 Well, thanks very much, and thanks for inviting me to present today and join the meeting. I'm a medical oncologist, and so what I'm going to talk about today is related to precision medicine, but in cancer precision medicine, specifically thinking about somatic genomic alterations and how we use those somatic genomic alterations to think about choice of therapies. But I hope that the approach that we're taking to improve our understanding of cancer precision medicine is actually, you guys think it's broadly applicable to other pharmacogenomic research. So as you all know, there's been a paradigm shift in how we think about cancer, where we've moved from just thinking about the anatomic region where a cancer arises to now including the key genetic and molecular dependencies that we identify in a tumor, and this shift has been catalyzed not only by the continued discovery of key genetic dependencies in various tumors listed here, but also the development of targeted therapies that hit those vulnerabilities as well as genomic and molecular profiling techniques that allow us in real time to interrogate patients' tumors to be able to find those vulnerabilities. And so here's an illustration, a dramatic illustration of this in practice. This was a patient who we studied some years ago. He was a 38-year-old man with metastatic melanoma. He had these terrible deposits, subcutaneous deposits all over his upper torso and really was not responsive to any therapies that he received, no immunotherapies. This was now eight years ago, and so using sequencing and choosing a targeted therapy was not standard of care, but as part of a clinical trial, his tumor was sequenced. It was found to have an activating mutation in the gene BRAF, and because of that discovery, he was treated on a phase one clinical trial of a drug at that time called PLX4032, now the FDA approved Vemurafinib, and you can see this really dramatic response. And so this is a very dramatic example of cancer precision medicine and choosing a therapy based on a somatic genomic alteration, but this is really our goal for every patient with cancer. And I'll say that we've made advances and we've been able to do something like this in many more patients over the years, but this is still the minority of patients, and for the vast majority of patients, we haven't identified those targets and those vulnerabilities or haven't developed the appropriate drugs for those patients and can't recreate this scenario in as many patients as we would like. And so our ultimate goal is to be able in every patient to understand what drives cancer, interpret every patient's cancer genome, identify the optimal treatments, and anticipate and preempt resistance before it arises. And as I said, we've made a lot of progress over the years, but we still have a lot more work to do and discover a lot more of these dependencies and implications of somatic genomic alterations. And what many of us think it will take to get there is really amassing and characterizing many thousands of tumor and germline samples connected to clinical information. So we really can be able to develop a database that we can learn from and understand who responds to which therapies and who becomes resistant to which therapies. And Dr. Rodin earlier in his talk mentioned the study of outliers, and that's proved very useful in studying responses to targeted therapies in cancer as well. Studying patients with extraordinary responses has allowed us to find some of these dependencies and vulnerabilities by studying far fewer patients, by studying those patients who have rare but exceptional responses to therapies, drugs that when in most patients either don't provide a response or provide a minimal response, and a handful of patients may have to provide some extraordinary response, those in when we've studied one or two or three patients with a response to a particular drug have identified particular genes or particular pathways that have been altered that then allow us to develop a general principle which help us think about this now as a biomarker to find additional patients where this might be relevant. And so a lot of us in the field think that studies of extraordinary responders could help develop methods for optimally matching patients to drugs to highlight effective uses of what are otherwise considered failed therapies and also to aid with the development of new therapies or new therapeutic strategies. The problem is that when we have started to study patients with extraordinary responses, we often rely on someone at our institution saying, by the way, I have this interesting patient who had an extraordinary response, we should study them or we should find out what happened. And it's very challenging to find patients this way. It's really by happenstance or even if it is in a systematic way, if you do it at one institution, by the very nature of the responses being rare and extraordinary, it's very hard to find patients like this. Part of the reason that these times of studies have been challenging is that the vast majority of adults in the U.S. with cancer don't participate in clinical trials. So less than 5% of adult cancer patients in the U.S. are enrolled in clinical trials and even amongst those patients enrolled in clinical trials, the vast majority of those clinical trials don't collect tissue and don't study the patients who might have had a great response to a particular drug. And even more importantly, the vast majority of adults in the U.S. are treated in community settings and so they go to their local center, they get care, their tumor tissues may be stored in their pathology departments for future clinical purposes, but no one studies that tissue and the main reason that no one studies that tissue is that no one's really asked those patients, those 85% of patients, if they would be willing to contribute their tumor tissue for this type of research. And so most tumor samples have not been readily available for study and over the last several years, multiple groups have started to think about how to address this issue and how to expand our ability to analyze the very many thousands of tumor samples that are stored in pathology departments around the country. The NIH started approaching this a couple of years ago with their extraordinary responder initiative where they reach out to physicians around the country and ask physicians if they have a patient who meets certain criteria of extraordinary response that they can contact the NIH and that starts a process for those tumors to be submitted to the NIH for further study and over the last couple years, I understand that there's been quite a few of these such extraordinary responder patients that have been identified in this way. Around the same time a few years ago, we thought about taking a complimentary approach, which incorporates the use of technology, social media, and cultural changes in which patients are now more empowered to advocate for research in their tumors and advocacy groups are more organized than ever and take some of these changes and really use this opportunity to engage cancer patients directly and partner with them in this type of research. So in late 2014, early 2015, we decided to pilot this type of approach of going directly to patients in one particular disease and metastatic breast cancer, which is what my lab studies. And what we did is we went and we met with lots of patients and patient advocates. We hadn't started a study. We hadn't even really conceived of what the study would look like. We really just went around the country and started talking to patients and advocacy groups saying, if we did something like this, if we wanted to partner with patients and advocacy groups around collecting tissue and samples and medical records, is this something that you would be interested in and you would want to participate in and you could help with? And over that several month listening tour, we learned a lot about how patients felt about this, about what type of messaging we might use, about what type of images we might use on a website. And along with the patients and advocacy groups, we built a project and we built a website and the project is called the Metastatic Breast Cancer Project. And this is what the website looks like. So it's at NBCproject.org and you can see it says help transform our understanding of metastatic breast cancer. And if you scroll down the website, it says your tumor and medical records could help unlock discoveries. And it asks patients to become part of a research movement and have a direct impact on the future and tells people how they can participate. And so if patients read through this and are interested in participating, they click this little button in the top right corner that says count me in. And when they click count me in, it asks for their first name, their last name, and their email address. And then they check a box that says I have metastatic breast cancer and I would be interested in answering some more questions and potentially sharing my medical records or my saliva or my tumor samples. And so we launched this in October of 2015. Hopefully that patients would sign on because we had developed this and designed this with many patients. And in the last 18 months, 3500 patients, men and women, women and men with metastatic breast cancer from around the US have signed up. And we have now patients in all 50 states. We have some patients outside the US have signed up as well. And there's been real enthusiasm in the metastatic breast cancer community to join and participate in something like this. So I'll walk you through our approach. And so once people sign up, we send them an online consent form. And the online consent form asks for permission to obtain and analyze their medical records, a saliva sample, a portion of their stored tumor sample, and most recently a blood sample. And when they sign the consent form, they also tell us their home address and they tell us the names of all their doctors or what hospitals they've gotten their care at. So then we send them a small kit which has a saliva vial to collect saliva. We send that to their home, they provide a saliva sample and they drop it back in the mail. It's already addressed to us, it has postage. And so they can drop that in the mail. We then contact their physicians and their hospitals and we ask for copies of their medical records. And so then their medical records are either faxed or mailed to us. We then review their medical records and we abstract all the important clinical information. And we find out where their pathology is, where their tissue is stored. And then call the local pathology departments and ask for a portion of their tumor tissue, which is then mailed to us as well. And then we do genomic analysis on the saliva sample. We do whole exome sequencing on the saliva. We do whole exome and RNA sequencing on the tumor tissue. And most recently, now that we're collecting blood samples, we do whole exome sequencing on cell-free tumor-derived DNA in the blood. And then basically the goal is to take all of this and create this clinical pathological genomic database that links all of the information about their treatments and what they've responded to with both germline and somatic data. And then this data is de-identified and will be regularly shared. And so this is gonna be posted both in databases like DBGAP as well as CBIOPORTAL so everyone can use it for research. So I'll show you a little bit about our enrollment over time, just to highlight a couple of points. And so this blue line you can see here are patients who have registered, who've gone to the website, clicked count me in, and typed in their name and said they're willing to participate. And you can see, we launched, I don't know if this works here. We launched in October of 2015, we had six advocacy partners at the time, they helped us, they emailed all their constituents. They, we posted on social media as did they, as did the many patients that we partnered with. And over the first month or two, almost 1,000 patients signed up. And we were, we were very excited because we were, we were, we were very pleased that 1,000 people wanted to participate in this project. And then it started to level off and we thought maybe the project was done. We found the 1,000 people who wanted to participate and that was it. And then in early 2016, we all of a sudden, without us really doing anything, just started seeing lots of people sign up, hundreds per day over a period of several days. And when we looked around to figure out why this was happening, it turned out that patients who were signed up had taken it upon themselves to go onto Facebook and onto Twitter and into closed, closed support groups and started to talk about this project and tell other patients that they should, they were signed up, they were, they thought this was important and they thought other people should sign up too. And so we got this big bump, a single patient posted on her Facebook page that everyone should do this in February of 2016. We got 300 people who signed up in one day. And really ever since then, this steady increase, I would say, is largely patient driven with patients recruiting other patients to participate. We started sending out consent forms in January and we now have 2,100 people who've consented. And we started sending out the saliva kits in March of 2016 and now we have more than 1,200 saliva kits in the house. Because this is a direct to patient project, we don't have a multi-center IRB, right? We have one IRB, which is our IRB. And there are now 1,000 institutions that are represented amongst these patients. And so you can see there are five big cancer centers that each have 40 patients enrolled, but we have this very long tail of 721 institutions with only one patient enrolled. And so these are presumably the community centers around the country that have a patient who wanted to participate in this. We also asked for patient-reported data, so we have 16 questions that were designed with the patients that they thought patients would be able to answer. Some disease characteristics, some questions about extraordinary responses, some demographic information. And the response rate to this optional survey is 95%, with 98% of questions being answered and an average of six minutes to complete. So we start out with detailed clinical information about 3,300 patients. And we can use this information to identify specific groups that are hard to identify by traditional methods. So patients with extraordinary responses, patients with resistance, patients who present with advanced breast cancer, people who are diagnosed with metastatic breast cancer at a young age. And underrepresented populations, groups of patients who may not have been represented in large studies like the TCGA. This is the question about exceptional responses. So have you been on any therapy for more than two years? Or have you had any extraordinary response to disease where your tumor disappeared completely? And you can see a lot of patients answered yes to this. And so we thought this question didn't work, everyone's saying yes. But actually, everyone told us what drug they responded to. So then you can look through the data and you can find these small pockets of patients, 138 patients who had an extraordinary response to the drug xylota, which is a very small number compared to the total number. And probably at least a lot of these are true extraordinary responses. We can also look at how long people are living with metastatic breast cancer. So the average survival once diagnosed with metastatic breast cancer is about three years. But here are over 150 patients who've been living with metastatic breast cancer for more than 10 years. So is there something about these patients that we might be able to learn from? And we're trying. As I said, all the data is being shared. So all somatic and germline genomic data and all the linked clinical data are being deposited every six months in the genomic data commons, as well as the C-bio portal, as well as the fire cloud at the Broad. And we're planning our first deposition for the first 100 to 200 samples in the first half of 2017. So there are a lot of studies we can do, not just studying extraordinary responders. So now that we're collecting all of this data, we think we can study specific patient cohorts, outliers, as we talked about earlier, the epidemiology of metastatic breast cancer, which is somewhat understudied, clinical behavior like response and resistance, side effects, toxicities, particularly important to this group here, and also real world practice patterns. What order of therapies do people get? This is, as I mentioned, a collaboration with now up to 26 advocacy groups. Advocates groups, once we launched this, have been great about coming out and reaching out to us and saying they wanted to help with outreach. And so really, patients and advocates, as I mentioned, have been involved from the very beginning in conceiving, designing, implementing, testing, and continuing to refine this project. And we continue to add new advocacy groups who are partnering with us all the time. And so I just want to close by focusing back on this idea of patient partnered research. One day, sometime in the middle of last year, we started seeing all these selfies appear online. We didn't tell people to do this. This wasn't a marketing plan that we decided to do. They just started showing up. And you can see these are patients participating in the project who are holding up their saliva kit. The saliva kit says, count me in. And I'll read just four of the quotes, of many quotes that we've seen from patients. One patient from Houston said, I want to live and watch my children grow up. But if I can't, then I want to leave a legacy and a cure. From Lake Tahoe, we heard, as someone who does not live near a research center and therefore cannot easily participate in trials, I finally feel like I can contribute. Amazing how happy that little box makes you feel. I felt like a two-year-old. Let me help. I feel a sense of pride and belonging because of this. And giving us hope for the future, and if not for some of us, for our families. And so we're excited about this as a model for patient driven research. About six weeks ago, we launched a second project in a rare sarcoma called Angiosarcoma. In six weeks, we already have 200 patients who've signed up for this project. It hasn't been systematically characterized before. There are only about 300 cases diagnosed per year, and we already have 200 patients signed up. And in a few weeks, we'll launch a third project called the Prostate Cancer Project. So just to summarize, we think that partnering directly with patients through social media and patient advocacy partnerships enables the rapid identification of large number of patients who are willing to share their tumors, saliva, and medical records to accelerate research. And this, in particular, enables the study of rare patients, like exceptional responders or rare cancers, who are otherwise challenging to find with traditional approaches. And because patients are sharing this, sharing their information, we think this is a shared research. So all clinical and genomic data will be shared widely with researchers. And again, relevant to this audience, we think this might be a proof of concept for patient-driven research, not just in cancer, but in general. So with that, I'll close. I just want to acknowledge many people who work on this, in particular, the NBC project team here. Thank you very much. Thanks, Nick. Todd, if you want to move up, we have time, maybe, for one quick question. Pat? Sure. Nick, that was a great presentation. Thank you. I just had a quick question and a little bit more information about the governance structure. Do patients participate at all in the prioritization of research topics using the data that's collected? There is not a formal sort of decision-making body around what the research topics are. And partly, that's because the clinical data that's abstract from the record and all of the genomic data are just going to be made accessible so people can download it and do whatever research projects they want. We do take feedback from patients pretty seriously. And we've already changed the project many times based on feedback from both patients and researchers. So changing the survey questions, adding survey questions, doing follow-up surveys. We have a plan to follow-up survey based on input from patients. So in that way, there's a lot of input from the patients around the research. But in terms of what we're studying or what other people are studying, we're going to leave that pretty open. Great. Thanks very much. OK, next is an ingenious presentation from Todd Scar, Indiana University.