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How to Build a Brain Tumor Research Center

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- Colleagues and friends, thank you for joining us for another session of The Virtual Operating Room from the Neurosurgical Atlas. My name is Aaron Cohen. Today we have most likely our dearest guest in the Virtual Operating Room series since we started a few years ago, Dr. Jim Rutka. His gravitas is unparalleled in neurosurgery. He's truly been almost the president of every neurosurgical organization and has affected the lives of more young neurosurgeons and residents and medical students than anyone else, I know in neurosurgery, including myself. He's been a dear mentor of mine. Today, he's going to talk to us about a very important topic and it's development of an excellent Brain Tumor Research Center. He has definitely developed his program to be the best in his country. It's the most well-funded program in brain tumor research in the country of Canada, and I would say the top three in North America, and the world. There were obviously other individuals that have assisted him along the way, including Dr. Allen Hudson, Harold Hoffman, two of the neurosurgeons who are his predecessors. And obviously we have to emphasize the importance of those philanthropic families like the Labatt Family, who really have endowed this program from the beginning and made such an incredible role in achieving its excellent impact as it is today among other centers in the world. So Jim, it's truly an honor to work with you. I'm very much interested in learning. I can't find anybody better than you to discuss this topic, which is so important in advancing the care of our patients with brain tumors. So with that, thank you, Jim. And one thing I wanna mention that is very important, which I'm sure you're gonna go through as well, is that most likely the greatest secret sauce is having the right people, the right talent on board, because it's all about the team. Brain tumor research, brain tumor care, all is about having the right people on the board and in the bus or on the boat, however you call it. And I can only imagine, number one, how important the Labatt Family have been in making this possible to start. And then your vision in terms of taking this move, the perfect team to the highest level is obviously quite incredible. So please, go ahead and thank you.

- Great. Thanks very much, Aaron. It's a real pleasure to be with you again and to help take part in this great series for the Neurosurgical Atlas. And this is a little different topic, I would agree with you, Aaron. It's how to conduct and build and then develop and nurture a scholarly and a research enterprise, in this case, the Brain Tumor Research Center at the hospital for sick children. It's known as the Arthur and Sonia Labatt Brain Tumor Research Center. I've been the director of this particular enterprise now for well over 25 years. And this to me has been one of the greatest contributions, if you will, that I've been able to take part in since I started my career in neurosurgery. So with that, Luke, perhaps we can launch the slides and I'll talk to you a little bit more about how we managed to do this at the University of Toronto. So in the beginning, there were very few centers that were conducting brain tumor research, and this is in the 1980s. One was Dr. Charles Wilson at UCSF. And he was a brilliant neurosurgeon, but also a tremendous administrator. Had his vision for establishing a brain tumor research center at UCSF. Then there was also a Duke University, one that was launched by Darell Bigner, he's a neuropathologist and he also started a research center at about that time. But pretty much that was about it in the 1980s. So Alan Hudson, who was the chair of neurosurgery at the University of Toronto, one of my mentors who hired me as a resident to enter the program at the university thought that because of the tremendous burden of brain tumors at the university and in all of Toronto, that it would be really worthwhile to develop a center for the purposes of studying brain tumors. What you need to know about Toronto is that, it's a city of size of Chicago, but with only one medical school, only one university enterprise that in encompasses all of the academic work, including the medical sciences in a medical school. And only that one center, so everything filters into the different hospitals within the University of Toronto complex. And so, he realized that if we could capture all of these materials from all the patients, that we would have a major center at our fingertips. He recruited Paul Mueller, who was a neurosurgeon, trained in Toronto, but went to the University of Calgary, who then came back and started his major research enterprise in photodynamic therapy. Also, Mark Bernstein, a dear colleague of mine, he was senior resident when I was a junior resident in my first rotation as a neurosurgery resident at the Toronto Western Hospital, University of Toronto. Mark did a research fellowship at UCSF with Dr. Wilson, actually under Dr. Phil Gutin. And then I followed Mark to UCSF where I did my investigations under Dr. Mark Rosenblum. And Mark was just recently feted at the Congress of Neurological Surgeons as the honored guest this past year. And there's a photograph of Dr. Allen Hudson. There you can see Dr. Paul Mueller, and there seen with my dear and close friend, Dr. Mark Bernstein. So there we are, the couple, and I must say I learned an awful lot from Mark and he's been a tremendous colleague over all these years. In the early days, so in the 80s, Mark returned to Toronto and he established the really first center and effort. And this was at the Toronto Western Hospital. It was a fairly small scale laboratory. Paul Mueller, as I mentioned, did photodynamic research at St. Michael's Hospital in Toronto. And then I established my lab. When I came back after my research studies were done at UCSF in 1987, I finished my residency in 1989, then I came back to Toronto after a fellowship in Japan with Sugita. And in 1990, I established my lab at SickKids. And I was a single person on the bench. And then I, you know, gradually over the course of months and years, hired people to work in my laboratory. Ab Guha, a big name in neuro-oncology. he went to Boston to study under Dr. Chuck Styles, very important individual for studying RAS signaling pathways in a variety of cancers, including brain tumors. He studied in Boston with Chuck Styles. And Alan Hudson, stepped down as chair of neurosurgery and then Charles Patter became the chair in 1989. And Charles was very interested in that whole notion of building a brain tumor center, the seed of which was planted by Dr. Alan Hudson. 1993, I mentioned this name Brainchild here. And what you'll see from Brainchild is, I'll discuss later, but this is an organization that's raised multiple millions of dollars for us for the work that we're doing in the Brain Tumor Center. Okay, a little bit later on then, oh, here's a photograph of Dr. Guha for you to see. And a little bit later on, Ab returned to Toronto and he did a postdoctoral fellowship with Tony Pawson,, who was very famous in the world for signal transduction pathways. And Ab established his laboratory within the laboratories at SickKids Hospital. We had a neuro-oncology committee established in the Division Of Neurosurgery. There was a decision made to establish a Toronto Brain Tumor Research Center. So we all had sort of pie in the sky dreams to establish this Brain Tumor Research Center. And then, then it became part of a campaign that was entitled The Spark of Life. And for The Spark of Life campaign, some very prestigious individuals came to Toronto, Christopher Reeves, you may remember the Superman figure in the movies, and Rick Hansen, he's a very well respected survivor of the spinal cord injury and has raised multiple millions of dollars for spinal cord injury research. But the two of them came to launch this campaign called The Spark of Life. And the Toronto Brain Tumor Research Center concept became a priority at both SickKids and at the Toronto Western Hospital. In what you're seeing here is a photograph from back in those days of Christopher Reeves. You may recall him. And the fact that he was rendered quadriplegic from a spinal cord injury, having fallen off a horse that he was riding in Virginia. And he was taken to the University of Virginia. John Jane Sr. operated on his cervical spine to stabilize it, but he never recovered sadly, of a function in his extremities and was maintained as a high cervical spine cord injured person who was on a ventilator the rest of his life. But what he did for spinal cord injury and for the support of science and research was absolutely phenomenal. And he came to launch our campaign as mentioned. Well, next along the line was Arthur and Sonya Labatt. So that's a big name, the Labatt family here in Canada, may be familiar to many of you in United States. But Arthur, he was co-founder of the Trimark Investment Company. And at the time that he was looking at a proposal with his wife, Sonya, who was a PhD in environmental sciences at the University of Toronto, a number of different proposals came across their desks so they could look at. They typically supported the arts, healthcare, and education. I had the great privilege of looking after one of the grandchildren of the Labatts who had a neurosurgical problem. They were delighted with the care that they received at SickKids. And Dick Thompson, who was from the Toronto Dominion Bank, CEO, he encouraged Arthur to consider donating to SickKids to support this brain tumor research effort. And of all the proposals they looked at, this is in 1997, Arthur and Sonia shows our effort to support. So we were thrilled that the funding would come to us to establish this. So initially, you know, back those many years, a 5 million donation was given to SickKids Hospital. And that, in those days, that was quite a lot of money. Was one of the biggest donations in its time in philanthropy of healthcare initiatives. So we were delighted about that. Here's a photograph of Arthur and Sonya Labatt, 1997. and some of the news media that we received for the establishment of our proposal. It was the only one in Canada at that time. One developed at McGill shortly thereafter, but ours was really the first to get launched and we were thrilled that the Labatts could be highlighted and also recognized for this very tremendous donation that they gave. You know, part and parcel Aaron, as you know, is as you're launching an enterprise that's new and you're trying to put a stamp on it, you're trying to develop a trademark or you're trying to brand it is creating a logo. So we created this logo for the Brain Tumor Research Center. It was an idea that I had that just came out of the blue for me. But what you're seeing on the screen is the idea of the logo, which is a dove symbolizing hope. And in the beak of the dive, you see the strand of DNA, which is like a twig, if you will, in the beak of the dove. And so this logo represents hope through molecular medicine or hope through molecular surgery. So, that was a concept of the logo. So, next we were able to establish a center. We actually had signage that you can see here on the wall of the building where this existed. It was called the Elizabeth McMaster Building right across the street from SickKids. So very close proximity to where I work as a neurosurgeon. It was fantastic. We were the only enterprise at SickKids in the research domain to have its own signage. And that was because of the large donation that we received from the Labatt family. Here you can see some further signage in the hallways. This was on the scale of things, a good beginning, but it was a small start, no question about that. And we continued our efforts. And the laboratory space that we got was good, state of the art at the time. But again, this is back in the 1990s, early 2000s. And you can see some of my research fellows there, actually residents in the University of Toronto training program at that time, Todd Mainprize and Michael Taylor, about whom you'll hear subsequently, who did some work for me, getting their PhDs in my research laboratory as time went on. And something I think we should talk about, Aaron, is fundraising activities. And I know that you're all about that. You understand the importance of that for the Neurosurgical Atlas? But for research, obviously is very important. And I've done a lot of this over the course of time. And it's made a huge difference, which I'll talk about. But I've been a part of it all. So, you know, going to these various summer festivals, taking part in these, these group activities, sometimes there are walks, sometimes there are jogs, sometimes they're rollerblading you, you know, a lot of different things over the course of time. But what eventually comes back is, you know, funding to support pilot projects in the research domain that you normally can't get from, for example, NIH or in our case the Canadian Healthcare System. So critically important that you have all of these available to you. We then moved to a place that was called MaRS, and that MaRS actually stands for the Medical and Related Sciences building, which was right across the street from SickKids. Nice new space. And this is the former Premier of the Province of Ontario. It would be the similar position as a governor in the United States in one of your states. And he came to visit with us. And his name is Dalton McGinty. And he came to see our setup, our initiative. He, you know, wrote nice letters of support for us and really the importance of these provincial dignitaries coming by and raising awareness, sending it out there. And this was before the days of social media, but in the press at the time, it garnered a lot of interest. Well, another piece of advice I would give to all of you out there who are in the business of fundraising for your various projects in North America is stewardship. And it's well known that if you continue to steward your donors well, they'll continue to be interested in your efforts and they'll continue to support you. So about a decade later, the Labatt family, you're seeing Arthur and Sonya Labatt here, and this is my good friend, Dr. Ab Guha here, and this is members of the Labatt family here, the children and myself, they were so generous to give us yet again another 5 million donation some 15 years ago. So, that was really marvelous. And Arthur wrote a book called, "A Different Road", which I've read. It's an excellent book. And he describes his career path. But at the time that Arthur made his first donation to us at SickKids, he had something like 250 million of surplus funds to donate as part of his business. And so, he was a very instrumental in getting our effort off the ground, but also he gave to, so him and Sonya gave to so many other amazing efforts and causes that it was truly an incredible family that we were so pleased to have made a relationship with and have mentioned the stewardship story continues. Well at this stage, enter Mike and Diane Traynor, who are shown here. So Mike and Diane, Diane Traynor were the ones who established the Pediatric Brain Tumor Foundation, which started at first as the Ride for Kids Program in 1984. And I'd have to say that their efforts led to the single most important agency for funding pediatric brain tumor research, more so than in fact NIH in my opinion, at that time. And they were keen to establish this institute's grants award program that included UCSF, SickKids and Duke University. And they also sponsored key conferences like the Society for Neuro-Oncology, but also the Asilomar Conference, which is an ongoing conference to this day. But they came to visit us here in Toronto. You can see them at our research center. And it was real pleasure to get to know them. Sadly, they've both passed away and just recently the Pediatric Brain Tumor Foundation has moved into another area. But in its day, as I mentioned, they supported research to a very, very high level for pediatric brain tumor research. So this was the institute's grant program with Duke, SickKids and UCSF. You can see as pieces of the puzzle. And supported by Gerald Bigner at Duke University and Mitch Berger at UCSF, and of course myself and Ab Guha at at SickKids Hospital. And these were the principal investigators back in 2012. So, a decade ago. And I think as Aaron mentioned at the beginning, getting the right people on the bus is truly important. And what's kind of unique about our center compared to other centers in the world is the fact that many of the independent investigators are neurosurgeons. So Dr. Peter Dirks, here, you have myself, you have Dr. Michael Taylor, Dr. Todd Mainprize, Sunit Das, all our neurosurgeons with MD PhDs. And they are the ones who have provided the glue that have attracted others. And the others in this particular photograph and panel here are Jane McGlade, who's a PhD scientist who works with us. So not an MD, but a PhD. Annie Huang, who's a Neuro-Oncologist, Cynthia Hawkins, who is a Neuropathologist. Uri Tabori Neuro-Oncologist. I failed to mention that Dr. Gelareh Zadeh, you'll hear about her again as I speak. But she's a neurosurgeon at Toronto Western Hospital. And Sid Croul, another Neuropathologist. So a mixture of individuals who are clearly working well together, synergizing, collaborating, writing papers together, grants together, and getting the right people together is a part and parcel parcel of success for this type of enterprise. Just wanted to show you some of the papers that have come out and I have more. And I do wanna just highlight, you know, where these papers are published because it becomes important when you think about impact of programs. So Medulloblastoma, Four Distinct Molecular Variants, Michael Taylor's work, you know. The Sonic Hedgehog went Group 3 And Group 4, that came out of Michael Taylor's hands. And that was Journal of Clinical Oncology. Here's a Letter to Nature. Again, Michael Taylor's work on clonal selection, genetic divergence in Medulloblastoma. Michael's work again with Stefan Fister on the two clinically distinct subgroups of Posterior Fossa Ependymoma, Group A and Group B. And that's in cancer cell. Some of the work that we did in genes chromosomal cancer on hepatocyte growth factor and signaling pathways in Medulloblastoma. Clinical implications of subgroups of Medulloblastoma, again, nature reviews in neurology. Subgroup specific alternate splicing. So, this is pretty much all about pediatrics. So, Medulloblastoma research in Michael Taylor's hands by and large, so excellent publications. And then, you know, life happens and sometimes we face tragedies. And Ab Guha, whom I mentioned at the beginning, he was the co-director of the program with me over many years. His life was cut short far too soon by virtue of his contracting Acute Myelogenous Leukemia. Ab and I were dear friends. We were co-residents virtually together in the program in neurosurgery. As mentioned, he went to Boston to train with Chuck Styles, came back, did his research efforts, got it off the ground. But he really had a vision for establishing this Brain Tumor Center. And sadly after a couple of years of diagnosis and two autologous, or sorry, heterologous stem cell transplants, he succumbed from his disease. As I said, far too early in the course of his life. So we then had an opportunity after we had continued to build our efforts. And I showed you publications and the group that was with us. And after Ab's passing, we ended up moving to a new site. And this is right across the street from SickKids again. And it's our new research center. And you can actually see what a wonderful place it is. We have the whole 17th floor, so that would be somewhere up here in the sky for where we have our research effort now. And that's the Labatt Brain Tumor Research Center now. And it's beautiful state of the art space that has been granted to us by a SickKids Hospital. And there we moved in 2013. And this is the compliments now, so in, well 2013. And you'll see that it'll morph as I show you another place mapped about five or six years from this date, 2013. But you can see all the individual principal investigators who are listed here and all of the colleagues who are working in their laboratories. It's a big effort, probably here about 80 or so individuals. And just as a reminder, when I started doing this brain tumor research, you know, I was one of the few that was kind of, trained in the molecular era. And when I started my laboratory, it was me and the bench. That was it. Two people eventually coming on board and then I was able to get some fellows to come train with me. And then I got research funding from national agencies. And then the effort grew pretty much over these 13 years to this level that you can see here, well over 80 individuals working together. Each year we produce an annual report that you can see here. And as part of our effort and our growth and our ability to show our prominence in brain tumor research, Aaron, we became the hosts of 19th International Brain Tumor Research and Therapy Conference. This was a conference started by Charlie Wilson, whom I mentioned at the beginning as one of the Asilomar conferences. And we held this in Niagara Falls. It was a wonderful fair and everyone who attended had an excellent time. We covered some great science. And it showed that we were clearly on the map for our brain tumor research efforts. These two individuals here, Dr. Peter Dirks and Dr. Michael Taylor, you know, are among the best neurosurgeon scientists, I would have to say in my biased way in the world. And they're both studying brain tumor research. Of course, Dr. Peter Dirks with his efforts in pediatric brain tumor stem cells and Michael Taylor with Ependymoma and Medulloblastoma. The two of them joined efforts and they received one of these very prestigious standup to cancer grants that you know about that are very hard to come by. And you have to demonstrate significant productivity and promise in order to get one of these stand up to cancer grants. And then more fundraising, Aaron. We have to continue to do this. This is a group called Megan's Hug, or Megan's Walk. I'll be mentioning this in more detail, but Megan was a child actually I looked after at SickKids. She was a young child who developed a diffuse intrinsic pontine glioma. Sadly, despite all efforts, she succumbed within two years of her diagnosis after radiation treatments failed to control her disease. But her mother, Denise and her father, Kevin, put together this initiative for raising funds in the name of Megan. And each year they've had a walk that raises funds for research. And this is now 20 years and beyond in terms of what they've been doing. And it's fantastic to see all the things they've supported in our brain tumor research efforts. I mentioned brainchild at the beginning. It stands for Brain Tumor Research and Information Network that you can see here. And October for you to know is Brain Tumor Awareness month. And this is the logo for Brainchild, a group of parents, families and friends who have the common experience of caring for a child with a brain tumor or who are survivors, a volunteer organization that provides support, education and research funding. And they've been a great group to work with over the years. And as mentioned, I take part in a lot of these activities each year in order to support their efforts to support the parents, to support the, you know, the children who are going through the fight of their lives with their diseases and to raise awareness for and funding for brain tumor research. And just some of the names Rigatoni for Research, Amy's Shining Star, Skate With Daniel, Walk With Grace and so on. These have kind of evolved over the years and most of them have kept going. There are some that have sunsetted that means they have their moment to shine and then they fade to a degree. But by and large, and many of these research efforts have been continuing over many, many years, which is an absolute tremendous tribute to the families and to the parents who have supported these efforts. But here are some of the things that we do. So as mentioned, you know, we did our rollerblading from Niagara Falls to Toronto, which was a whole day effort. Here you can see people gathered for Megan's Walk. Here you can see the very first fundraiser that we had. This was called Summerfest and in the summer, small festival in a community. But you know, hundreds of families and kids would come to support the effort. And here you can see at one of the dinners, we would have many dinners, you know, to celebrate these events and to thank the families for all that they were doing to support our research efforts. And the funding goes a long way, as you can see here, 7 million so far and and counting, maybe now closer to 10 million for the support of our research efforts. And what this funding does is it allows us to support pilot projects in brain tumor research that normally grant agencies aren't interested in because they want, you know, evidence that you're already done the work and then you're moving forward in a tangible way. But you can take high risk projects that could then lead to a formal grant application and have those funded through the monies that brainchild supports. So really, important pipeline of funding for us in our brain tumor research efforts. Yeah, so just some more opportunity for you to see fundraising efforts. This is just outside the hospital. And on this day, hundreds of people gathered for one of these fundraising events. And to be present, Aaron, is really key to show support for these efforts. This is Dr. Cyra Ali here, who is a neurosurgery resident in our training program. Got her PhD in my laboratory. Wrote an excellent proposal on MR Guided Focused Ultrasound for the treatment of diffuse intrinsic pontine glioma, which is now moving into clinical trials at SickKids Hospital with Health Canada approval. Fantastic. And here's support that we received from one of the DIPG foundations in the United States. So really important for these efforts to take place. I'm not much of a golfer, Aaron, but I can tell you that, you know, I'm on the pitch with everybody. When it takes a place for us to participate, I'm there. I support. And here I am with some of my research fellows and other researchers in the Brain Tumor Center to support one of these golfing fundraising events for our efforts. Okay, and further along the lines of having dignitaries come by, this individual here is really a high level authority in the Canadian government. This happened to be the honorable Rona Ambrose who was Canada's Federal Health Minister who came by to see our center. And here you can see we're putting air into action, doing some pipetting in a major way. So yeah, having, you know, the highest authorities come and see your program, you know, justify what you're doing, also support your efforts, you know, have publicity events surround it, are also part and parcel of success. Well, here's the Labatt family some years later. This is now celebrating our 20th Anniversary since the founding of our research center. Arthur and Sonya is shown here. And again, this is our annual report, it's called Imagine and this was from just a few years ago. But tremendous that they gave us. And this endowed fund that has grown so much and helps us to support all of the researchers within the center. So just incredible now that we have this longevity in our program. Something we've moved into in the last few years has been the pursuit of partnerships through industry partnerships and commercialization. This is Dr. Jenny Huang who helped us kind of move things along with our relationships with industry. There is opportunity, as you know, to partner with industry in a meaningful and unbiased way that can help support both, both industry and the research work that you're doing. And you know, the work that we've done, both with industry and with our philanthropy, has led to all of these different seed grants awarded just since 2013 that have enabled us to high risk projects in Neuro-Oncology. But what Jenny Huang allowed us to do in terms of our partnership with industry is to have a pipeline of drugs, for example, you know, going from In Silico mediated targeting, so on the computer, to In Vitro assays shown here. These are the different assays that we would have for proliferation, migration, survival and differentiation. And then, going to animal studies for preclinical testing as shown here, and then characterization, top candidates, and then leading to the partnership as mentioned in hopefully on then to clinical trials. So yeah, we may have been a little bit late getting into this space, meaning that in the last five years we've really paid attention to this. But our industry partners now, are very keen to collaborate with us. And these are some of the industry partners. And I have no, you know, preference for any one of these by just mentioning all of them at once. just to show that we are definitely open to collaborations with a whole host of industry partners. Now, again, back to impact Aaron, it's really important that once you've got your work set for publication, you try to promulgate the information in the highest impact journals. And just to show that, you know, we are publishing, so in "Nature Genetics", "Cancer Cell", "Nature", "Cancer Cell", again, here we have "Nature Genetics". So these are, you know, papers by neurosurgeons. Here you can see Dr. Zadeh's name, Dr. Dirk's name, Dr. Taylor's name, but also by our neuro oncologist, Dr. Huang for example. So amazing that we have these, you know, very high impact papers. Just to focus on this again, other additional high impact papers, ultra high, I've called them here. So here you can see this paper in "Cancer Cell". This is Michael Taylor work. First one was Ependymoma, this one on Medulloblastoma subgroups. Here you can see ACVR1 mutations in the context of diffuse intrinsic pontine glioma by Dr. Hawkins Neuropathologist in our mix. And just wanna mention this paper. This actually is the most highly cited brain tumor research paper in the world as far as I know. And this is the original paper by Dr. Peter Dirks on stem cells in brain tumors. It was Peter's idea once he graduated from the PhD program in my lab and he became independent investigator at SickKids. Subsequently, he had this idea to study brain tumor initiating cells. And this solitary report Aaron has had well over 8,000, maybe close to 10,000 citations. So staggering how influential this single paper on brain tumor initiating or stem cells has been in the literature and how it's moved the whole field of neuro-oncology research. Other papers, this one was when Michael Taylor was a research PhD student in my laboratory on a Suppressor Of Fused Mutations published in Nature Genetics in my laboratory. Again, the four different subtypes of Medulloblastoma, Cancer Cell, this one by Annie Huang, excellent paper on atypical territory rhabdoid tumors. And then this one by Dr. Hawkins on 1.000 pediatric low-grade gliomas studied in cancer cell leading to targets that we hither to didn't know about for this particular disease. And now this is our annual report, 20 years since the development of Megan's Walk, celebrating Megan's Hug 20 years later, our most recent annual report. And in it we highlight Dr. Eric Bouffet, who's a Clinical-Oncologist, Neuro-Oncologist in our program. Eric is just received actually, the lifetime achievement award from the Society for Neuro-Oncology. His excellent clinical trialist, has devoted his career to pediatric neuro-oncology and has also developed numerous pediatric neuro-oncology trials, clinical trials for children with a variety of different brain tumors. Eric has been a great colleague over so many years. I mentioned earlier Dr. Gelareh Zadeh shown here, now she's Chair of the University of Toronto Training Program and entire Neurosurgery Program at the University of Toronto. But she received the 2021 Ab Guha Award and has been noted to be one of the top 25 women of influence in the world. So really a tremendous individual with amazing research program and now leading the University of Toronto, one of the largest training programs in the world for neurosurgery. So, she's part of our center. Something I think you would also appreciate, Aaron, is the requirement to make your work known through proper visualization, which means, you know, medical or scientific art. So we hired a medical illustrator to help us with our efforts to make accessible the work that we're doing to the lay press by virtue of some tremendous talent in medical artistry. And this is Dr, this is Stacey Krumholtz who got her Master's Degree in the Biomedical Illustration Group at the University of Toronto. And she has put together for us tremendous visual displays of the stuff we're doing in brain tumor research and our scientific efforts. So it helps, you know, to promote the brand as mentioned. You know, I talked about the logo early on, but having a way to distribute this information that's accessible to the world is really important. Okay. We also, now that we're a full-fledged group with well over 100 individuals attached to this effort, we held, as a lot of groups do, a scientific retreat. And here you can see members of this Brain Tumor Research Center up north in Canada. And we're hosting just a scientific retreat of all of our members so that the students, the fellows, the principal investigators would present their work before everybody, get comments and also to spawn collaborations between the members. And that's been a tremendous asset. And I know many groups do that as well. I mentioned her name earlier, but this is Denise Bebenek, whose daughter, Megan, had the diffuse intrinsic pontine glioma. But she's been supporting these efforts for over 20 years. She is a true force to contend with, and meaning that, she is fully supportive of the brain tumor research that we're doing and that she recognizes the importance of having research in order to take things to the next level for children with brain tumors, including those like her daughter who had diffuse intrinsic pontine glioma. But a big thank you to them, the Megan's Walk, Megan's Hug team for all that they've done to support our research efforts. We have annual lectureships. We just recently hosted Amy Heimberger in a virtual format because of the pandemic. But Amy, now at Northwestern, previously at MD Anderson, trained at Duke, came and gave us a lecture. What you're seeing here at the list of the previous lecturers going back to 1999 when Bob Martuza was the very first academic lecture for the Brain Tumor Center. But, you know, look at some of the names here, big names in brain tumor research, Eric Holland, Darrell Bigner, Web Cavenee and so on, Henry Bram, Ken Aldape, Fred Lang, Bill Weiss, Jeremy Rich, Nada Jabado, Mitch Berger and so on. So many, many luminaries in the field come to grace us with their phenomenal talks. We also have a Mike and Diane Traynor Lectureship. And here are some of the posters that were set out to kind of welcome these individuals with us. And I'm listing their names here that you can see from around the world. This tends to be more of a clinical lectureship, whereas the Labatt Lectureship is more of a basic science research lectureship. And here's where we are today or close to today. Just, you know, a few more members. So grown to well over 100 individuals all supporting the research and science of brain tumors with the principal investigators and their lab teams. And it's been just wonderful. When I think about, you know, starting my own effort some 30 years ago, me and the bench, and then, being able to grow this effort now to well over 100 individuals. It was a fully dedicated to brain tumor research is something I'm extremely proud of. And choosing the right principle investigators, as we mentioned at the beginning, Aaron, getting the right people on the bus. So Dr. Cynthia Hawkins, Sunit Das, Peter Dirks, Vijay Ramaswamy now, Ute Bartels, these are some of our principal investigators doing great work during Mitch Burger's lectureship when he came to the 20th anniversary celebration of our center. I can't stress the importance of having these individuals work with us. And what about the future? Well, some things that we're in the process of doing are program project grants, doing collaborations as mentioned with the institute's, continuing our fundraising effort, moving to clinical trials as mentioned, the DIPG trial that we're embarking on MR guided focus ultrasound. And a City Wide Brain Tumor Bank. So interestingly, these two individuals, this is Amira and Michael Dan, these are alumni of the University of Toronto, but Michael himself was a former neurosurgeon but has become a business entrepreneur. And he and his family donated 2 million to help us establish a bank across the whole city. So every tumor specimen from across the city, including the solid specimen, the CSF, the blood, other things are banked and kept in a virtual bank. So we can track the numbers, but it's staggering. It's something like as many a thousand tumors a year that we're able to take care of into log on and to study over the course time. And having that starting material, absolutely no substitute for that in brain tumor research. So, thanks to the Dan family for their very generous donation to us. And then, you know, over the course of time, celebrating victories, you know, once you have a big paper that you've been able to celebrate, it's good to go out with your colleagues and have a nice evening. Now, these are my lab folks working with me, combination of postdoctoral fellows, PhD students, master's students, lab associates, technicians and so on. This was a lot of fun over the course of my career, doing this and recognizing it. And also everybody appreciates these tokens of kind of gratitude. And that is something I've learned over the years is to celebrate, you know, welcome everybody, thank everybody, and also to support everyone that's in your domain and it'll come back to you in spades. And then back to dignitaries one more time. This individual is a big name now in Toronto. He's the mayor, his name is the honorable John Tory. But he came to support our efforts and again, publicity around the work that you're doing can never hurt. And today, of course we have social media, which we never had when we started our center and we are quite active on social media. And at the very end, Aaron, as we close, I just wanna mention that behind all of these efforts, of course, are the stories that relate to our patients. And I have permission to show this, but this is Jessica on whom I had operated. She had a very large central thalamic, deep, low-grade glioma that was causing significant mass effect. And there were some atypical features about her tumor that required her to go on to receive postoperative chemotherapy. And her tumor has been stabilized now and she had small residual that required this chemotherapy, but she's been fantastic and is now some 10 years later has gone and graduated from SickKids. But there are countless stories like this. And if nothing else, this roots us in our place. It brings us back to why we all did neurosurgery in the first place and reminds us of what families, what children, what parents go through, what families go through, thinking about all this whole spectrum of patients with brain tumors. And we just lost one of my very close associates here at the University of Toronto, Dr. Fred Gentili, amazing skull base neurosurgeon, but he himself developed glioblastoma. So it inflicts the patients, it inflicts our colleagues. It's something that none of us is immune to, but how we must think about the future in terms of the research so that we can come up with novel ideas that will help move this field forward. So with this concluding slide, Aaron, I'm very happy to answer any questions that you may have about our center, how we got this off the ground, some of the starting points for how this took place, vision for the future, and also giving pearls, I hope, to individuals who are thinking about doing a similar thing in their domains. And hopefully this information will be very helpful and useful to them. Thank you ,Aaron.

- Spectacular. Very inspiring. Truly inspiring, Jim. I want to just sort of echo some of the important aspect of this talk that are so dear to my heart. First of all, God bless Fred Gentili for all he did for neurosurgery. We miss him dearly. You know, I lost my own niece last year to thalamic GBM and this really brings it home, the importance of this research in advancing the care of our patients. It just brings you totally in a different dimension of how important this is. But before we go further, I wanted to emphasize the importance of philanthropy. You know, unfortunately, physicians in general and neurosurgeons in particular do not feel comfortable being the front face of philanthropy. You have to be. There's just no other options. Philanthropy is the lifeline of our work. Again, philanthropy is the, not one, the most important aspect of living, of all we two every day in academics. And each one of these donors are approached by many development officers per month, per week. So, that for them is a numbing effect. The neurosurgeon has to be frontline, the first line. And so I personally, in fact took six months of philanthropy education. I say, you know, I'm gonna step away become, you know, widen up a little bit my operative loads, and I just gonna have to immerse myself because I have to be first a philanthropist, then a neurosurgeon, then a researcher. It's just no way rounded in that order. And so, after getting my MBA, which took two years, which is so critical in this whole picture of leadership development, business management, which is reality of life, is that we had to focus on becoming a philanthropist. So we have a school here, Lily School of Philanthropy at Indiana University, which is very effective. I got to know the Dean of actually a philanthropy school. I developed incredible relationships. And I really learned a lot how important this is. Unfortunately, and I'm just being blunt about it, as neurosurgeons, we're so confined in our world that neurosurgery isn't everything. Operating is who we are. And therefore we have achieved everything we wanted. That's not the case. In fact, becoming a neurosurgeon is less than 30% of what you need to be successful in an academia and make a difference in the lives of your patients. So to emphasize the importance of the Labatt family philanthropy, God bless them, that is so extremely critical and laudable, is that as a neurosurgeon, you have to be the front line. You are the surgeon who is facing these patients, and therefore, you are the most important connection to those who donate. And so, you have to be in the front line, communicating with the donors, emphasizing reverse, you know, ROIs, return on investment so they can understand how important that is. Again, it's all about relationships. Philanthropy is about relationship. And relationship is not about your philanthropy officer and a donor. That's not what we're talking about. Relationship is about you as a surgeon, relating and connecting with the donors. You have to be on the front line. This is a everyday job. I even joke about it and say, I'm on call 24 hours a day for philanthropy. You can see at, you know, eight o'clock at night, I get a phone call from our philanthropy officer says, we have this donor who has agreed. We really need to do something asap. And I'm on It. We're doing this. So I can just not emphasize the importance of philanthropy that neurosurgeons historically have not paid attention to. Number two is the importance of the team. I never say that philanthropy is just charity. Philanthropy is really about philanthropic investment. So the donor who is most often a very big businessman or woman is looking at it as what is the return on investment? And that's the business aspect, the MBA version that comes in. So you really have to be able to justify for that businessman, what is the return on investment that they can get? It's not just the money is coming to you and you can use it and you know, I got the money, I can do what I want. It's, you have to be able to invest it exactly like an angel investor around A, B, C investment. It's all business principles that neurosurgeons don't take time to pay attention to. So I always emphasize more and more and more and more that an MBA is almost a precursor of a PhD because you have to learn how to handle money, how to lead the teams in the lab, and to be able to demonstrate value. What is your value proposition? It is a completely a business model. It is not academia in the sense that we can think about it. Maybe worked in the past, but not anymore without a question. Something very well you mentioned is the importance of high risk research. NIH or other health funding services, unfortunately are extremely uninformed and misguided. They support research that only moves the needle a little bit. They take very little risk. That ain't gonna help GBM research. We're on the wrong path. Therefore, philanthropy is even more important than NIH dollars because you as a surgeon, as a researcher, can make the decision how the dollars are used and bring a much bigger investment. And something that Labatt Family have to be agar and congratulated about, and I wanna really emphasize that, is the first donation is a test donation. They just wanna see how you're gonna do it. Just like you are a business entity, you are giving you angels sick dollars of 100,000, 200,000 something and they wanna see what you're gonna do with it. If they see you have a reverse the ROI, a return on investment, they're gonna come back to you and they're gonna invest in you as a business. So, because philanthropy is the most important factor in medicine, in research, in academic neurosurgery, therefore you're dealing with business minds and therefore you have to be a businessman or a business woman. There is just no way around it. You have to be a business person, you have to be a philanthropist, you have to be a neurosurgeon, you have to be a researcher, you have to be a great family man, a great father, a great husband, a dear friend. Those are just the components in that priority that you just cannot overlook. Therefore, again and again, I emphasize to everyone who comes and try to work with me and become a neurosurgeon and academic, you know, neurosurgeon, I say that the priorities are very different. You have to be a great academician, a great neurosurgeon but that's only a very small part of the story, unfortunately. So with that very long sort of, philosophy discussion, our philosophical discussion, what do you think, Jim?

- Yeah. Thank you, Aaron. I mean, you're speaking also from your experience, which is substantial for philanthropy, which was a large part of what you were just discussing. And I'll just tell you quite honestly, the relationship that we've established with the Labatt family has been one of the most gratifying I can recall in my years as a neurosurgeon because they're just amazing individuals and they were, yeah, of course they were definitely interested on return of investment and making sure that our effort was moving forward before they so generously donated again. But as part of this, Mari and I, my wife and I became very good friends with them. And I can tell you that one of the best moments in our lives professionally has been to spend an evening with them. Every year we go out to celebrate what their donation has done. And we go out for a dinner, which they always look forward to, and they get an update from us, but it's every year, year after year, we're in touch with them. Just as you say on the front line, of being in touch with them, allowing them to see the progress that's being made, how the return on their investment has escalated, catapulted our research into a higher level. And it's been fantastic. And those relationships are what you, you know, should all strive for and that's something that, you know, I've come to appreciate over the years. But you can't do this. I suppose you could raise funds, but it's hard to raise funds if you don't have the substance, you know, behind the efforts. You actually have to have the good research going on. You need to, mention here, you have the right people on the bus. You need to demonstrate that your lab group has research funds, either at the NIH or Canadian equivalent level and so on, which we do. So we're an organization that has engendered a lot of support by virtue of our long track record and our ability to show that not only do we do good science, but we're also doing, you know, high risk science that allows for the next discovery phase to come forward and people pay attention. And as a result, individual's interest to donate to our cause is heightened. And I would say that, you know, as I showed in my slides, I've spent a lot of time just as you have, going out to these various events and meeting with donors, meeting with the, you know, the families that are raising funds for your efforts. And it's an effort that's well worth every moment of your time. For all the reasons that we mentioned, to get to know the groups, to get to know the individual, established those relationships, to raise the awareness and raise the funds, it's one of these snowballing effects that gains momentum over time. And it takes you to a place where you wouldn't be had you not done all of this effort. But I agree that it's a tall task to be able to do all these components of neurosurgery, but it's one that will come back to you in spades if you are so fortunate to have these great philanthropists who are supporting your effort and those relationships that you can uniquely build with them.

- Very well said. You know, I always say GBM research and our kind of research requires innovative ways, thinking of the box. Just cannot use the same methods in the past and expect a different result. That just doesn't work that way. Every generation has to find its own way to prove its innovation and its value. You cannot say, okay, my predecessors used that technique and maybe worked well and let me just reproduce that. We all have to come out with our own ways of doing things. And these present times require individuals who are multi-talented, who are flexible, who are adaptable, who are able to think outside the box and take the train or the bus in a new direction with inspiring leadership, multi-dimensional talents and personalities, passionate missions, and really, a personal belief in excellence. I think those are components that are so incredibly critical ingredients of success in neurosurgery in general and research in particular. So Jim, I just cannot be so proud of your incredible, you know, gravitas, executive power, leadership, and so many people you have inspired, including myself, to be where we are. I mean, the Neurosurgical Atlas for sure was so much inspired by your mentorship. And so, so many patients that have been affected and their care has been improved across so many years from the Neurosurgical Atlas and along, you know, over the entire world are so thankful for your inspiring leadership for the Neurosurgical Atlas, your contributions, your mentorship, and we sincerely appreciate it. Thank you, Jim.

- Thank you, Aaron. And it was a pleasure as always to spend time with you.

- Thank you.

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