentally transform the efficiency and accessibility of CAR-T therapy and establish a new paradigm for immune cell engineering, positioning Canada as a leader in next-generation cellular immunotherapy. Read more

Heejae Lee

Supervisors: Dr. Jongbok Lee, Dr. Nicole Culos-Reed

Exercise to enhance adoptive (double-negative) T cell therapy for acute myeloid leukemia

By investigating how exercise improves immune cell function, this study aims to uncover new ways to enhance the effectiveness of DNT therapy, identify novel pathways involved, and address significant challenges in cancer treatment. At a novel intersection of cancer immunotherapy and exercise science, this research will pave the way for new applications of exercise to develop more effective treatments, advancing our understanding of leveraging lifestyle interventions to enhance patient outcomes. Read more

Shanshan Wang

Supervisors: Dr. Jongbok Lee, Dr. Douglas Mahoney

Investigating the therapeutic potential of CD4-targeted CAR-double negative T cells in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive blood cancer with very poor survival rates. Standard treatments like chemotherapy often fail, and many patients relapse, leading to limited long-term survival. Bone marrow or stem cell transplants from healthy donors can sometimes cure AML by enabling the donor's immune system to attack leukemia cells. However, this approach carries major risks: if the immune attack is too weak, the leukemia returns (relapse); if it is too strong, it causes a serious complication called graft-versus-host disease (GvHD), in which donor cells attack the patient's healthy tissues. My research focuses on a unique type of immune cell called double-negative T cells (DNTs). These cells naturally recognize and kill leukemia with minimal side effects, and our team has already demonstrated that they can be safely expanded from healthy donors and administered to patients in an early clinical trial. However, in some cases, DNTs alone are not potent enough to fully eliminate AML. To overcome this, I am enhancing DNTs by engineering them with a special receptor called a chimeric antigen receptor (CAR) that enables them to recognize CD4-a marker found on most AML cells but not on healthy stem cells. Read more

Liam Wilkinson

Supervisor: Dr. Johnathan Canton

APOL9A exposes hidden Staphylococcus aureus in Kupffer cells to trigger enhanced anti-bacterial immunity

Kupffer cells (KCs) are immune cells contributing to the filtering functions of the liver. KCs are efficient at eating bacteria like Methicillin-resistant Staphylococcus aureus (MRSA) which reside in compartments called phagosomes. Phagosomes act as the stomach of the cell where killing and digestion of bacteria occurs. However, some bacteria can hide within phagosomes, grow, and escape to other sites of the body. KCs sense the presence of live bacteria by recognizing shed molecules, leading to enhanced killing. Interestingly, these bits of live bacteria are sensed outside the phagosome. It is unclear how these molecules trapped within phagosomes escape. We study proteins which poke holes in these cellular stomachs, allowing material to travel outside of phagosomes and into the main body of cells. Apolipoprotein L 9A (APOL9A) is specifically found in KCs and it resembles other proteins which can puncture phagosomes. Therefore, we hypothesize APOL9A pokes holes in phagosomes to facilitate the escape of molecules associated with live bacteria to the cytosol. Read more