The Porter Lab was a success at the WCRG2018 this weekend. Our lab marked presence with one of nine Rapid Fire Session presentations and had a total of 10 posters presentations from a total of 58 conference posters. One of our students received a Student Research Excellence Award for his poster presentation and a Porter Lab alumni also received a Student Research Excellence Award for her poster presentation.

Thanks for visiting and please leave comments below.

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The Porter Lab new logo was designed by our talented Ph.D. student Martin K. Bakht. The logo depicts the main research areas of our lab.

The P of Porter shows the following:

Asymmetric Cell Division

Speedy Cell cycle

The  L of Lab shows the following:

DNA technology

Zebrafish used by our Lab as a xenograft model

The colours match the University of Windsor, Windsor Hospital and WCRG logos, connecting research and health care.

Hope you enjoy our new logo, please leave your comment below.

Elizabeth Fidalgo, Ph.D

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One more time Dr. Porter made us proud!

Here is the video of her brilliant talk.

Please leave your comment below.

Elizabeth Fidalgo, Ph.D

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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What makes up a true neural stem cell?

What controls its self-renewal and commitment?

How is the symmetry of division regulated and kept in check?

Can we pinpoint the origin of brain cancer?

Questions about molecular mechanisms behind the regulation of cell fate within the mammalian brain have been fascinating scientists around the world for centuries. The effort to address the essential topics is not only a delightful and captivating everyday struggle of neuroscientists but it’s also a part of a global movement and a world-scale attempt to improve and fight for lives of people touched with neurodegenerative diseases, neurotrauma and brain cancer. In Porter Lab, we have that great privilege to contribute to this global effort. The Brain Group, as the vital organ of our lab, is committed to high-quality research, breakthrough discoveries and new, exciting ideas.

Several of The Brain Group projects are focused on the role of a cyclin-like protein Spy1, aka Speedy-1, SPDYA, RINGO A, in neurogenesis and neural types of cancer. We know that Spy1 activates CDK1 and CDK2 in a unique way and promotes the degradation of the CDK inhibitor, p27^Kip1. Since CDK2 and p27^Kip1, play a regulatory role in many developmental events including neurogenesis and these effectors are aberrantly regulated in several aggressive forms of cancer like glioma, we consider investigating Spy1 function of high importance.

NTA Joint Venture

Our brilliant Ph.D. candidates, Ingrid Qemo and Frank Stringer, are the main investigators of Spy1 role in neurogenesis and expansion of neural stem cells. Based on studies of other neural systems in the lab, like neuroblastoma, we’ve learned that Spy1’s cell cycle-mediated effects are key factors in regulating terminal differentiation in neurons. In addition, examination of the developmental time course of the mammalian brain revealed that significant decline of Spy1 levels coincides with events of neuronal differentiation and apoptosis, whereas the peak of expression overlaps with the phase of increased stem cell proliferation.

Now, a question arises about the importance of Spy1 in maintaining pools of adult neural stem cells and potential consequences of its aberrant regulation.

To address this question we were successfully funded by Canadian Cancer Society, initially with Innovation, and later on, with Innovation to Impact grants which allowed us to generate tools and purchase sophisticated equipment required for detailed and high-quality investigation.

Although one of our dedicated undergraduate students, Dalton Liwanpo, is yet to pinpoint specific neural cell populations abundant in Spy1 protein and mRNA, Ingrid and Frank are already utilizing an inducible transgenic NTA mouse model (Nestin-Spy1-pTRE mouse) to obtain upregulation of Spy1 protein in select, Nestin+, populations of neural stem cells. So far, this system successfully allowed for investigation of the spatiotemporal function of Spy1 in vivo. Ingrid’s expertise in primary cell cultures and Frank’s proficiency in immunoassays on tissue sections, which is currently being passed on to Dalton, came together to establish ample data containing surprising results and exciting phenomena, currently put together in a manuscript to be shortly published as an original article.

Although to date, we have not observed brain tumours in those mice, Spy1, due to its unique functions, constitutes a perfect accessory to ”the crime of brain tumourigenesis”, and this is the main focus of currently ongoing studies and in part a leading objective of another undergraduate project thesis by a diligent student and an Outstanding Scholar, Youshaa El-Abed.

The Glioma Enterprise

In spite of the fact we are yet to discover where the story of Spy1 in brain tumourigenesis starts and ends; whether Spy1 is a factor during initiation or a promising therapeutical target, we did establish its role in glioma maintenance and progression. The funding obtained from Cancer Research Society was crucial in the initial groundbreaking phase of this study. With an amazing support of the co-authors and our collaborators, I was finally able to share six years worth of data in a high impact study, Cancer Cell 25:64-76. We utilized primary cell cultures derived from GBM (Glioblastoma Multiforme) patients and isolated CD133+ cell populations, known to have an extremely high capacity of glioma formation upon orthotopic injection into mice. The depletion of Spy1 levels in those cells caused a significant increase in differentiation markers and enhanced frequency of tumorsphere formation. Further investigation revealed a striking effect of Spy1 depletion on the mode of division of CD133+ cells; we found that decline in Spy1 levels caused a highly significant increase in the rate of asymmetric divisions. We are currently building upon this exciting data, trying to further dissect the heterogeneous cell populations of GBM in respect to its established subtypes. Alex Rodzinka, who is an outstanding and a very bright undergraduate student, awarded with the Brain Tumour Foundation of Canada Research Studentship, is attempting to shed light on the essentiality of Spy1 in the expansion of those populations and targeting Spy1 for their potential eradication, which is tested using Zebrafish platform.

Another burning aspect, awaiting answers, is the mechanism behind our results; although we established WHAT it is, that Spy1 is doing in those GBM cells we still don’t know HOW. Mat Stover is The Brain Group’s only MSc student, his persistence and dedication are exactly what’s needed to take on this task. In addition to molecular pathway determination, Mat is studying how changes in Spy1 levels affect cell cycle profile in glioma subpopulations and how we can utilize that modulation for therapeutic purposes.

The complexity of GBM makes it extremely hard to treat and ironically that complexity expands as our knowledge about it advances, hence, the therapeutic progress always ends up behind.  Can we win this race? Current literature suggests that the patient-tailored treatment has the potential for best clinical outcomes. Now, to determine individual approach, should the patients be evaluated genomically only? Or proteomically, phosphoproteomically, metabolomically or by the cell subpopulation composition? Should we search for additional tools to predict the response of a tumour to therapy?

Tumour Stress Alliance

Our collaborators from Henry Ford Hospital (USA) have developed imaging method (DCE-MRI) module to measure brain tumour physiology and tissue properties such as cellularity, Extracellular space, and perfusion.

Patients presenting with low rates of tumour perfusion due to solid stress (pressure from solid components of a tumour) causing extensive hypoxia and impaired drug delivery, exhibit poorer prognosis with worse chemotherapy response and shorter survival in comparison to patients with high tumour perfusion. Therefore, a tool allowing for measurement of the tumour solid stress and for subsequent therapy response prediction could make a substantial difference.

In our lab, we were able to develop, optimize and validate a 3D platform mimicking patient brain tumour growth in vitro. This system offers an extensive flexibility of environment manipulation and a high throughput approach for drug testing, which are impossible in vivo. Therefore this model has become an in vitro approach to study and compare, to the results obtained through DCE-MRI, the biology of the tumour under solid stress. Jonathan O’Beid is a very enthusiastic undergraduate thesis student who has gained ample of experience on immunostaining of DCE-MRI- assessed brain tumour tissues and analysis of the expression of crucial stress related marker proteins. Jonathan is utilizing the 3D system to manipulate solid stress-related factors and study their effect on drug response in vitro.

Due to the fact that our 3D system allows to entirely control tumour growth and to establish a high throughput time course, we are able to collect data on changes to the cellular layers of our tumour model. The results can be utilized to mathematically model tumour growth before, during and post-therapy and how the arising internal solid stress affects the cellular composition. We are currently in process of collecting and analyzing data which will be forwarded to our collaborators at the Department of Engineering. They are motivated to establish a mathematical approach to the brain tumour growth and drug response prediction.

Our novel 3D platform is fully patient customized and, in combination with the above unconventional interdisciplinary methods, it can, not only, potentially move forward our knowledge on GBM biology but also become a drug response prediction tool, pointing at the necessity of  diverse fields of science to come together in understanding to tackle the most complex phenomena.

Medulloblastoma Incorporated

The medulloblastoma story is slowly coming together as it is one of the projects in our lab which are being passed from hands to hands of very keen and skilled undergraduate students who take over, one after another, bringing all the pieces together at the end. This project was funded by  Brain Tumour Foundation of Canada which also generously offered several Research Studentships related to medulloblastoma studies in our lab.

Over the years we have discovered that medulloblastoma cells cultured as neurospheres enriched in Spy1 but not in Cyclin E1, suggesting a unique role of Spy1 in this particular tumour. Utilizing in vivo zebrafish assays we found that Spy1 levels downregulation is essential in increasing efficacy of medulloblastoma response to synthetic CDK inhibitors.

Philip Habashy, who took over this project, performed further analysis of FACS derived stem-like medulloblastoma cell populations and revealed that Spy1 is an important factor in maintaining their character. Interestingly, Phil’s curiosity made him shift gears recently and work on a novel idea, together with Dr. Huiming Zhang (University of Windsor, Biology), trying to address the role of GABA_B receptor activity in the proliferation of medulloblastoma cells.

The Brain Group’s mission is to dissect mechanisms responsible for control over the fate of neural stem cells and progenitors utilizing diverse in vitro and in vivo systems. The data obtained on Spy1 role in glioma suggest that this unique protein has a potential to become an important therapeutic target. Overall we hope to contribute to better understanding of brain cancer biology and finding new potential ways to target tumours in a specific and efficient way.

I hope you enjoyed getting to know a bit about the Porter’s Lab Brain Group; let us know your thoughts in the comments below!

Dorota Lubanska, Ph.D

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The research in Porter Lab is divided into 4 main groups, one research associate fellow is responsible for the projects, grants, and students into each group. I’m Elizabeth Fidalgo, Ph.D., and I’m the leader of the Tuberin group. As the group name states our group studies a protein named Tuberin. This protein is a Tumour suppressor protein that controls cell growth and cell proliferation. Mutations in the Tuberin gene (TSC2) lead to several diseases, including Tuberous Sclerosis where patients present with large benign tumours (hamartomas) that affect primarily the skin, heart, brain and kidney and lead to compounding problems like autism and seizures. Mutations in Tuberin also result in Pulmonary Lymphangioleiomyomatosis (LAM), a cyst condition that affects the lungs and surrounding tissues in primarily young women. Mutations in TSC2 have been found in several cancers, including cancers of the skin, breast, kidney, and brain. As you can see, Tuberin is an essential protein for the control of cell growth and proliferation.

My group was the first one to report the role of Tuberin in the regulation of an important checkpoint in the cell cycle. Our results were published in the Cell Cycle 10: 3129-3139 with the title: The tumor suppressor tuberin regulates mitotic onset through the cellular localization of cyclin B1. Since then we have been investigating the mechanisms behind the essential control of cell division by Tuberin.  Understanding the basic biology is necessary for us to understand what this protein does in disease. This work is the foundation of our NSERC (Natural Science Engineering Research Council of Canada) work.

Tuberin is a large protein (200KDa) and is regulated by phosphorylation and it’s the main player of diverse pathways inside a cell.  It isn’t easy to work with it, so my group has developed tools to make a little bit easier to understand the functions of Tuberin towards the cell cycle. One of the first tools we developed using molecular biology techniques is a G2/M reporter, a vector that is transfected into the cell to monitor the Tuberin checkpoint. The cells turn blue when at the checkpoint, this way we can monitor the time that takes for the cell to move from one phase of the cell cycle to other. We’ve published the engineering steps for the construction of this reporter in Cytotechnology 2016 (1): 19-14 Title: Derivation of a novel G2 reporter system. This work was largely conducted by an undergraduate student in our lab, Sabrina Botsford.

Another tool under construction is the BiFC system (Bimolecular Fluorescence Complementation) where the cells turn yellow when Tuberin is actively participating of the checkpoint. These fluorescent tools are important because through them we can use time-lapse fluorescence microscopy and flow cytometry techniques to better understand the functional role of Tuberin in the cell cycle. This BiFC project was started by another undegraduate student, Marisa Market. We are also genetically modifying the genome of HEK293 (kidney) and HeLa (cervical tumour) cells using CRISPR-CAS system. We are introducing TSC2 clinical mutations in the genome of these cells lines to study the pathways affected by these mutations in hopes of revealing how these mutations regulate aberrant cell division. This basic information is essential for research to lead to new treatments for diseases ruled by Tuberin mutations.

This fundamental work supported by NSERC has provided the foundation for several other projects. We collaborate with Dr. James Gauld (Chemistry/Biochemistry UWindsor) on a Seeds4Hope grant sponsored by our local Windsor Cancer Centre Foundation (http://windsorcancerfoundation.org/seeds-4-hope/). This work is figuring out the important binding regions between Tuberin and its partners using computational (computer-based) approaches. In 2013 I was awarded a Seeds4Hope grant to study the role of Tuberin in the formation of Medulloblastoma, the primary brain cancer affecting children; an undergraduate student, Santo Spencer Briguglio, was supported to work on this project by the Brain Tumour Foundation of Canada. We are also currently working with Dr. Andrew Swan (Biology, UWindsor) to expand our cellular studies of Tuberin-Cyclin B1 into an in vivo Drosophila (fly) system. Our results have been presented at many local and international conferences.

One of the strengths of our group is the training of undergraduate and graduate students. We’ve trained several brilliant students, some of them have received awards/fellowships from our department, university, and the province and most have been successfully accepted to Medical and Pharmacology schools through Canada.

Being a tough protein to figure out we often joke that this project trains students to be strong! As an example, one of our past Tuberin undergrads Ryan Ard did his Ph.D. in the Allshire lab in the UK and is now a postdoc in the Marquardt lab in Denmark. Ryan received an international scholarship and has 7 publications including a Nature Communications paper. We are proud of our successful students! We currently have a great group: 2 undergrad thesis students (Jackie Fong and Gillian Denomme), an MSc student (Adam Pillon) and a Ph.D. student in collaboration with Dr. Andrew Swan (Mohammed Bourouh). We are looking for great things to come from this team.

Hope you enjoyed to know a little bit more about one of the research groups in the Porter Lab.

Please leave your comments and/or suggestions below, I’ll be happy to answer them.

Elizabeth

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