Department of Molecular Oncology at BC Cancer

Internationally recognized pediatric cancer researcher Dr. Poul Sorensen has been named the eleventh recipient of MSFHR’s Aubrey J. Tingle Prize. Created in honour of MSFHR’s founding president & CEO, the Aubrey J. Tingle Prize is awarded annually to a BC-based clinician scientist whose work in health research is internationally recognized and has had a significant impact on advancing research – and its implementation – to improve health and the health system in BC and globally.

• https://www.msfhr.org/news/dr-poul-sorensen-awarded-2020-aubrey-j-tingle-prize
• https://lifesciencesbc.ca/announcements/2020-lifesciences-bc-annual-award-winners-announced
• https://www.bccrc.ca/articles/dr-poul-sorensen-awarded-2020-aubrey-j-tingle-prize
• https://pathology.ubc.ca/category/awards/research
• https://twitter.com/bccancer_molonc/status/1233482051980070916

Dr. Poul Sorensen and Dr. Mads Daugaard were awarded the St. Baldrick’s Foundation Martha’s Better Ewing Sarcoma Treatment (BEST) Grant

• $1,297,000 ($975,000 US) over the next three years
• tackling Ewing sarcoma, an aggressive bone and soft tissue cancer in children and young adults.

Ewing Sarcoma (EwS) is an aggressive bone and soft tissue tumor occurring in children and young adults. Approximately 25-30% of patients already have metastases at diagnosis and in spite of aggressive treatment, the survival for patients with metastatic disease remains dismal. EwS is considered an immune cold tumor that is largely resistant to conventional immunotherapy. Alternative treatment approaches are sorely needed, particularly in patients with metastatic disease. Here, we propose three novel strategies for targeting EwS tumors: 1) Inhibiting an EwS specific fusion protein that drives EwS tumor development. We have identified an experimental drug-candidate for downstream clinical development and generated preliminary data suggesting specific targeting and killing of fusion positive EwS cells. 2) Targeting a surface protein called IL1RAP. We have recently identified IL1RAP as a highly expressed molecule on the surface of EwS cells. We have further developed an antibody that specifically binds IL1RAP on EwS cells. We are currently linking this antibody to toxins to create highly specific therapeutic antibody-toxin conjugates that target and kill EwS cells. Our preliminary data is encouraging and the conjugates are being positioned for clinical development. 3) Recruiting natural killer (NK) immune cells to EwS tumors and priming them to attack the tumor. We have developed a reagent called VAR2-IL2v, which specifically binds sugar chains on the surface of tumor cells in one end and immune cells called NK cells on the other end. We propose developing VAR2-IL2v as a novel immunotherapeutic strategy for recruiting NK immune cells to EwS tumors and priming them to attack and kill tumor cells.

Dr. Poul Sorensen, along with Dr. Elizabeth Lawlor from the University of Washington has been awarded the Stand Up To Cancer (SU2C) Phillip A. Sharp Innovation in Collaboration Award for their project, “Enhancing ferroptosis to block Ewing sarcoma metastatic capacity” ($250,000 USD over two years).

Despite maximally intensive cytotoxic therapy, outcomes for patients with metastatic Ewing sarcoma (EwS) are dismal and have not improved in over 30 years. Thus, there is urgent need to better understand mechanisms of EwS metastasis and to develop therapies that specifically target metastatic progression. In recent years metabolic reprogramming has been defined as a critical mediator of metastasis, particularly in the precise control of redox and amino acid homeostasis that are essential for tumor cell survival during the highly stressful multistep metastatic process. Further studies in this area of research could profoundly impact our understanding and treatment of EsW metastasis.

Laks E, McPherson A, Zahn H, Lai D, Steif A, Brimhall J, Biele J, Wang B, Masud T, Ting J, Grewal D, Nielsen C, Leung S, Bojilova V, Smith M, Golovko O, Poon S, Eirew P, Kabeer F, Ruiz de Algara T, Lee SR, Taghiyar MJ, Huebner C, Ngo J, Chan T, Vatrt-Watts S, Walters P, Abrar N, Chan S, Wiens M, Martin L, Scott RW, Underhill TM, Chavez E, Steidl C, Da Costa D, Ma Y, Coope RJN, Corbett R, Pleasance S, Moore R, Mungall AJ, Mar C, Cafferty F, Gelmon K, Chia S; CRUK IMAXT Grand Challenge Team, Marra MA, Hansen C, Shah SP, Aparicio S. Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing. Cell. 2019 Nov 14;179(5):1207-1221.e22. doi: 10.1016/j.cell.2019.10.026. PubMed PMID: 31730858; PubMed Central PMCID: PMC6912164.

This paper highlights a new platform for cancer research, performing large-scale population analysis over thousands of cells. A central problem in cancer control is the capacity of tumour cell populations to evolve over time, contributing to cancer cells spreading to other locations, treatment resistance, evasion of the cancer patient's immunity, and differences found within the tumour tissue itself due to single cells evolving and changing over time in different manners from each other. This new approach allows researchers to decode cell population dynamics from genomes, transcriptomes and proteomes of single cells, ultimately translating these findings into better combinations of treatment and identifying factors causing treatment resistance.

A Basser Initiative grant for which Dr. Samuel Aparicio is co-PI, was funded by the Gray Foundation and awarded to Harvard Medical School (Dr. J. Brugge leading). Just initiated in September, we will be developing strategies to track and prevent breast cancer development in BRCA mutation carriers. Total amount to BC Cancer is $505, 290 USD for a 3 year period. Total award to all recipients is $3M. Grant title is, “Development of strategies to track and prevent breast cancer development in BRCA mutation carriers” .

Lay Summary:
It has been difficult to track and prevent breast cancer in BRCA1/2 mutation carriers because we do not yet understand how their cancers begin and progress. Using transformative new technologies, we have examined hundreds of thousands of individual cells from breast tissues of BRCA1/2 mutation carriers in order to identify the earliest changes in cells from ostensibly normal tissues, opening an unprecedented opportunity to track breast cancer development and develop strategies for cancer prevention. We have identified two specific subtypes of cells that accumulate significantly in breast tissues from BRCA1/2 carriers and are rare in breast tissues without BRCA1/2 mutations. Initial characterization of these cells provides intriguing clues as to why they accumulate, and how to prevent their accumulation. Our internationally recognized team of basic and clinical scientists will build on these exciting new findings, to decipher in detail why BRCA mutations cause these cells to accumulate, and to expose vulnerabilities that could lead to new strategies for their elimination. By identifying specific markers for these cells, we will devise clinical approaches to track their accumulation in BRCA1/2 mutation carriers, in order to precisely time clinical interventions. The proposed work could transform both our understanding of breast carcinogenesis in BRCA1/2 mutation carriers and our ability to predict and prevent it.

Zhang AW, O'Flanagan C, Chavez EA, Lim JLP, Ceglia N, McPherson A, Wiens M, Walters P, Chan T, Hewitson B, Lai D, Mottok A, Sarkozy C, Chong L, Aoki T, Wang X, Weng AP, McAlpine JN, Aparicio S, Steidl C, Campbell KR, Shah SP. Probabilistic cell-type assignment of single-cell RNA-seq for tumor microenvironment profiling. Nat Methods. 2019 Oct;16(10):1007-1015. doi: 10.1038/s41592-019-0529-1. Epub 2019 Sep 9. PubMed PMID: 31501550.

CellAssign fills an important role in the sequencing analysis toolbox for researchers. We anticipate the CellAssign approach will help unlock the potential for largescale population-wide studies of cell composition of human disease and other complex tissues through encoding biological prior knowledge in a robust probabilistic framework.

OVCARE researchers (past/present) amongst the world's top 15 most impactful ovarian cancer pathology researchers for the past 5 year period, according to IARC-WHO (International Agency for Research on Cancer-World Health Organization - David Huntsman (ranked #2)

Short bio:

I obtained my PhD degree from Nankai University, China. After that, I went to the University of Wisconsin-Madison as a postdoctoral associate, my research focused on b cell lymphoma biology. Then I transferred to Shanghai (China), and worked in WuXi Apptec and Johnson & Johnson (China) company to co-lead anti-cancer drug projects. In Sep 2019, I joined Samuel Aparicio’s lab at BC Cancer. The current projects are to dissect triple negative breast cancer clonal evolution/fitness with PDX and organoids models and do research on therapeutic interventions based on gene signature by single cell sequencing. When I do have free time I enjoy travelling and watching soccer games.

Short bio:

I am pursued a PhD in machine learning and image processing at the university Pierre and Marie Curie, Paris, France. My thesis was about the analysis and modeling of spatial organization of 3D tissues in biological images. Then later, I have joined the Singapore Immunology Network, A*STAR as a postdoc fellow, and my research focused on data analysis of single-cell and system immunology. Early this year, I started working at Aparicio's lab and my research focus on analyze single cell RNA-seq and DNA-seq data.

In my spare time, I usually go jogging and go hiking. I love the nature in British Columbia.