September 18, 2019
Dr. Ina Anreiter joins OICR as a Schmidt Fellow, bringing her background in behavioural genetics to bioinformatics
While writing her doctoral thesis, Dr. Ina Anreiter realized that there was a missing piece to her research. What she didn’t realize was that this missing piece would lead her into a prestigious postdoctoral fellowship in an entirely new scientific discipline. For decades, scientists have known that RNA – often referred to as DNA’s cousin – undergoes chemical modifications before running its course. These modifications, like RNA methylation, have an important effect in cancer cells, but without the tools to study RNA modifications, progress in this field had stalled for many years.
Recently, the study of these modifications – also known as the field of “epitranscriptomics” – has garnered new attention as the research community develops new methods to study RNA. These methods, Anreiter says, still rely on common chemistry lab techniques and cumbersome procedures that make studying RNA methylation difficult, especially in application to diseases like cancer.
“I found myself in need of a tool,” says Anreiter. “I needed a way to easily analyze RNA methylation across large datasets and found that nothing existed – well, nothing existed yet.”
From fruit flies to machine learning
Anreiter’s doctoral research focused on the behaviour of fruit flies, specifically how inherited characteristics and environmental factors influence their feeding patterns. While searching for a way to study RNA methylation, her background led her to a unique idea.
Anreiter knew of nanopore sequencing – a relatively new type of sequencing technology that could decode DNA and RNA as it passes through a tiny channel. By directly reading a strand of RNA, Anreiter says, nanopore sequencing has the potential to revolutionize how we study RNA modifications. To this day, however, there are no algorithms or tools that can accurately find RNA methylation patterns in the output data of a nanopore sequencer.
Anreiter had also heard of Dr. Jared Simpson’s breakthrough methods for detecting DNA methylation using nanopore sequencing. His computational methods allowed the nanopore community to sequence the entire – highly-methylated – human genome in 2017, and since, he has been working in part to study RNA modifications, like RNA methylation, using nanopore sequencing.
Anreiter pitched her idea to Simpson.
“RNA methylation occurs in normal fruit flies, but not in a certain type of mutant fly,” says Anreiter. “I had a crazy idea that we could sequence both of these types, and use the datasets to develop a machine learning algorithm that could find RNA methylation on its own.”
The potential of her idea would win her the prestigious Schmidt Science Fellowship and a $100,000 USD stipend to work with Simpson for a year.
From machine learning to cancer patients
Anreiter recently began her year-long postdoctoral fellowship in the Simpson Lab at OICR where she is working alongside a team of computational biologists to turn her idea into an algorithm. She is cross-appointed with the University of Toronto’s Department of Computer Science.
“At this point, we’re working on a preliminary dataset, but I’ve already learned so much. The team has been very welcoming and supportive and we’re working together to make better tools to understand diseases.”
The Schmidt Fellowship, which was co-founded by the former CEO of Google, is awarded to exceptional, early-career researchers making a “pivot” in their work. Anreiter saw the fellowship as an opportunity to immerse herself in a completely new field.
“If we can develop this tool, it would allow us to study human diseases in a new way,” Anreiter says. “When we look at a problem in a new way, we don’t know what solutions we’ll find, but this angle could lead us to new cures.”
September 11, 2019
OICR researchers have recently teamed up with a team of medical oncologists and surgeons at The Ottawa Hospital to launch a new breast cancer clinical trial – one that begins before a patient undergoes surgery.
“There’s a gap between when a patient is diagnosed with cancer and the start of their surgery,” explains Dr. Melanie Spears, trial co-investigator and Principal Research Scientist at OICR. “A window of opportunity study allows us to use this gap to look at novel targeted therapies.”
September 3, 2019
OICR is proud to welcome Dr. Parisa Shooshtari as an OICR Investigator.
Shooshtari specializes in developing computational, statistical and machine learning methods to understand the biological mechanisms underlying complex diseases, like cancer and autoimmune conditions. She is interested in uncovering how genes are dysregulated in complex diseases by integrating multiple data types and applying machine learning methods to analyze single-sell sequencing data.
Of her many achievements, Shooshtari developed a computational pipeline to uniformly process more than 800 epigenomic data samples from different international consortia. She then built and led a team that developed a web-interface and an interactive genome-browser to make the database publicly available to download and explore.
Shooshtari joins the OICR community with research experience from Yale University and the Broad Institute of MIT and Harvard. She also served as a Research Associate with the Centre for Computational Medicine at the Hospital for Sick Children (SickKids).
Shooshtari recently became an Assistant Professor in the Schulich School of Medicine and Dentistry at Western University, where she officially began her career as an independent researcher. Here, Shooshtari discusses her commitment to collaboration and her transition to professorship.
Your work spans multiple disease areas from autoimmune diseases to cancer, what do these diseases have in common? Is there a specific disease that you’re more interested in?
My work focuses on complex diseases, where instead of one gene causing the disease, there are sometimes tens or hundreds of genes working together to give rise to an ailment.
When it comes to complex diseases, we also know that there are multiple factors that we need to consider, including genetics, epigenetics and environmental factors. We live in an era where we have rich datasets with many different types of data. Each of these data types sheds light upon a different aspect of the disease mechanism, but we need to integrate these data types to gain a comprehensive understanding of how a complex disease works.
I develop computational methods for integrative analysis, so complex diseases are definitely the most interesting to me. I feel lucky to be a researcher at this time when I can help bring these data types together to understand mechanisms of diseases, which in turn will help inform treatment selection or help find new therapeutic strategies.
I am interested in applying our data integration methods to several complex diseases but I am currently working with a few Canadian groups to help better understand Diffuse Intrinsic Pontine Glioma (DIPG) – a type of fatal childhood brain cancer.
Your current collaborators include researchers from Yale, Harvard, MIT, SickKids and other leading organizations. How did you initiate and sustain these collaborations?
At the beginning of my research career, I would reach out to scientists who were working on interesting, challenging and cutting-edge problems. I enjoy working in collaborative environments because I believe the key to success in biomedical research is through collaborations between researchers from diverse backgrounds.
With the support of my collaborators, I’ve been able to learn and shift my focus from theoretical computational sciences to applications of data science in genetics of complex diseases. Now, sometimes collaborators approach me with their rich data, which I’m eager to help analyze.
With your new appointment, what are you looking forward to over the next few years?
I am eager to continue expanding my research program and working with new scientists on exciting cutting-edge problems in genetics and epigenetics of complex diseases. New technologies have revolutionized how we study diseases, and we are transitioning to a point where these new technologies are revolutionizing how we treat diseases. I am confident that we will have better ways of treating these diseases in the future using personalized medicine, and I want to help make that a reality.
August 29, 2019
Did you know that in addition to conducting and enabling cancer research, OICR plays a key role in training the next generation of cancer researchers? Several postsecondary students spent the summer at OICR and gained valuable experience in, and exposure to, the world of cancer research. In this series of videos, five of these students share what they learned during their time at OICR and how their experiences have helped shape their plans for the future.
August 29, 2019
OICR and Cancer Care Ontario’s Health Services Research Network releases the 2019 Synthesis Report, summarizing 14 studies that address high priority issues in cancer care
An excerpt from the foreword by Drs. Christine Williams and Eva Grunfeld:
Optimal cancer care across Ontario cannot be solely provided by a clinician or implemented by a researcher, enacted by a policy maker or attained by a patient. To improve the delivery of cancer services, we need to work together with stakeholders from across our rich cancer care ecosystem and involve them in prioritizing concerns, designing interventions and implementing solutions. For these reasons, OICR and Cancer Care Ontario (CCO) teamed up to co-create the OICR-CCO Health Services Research Network (HSRN).
Now, a decade later, we present our second Synthesis Report with an additional 14 studies that have emerged from this network. These studies have addressed high priority issues in cancer care including the gap in follow up after a positive colorectal cancer screening test, and the challenges that cancer patients face with co-existing chronic conditions like diabetes. The studies have led to the development of new methods to determine the burden of cancer in Ontario, and new resources to facilitate health services research across the province. This report provides summaries of these studies and others and their impact to date.
August 13, 2019
The Canadian Cancer Clinical Trials Network launches new pilot project at Windsor Regional Hospital to help patients understand their treatment options and access current clinical studies
In early 2012, Ron Truant, the former Board Chair of Windsor Regional Hospital (WRH), became a patient when he was diagnosed with pancreatic cancer.
Facing a disease with a dismal prognosis, Ron and his wife, Noella Truant, made an appointment for a second opinion at a hospital outside of Windsor. It was there that the Truants learned about an open clinical trial and secured the study’s last available spot.
Noella says not everyone is as fortunate as they were.
“We were lucky to gain access to an immunotherapy trial, which – in combination with a new chemotherapy treatment – gave us another four years together,” says Noella. “Throughout his own treatment, Ron was always thinking about others and realized there were many others who weren’t as fortunate as we were to find a trial. He knew that trials are complex and not everyone can navigate them, so he saw an opportunity to help.”
Last year, only eight per cent of cancer patients in Ontario were recruited to clinical trials and in community hospitals, like WRH, that number drops to fewer than two per cent. These statistics, Noella says, indicate that patients are missing opportunities to gain access to new treatment options and contribute to clinical research.
Currently, each cancer centre in Ontario has a clinical research team that recruits patients for available trials at their respective sites but patients, like Ron, often want to explore all treatment options, including those at other nearby hospitals. These patients and their care givers are frequently left to research trials on their own through websites that may not contain current information or online trial databases that may be difficult to navigate. Even if a patient finds an available trial, understanding eligibility criteria requires specialized knowledge and advanced medical literacy.
Ron, a long-standing advocate for the quality of patient care, teamed up with Dr. Caroline Hamm, an oncologist at the WRH, to develop a better way for patients to navigate clinical trials.
“We want to make sure patients are offered the best treatments available for their individual needs, and that requires more than a database of trials,” says Hamm, who is also the Director of the Windsor Cancer Research Group. “There are many considerations that a patient weighs when deciding to participate in a trial and we need a more considerate approach to help patients with these decisions.”
With support from the Canadian Cancer Clinical Trials Network (3CTN), Hamm and the Truants designed a program where a designated clinical trials specialist – a Clinical Trials Navigator – would help patients find and understand the trials available. A patient could refer themselves to the navigator or they could be referred to the navigator by their oncologist. After reviewing the patient’s case and considering their preferences, the navigator could then identify available trials for which the patient is likely eligible, and help facilitate the connection between a patient and the study team.
Hamm, in Ron Truant’s legacy, launched the Clinical Trials Navigator pilot project at WRH in January and so far the project has since helped more than 40 patients explore trial options.
Youshaa El-Abed, the project’s navigator, sees the impact of this initiative on patients and their care givers first-hand.
“When a patient comes to us, they’re looking for a trial,” says El-Abed. “But even if there are no trials available for them, the patient – and their loved ones – gain reassurance that they have explored their options.”
Due to growing demand for clinical trial navigation services at other hospitals, the project is now open to receive patient referrals from across Ontario.
Hamm, who has been recognized for her patient advocacy in Windsor, hopes to expand this initiative to new sites as she has in the past for a cancer drug access coordinator program. In addition to helping current patients with cancer, Hamm sees the Clinical Trials Navigator project as a way to accelerate clinical research so patients can benefit from research sooner.
“If we can help patients access trials, we can help trials reach their accrual targets sooner – a win-win for patients and for local clinical research,” says Hamm. “A health system with accelerated clinical research allows us to attract more study sponsors, bringing leading edge treatment options to our hospitals. Ron envisioned this solution and we’re proud it’s in action today.”
August 12, 2019
OMPRN grantee and former Transformative Pathology Fellow discusses her recently-awarded faculty appointment with the University of Toronto
Despite research advances in identifying the subtypes of kidney cancer, treatment decisions are often based on the size of a patient’s tumour. Dr. Rola Saleeb, who has been studying kidney cancer for nearly a decade, thinks there’s a better way to make these decisions.
“Each month, more than 500 people are diagnosed with kidney cancer in Canada,” says Saleeb. “These individuals and their oncologists face tough decisions to make about their treatment options and I want to help make that decision easier.”
Saleeb, a former OICR Transformative Pathology Fellow and two-time Ontario Molecular Pathology Network (OMPRN) grantee, has recently become a certified pathologist and faculty member in the Department of Laboratory Medicine and Pathobiology at the University of Toronto.
Throughout her doctoral research, Saleeb developed a classification system that could help pathologists distinguish between aggressive kidney cancers and less aggressive cancers. She says this system could, one day, help spare patients from unnecessary surgery if they don’t have aggressive tumours. Additionally, she says classifying these tumours could enable the development of new therapies for these subtypes.
Now as a certified pathologist, Saleeb is the second Transformative Pathology Fellow to have been recruited to a faculty position. Both former fellows have committed to a career where research and development is central to their practice of pathology.
“Not all pathologists do research,” says Saleeb. “But for me, I feel like I can help more patients if I can help find solutions to unsolved problems.”
Saleeb is currently completing a validation study on her classification system. She looks forward to implementing the system at St. Michael’s Hospital and broadening her research to study the molecular origins of kidney cancers and new kidney cancer prevention strategies.
July 30, 2019
Genome Canada, Ontario Institute for Cancer Research and Thermo Fisher Scientific to focus on pancreatic, prostate and breast cancer
CARLSBAD, Calif. – (July 30, 2019) – Genome Canada, the Ontario Institute for Cancer Research (OICR) and Thermo Fisher Scientific are collaborating to develop a complete solution of targeted next generation sequencing (NGS) assays and analysis software designed to more effectively assess – and eventually improve management of – pancreatic, prostate and breast cancer.
The $6 million, three-year initiative aims to standardize advanced molecular profiling in these disease areas and make the assays commercially available globally. Focusing on rapid genomic diagnostics in pancreatic cancer and targeting treatment in breast and prostate cancers, the partnership builds on previous clinical research between OICR and Thermo Fisher and will inform development of three assays that will be utilized to stratify patients in clinical trials in Ontario and other jurisdictions.
“By supporting research and clinical trials, Genome Canada is helping to put more of Ontario’s innovative cancer diagnostics research into clinical use,” said Dr. John Bartlett, program director, diagnostic development at OICR. “This project has the potential to springboard advanced next-generation sequencing to routine clinical use in Ontario and across Canada.”
Breast and prostate cancer are among the most common types of cancer in Canada, and the country’s five-year net survival rate for pancreatic cancer is only 8 percent. However, there is clear evidence that patient outcomes can be improved with NGS-based testing strategies. A recent U.S. health economics study has shown that advanced cancer patients who received treatment based on NGS testing results experienced double the length of progression-free survival without increasing health care costs.1
While some solutions analyze only DNA sequences, the new targeted NGS assays will provide comprehensive genomic profiles by simultaneously assessing DNA and expression signatures from RNA to provide significantly more insight into driver mutations. The OICR/Thermo Fisher team will leverage this advantage by supplementing the new assays with unique DNA/RNA stratification biomarkers – specific to pancreatic, prostate and breast cancer – previously qualified by OICR translational researchers.
The collaboration is partly funded with a grant from Genome Canada through the Genomic Applications Partnership Program (GAPP). Genome Canada will contribute $2 million, the highest possible level of funding support, with the balance split between OICR and Thermo Fisher, which will cover development costs and validation activities.
Previous research collaborations led by OICR and Thermo Fisher are already well on their way to impacting cancer treatment in the future. Of particular note is a 2016 study designed to identify mutations and copy number variation changes in breast cancer, and clinical research utilizing the Oncomine Comprehensive Assay, which also supports both the National Cancer Institute’s Adult and Pediatric MATCH trials in the United States.
“OICR is a leader in clinical research, with extensive clinical trials in progress to improve care for patients with pancreatic, prostate and breast cancer,” said Jeff Smith, global lead of NGS precision medicine initiatives, clinical NGS and oncology for Thermo Fisher Scientific. “When OICR approached our team with the idea for this project, we saw it as another exciting for opportunity to bring Thermo Fisher’s proven Ion Torrent technology to clinical laboratories across Canada and to contribute to future improvement of patient care.”
1 “A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression- Free Survival Without Increased Health Care Costs,” Journal of Oncology Practice, Vol 13, Issue 2, February 2017
July 29, 2019
OICR researcher looks into what non-tumour cells can tell us about breast cancer
When a biopsy is drawn from a patient, it consists of a mix of cancerous and healthy cells, like fat and blood cells. Researchers are often interested in diseased cells, but without looking into the surrounding tissue, they could be missing part of the story.
Natalie Fox, a PhD candidate at OICR, is investigating what we can learn from the cells surrounding cancer cells.
“When we look into a patient sample computationally, we see distorted signals because of overlapping data from many different types of cells,” says Fox. “We need to dissect the parts we want to study, but instead of using a knife or a laser, we use computers.”
Fox and collaborators have analyzed nearly 1800 tumour samples from patients with breast cancer, examining the transcriptome of tumour cells and the cells around tumours – or the tumour’s microenvironment.
Her study, recently published in Nature Communications, reveals the landscape of transcriptomic interactions between breast cancers and their microenvironments. Her study also sheds light on associations between these transcriptomes and patient survival, gene mutations and breast cancer subtypes.
“We now have a clearer picture that tells us more about the breast microenvironment than we’ve known before,” Fox says. “Bit by bit, we’ve analyzed and scrutinized these data, then assembled these bits into a comprehensive landscape.”
Fox found that mutations in cancer genes such as CDH1 and TP53 are associated with changes in the transcriptome of the tumour’s microenvironment. She says more research is needed to clarify the biologic rationale behind her observations, but her work has set the stage for researchers to do so.
“Above all else, this work demonstrates an important approach for improving our understanding of associations between the tumour and the microenvironment,” Fox says. “We presented a framework that others can use to analyze the tumour microenvironment in their cancer of interest and potentially develop new biomarkers for predicting cancer patient outcomes.”
July 24, 2019
OICR funding for Ontario drug discovery projects will accelerate development of new cancer therapies
The Ontario Institute for Cancer Research (OICR) has selected two new Late Accelerator projects to receive support through its Cancer Therapeutics Innovation Pipeline (CTIP) initiative. The projects, detailed below, will each receive up to $250,000 per year, for up to two years, to advance the development of drug candidate molecules. The projects were selected by an international expert review panel from 18 applications.
By joining the CTIP portfolio, these projects will receive more than just financial support – they will also benefit from the guidance of the Therapeutics Pipeline Advisory Committee, a group of industry and academic experts that provides advice on the scientific and strategic direction of CTIP projects.
“CTIP projects have great potential to improve treatment for patients, promote scientific collaboration and drive investment to Ontario’s biomedical research sector,” says Dr. Christine Williams, OICR’s Deputy Director and Head of Therapeutic Innovation. “These new projects are great examples of the innovative cancer therapeutics research happening in our province. We are excited to add them to CTIP’s portfolio of promising drug candidates and look forward to their progress.”
Identification of kinase inhibitors to block the tumour-promoting activity of YAP/TAZ for cancer therapeutics
Liliana Attisano, Principal Investigator, University of Toronto
Rima Al-awar, Principal Investigator, OICR
Frank Sicheri, Co-investigator, Lunenfeld-Tanenbaum Research Institute
Jeff Wrana, Co-investigator, Lunenfeld-Tanenbaum Research Institute
David Uehling, Co-investigator, OICR
Richard Marcellus, Co-investigator, OICR
Methvin Isaac, Co-investigator, OICR
The highly conserved Hippo pathway is a key regulator of cell and tissue growth. Virtually all solid tumours display pathway disruptions, which drive cancer initiation and progression. Mutations in pathway components are rare, making it unclear how to target the pathway for cancer treatment. This research group has shown that certain kinases are key regulators of the pathway that promotes tumorigenicity and observed that diverse human cancers display elevated levels of these kinases. Kinases are highly amenable to the development of targeted inhibitors; therefore, this project will identify potent and specific inhibitors with the long-term goal of establishing novel cancer therapeutics.
Development of kinase inhibitors for ovarian cancer: A novel first in-class immune-oncology therapeutic agent targeting tumor intrinsic stress states
Rob Rottapel, Principal Investigator, Princess Margaret Cancer
Tracy McGaha, Principal Investigator, Princess Margaret Cancer
Rima Al-awar, Principal Investigator, OICR
Methvin Isaac, Co-investigator, OICR
David Uehling, Co-investigator, OICR
Richard Marcellus, Co-investigator, OICR
Ahmed Aman, Co-investigator, OICR
The development of new cancer immune therapeutics has triggered a revolution with the recent advent of diverse strategies that engage the patient’s immune system. This research group has identified a novel kinase target that has the unique property of being both an emergent essential gene in high-grade serous ovarian cancer and a repressor of the innate and adaptive immune system. Additionally, they have demonstrated that target inhibition sensitizes cancer cells to cisplatin – a standard of care chemotherapy drug. This project will work to develop a “first-in-class” dual-action, anti-tumour and immune-oncology kinase inhibitors for ovarian cancer and potentially other cancer types.
July 23, 2019
Biostatistics Training Initiative (BTI) alumnus brings on new BTI trainee to study Canada’s largest population health dataset using today’s top technologies
Recently, circulating tumour DNA (ctDNA) – DNA released from cancer cells that freely circulates in the blood – has garnered much attention not only as an alternative to traditional tissue biopsies, but as a potential blood-based biomarker for early cancer diagnosis.
The ability to detect the earliest blood-borne traces of cancer largely rests in our ability to determine which molecular markers indicate that a cancer is developing – or which patterns in ctDNA can predict whether a cancer will grow. Dr. David Soave sees this as a mathematical challenge that, if solved, could have huge impact for better predicting and diagnosing a wide variety of cancers.
“To find cancer earlier or predict who will develop the disease, we need to carefully compare human samples from those who will develop cancer and samples from those who won’t,” Soave, an Assistant Professor at Wilfrid Laurier University and OICR Associate, says. “This type of challenge requires new statistical models, methods and computational techniques that can decipher large, complex and high-dimensional data.”
Last year, the Canadian Partnership for Tomorrow Project (CPTP) unified the data from several provincial longitudinal health studies into a national cohort consisting of more than 325,000 participants who are voluntarily donating their health and biologic samples to research. As some CPTP participants will develop disease and others will not, this dataset provides an unprecedented resource for researchers like Soave to discover the earliest traces of cancer that appear several months to years prior to an initial diagnosis.Continue reading – Blood samples, biostatistics and a fresh perspective: The makings of a cancer prediction machine
July 22, 2019
Trevor Pugh, OICR’s new Director of Genomics, talks about what’s happening in the OICR Genomics Platform.