January 8, 2021
Q&A with new OICR Investigator Dr. Shraddha Pai on uncovering the hidden differences between cancers
OICR is proud to welcome Dr. Shraddha Pai to its Computational Biology Program as a Principal Investigator. Here, Pai discusses current challenges in understanding diseases and what motivates her to tackle some of the biggest challenges in biomedical research.
What are some of the research questions you’re interested in?
I’m very driven to understand why different people with the same cancer type, have different outcomes and respond differently to the same treatment. As genomic assays get cheaper, we learn more about molecular interplay in different cells, and our population datasets become larger and mature, we are able to integrate different layers of the genome and cell types, to try to get at this question. For example, we now believe there are four main types of medulloblastoma with different underlying molecular networks and outcomes. This field of research is called ‘precision medicine’: using patient profiles to match them with the most effective treatment. But really this is just a new phrase to describe what doctors have been doing since the dawn of medicine; it just means that now we’re using powerful computers and algorithms to find patterns in much larger and complex genomic datasets. The principle is the same.
As a trainee in Dr. Gary Bader’s group, I led the development of an algorithm that integrates several types of patient data to classify patients by outcome. Our method – called netDx – adapts the idea of recommender systems, used by Netflix and Amazon, to precision medicine. Just as one would ask Netflix to “find movies like this one”, netDx helps identify patients “with a treatment profile like this”. In a benchmark, netDx out-performed most other methods in predicting binary survival in four different types of cancer. Importantly, netDx is interpretable, and recognizes biological concepts like pathways. This makes it a useful tool to get mechanistic insight into why a predictor is doing well, and provides a way to understand the underlying biology and perhaps drive rational drug design.
I also have a special interest in understanding the link between epigenetics and disease, particularly as this pertains to the brain. Epigenetics refer to molecular changes that change how the genome behaves – for example, turning a gene on or off in a given cell type. My own previous research in mental illness has found epigenetic biomarkers related to psychosis, which explain the distinctive features of this condition. The same may be the case in certain types of cancers, particularly those of developmental origin.
How do you plan to unravel these complex layers of biology?
My research program has two main goals. The first is to build models for precision medicine – predicting disease risk, treatment response – starting with population-scale datasets that have several types of patient data. I’m hoping to use existing and emerging data such as UK BioBank, CanPath, ICGC-ARGO and the Terry Fox Research Institutes’ datasets, and ongoing clinical trials, to identify which clinical outcomes are easily amenable to our approaches. The models my group builds will incorporate prior knowledge about genome organization and regulation, so that these are interpretable. For example, we will use epigenomic maps of specific tissue types, or data from single-cell resolution maps, pathway information, to find and organize relevant needles in the genomic haystack. This feature will give us interpretability, which is key to increasing confidence in a model, as well as to improving the understanding of cellular pathways that affect disease and eventual drug development.
My second goal is to understand the epigenomic contributions – particularly developmental changes – to cancer risk, using a combination of molecular biological, genomic and analytic techniques.
As I work toward these goals, I hope to collaborate on complementary projects, such as identifying DNA methylation changes in circulating tumour DNA and improving how we subtype adult tumours. These projects will hopefully lead to new biomarkers, and ultimately improvements to how we diagnose and treat cancer.
Importantly, the software that my team builds will also be openly available to the research community, so others can apply my methods to different types of diseases. I’m excited to get started.
Your work applies beyond cancer. How do you traverse these different disease areas?
The reclassification of disease based on molecular or other biomarkers, and how disease subtype affects risk and treatment response, isn’t unique to cancer – the same research questions extend to other types of disease such as metabolic diseases, autoimmune diseases and mental illness. At the end of the day, we are looking at the same system organized at the molecular, cellular and organ-level, with similar principles of genomic regulation and perhaps similar considerations for drug discovery. Our algorithms are based on these general principles and can therefore be used to answer similar questions for different disease applications, or very different types of cancer. Of course, it’s important to collaborate with teams that have domain expertise to make sure the algorithms are “fine-tuned” for a particular application, and I look forward to benefitting from those partnerships.
What excites you about this type of work?
I’m excited to join a community where basic research is so strongly connected to clinical purpose. Personally, I am very motivated by the prospect of a positive impact on patients within my lifetime and feel that my group’s work is more likely to have a valuable impact in an environment that combines basic and translational research. That said, we’re only just beginning to see the benefits of precision medicine and many challenges remain to bring genomic knowledge into practice. I hope that I can create more useful methods and models for precision medicine and improved clinical decision-making in the coming decade.
I’m especially excited to be at OICR because of the Institute’s access to clinical trials, strong genomics and computational biology program, and pharmacology team. If my group can find promising biomarkers and leads, we can work with OICR collaborators in the Genomics and Drug Discovery groups to move from basic research to application.
September 21, 2020
Q&A with new OICR Investigator Dr. Anastasia Tikhonova on tackling cancer cell cross-talk and adapting in a rapidly evolving field
OICR welcomes Dr. Anastasia Tikhonova to Toronto as an OICR Investigator and Scientist at the Princess Margaret Cancer Centre
The pandemic has compelled many people to adapt, and researchers are no exception. For Dr. Anastasia Tikhonova, adapting has always been an essential part of her career.
Tikhonova recently joined the OICR community as an OICR Investigator working at the Princess Margaret Cancer Centre. Her research focuses on hematological malignancies – or blood cancers – and how the environment around these cells can regulate their growth or help them resist standard treatments. Her research in this area will support the development of new cancer therapies that can ultimately help patients live longer and healthier lives.
Here, she describes her research program and why this community is a great place for her.
What is your research all about?
AT: Cancer cells do not exist in isolation. They are surrounded – and influenced – by their healthy neighbouring cells. For a long time, we didn’t fully understand the interactions between a cancer cell and its surrounding environment and how this dialogue impacts tumour growth. The last five years have significantly advanced imaging and genomic technologies that allow us to precisely decode the cross-talk between diseased cells and their environment – or their niche.
This is what my research is all about. My team uses single-cell transcriptomics, high-resolution imaging, and functional genomics to understand the connection between the complex elements in the bone marrow and cancer. Our goal is to untangle these connections and devise new strategies to target the interaction between leukemic cells and their environment, with the goal of eliminating blood cancers.
What got you interested in this space?
AT: I was fascinated by biology as a child. I remember learning about evolution in my first biology class in the fifth grade – I have been hooked ever since! I love being in the lab. I am exhilarated by seeing results for the first time and being able to connect the dots between different experiments. When I recognize a gap in my understanding, I feel compelled to learn more. This is how I became interested in the stem cell niche and leukemic microenvironment. As a Postdoctoral Fellow, I was fortunate to have had the opportunity to work in a top hematopoietic lab where I started to scratch the surface of understanding the niche’s molecular architecture, but many questions remain. Continuing this line of inquiry, I look forward to translating my findings into innovative therapies here in Ontario.
Why did you choose to come to Ontario?
AT: Princess Margaret is one of the top cancer research centres in the world. During my recruitment I had an amazing experience interacting with the faculty and trainees here. They were highly engaged and asked great questions, indicating a rich intellectual environment. Since most of my ideas come to me when I am working with others, this is the ideal place for my young lab to grow intellectually. Plus, the people here are genuinely supportive. My move was delayed due to COVID, but everyone here has been exceptionally helpful.
How has COVID impacted your work?
AT: An important trait to have as a scientific researcher is agility or the ability to quickly adapt to changing environments. Furthermore, COVID made me realize that nothing can shake my enthusiasm for starting a research group.
As a result of pandemic, I think people have become more open to collaboration. In some ways, online communication has leveled the playing field, bringing geographically distant researchers into the same space as colleagues accustomed to side-by-side interactions.
I also think COVID has brought science into public view. For the first time in my life, I hear immunology terms on the morning news. I’m excited by the prospect of biomedical research being a common discussion topic.
Does your work apply to other diseases?
AT: Yes, it does. I have a specific focus in a rare form of leukemia, called T-ALL. My research applies to other cancers as well. Insights from one disease can often guide our understanding of other malignancies.
Notably, my research in the regenerative medicine space of the bone marrow niche has the potential to impact thousands of patients treated every year with bone marrow transplantation. Additionally, if we can better understand how to regenerate the bone marrow microenvironment, we could bring a whole new treatment paradigm to patients with a wide spectrum of benign and malignant diseases. At the end of the day, this is what it’s all about.
July 29, 2020
OICR welcomes Dr. Courtney Jones to Ontario’s cancer research community
Starting up an independent research lab in the midst of a pandemic is difficult but Dr. Courtney Jones is up for the challenge. Jones moved to Canada prior to the lockdown and has been gearing up for new experiments since. Now, as an OICR Investigator, she has safely started working in her lab at the Princess Margaret Cancer Centre to find new solutions for the leading cause of leukemia deaths in Canada – acute myeloid leukemia (AML).Continue reading – Q&A with new OICR investigator Dr. Courtney Jones on benefitting patients through research
November 26, 2019
Toronto – (November 26, 2019) Today, the Ontario Institute for Cancer Research (OICR) announced three new Investigator Award (IA) recipients, reinforcing OICR’s commitment to recruit and retain world-class cancer researchers across Ontario.
The awards are for up to $350,000 per year for up to six years, providing stable research funding and salary support for recipients to establish their laboratories and build their research platforms within Ontario. They bring with them expertise in big data, machine learning, multi-omics analysis and immuno-oncology. The new recipients are:
- Dr. Tricia Cottrell
Clinician Scientist I Award
Cottrell is a pathologist and immunologist from Johns Hopkins University who recently moved to Kingston to become an Assistant Professor at Queen’s University and Senior Investigator in the Canadian Cancer Trials Group. Cottrell focuses on mapping the interactions between the immune system and cancer cells as patients undergo treatment in order to develop new biomarkers that can better predict the course of a patient’s disease.
- Dr. Anna Panchenko
Senior Investigator Award
Panchenko was recently recruited to Kingston from the National Center for Biotechnology Information where she developed several methods and algorithms to study the molecular mechanisms behind cancer. Panchenko’s methods have been widely used by thousands of scientists from around the world to better understand the causes of cancer progression. She is now a Professor at Queen’s University and holds a Tier I Canada Research Chair.
- Dr. Parisa Shooshtari
Investigator I Award
Shooshtari is an Assistant Professor at Western University in London, where she is establishing her first laboratory as an independent researcher. Joining the OICR community with experience from Yale University, the Broad Institute of MIT and Harvard, and The Hospital for Sick Children (SickKids). Shooshtari brings unique expertise in developing computational, statistical and machine learning methods to understand the biology underlying complex diseases like cancer.
With their new appointments as OICR Investigators, Cottrell, Panchenko and Shooshtari join 25 other IA recipients as part of OICR’s collaborative cancer research community of more than 1,900 highly-qualified personnel across 23 Ontario institutes. Since its inception in 2006 the IA program has provided funding to recruit and keep world-class cancer researchers and clinician scientists in universities, hospitals and research centres across Ontario.
“Sustainable funding for talented scientists is critical to building a strong research ecosystem that will deliver the next wave of innovations and discoveries. The Investigator Award program is key to attracting and keeping top cancer researchers in Ontario,” says Dr. Christine Williams, Deputy Director and Interim Head, Clinical Translation at OICR. “We are particularly pleased that all three awards have been given to accomplished female scientists and are proud to offer our support as they establish their research programs in Ontario.”
“We are thrilled to welcome these highly-regarded researchers and look forward to their contributions to the health of Ontarians and the province’s cancer research sector,” says Hon. Ross Romano, Ontario’s Minister of Colleges and Universities. “Investing in top talent will allow Ontario to stay at the forefront of bio-medical research and realize the benefits of advancements in cancer prevention, diagnosis and treatment more quickly.”
As professors at their respective academic institutions, the three new IA recipients will take part in providing high-quality training to students in areas such as computer science and machine learning. Technological advancements and an evolving global economy are changing work in Ontario. These new, unique, cross-appointed positions will strengthen Ontario’s cancer research capacity while helping prepare students for careers in a rapidly-evolving knowledge-intensive industries.
For more information about the Investigator Award program, visit www.oicr.on.ca/investigator-awards.
October 8, 2019
OICR is proud to welcome Dr. Tricia Cottrell to Ontario’s cancer research community.
Dr. Tricia Cottrell, who is an immunologist and pathologist by training, is focused on the interplay between cancer cells and the immune system. She maps these complex interactions, as patients undergo treatment, to develop new biomarkers that can better predict the course of a patient’s disease.
Joining OICR from Johns Hopkins University in Baltimore, MD, Cottrell brings unique expertise in studying the tumour immune microenvironment, specifically in lung cancer. Here, she discusses her transition and her new appointments at the Canadian Cancer Trials Group, Queen’s University and OICR.
How did you become interested in the field of immuno-oncology?
The idea of harnessing the immune system to control and eliminate cancer fascinates me.
My PhD research on the autoimmune disease scleroderma left me eager to find ways to study immune responses in human tissue. While pursuing this research through my anatomic pathology residency, I stumbled upon the revolution happening in cancer immunotherapy. There are a lot of interesting intersections between cancer immunology and autoimmunity, and I knew I wanted to dig in.
What problems and questions are you working to solve?
Generally, I look at different features of the immune response to cancer and find patterns in these features that are associated with a response to therapy. I’m addressing the question: can we predict which patients are most likely to respond to treatment?
When we have tools to answer that question, we can help patients decide which treatment is best suited for their unique disease.
How are you addressing those big questions?
As a pathologist, I start with simple observations made through a microscope. Then, I use techniques like multiplex immunofluorescence to understand the cells and molecules driving the patterns I see in the tissue. Finally, I integrate these observations with other –omics analyses of the same sample, like DNA or RNA profiling, in pursuit of better biomarkers. The ultimate goal is to have biomarkers that can accurately predict which therapy or combination of therapies is most likely to empower a patient’s immune system to eliminate their cancer.
Through these studies, we also identify patterns and molecular characteristics in the tumours of patients who respond poorly to treatment. We can use this knowledge to find mechanisms of resistance, or the ways that the cancer can evade treatment. Then we can develop new therapies to address these mechanisms.
You’ve been recognized and awarded for your research on several occasions. What is an achievement that most people don’t know about?
I never anticipated that my research as a pathologist would lead me to analyzing big data. I’m quite proud that I learned some computer programming and I continue to integrate new technologies and cutting-edge analytic approaches into my research.
A specific achievement I am proud of is developing a method to measure the response of lung cancer patients to checkpoint blockade therapy using microscopic features of their tumours. This method is now being validated in a large clinical trial and has been shown to work in other cancer types as well. We are currently investigating its potential as a pan-tumour biomarker that would allow unprecedented standardization of clinical trials across different cancer types.
Why did you choose to relocate to Kingston?
I was looking for an opportunity to expand my research focusing on patients enrolled in clinical trials. Kingston offered that opportunity through an appointment with the Canadian Cancer Trials Group (CCTG), which is based at Queen’s University where I am also an Assistant Professor.
At CCTG, I get to participate in the design of clinical trials, including arranging tissue collection and planning the correlative science (the study of the relationship between biology and clinical outcomes) that goes along with those trials. My goal is to make sure my research will be translatable to the clinic, or in other words – to find solutions that can be applied in practice.
I’m also personally very excited about the opportunity for my family to be here in Canada.
What are you looking forward to over the next year?
I look forward to maintaining my existing collaborations while broadening my research scope. I’ll be working to establish a laboratory-based platform that produces high-quality, large-scale multiplex immunofluorescence data from tumour tissue specimens. I also look forward to laying the groundwork for a data integration and analysis pipeline for tissue-based immunology studies.
Most of all, I’m excited to begin growing my own lab group. I hope to foster a collaborative team environment with individuals from diverse backgrounds in pathology, biology, immunology, bioinformatics and more.
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.