Chris Morrow

Drs. Rachel Murphy (pictured) and Andrew Roth (not pictured) are recipients of the 2022/2023 Precision Health Catalyst Grant award for their project entitled “Improving Breast Cancer Screening Efficiency with Administrative Health Data”

Read a summary of the project here.

“This project aims to use administrative health data to a) develop individualized risk assessment models that improve the ability to estimate a woman’s risk of developing breast cancer, and b) tailor risk models to breast cancers: pre- vs post-menopausal, hormone receptor negative vs positive, triple negative and early vs advanced stage.”

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1. Can you tell us about the precision health research work you’re collaborating on?

Early detection of breast cancer via mammographic screening saves lives. For most women, recommendations for breast cancer screening are a one-size-fits all approach, with recommendations to engage in screening at given intervals (1 to 2 years) and within a defined age range (50-74). However, some women will develop breast cancer that is not be detected because they do not meet criteria for screening, while others may undergo unnecessary screening. Our proposal applies machine learning methods to administrative health data to estimate an individuals’ risk of developing breast cancer. This individualized approach has the potential to better predict and prevent breast cancer by identifying those most likely to benefit from mammographic screening and/or prevention.

2. What results have you seen so far?

Our results to date have confirmed that the individual risk assessment methods can be applied to predict personalized breast cancer risk, including time until breast cancer onset, and the probability of breast cancer onset within a defined period (e.g. 5-years). We have also identified several factors that were strongly predictive of breast cancer, and may help inform prevention approaches for an individual.

3. From your perspective, what do you think is exciting about the future direction of precision health?

I am an epidemiologist and population health researcher. So, naturally I am excited about the interplay and expansion of precision health to public health. Individualized prevention and health care are central to precision health, which seems at odds with traditional public health approaches. However, increasingly, precision is being integrated into public health interventions. Ensuring a strong evidence base to inform precision public health interventions is critical, and I’m looking forward to leading part of this effort, and learning along side others.  

About Dr. Rachel Murphy

Dr. Rachel Murphy is a Senior Scientist in Cancer Control Research at BC Cancer, an Associate Professor and the Associate Director, Research in the School of Population and Public Health at UBC. She holds a PhD in Nutrition and Metabolism and completed postdoctoral training in epidemiology at the National Institutes of Health. Her research program is focused on the intersections of nutrition, human health, and public health challenges. Dr. Murphy has received a number of awards recognizing her contributions, including a Michael Smith Foundation for Health Research Scholar award and a Canadian Cancer Society Early Career Development award in Cancer Prevention. 

Drs. Eric McGinnis (left) and Ryan Stubbins (right) are recipients of the 2022/2023 Precision Health Catalyst Grant award for their project entitled “Rapid targeted gene sequencing and high-resolution optical genome mapping to optimize selection of targeted therapies in acute myeloid leukemia”

Read a summary of the project here.

“This project aims to: 1) Evaluate the feasibility, in a clinical laboratory, of high resolution rapid genomic testing using nanopore LRS and OGM in AML and 2) Evaluate the increase in clinical yield of combined OGM and LRS relative to current standard-of-care methods for timely identification of therapeutically actionable or diagnostic entity-defining genetic abnormalities.”

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1. Can you tell us about the precision health research work you’re collaborating on?

In acute myeloid leukemia (AML), the genetic abnormalities we are able to identify in a clinical laboratory in cancer cells play a central role in how we diagnose these cancers and how patients are treated – in many cases determining what type of chemotherapy a patient receives and whether they will undergo bone marrow transplant. In addition to this, identifying genetic drivers in AML often results in patients being eligible for targeted, precision therapies that have been demonstrated to significantly improve outcomes. In many clinical laboratories the bulk of this work is done using decades-old technologies (mainly banded karyotyping) which have limited ability to resolve small or subtle changes in combination with highly targeted sequencing covering a small portion of the genome, and many genetic changes in cancer cells which could potentially inform diagnosis and treatment are not detectable as a result. Up to 25% of patients can have additional genetic drivers identified by newer technologies, and this can also identify targetable lesions. Our research explores applications of two newer technologies, optical genome mapping (OGM) and nanopore-based whole-genome long read sequencing (LRS) using adaptive sampling-based enrichment to clinical testing for patients with AML to determine the potential added benefit of applying these higher resolution tests as well as their feasibility of use in a clinical laboratory setting.

2. What results have you seen so far?

We observed that applying OGM and LRS to detection of genetic abnormalities in AML identifies an enormous number of abnormalities not detected by established standard-of-care testing – in the case of OGM often hundreds to thousands of such changes and in the case of LRS (in preliminary results) several orders of magnitude higher as this technology detects sequence abnormalities. These technologies have inherent advantages (for example the ease of translation of OGM for detection of structural variants and the higher overall resolving power of LRS to incorporate sequence-level variants) and disadvantages, including technical hurdles to implementation still being evaluated to enable us to fully understand the potential strengths of these tests separately and in combination. As we identify more of these previously hidden genetic changes in AML, we are also increasingly realizing that more clinical research is needed to understand how we apply these changes in clinical practice. A key focus of our research is now to understand how the additional genetic variation now detectable can inform treatment of patients with AML and other diseases to inform a precision medicine approach to diagnosis and therapy selection.

3. From your perspective, what do you think is exciting about the future direction of precision health?

It is clear from results of this and other similar studies that we are only beginning to scratch the surface with our understanding of diseases like AML, and with the rapid evolution of genomics technologies such as OGM and LRS (among many others) and their translation to clinical applications the potential for refinement in our approaches to diagnosing and treating these diseases is enormous – diseases we now think of as relatively homogenous entities in the context of our limited understanding may be meaningfully picked apart based on their underlying biology, and patients may derive substantial benefit. The use of these technologies has already started to change how we think about patients with AML and is now starting to change how we treat. With the availability, wider application, and improving understanding of these tools, we are excited at the emerging prospect of truly personalized and precision cancer medicine, in which understanding of the biology of a patient’s malignancy, developed through genomics and related techniques, can be exploited to meaningfully improve outcomes.

About Drs. Eric McGinnis and Ryan Stubbins

Dr. Eric McGinnis is a Hematopathologist at Vancouver General Hospital with subspecialty expertise in cancer cytogenetics and molecular genetics and a Clinical Assistant Professor at the University of British Columbia. His main research interests are in improving evaluation and classification of chronic myeloid neoplasms and acute leukemias through clinical applications of novel genomics technologies, particularly optical genome mapping and long read sequencing.

Dr. Ryan Stubbins is a Hematologist and Transplant/Cell Therapy physician in the Leukemia/BMT program of BC. He previously did his medical school, residency training, a MSc, and hematology/BMT training at the Universities of Saskatchewan, Alberta, and British Columbia. He has performed additional research training at the BC Cancer Genome Sciences Center and the University of Chicago. He has clinical and research interests are focused on cell therapy, transplantation, and its application to hematologic malignancies.

Drs. Anna Blakney (pictured) and Jayachandran Kizhakkedathu (not pictured) are recipients of the 2022/2023 Precision Health Catalyst Grant award for their project entitled “Next-generation anti-cancer antibody formats enabled through development of novel low immunogenic RNA delivery”

Read a summary of the project here.

“This project will develop a low immunogenic novel delivery platform that enables the development and formulation of high-efficacy RNA-launched therapeutic anti-cancer antibodies with immense commercial potential. This platform will simultaneously circumvent existing bottlenecks in antibody development and manufacturing, whilst overcoming a key current limitation in the delivery of RNA therapeutics.”

1. Can you tell us about the precision health research work you’re collaborating on?

Our collaborative work, between the Blakney and Kizhakkedathu labs, focuses on developing next-generation lipid nanoparticle formulations for RNA cancer immunotherapies. Two of the main challenges in the field are developing more stable formulations that don’t require storage at -80C and engineering new formulations that don’t include polyethylene glycol (PEG). Many patients have antibodies against PEG, which results in faster clearance and lower efficacy of the therapy. Here, we’re aiming to develop new polymers that confer stability and eliminate the need to use PEG in LNP formulations.

2. What results have you seen so far?

We recently published a joint paper in Advanced Function Materials that shows that our new ultra-hydrating polymer is able to stabilize not only RNA and LNP formulations, but also protein therapeutics, against a variety of stressors including freezing, heat and lyophilization. This is a great first step to replacing PEG in these formulations, and we’re now using this knowledge to create further designs.

https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202406878

3. From your perspective, what do you think is exciting about the future direction of precision health?

We are gaining so much information about patient health, including personalized measurements for blood chemistry, genomes and microbiomes. This is highly complementary to the RNA LNP platform wherein we can design therapies for a variety of potential diseases, and manufacture them at smaller scale and lower patient cost, which will enable a new era of personalized medicine.

About Dr. Anna Blakney

Dr. Anna Blakney is an Assistant Professor and Tier 2 Canada Research Chair in Nucleic Acid Bioengineering in the Michael Smith Laboratories and School of Biomedical Engineering at UBC. She received her Bachelor of Science in Chemical & Biological Engineering from the University of Colorado at Boulder, and her PhD in Bioengineering from the University of Washington. She completed a postdoctoral fellowship at Imperial College London on the development of molecular and biomaterial engineering strategies for delivery of self-amplifying RNA. Her lab uses bioengineering, molecular biology and immunology approaches to develop the next generation of RNA vaccines and therapies. Her research has been published in a variety of top tier journals including ACS Nano, Nature Communications, Molecular Therapy, Biomaterials, Journal of Controlled Release, and Advanced Materials. She is also a passionate science communicator and runs a TikTok channel dedicated to educating the public about RNA biotechnology, which now has >250,000 followers and >18M views.