Snapshot of news and activities within BCCA


SCCOHT Retreat in Vancouver

Dr. David Huntsman, Dr. Yemin Wang, Dr. Anthony N Karnezis

Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) Retreat in Vancouver

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare and deadly cancer of young women and children. In order to bring hopes to defeat this disease, Dr. David Huntsman’s team have been working closely with Dr. Jeffrey Trent at the Translational Genomics Research Institute (TGen) and Dr. Bernard Weissman at the University of North Carolina through a joint research grant from the National Institutes of Health since 2014. They have discovered that the majority of SCCOHT is characterized by simultaneous inactivation of SMARCA4 and SMARCA2, two mutually exclusive ATPases of the SWI/SNF chromatin remodeling complex, through genetic and epigenetic mechanisms respectively, which have been adopted as definitive diagnostic markers for the diagnosis of SCCOHT. This work, published in the Journal of Pathology in 2016 (Karnezis, Wang and Ramos, et al), has been awarded the 2017 Jeremy Jass Prize for Research Excellence in Pathology by the Editorial Team of the Journal (see below).

On October 26 and 27, these three research groups held their bi-yearly team grant retreat in Vancouver to provide updates on the latest findings in their research. They have recently discovered that loss of SMARCA4/SMARCA2 caused an addiction of SCCOHT cells to the enzymatic activity of a protein called EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), a different chromatin remodeling complex. This work has been just published in the Journal of Pathology (Wang et al). Based on this discovery and a similar independent discovery by Epizyme Pharmaceutics (Chan-Penebre et al. 2017), clinical trials are now underway to evaluate the efficacy of EZH2 inhibitors in SCCOHT patients. In addition, our collaborative team has found that an FDA-approved multi-kinase inhibitor, called ponatinib, is effective in various pre-clinical models of SCCOHT (Lang and Hendricks et al, manuscript in revision), which could represent another potential treatment opportunity for patients.

In addition to the studies on SCCOHT, the three groups are also studying how mutations in other components of the SWI/SNF chromatin remodeling complex lead to the development of other malignancies, such as rhabdoid tumors, ovarian clear cell carcinoma, de-differentiated endometrial carcinoma and chordoma. These proposed activities will likely involve more scientists from our department, such as Drs. Cheng-Han Lee and Stephen Yip.

Jeremy Jass Prize for Research Excellence

Each year, the Journal of Pathology awards the Jeremy Jass Prize for Research Excellence in Pathology to the authors of the paper published in the preceding year that is considered best by the Editorial Team of the Journal. The prize is awarded in memory of the late Jeremy Jass, a renowned scientist and pathologist, who just before his sad and untimely death had become an Associate Editor of the Journal. For 2016, the prize has been awarded to UBC Department of Pathology members (in bold):

Anthony N Karnezis †, Yemin Wang †, Pilar Ramos †, William PD Hendricks, Esther Oliva, Emanuela D’Angelo, Jaime Prat, Marisa R Nucci, Torsten O Nielsen, Christine Chow, Samuel Leung, Friedrich Kommoss, Stefan Kommoss, Annacarolina Silva, Brigitte M Ronnett, Joseph T Rabban, David D Bowtell, Bernard E Weissman, Jeffrey M Trent, C Blake Gilks* and David G Huntsman*. Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type. J Pathol 2016; 238: 389–400.

† These three authors contributed equally, * Co-corresponding authors

A medal for the first authors and certificates for all the authors, and we hope kudos for all involved. An announcement of the winner of the prize will be published in the January 2018 issue of the Journal of Pathology. The award of the prize will be presented to Drs. Karnezis, Wang and Ramos (first co-authors of the paper) in-person at the Winter meeting of the Pathological Society of Great Britain and Ireland to be held in London on January 25, 2018.

Amal El Naggar
Postdoctoral Research Fellow

MSFHR Fellowship awarded Amal EL-Naggar

"Targeting stress granules: A novel strategy to inhibit Ewing sarcoma metastasis"

I was born and grew up in the mother of civilizations, Egypt, where I completed my medical degree, pathology residency, as well as my master degree prior to joining Dr. Poul Sorensen lab in January 2009 for pursuing my PhD.

“There is nothing like a kid smile and nothing like seeing a kid in pain”, this is how I get my inspiration and motivation to study childhood cancers and how I decided to focus on sarcomas in my doctoral work. I successfully completed my PhD in December 2013 and started my postdoctoral training in January 2014. Joining Dr. Sorensen's lab paved my way for the opportunities in UBC and worldwide to work with dedicated oncologists and researchers, a critical step in my aspiration to be a research scientist.

My work focuses on deciphering the mechanism of sarcoma metastasis, the single most powerful predictor of outcome in these patients, and identifying potential targetable components with the hope of providing new therapeutic options for patients with metastatic disease. My doctoral work characterized a previously unrecognized pathway involved in sarcoma metastasis. Targeting vulnerable components in this pathway is currently under investigation. Recently, I’ve been greatly honoured to be receiving Michael Smith Foundation for Health Research (MSFHR) 2017 trainee award. This award means recognition to our hard work. It really means a lot and it also demands more responsibilities and more challenges to take on.

I have a wonderful 10-year old son; Abdalrahman. He is the most precious gift of my life! He is my hero! He inspires, supports, and encourages me all the time! I cannot thank him enough for his understanding and incredible tolerance to the countless hours I am spending in the lab weekdays and weekends. The time we spend together, we enjoy walking, reading, playing tennis, volunteering, watching movies, discussing our hopes and dreams! One of his dreams is to complete the run that Terry Fox hoped to finish! I am really thankful to all amazing people in my life, in Egypt and in Canada, who generously support me and believe in me and in my work, especially my parents and my God father Dr. Hesham EL-Naggar for teaching me to always aim high and strive for the best.

Andrew McPherson
Postdoctoral Research Fellow

MSFHR Fellowship awarded Andrew McPherson

"Evolutionary Determinants Of Treatment Resistant High Grade Serous Ovarian Cancer Investigated At Single Cell Resolution "

I was born in Vancouver, and spent my childhood partly in Vancouver and partly in New Zealand. After finishing high school and a degree in Engineering Science at SFU I landed my first job at a small video game studio in London, UK. I worked in the UK for 2 years, then moved back to Vancouver and worked on the Need for Speed series for Electronic Arts. During my time in the video game industry I frequently found myself implementing interesting graphics techniques developed by academic researchers. After 2 years at EA, I returned to academia with lofty aspirations of being able to contribute to the generation of new knowledge. I gained entrance into the CIHR bioinformatics training program, and with additional funding from the Alexander Graham Bell NSERC scholarship, worked towards my PhD in computational cancer genomics under the supervision of Dr. Cenk Sahinalp at SFU.

After completing my PhD, I continued my work with my PhD co-supervisor Dr. Sohrab Shah as a post-doc. In collaboration with Dr. Aparicio, Dr. Shah has developed novel methods for genome sequencing at single cell resolution, and is applying these techniques to further our understanding of the evolutionary dynamics of breast and ovarian tumours. Scaling up our capacity for sequencing and bioinformatics analysis has necessitated a significant investment in computational infrastructure, my principle responsibility at present. I currently lead a team of 4 undergraduate co-ops and 1 full time employees laying the groundwork for future research endeavors, and working towards our goal of sequencing the genomes of 1 million tumour cells. With the new sequencing technologies nearly stabilized, I will leverage these technologies to study how tumours evolve in response to therapy at single cell resolution using mouse models.

I, like many people, have witnessed family and friends deal with the devastating realities of cancer. I feel privileged to be given the opportunity to work on such an inspirational field of research alongside the talented individuals at the Shah and Aparcio Labs. I am lucky to work with a fun group of people who enjoy escape rooms, board games, and summer picnics. I spend most of my time outside of work with my wife and 2 young children, enjoying the many outdoor activities BC has to offer including rock climbing, skiing, and mountain biking.

On the road (in Bavaria):

Dr. Poul Sorensen, BSc, MD (UBC), PhD, FRCPC
Professor, Department of Pathology & Laboratory Medicine

As a researcher, sometimes you just need to get out of Dodge. The daily grind of fighting the same old traffic to get to the office, time-pressured grant-writing, attending stultifying meeting after meeting, rushing to student committees, and answering endless “urgent” Emails from colleagues and administrators, can sap the creative spirit from most scientists. So, what can you do about it? Well, it’s obvious, go on sabbatical! That’s exactly what I did. UBC has a wonderful sabbatical system for Professors, 6 months for every 7 years of duty, but many of us don’t take advantage of this great opportunity to recharge, or even to change our focus a bit.

So, I packed up the family (wife, Carmen, youngest kid, 9 year old Anika, and even the dog, Chester, a 3 year old Golden Retriever), and went to Munich for 10 months from September, 2016 to June, 2017. Why Munich? First, Carmen is German-born and speaks the language. Second, Technical University Munich (TUM), the highest ranked research university in Germany, actually offered me a Professorship, called an August-Wilhelm Scheer Gastprofessorship from the Institute of Advanced Studies at TUM, for foreign Professors, and designed to forge collaborative links with TUM Professors. My host was Prof Stefan Burdach, Chair of Pediatrics and Pediatric Hematology/Oncology at TUM, one of the top pediatric oncology departments in all of Europe. Prof Burdach is a renowned expert in Ewing sarcoma, one of the tumour types that we are deeply interested in (more on that below). So, we found a house with a yard (not so difficult, as there are lots of websites), filled out endless bureaucratic forms (wow, in Germany even dogs are expected to read the rules; see Figure 1), bought a car (German, of course), sent Anika off to German-speaking Grundschule (she did great there), and Carmen got to reconnect with her German heritage for a while.

So, what did I do there? Well, they gave me an office and a computer. Having the time to actually think, I got the opportunity to focus on some questions in Ewing sarcoma research that I believe are really important. Ewing sarcoma is a highly aggressive bone and soft tissue sarcoma most commonly affecting children and young adults. The disease is driven by pathognomonic translocations fusing the EWS gene (chr22) to an ETS family transcription factor gene, most commonly FLI1 (chr11) in 85-90% of cases, or the chr21 gene, ERG, in 10-15% of cases. Even knowing this, outcomes for Ewing have been largely unchanged for the past two decades, partly because we do not understand the molecular basis of metastasis in this disease, which is the single most powerful predictor of poor outcome in Ewing sarcoma. This does not appear to be related to expression of EWS-ETS fusions, which are found in both localized and metastatic disease. So, working with Prof Burdach, we thought a lot about what might be driving Ewing sarcoma metastasis. Being relatively quiet at the genomic level, we reasoned that other mechanisms might be at play. My lab has a longstanding interest in how mRNA translational control is involved in adaptation to microenvironmental stress in tumours (e.g. doi: 10.1016/j.cell.2013.04.055 and doi: 10.1016/j.ccell.2015.04.003), and we have previously shown that formation of RNA aggregates in the cytoplasm called stress granules is important for tumour progression in sarcomas (doi: 10.1083/jcb.201411047). Under stress conditions such as oxidative stress or hypoxia, mRNAs are sequestered and silenced along with RNA binding proteins in cytoplasmic stress granules (stress granules, guardians of tumour cell fitness under harsh environments? Figure 2). This reduces overall mRNA translation and protein synthesis to save energy, but with selective translation of what we believe are largely stress adaptive mRNAs to synthesize proteins designed to protect cells from stress. This is a highly conserved process, and stress granules have even been observed in yeast. So, over countless excellent Munich coffees, and yes, many 1 litre beers in Munich biergartens (not hard to find), Prof Burdach and I came to realize that maybe one area we should be focusing on more in our research is the role of stress granules in Ewing sarcoma metastasis. It has long been postulated that metastasis is a highly inefficient process, with only a very small percentage of micrometastatic cells having the potential to survive the many stresses of the metastatic cascade to form distant metastases. Maybe stress granules provide tumour cell fitness for survival under metastatic stress. This has prompted me to embark, with renewed enthusiasm, on the role of stress granules in Ewing sarcoma progression, the goal being to better understand the process as a way forward to identify new targets to block or reverse the process. I think that, if successful, this could have profound implications for developing novel therapies to prevent or treat metastatic Ewing sarcoma. In fact, Prof Burdach and I have written some grants together and are working on several manuscripts focused on this concept.

The sabbatical wasn’t just about the science. We made great new friends, traveled around Europe (Munich is so central), skied many times in the Alps (Ah, St. Anton in the Austrian Alps; Figure 3), and I even learned a bit of German (Jawohl, mein Schatz). And yes, there was Oktoberfest (Carmen, Anika, and Poul, good Bavarians on the way to Oktoberfest; Figure 4). The punch line of this little narrative--we work hard in this business, and so take advantage of one of the real perks. Go and do a sabbatical, if you can, and rediscover your inner scientist, and come back with renewed vigor. Even your students will forgive you (eventually) when you bring back lots of new ideas for them to work on.

BCCA Department of Molecular Oncology, New Students

Hak Woo Lee

Hak Woo Lee

I’m a Master’s student in the Department of Pathology and Laboratory Medicine. I was a breast cancer surgeon in South Korea and came here to study and do a research on breast cancer. Currently, I’m working at the Department of Molecular Oncology, BC Cancer Research Centre. I’m interested in molecular oncology in advanced breast cancer as well as treatment resistance and cancer metastasis. It is the most undiscovered and frustrating field in clinic because there is no effective treatment for metastatic patients at this point. In our lab, we are interested in clonal dynamics and evolutions in cancer and we are doing a lot of research on breast cancer and ovarian cancer. I’m planning to work on xenograft mouse models in breast cancer metastasis trying to understand what is going on during cancer progression. I’m having a great experience and learning a lot from this program. UBC is a great place to learn and improve your knowledge. Also, it is located in the beautiful city of Vancouver. So, I highly recommend UBC graduate school to prospective students!
Busra Turgu

Busra Turgu

I am a new PhD student at Dr. Sorensen’s Lab. I am very excited to be in such a beautiful city, have started my PhD in UBC Medical Faculty and be a part of Dr. Sorensen’s group. Currently, I am working on adaptation mechanisms to genotoxic stress in childhood cancers as well as the role of tumor suppressor Hace1 in carcinogenesis. I have graduated from Department of Biology at Middle East Technical University (METU) as a high honor student in 2015. In addition to my major degree in Biology, I have a minor degree in Chemistry. After my graduation, I did my masters in Ludwig Maximillians University of Munich (LMU), Germany. For my master thesis project, I worked at German Cancer Research Center (DKFZ) on ‘Antigenic target identification of H. pylori using whole-proteome microarrays’ in a collaboration project between Dr. Hoheisel and Dr. Waterboer. Before my master thesis, I did four different internships. In these internships, I worked on cancer, epigenetics and stem cells using different approaches. I did my first internship at DKFZ as a member of Dr. Hoheisel’s group in 2014. I worked on ‘The effect of pancreatic stellate cells on pancreatic cancer cells through ELF4E gene signaling pathway’. I did my second internship at Biomedical Center Munich as a member of Prof. Schotta’s group. In this internship, I worked on ‘Contribution of different domains of ATF7IP to the regulation of methyltransferase SETDB1 using CRISPR/Cas-assisted insertion of the MIN-tag’. In my third internship at LMU as a member of Prof. Böttger’s group, I worked on ‘The role of Notch and Wnt signalling pathways on differentiation of Hydra stem cells’. Lastly, in my fourth internship at LMU, I studied the function of different condensins in chromosome segregation during cell division. I am looking forward to combine my experiences in molecular oncology with my PhD project and have a wonderful and inspiring time here!
Andrii Vislovukh

Andrii Vislovukh

From the beginning of my scientific career, I was interested in the impairment of translational control during cancer development. I have obtained my Ph.D. from the Institute of Molecular Biology and Genetics, Kyiv, Ukraine. In collaboration with the lab of epigenetics and cancer, Orsay, France, I was studying the miRNA mediated control of the proto-oncogenic translation elongation factor 1A2. After completing my Ph.D. I moved to Belgium, where the topic of my investigation was tRNA modifying enzymes and its involvement in colorectal cancer induction. Since April 2017 I am working in Dr. Sorensen’s lab in the BC Cancer Research Center, investigating the role of the eEF2K kinase in neuroblastoma, namely discovering the mechanisms by which eEF2k makes cancer cells more resistant to the nutrient deprivation. I am enjoying reading, listening to contemporary classical music and spending time exploring beautiful parks of Vancouver with my wife and 1-year old son.
Andrii Vislovukh

Alborz Mazloomian

2017 PhD Graduate | Shah Lab

Grants Awarded

CANARIE (Sohrab Shah)

Dr. Sohrab Shah was awarded a grant with CANARIE, an organization that manages and develops components of digital research infrastructure for Canada's research, education and innovation communities. The award is for 3 years starting July 1, 2017, total amount $487,800, title “Montage: a software platform to drive the revolution in single cell cancer genomics”. Montage aims to encapsulate a number of existing software packages (Kronos, Biconductor, TimeScape, MapScape, and CellScape) for cancer genomics analysis in the form of a unified web application to be used by new research teams.


Cancer cell populations emerge through branched evolutionary processes leading to variation in fitness and differential growth patterns. Cell population dynamics fundamentally impact biological and clinical properties and motivate key questions for cancer focused biomedical investigators. Advances in high-throughput sequencing and computational methods have recently enabled the quantification of clonal dynamics through analyses of how mutations distribute across cancer cell populations over temporal and spatial axes (e.g., 1-3). This has led to an increased understanding of how cancer evolution impacts treatment resistance, cancer progression and metastasis. Further progress has traditionally been impeded by limited capacity to profile the genomes of individual cancer cells at scale. Recent breakthroughs by our group 4 and others 5 have introduced a robust, scalable, and high-fidelity method for single-cell wholegenome sequencing. This has created a revolution in the field of cancer genomics enabling 1000s of individual cells of a tumour to be profiled at ultra-high resolution. This in turn permits, for the first time, the ability to study a patient’s cancer as a population of interacting cells – each of which have different genomes and therefore different molecular behaviour in response to treatment. Our new research teams are leading efforts to leverage this technology at scale to study tumours in entirely new ways to a) determine the molecular basis of treatment response in the hardest to treat forms of breast cancer (Stand Up 2 Cancer, Aparicio) and to learn at the highest possible levels of resolution how tumour cells interact with the immune system (CRUK IMAXT, Hannon).

While significant progress in molecular biology, biophysics and DNA sequencing have advanced the field of single cell genomics, significant analytical challenges have been newly introduced. Importantly, scale and complexity of data generation for single cell genomics impede progress to biological insight. We have developed scalable solutions for the purposes of analysing data from our own lab 3,6,7, and we believe that now we are extremely well-positioned with CANARIE funds for additional software development such that other labs could take advantage of our progress. To address the informatics challenges of single cell sequencing, we have developed a number of platforms to interrogate cancer cell populations at the single cell resolution. These platforms span across the entire scientific workflow: from experiment meta-data tracking through a custom, purpose built laboratory information management system (LIMS), to performing bioinformatics analysis and, finally interactive visualization of the data.