We are grateful to the Super Sam Foundation for supporting Noah as the first Super Sam Fellow.  Learn about Sam here.   Noah will present the logistics of his work online at this blog – please bookmark it and visit weekly!  Here’s Noah:  see also the video about Noah’s work at https://www.facebook.com/SuperSamFoundation/videos/1913393832243243/        08/08/2017:  Hi everyone! First edition of the cancer math blog. First, a huge thank you to Cassie Santhuff everyone at the Super Sam Foundation, and everyone who supports the amazing work they do to push the world of children’s cancer treatment forward. Without the support of the Super Sam foundation, we wouldn’t be able to do what we do, and I cannot ever thank all of you enough.   
Now, to the science. I’m currently working with a stellar team of interns from Oregon State University to develop a pipeline rapid, high-throughput analysis of sequencing data from pediatric cancers. It’s a privilege to mentor them, and their knowledge expands daily. Excellent taste in coffee, too. This pipeline will reduce the time commitment from a knowledgeable bioinformaticist required to generate standard analysis data, i.e. 40 hours of work per week of active data management will be reduced to a few hours. And that means my work on cancer math continues, as I’m working every day to develop the next iteration of algorithms. I’m excited to engage my colleagues with some of the new capabilities of cancer math, including a standardized approach to disease-wide cancer math modeling, which we will be using as soon as it’s ready.

More to come on cancer math, and this approach to picking the best treatment for an individual, or a group of individuals in need of a relapsed therapy recommendation! 08/30/2017: It’s been a busy couple of weeks. We at cc-TDI had the true privilege of hosting families touched by pediatric cancer and diseases at the 2017 Pediatric Cancer Nanocourse. We welcomed people affected by myriad different diseases; Alveolar Rhabdomyosarcoma, Epithelioid Sarcoma, Bloom’s Syndrome, and Embryonal Tumours with Multilayered Rosettes (ETMR) to name a few. This event occurs every year and the disease focus changes, but the emotional impact is always profound… this chance to connect with parents and families always hits hard, and always strengthens our resolve as individual scientists and as a lab. It’s sometimes hard to believe that I can be a part of something bigger than myself, but spending time with families reminds me that my work in cancer math, and everyone’s work at cc-TDI, offers the promise of new treatments for children’s cancer.   On a lighter note, I’m also happy to report that our SciClone Liquid Handling Robot (a recent major equipment acquisition for cc-TDI) is up and running thanks to the efforts of my parent-turned-scientist/mentee Andy. Here’s us giving a demonstration of this powerful new research tool during the nanocourse to build drug screens on-the-fly in a matter of seconds, a task that previously took hours!  I’ll probably brag about Andy a few more times, because mentoring him and working with him is one of my favorite parts of my life at cc-TDI.   09/14/2017: Stress-testing project building code for the Cancer Math GUI. One of the key aspects of developing software is to make it accessible to everyone. Developing this front-end GUI to enable the whole lab to access Cancer Math algorithms quickly and easily. One of the most important features is the ability to develop disease-wide combination therapies; the more well-characterized samples we have to work with, the better combinations Cancer Math can develop. It just so happens we have dozens of characterized mouse models of sarcoma ready for Cancer Math modeling… more to come! 

09/27/2017: Last week was a busy week indeed! Aside from progressing on several scientific and programming projects, I also had the opportunity to visit our veterinary collaborators at the CSU Flint Animal Cancer Center in Fort Collins, Colorado. Dr. Bernard Seguin has been a wonderful collaborator over the past few years, and this was my first opportunity to present Cancer Math to the scientists and clinicians there. it’s exciting to lay out our vision for the future of personalized cancer treatment. You may be wondering what children’s cancer and animal cancer have in common… well, it turns out that dogs spontaneously develop the same sorts of tumors often seen in children, especially sarcomas. And since humans and dogs live side by side, we have long considered that dog cancer patients might be a great way to explore new treatments that can be translated to children’s cancer treatment. This presents a great way to test personalized cancer therapy built by cancer math… by testing it in dogs with cancer who also need new treatment options built for their biology. With a few successful tests in dogs, it will be that much easier for oncologists to explore using cancer math to help treat children’s cancer. See you soon, Super Sam foundation!

10/23/2017:  Lots to report on since my last post! Biggest of all is my trip to the Super Sam Foundation Hope Gala. It was an unbelievable privilege to visit Matt, Cassie, Ava, and all the wonderful people who made the Hope Gala happen. It was great working alongside all of you on the last minute preparations to what proved to be a fun, fantastic, and heartfelt event. Sam’s story is powerful, and experiencing the emotion in the room firsthand is always a source of motivation for a researcher in the trenches. A big thanks to Ava for the lovely introduction, for all in attendance who listened to my presentation on my years of research, and for the support of everyone at the Hope Gala for supporting my work in changing the way children’s cancer is treated. (Full disclosure: this is probably the only picture I ended up with after the Hope Gala. I took quite a few Snapchats of the gorgeous venue for my friends, but I was a little too focused on my upcoming presentation to remember to keep any pictures for myself!).  On the science front, a lot of work has gone into wrapping up the manuscript that will be critical to the next stage of moving Cancer Math to clinical utility. Concomitantly, we have been planning strategies to bring Cancer Math into the clinic to meet the needs of those cancer patients seeking new options to continue their fight against cancer (and those patients with diseases lacking defined clinical treatments from the outset). Manuscript writing is always a time-consuming process, but alongside that has been working with our new scientist (Cora) on computational modeling of patient stratification for rhabdomyosarcoma, supporting the research on Osteopontin in rhabdomyosarcoma with Naren and Ali, and statistical analysis of in vivo experiments with Megan, and submitting two letters of intent for research projects ready for further development. I’m proud to work with and support my friends and colleagues. And coming up, we have some important experiments to determine if cell cultures we have developed are cancerous in behavior. More to come!

11/06/2017:  This week we welcomed a new potential collaborator into the fold, Dr. Stephen Ramsay at Oregon State University. Like me, he’s an electrical engineer working on cancer biology, and like cc-TDI, he’s working on sarcoma! In his case, it’s feline-origin cancer which makes a nice partner to our data on human and canine sarcoma. Seems there are some common biological signals amongst the three species, and it happens to be a biological pathway we’re currently exploring. There could be some interesting joint work going forward, and after a great couple of summer interns (Nick and Chandler) we’re excited by the coming possibilities of future collaborations with OSU.    On the cancer math and cc-TDI front, the cancer math manuscript is going through final revisions before resubmission! This manuscript is critical to the continued development of Cancer Math. We’re almost almost there. The DIPG manuscript is also in the final stages as well. We’re counting on the Tech Transfer office at Hospital for Sick Children in Toronto to come through for us quickly. It was also a productive week on the grant front!  Grants are one essential mechanism that helps support our research, and this past couple of weeks I submitted two letters of intent for promising research projects! It will be a busy grant cycle the next few months, so that means late nights in my favorite coffee shop. It’s ok, they know me (and Stormy!) there.  Final thoughts, I’m starting a new project on the biology side. I’ll be transforming a mutant plasmid via E. coli to build up a large enough plasmid vector population to transfect into sarcoma cells and normal cells. Basically… giving sarcoma cells a rare mutation that will enable us to study how this rare mutation changes the behavior of the cancer. It’s a small but important project, and like most things in the lab, it’s motivated by a child struggling with a rare disease. picture credit: BioCat.com (https://www.biocat.com/cdna-clones/clones/RC403308-OR)  

11/22/2017:Thanksgiving is fast approaching, which always means everything in the scientific world slows down. Not really the case here at cc-TDI! This past week I’ve been focused on concluding the two key manuscripts and working on a few key Cancer Math grants, the most recent draft was sent for review today! Our associates at Beijing Genomics Institute, the organization to which we contract all of our physical sequencing work, provided us with a few critical data sets today, including those necessary for the final piece of the Cancer Math manuscript. I’m moving them to the servers where I will begin computational analysis via analysis pipelines on our high-performance computing servers. Results should be available tomorrow… which is indeed another workday for me (maybe half workday, I have a vegan Thanksgiving to attend).  On the biology front, we’re starting xenograft (human tissue into mice) experiments to attempt to develop important cancer models for alveolar soft part sarcoma (ASPS) and Ewing’s Sarcoma. We should know in the next month or two whether the mice are able to grow tumors. Additionally, the RET in rhabdo project should be expanding in the near future, which will require educating myself in the particulars of lentivirus-based genome altering (using modified HIV virus to stably change the genome of human cells) in order to add a mutant gene into several models of human and mouse cancer cells. Finally, there are some exciting steps forward for supporting the continued development of Cancer Math. Nothing I can report on at present, but there should be some exciting news in the next few months!Have a great Thanksgiving holiday, everyone!

12/22/2017:  The past few weeks have been a rush at cc-TDI. One of them a rush of a different sort, as I took a week’s vacation/journey to Scotland and Iceland. It was deeply needed after two years of no personal travel. Even in the middle of winter, the European North is a sight to behold. Please enjoy a couple pictures from my travels!     On the research side, the big announcement this week is resubmission of the Cancer Math manuscript!  It’s been a long (but necessary) time coming. With the support of my friends and colleagues at cc-TDI, and all of my collaborators on the manuscript, the revised manuscript is in the hands of the editors and should soon be out for a review. If everything goes well, the manuscript will be published soon after the new year.  At the same time, our DIPG manuscript should be published in short order, which will lead into a great new research project on a promising new target (or target combination!) for the treatment of DIPG. We have received positive responses to letter of intent submissions, so we’ll be submitting to a couple grant opportunities coming up.   Meanwhile, several xenograft mice are growing to establish tumors for model development and experimentation. Everything is wrapping up as the year comes to a close, and everything is happily well timed. The new year will start fresh with several new projects and hopefully some further coding with Chandler and Nick, the summer interns! We are close to concluding our easy-to-use software pipeline. With my plate mostly clear, it’s time to delve deep into analysis and programming to push Cancer Math modeling forward, and resume my role as support to everyone at cc-TDI. Cancer Math’s next big role: helping Andy integrate newly generated sequencing data to identify promising drug combinations for classical and anaplastic Wilms’ Tumor! Happy holidays, everyone!   

01/11/2018:   The new year is off to a great start at cc-TDI!  Everyone is back from their much-needed days off, and we are back in full production. The past couple weeks have been busy with coding and grant writing, though it’s been a very productive few weeks. From the coding side, Nick and Chandler each visited for a day. It was a pleasure to see them, as always, and we made some positive progress on the back end of analysis pipeline. Following their visit, I continued developing the back-end code to complete the software pipeline, and I’m pleased to report it is now fully tested for matched exome samples, tumor-only exome samples, and the RNA sequencing samples. This leaves some GUI finalization and a few more tools before it’s fully ready for deployment. Good things take time. Here’s hoping we have Nick and Chandler back soon! From the grant writing side, there is a critical grant coming up in a month, to which my night shifts will be dedicated. This is a K99 path to independence grant, which would transition me from postdoctoral fellow to an independent researcher, essentially in charge of starting and running my own lab at cc-TDI. It’s one of the next critical steps in my development as a scientist. There’s a lot to do in a month, but nothing I haven’t done before! This past couple of weeks also saw the submission of two letters of intent (one for DIPG, and one for cancer math) and the submission of a full grant application for a DIPG research project. My next project will be the ramp up of the GEAR (Endotypes in Rhabdo) project to identify endotypic subtypes in aRMS, which can potentially lead to better targeting therapy for aRMS subgroups. There may be another blog on the matter starting soon, so please stay tuned to both!
01/29/2018:  It’s been a busy few weeks! I suppose it always is at cc-TDI, but this has been a particularly memorable couple. First and most important news, we have finally completed all the pieces necessary for publication of our DIPG manuscript. The database repository project is set up and running, and we have a proper accession number… and that means we can submit our manuscript for final publication approval! Which, of course, I have already done. We should be hearing back about the final decision in the next week or so. This is perfect timing for the next steps in development of treatments for DIPG, since this will go hand-in-hand with two grants (and more from my colleague Ali!) in the coming months. This is where new DIPG research at cc-TDI will really take flight, and I’m proud to be a part of making that happen.
The Cancer Math manuscript is under a new set of revisions, which is always positive news! I’m nose to the grindstone on the GEAR project at present, working with my colleague Cora as we deepen our datasets for both alveolar rhabdomyosarcoma (through GEAR UP) and embryonal rhabdomyosarcoma (through the Building Blocks project). The two diseases have much in common and yet are so different. But those commonalities and differences can both drive forward our understanding of the biology of the disease, and thus how to treat it. Cancer Math will play an important role in the downstream analysis of disease subtypes, and should be valuable in defining how the groups of otherwise unique cancer patients may have critical similarities in disease response. The project is well underway, but there’s a lot to do still ahead.
This wouldn’t be possible without all of our friends and supporters, especially everyone at the Super Sam Foundation! Thank you as always for your incredible support of our mission.
02/22/2018: There’s been some positive movement on Cancer Math this update! The next set of revisions for the Cancer Math manuscript are nearly complete and it’s a rush to resubmission! There are quite a few grants we are eyeing as the next stage of support for Cancer Math validation, but as always in the world of preclinical research we have our non-traditional paths we can pursue as well. The goal is, and has always been, to make Cancer Math a clinical tool to help children struggling with rare and refractory cancers. Publication of this manuscript brings us closer than ever, and will kick start the next big steps. It’s going to be a good year for Cancer Math and cc-TDI.
On that front, there is some exciting news coming up. We can’t reveal exactly what yet, but there’s some exciting things to reveal in the next month or so. Frustrating that can’t reveal it just yet, but such is the nature of progress in academics. As soon as we can report on it, we will.
On the grant side, we recently had two LOIs approved by the St. Baldrick’s foundation (one for DIPG driven by me, and one for Medulloblastoma driven by our new biologist Dina, big congrats to her!). Our DIPG grants have been finding a lot of traction lately. We were even able to submit a full application to the Rally foundation this past week. With the Iron Matt foundation and St. Baldrick’s that’s three possible places for the next steps in DIPG research. Now begins the big grant cycle of writing K99 (5 year grants through the NIH!) and SBIR grants (joint academic and small business pilot grants). The SBIR side will have to remain a secret for the time being, but what we have planned is really exciting!
This blog post is highly clandestine this time around. All I can say is stay tuned, I promise we have lots of exciting news coming up! Thank you as always, SuperSam supporters, and please stay tuned!

03/05/18: Last week at cc-TDI was filled with interesting visitors! Our first of the week was a molecular biology expert with years of experience working in pharma. His depth of experience in non-cellular biology is impressive and interesting to see. Our second visitor hails from Australia, and shared his work in machine learning approaches to challenges in clinical care. It’s fascinating work, and while I can’t share the details of unpublished work, it nicely serves a need before Cancer Math would come into play. I will keep an eye on upcoming publications, as I think there’s the potential for collaborations to bring computation to the clinic.

The cancer math manuscript will be resubmitted this week, just waiting on final overview from Charles!

Similarly, last week’s DIPG grant to St. Baldrick’s is mostly written and in local peer review. I’ll be submitting it shortly with plenty of time to spare. Everything should be coming to fruition soon.

Much of this past week was spent on working with sequencing data for my colleagues, finishing papers, finishing grants, and pushing forward on the GEAR project. Happily, the first round of GEAR experiments will begin this week, and Cora will soon be finalizing the eRMS dendrogram. Soon we’ll have some promising data-driven hypotheses to explore!

Thank you as always, SuperSam supporters, and please stay tuned!



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