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Garron Family Cancer Centre

GFCC Research Fellows

The GFCC fellowships support clinicians, scientists and graduate students on an annual basis who are looking to advance their knowledge of cancer care and research. These fellowship opportunities aim to provide training through direct participation in basic science or clinical investigation under the supervision of world leaders in oncology research and clinical care.

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Dr. Sarah Cohen-Gogo, Scotiabank Clinician Scientist Fellowship
Supervisor: Dr. Daniel Morgenstern

PARP Inhibitors and Chemotherapy for children, adolescent and young adults harbouring Tumours with homologous Recombination repair deficiency: a phase II pilot study

While the survival rate in Canada approaches 82 per cent for all child, adolescent, and young adult cancer patients, the prognosis for patients with refractory, relapsed or metastatic disease remains unacceptably poor.
A pan-Canadian collaboration called PRecision Oncology For Young peopLE (PROFYLE) was created to improve survival for the patients with ‘hard-to-treat’ cancers by providing better access to next generation sequencing and targeted therapies. The PROFYLE program expands and integrates the Toronto regional paediatric cancer precision medicine program called KiCS (Kids Cancer Sequencing).
Among the identified genetic aberrations, those leading to deficiencies in a DNA repair pathway called homologous recombination are a promising group for targeted therapy. A family of drugs called PARP inhibitors is now part of the treatment for some adult cancers (ovarian, breast) that have such abnormalities.
As it remains unclear how to best identify paediatric, adolescent and young adult patients who may benefit from these drugs, we are developing a Canadian pilot clinical trial that will provide access to these new drugs for patients with hard-to-treat cancers, and take into account the information from the PROFYLE sequencing study to look for potential biomarkers.

 

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Dr. Grace Egan, GFCC Leukemia Clinician Scientist Fellowship
Supervisor: Dr. Aaron Schimmer

Nuclear Hexokinase 2: Mechanism of Regulating Stemness

Acute myeloid leukemia (AML) remains one of the most difficult to treat childhood cancers given its high rates of relapse and treatment-related toxicity.  Leukemic stem cells (LSCs) are thought to be responsible for initiation, maintenance, and recurrence of AML. Understanding the biology of leukemia stem cells is crucial for developing effective, targeted, therapies for AML. Previous work has shown that enzymes involved in metabolism can influence gene expression when they move from the mitochondria to the nucleus. Little is known about this process in AML. Hexokinase 2 (HK2) is a metabolic enzyme involved in glucose metabolism. Recent work in our lab has demonstrated that leukemia stem cells have increased levels of HK2. When nuclear HK2 is over-expressed in AML cells, it is associated with a stem-like phenotype, making cells resistance to differentiation with chemotherapy. The mechanism of how nuclear HK2 contributes to stemness is unknown. My project will decipher these mechanisms, which appear to involve epigenetic processes and DNA damage repair signaling pathways. By exploring the interacting proteins and pathways of nuclear HK2, it may be possible to discover novel therapeutic ways of selectively reducing the leukemia stem cell population in AML.

 

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Dr. Reena Pabari, Scotiabank Clinician Scientist Fellowship
Supervisor: Cynthia Guidos

The use of high dimensional mass cytometry to detect and characterize relapse-originating cells in acute myeloid leukaemia

Patients with acute myeloid leukaemia (AML) have high rates of relapse, despite initial apparent responsiveness to chemotherapy in many cases. There is evidence that the relapsed disease derives from a population of leukemic stem cells that are present at the time of diagnosis. In patients with acute lymphoblastic leukaemia (ALL), flow cytometry is used to identify the persistence of leukemic cells (minimal residual disease) after induction chemotherapy in order to guide and intensify treatment if needed. In contrast, AML is a heterogeneous disease that is difficult to characterize with routine flow cytometry. I will be using high dimensional mass cytometry to characterize and evaluate the relapse-originating cells in diagnosis-remission-relapse samples from patients with AML. Mass cytometry can profile up to 40 markers per cell and has a greater ability to characterize heterogeneous cell populations. Our goal is to be able to identify and monitor the relapse-seeding clones in patients with AML in order to better guide therapy and prevent further progression of disease.

 

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Dr. Bryan K. Li, BMO Financial Group Oncology Fellowship
Supervisor: Dr. Annie Huang

Genomic Landscape of Pineoblastoma

Pineoblastoma is a rare brain cancer affecting mainly young children. They are difficult to treat, with only half of patients surviving despite aggressive therapy.  Little is known of pineoblastoma due its rarity and the surgical difficulty in acquiring enough of a sample for detailed analysis. Through the international Rare Brain Tumour Consortium, we have gathered and are analyzing the largest known collection of pineoblastoma samples. We are currently working to find what molecular factors drive these cancers to behave so aggressively. Our goal is to determine which of these can be targeted with current and experimental drugs, then validate them using cell culture and mice studies. Our findings will be used to design the next clinical trial for children with pineoblastoma to advance treatment and improve survival.

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Dr. Fyeza Hasan, BMO Financial Group Oncology Fellowship
Supervisor: Dr. Lillian Sung

Children with Cancer as Participants in End of Life Research

Survival rates for childhood cancers have increased dramatically, but 20 per cent of patients still die of their cancer or its treatment. The end-of-life (EOL) care of these children is difficult and includes addressing complex symptoms, and challenging issues around decision making, such as decisions about resuscitation, ongoing therapy and clinical trials.
Palliative care research studies can help us to identify evidence informed strategies for managing the complex EOL issues faced by children with cancer and may improve quality of life and satisfaction with care for patients and their families.
Despite the need for this type of research, palliative care studies are extremely rare in paediatric oncology. There are a number of possible barriers including the reluctance of physicians to offer research to families, and reluctance of families to take part, or remain enrolled.
My research aims to explore stakeholder perceptions about the enrolment of children with cancer in paediatric oncology palliative care research. Studying the views of potential research participants will allow researchers to understand parents’ and clinicians’ decision making processes. This will assist them in designing studies that are meaningful and acceptable to stakeholders, improving recruitment and creating knowledge that ultimately improves EOL care.