The reportage covers the collaboration between researchers and clinicians in Windsor and how this teamwork is helping cancer patients in our community.

Check the link below to watch the videos.

Windsor-area researchers and doctors collaborate in search of a cure for cancer

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The Porter lab has always enjoyed great diversity in the mix of personalities and talents in the lab. At a fundamental level our four Research Associates (RA) are the force that keeps our lab running smoothly and each RA brings invaluable expertise that benefits our entire team. Here are some highlights for each of them this year (there are too many to cover them all):

As the head of our Tuberin group Elizabeth has continued our NSERC funded work focusing on the importance of the novel interaction between Tuberin and Cyclin B1. Elizabeth’s discovery that this interaction plays a role in regulating mitosis has begun to get the attention of the research community and was the focus of an Oncology Letters paper in 2017 published by the Wang Lei group. It is Elizabeth’s patience, care and guidance that is allowing us to dissect this complicated interaction – the data that will be revealed in her upcoming manuscript provides very clear confirmation that this is a novel checkpoint regulating how a cell controls size according to available nutrients. In addition to her work on our NSERC program, Elizabeth has collaborated with the Gauld group on a Seeds4Hope funded project to model the structure of Tuberin when bound to either Cyclin B1 or Hamartin. She has also started a collaboration with the Swan lab to study how Tuberin and Cyclin B1 interact in a Drosophila model system (a new grant submitted to Seeds4Hope). Elizabeth has continued to train students both in our lab and surrounding labs on microscopy, and she runs and maintains the flow cytometry facility. Of course she is also the Yoda for all complex cloning projects in our lab, for which we are so grateful! I’m always constantly amazed by the scope of talent that Elizabeth has – now taking over the Porter lab website and kicking off this awesome blog!

The brain group was excited to have Dorota back from maternity leave this fall (welcome baby Anthony!). While juggling 2 kids at home Dorota’s review article summarizing the implications of CDK inhibitors in brain tumour treatment came out in Drugs in R&D Jun; 17(2):255. Dorota also came back with a paper written (of course she did!) and a new patent application in hand – both of which are in progress now. As part of our CCSRI funded work Dorota has developed a platform for studying individual patient brain tumours using her own advances on organoid modeling. She has also established a collaboration with Dr. Tirupati Bolisetti in Engineering to use mathematical modeling to predict how individual patient tumours respond to drug treatment (Seeds4Hope and CCSRI LOI submitted). She has advanced a collaboration with Dr. JR Ewing in Physics at Henry Ford to study how mechanical forces impact brain tumour properties – this work received a grant from Henry Ford in the summer and will be submitted as an NIH RO1 grant in the spring.

Bre-anne and Rosa co-lead our CIHR funded work and the breast group. Bre-anne also juggles our constantly expanding mouse colony – managing over 23 mouse lines! 2017 has been a productive year for BreAnne – she published an EMBO paper in collaboration with the Rubin lab (UCSC) solving the structure of Spy1 when bound to Cdk2, which incidentally is one of my favorite papers ever! She has also submitted 2 very important papers characterizing the phenotypes of one of our Spy1 transgenic mouse models – these are both in review at Oncogene. One of the surprising results from this work is that elevated levels of Spy1 induces liver tumorigenesis in male mice, this work is the subject of our upcoming CRS application. Breanne is part of a Seeds4Hope funded project led by Dr. Sindu Kanjeekal from the Windsor Regional Hospital to help advance personalized medicine here locally. Breanne is a leader on a full US patent secured this year (with Dorota and Ingrid) for a new mouse model of brain cancer.

Rosa has been instrumental in setting up our new zebrafish drug screening platform (although we learned that writing ‘drug screening’ on a door sign is not a wise move! … door is finally fixed). We obtained funding from Caesars Windsor to expand this platform as part of a core facilities network led by the Windsor Cancer Research Group (WCRG) termed NUCLEUS. Rosa used this model in her Oncotarget paper that came out in April this year, which showed that elevated levels of Spy1 contribute to Tamoxifen resistance in ER+ breast cancer patients (Oncotarget 8(14): 23337). The first Spy1 clinical trial in collaboration with Dr. Caroline Hamm from Windsor Regional Hospital is now complete … we are excited for this data to be published in 2018! Rosa has mastered creating our own tissue microarray panels – and we now have a large cohort of local Triple Negative Breast Cancer patients tissues in these panels with clinical information. Rosa has some exciting data from these patients that will come out in 2018!

Our graduate students have been working hard and making very important progress on their projects. Janice is pulling her data together for publications and thesis write up while on maternity leave with her latest addition baby Joseph. Ingrid published a paper in Genomics (in press) in collaboration with the Reuda lab. This work used computational biology to isolate potential biomarkers that indicate progression of prostate cancer. Ingrid also published a book chapter (in Methods in Molecular Biology) to teach about using flow cytometry to study the cell cycle in brain cancer stem cell populations. Ingrid has two more publications that she aims to get out on her brain cancer work early in 2018 as she is targeting a late spring/early summer graduate date (sniff sniff). She presented her unpublished work at the London Oncology Day – winning the top poster award! Frank has pulled together some fascinating data showing the role for Spy1 in aggressive gyneaecological cancers and continues to use his pathology expertise to advance many areas of our research program. Our newest PhD Martin is expanding our focus on prostate cancer and has found some very important data to support a role for Spy1 in prostate cancer progression. Martin published a paper in Current Pharm Design and has another in late stage preparation for submission in 2018.

Within our MSc cohort, Ellen is putting the finishing touches on her thesis with graduation date early in 2018 and Iulian has made headway on demonstrating a molecular role for Spy1 in one of our mouse mammary phenotypes. In 2017 we welcomed a new MSc student Adam, originally from Windsor recruited back from Western Ontario. Adam is working with Elizabeth on the Tuberin project and will dig into the collaboration with Dr. Swan.

Undergrads are always a big part of the Porter lab environment and contribute to our ideas, energy and FUN!. We said farewell to our thesis students and long time lab members John Kelly (now doing a MSc at Western), and Melanie Grondin (currently in the MD/PhD program in Ottawa) – John and Melanie we wish you both well and don’t forget to visit!! We were lucky to get back our talented artist and scientist Phil Habashy as a growing collaboration with the Zhang lab. Our new group of EIGHT thesis students is the largest group in the tenure of the Porter lab – Amy, JT, JO, Jackie, Youshaa, Gillian, Dalton and Phil – each has teamed up with a research associate or graduate student and are well on their way to answering their research questions set out in Sept. This year we had 10 outstanding scholars in the lab (Amy, JT, Jackie, Youshaa, Jake, Catalin, Isabelle, Anne, Melanie and John). Summer 2017 we had 4 awesome NSERC USRA students (John, Amy, Anne and Catalin), a very bright and keen SWORP medical student (Joshua Samsoondar) and we were very proud of Alex Rodzinka for securing a Brain Tumour Foundation Scholarship. Because of this group of undergrads we held our first ever Christmas gift exchange – yes I gave the only blooper gift (sorry Adam – hows that fart gun?) – and I particularly loved Ingrid’s gift – providing her with an RA contract and mug that will bind her as a Porter lab member forever.

In addition to our progress on papers, patents and advancing science – our lab puts a lot of effort into communicating our research in many different ways and advocating for the research community. Porter lab has been an instrumental component in the organization and delivery of the WCRG quarterly ‘think tanks’ that advance cancer research ideas and partnerships. These think tanks have advanced 24 research projects and have brought together 233 researchers from across 4 different hospitals, 7 universities/colleges and 4 industrial partnerships. I have delivered 9 talks to the public and our group has hosted countless lab tours to interested students and community members. Ingrid and Breanne kicked off a RIOT (Research Information Outreach Team) in collaboration with the Canadian Cancer Society (making Windsor one of only 4 in Ontario). Ingrid was the guest speaker for the CCS Volunteer night for both Windsor and Chatham this year. Ingrid has also helped in organizing a Windsor “Lets Talk Cancer” and has been a true leader in advocacy for research – her efforts in this area were recognized by winning the Faculty of Science Ambassador Award. Ingrid and I helped to organize a Windsor effort to meet with our local politicians and community leaders to inform about the changes to research funding and the important impacts that this would have on Canada. Rosa made us all proud by presenting her research at SoapBox Science at York and is now leading a similar event for Windsor in 2018. Our lab participated in events like the Brain Tumour Spring Sprint, CCS Relay For Life, Science Rendezvous, Katelyn Bedard Bone Marrow Bowl-a-Thon and swab events, Devonshire Mall Research Showcase – with the motivation to educate, empower and better our local cancer community. The extra mile that my group goes to support our community in this way truly makes me proud!

When I look over the scope of research ideas and activities that our group covers I’m always blown away – and admittedly a little terrified. A visiting scientist once lectured me on ‘staying focused’. I’ve thought a lot about this since then and I’ve concluded that there is a clear difference between not successfully following through on a good idea – and not doing the idea just because its out of your comfort zone. Cancer is a complex problem and it requires bold aggressive ideas to move the field forward. We aren’t going to get amazing cures by ignoring good ideas – or skating around unexpected results to play it safe. I’m thankful for my group who never raise an eyebrow when I throw out one of my “can’t we just make a liver?” comments – but rather research the idea and come back with a plan of how to do it better than I imagined.

Cheers to a great 2017 – I have the best group ever and I’m excited for where our ideas and results are going to take us in 2018!!

Lisa Porter

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Out with the Old, In with the New!

Biological aging or senescence is the steady decline of cellular function with age. There are a number of rationales that explain why senescence occurs, including changes in gene expression, or damage that is accumulated throughout the lifetime of a cell. Many questions surrounding how to overcome senescence by means of slowing it down, stopping it or potentially reversing it, are the focus of my research project.

The cell cycle lies at the heart of understanding senescence. Teasing apart cell cycle regulation mechanisms and how they are involved in bypassing senescent barriers is critical, especially regarding implications that these mechanisms may have on cellular reprogramming, neural stem cells and tumourigenesis of the central nervous system.

My research focuses on the role of Spy1, a cyclin-like protein, which has been shown to override replicative senescence. As has been previously mentioned by my lab mates, Spy1 can bind, and activate CDK1/2 uniquely without the need of activating phosphorylation and dephosphorylation events to take place. My curiosity with cellular senescence began when I started elucidating Spy1’s role in overcoming reprogramming induced senescence; a unique senescent barrier that somatic cells succumb to on their way to induced pluripotency. Induced pluripotent stem cells have changed the world of regenerative medicine and remain a hot topic with researchers around the globe. We’ve gathered some interesting data that suggests Spy1’s role is essential in overriding reprogramming induced senescence and this is unique to other cyclins. We’ve shown that this leads to an increase in the number of induced pluripotent stem cells that are created from the process. We are currently picking apart some interesting mechanisms of why this may be.

Another piece of my project focuses on Spy1’s role in the neural stem cell population of the brain. We have created a transgenic mouse model system where we can induce the expression of Spy1 under the Nestin+ stem cell population of the brain at any given time, allowing us to investigate its role in neurogenesis and neural stem cell populations throughout life. To date, I’ve been able to show the inability of these cells to terminally differentiate into neurons. Interestingly, although cells expressing Spy1 have increased proliferation rates, their population is maintained throughout life. This naturally brings forward hypotheses of how this stem cell pool is maintained into old age, and what this means to the whole organism in terms of central nervous system tumourigenesis and neurodegenerative diseases. I am lucky to work alongside an amazing research associate in the lab, Dr. Dorota Lubanska, as well as a group of highly motivated and dedicated undergraduate students in a concerted effort to contribute to science every day.

It All Comes Full Circle!

All scientists, whether they are biologists, physicists, chemists, computer scientists, to name a few, are driven to their work because they want to make things better. The knowledge that we gain from science helps us figure out novel ways to fight diseases, create energy, protect natural habitats, connect populations, overcome adversity and much more.

As demanding as a Ph.D. can be, the privilege of getting to be creative and answer important questions in a fascinating environment truly makes up for the workload. Answers to these questions will help us understand the world more and more every day. However, the curiosity behind research questions inevitably means that failure will occur, sometimes more than we’d like. Experiments have to be repeated over and over. Some days it gets hard to remind ourselves of our goals and our vision, especially days when we are fed up with yet another failed experiment. I must note, that with persistence, patience, and continued motivation, you’ll happily surprise yourself by learning something fascinating along the way and ultimately contributing to science.

Induced pluripotent stem cells have taught me the importance of resetting and redefining. Every day we have the potential to re-evaluate our priorities. One thing that keeps me motivated and helps me escape the repetitiveness of the lab bench is communicating my science to others. I truly value how important public education is, and how everyone should be encouraged to gain insight into what I do as a scientist and to support research. This way, I am also challenging others to reset and redefine their views on research. In addition, cellular senescence constantly reminds me that our lives do in fact have an end. It is imperative that we are continually aware of this and adapt the mantra of “sometimes you win, sometimes you learn”. If put into perspective, nothing in science is ever a loss.

Ingrid Qemo, Ph.D. candidate
 

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Yesterday afternoon the Porter Lab welcomed members of the Brain Tumour Survivors Group to the lab. The members were treated to an exciting presentation by Dr. Lisa Porter detailing a brief history of cancer and how Porter Lab is working to advance the frontier of cancer treatment – from basic research to the development of revolutionary techniques of personalized medicine. It is well known that many cancers may not respond as desired to many of today’s common treatments. Likewise, some cancers may appear to be eliminated only to reoccur at a later date. By examining each person’s cancer individually, Lisa explains, we can better assess how their cancer will react to certain drugs. Subsets of cancerous cells may remain (possibly undetected) while the majority are eliminated by chemotherapy. Providing a more comprehensive assessment of a patient’s cancer, the methods being developed in Porter Lab give doctors more tools and direction to improve patient prognosis and reduce the possibility for reoccurance.

Following the presentation, the Survivours Group members were given a tour of the Porter Lab facilities and had the opportunity to experience some of the ins and outs of basic research. Most of all, the members were particularly impressed by the flow cytometry and cell sorting instruments and how they can be used to isolate single cells from a suspension and sort them according to specific characteristics determined by the researcher. Additionally, the tour provided insight into some basic biotechnology (such as western blots) and the zebrafish model being developed. “It’s almost unimaginable that we can develop this technology and have so many people dedicate their lives to cancer research but we still do not have a cure!” one member was heard saying, highlighting the complexities of cancer’s biology and biochemistry.

Opening up the lab and getting the community involved is believed to be one of the most effective ways of conveying just how important research and development is to everyone. It gives patients and those afflicted a better understanding of what is being done to help them, especially when it seems like there has not been much major progress in cancer research to many people. Some of the Brain Tumour Survivors Group members noted that, before the visit, they were not aware of just how much has been done and one expressed how important it was that we all work together as a community towards a better understanding of cancer for researchers and patients alike.

Porter Lab also enjoys the opportunity to open up to the community and we are honoured to have the Brain Tumour Survivors Group members in the lab! None of this would have been possible without them as they, and the greater community, all give us the determination to come back to lab in the morning (even to do western blots) and continue with our research.

Thank you Brain Tumour Survivors Group Members for taking an interest in us and visiting Porter Lab, it was an honour!