In this episode of On the Edge of Breakthrough: Voices of Cancer Research, John Carpten, Ph.D., Chief Scientific Officer at City of Hope, discusses the evolution of cancer genomics—how early genome mapping enabled today’s targeted approaches and what infrastructure and equity considerations will determine what comes next.
Dr. Carpten traces the less-linear path that brought him to the forefront of the field, from his early interests in biology and sports to a pivotal moment in college, when a red-covered Life magazine helped crystallize his career trajectory toward genomics.
This curiosity led Carpten to his work on the Human Genome Project, where he significantly contributed to mapping the human genome years before a reference sequence existed. He later helped build translational genomics programs from the ground up, including as a founding member of the Translational Genomics Research Institute (TGen), turning limited resources into platforms for discovery and application.
The episode tackles what makes breakthroughs durable: building programs, technologies and teams that are inclusive, scalable and designed for clinical impact. Carpten shares how City of Hope is integrating genomics, spatial biology and emerging approaches such as AI to accelerate translation—with an emphasis on rigor, implementation and access.
Speaker 1:Welcome back everyone. Our title is on the Edge of Breakthrough, of course. And I have to tell you today, I am a little bit on edge 'cause I'm here with the Cancer Center director of City of Hope, the Chief Scientific Officer, Dr. John Carton. John, welcome to the program.
Speaker 2:Good morning, Monty. It's great to be here.
Speaker 1:Oh, well, I've been waiting for this, the opportunity to sit, you know, across the table from you and really, you know, hear about your vision for City of Hope. You know, what you have planned for the future. But before we get to that, I wanted to start sort of with your origin story. It, it's really a fascinating journey that you've had in terms of oncology research. Um, and it all begins with your upbringing, I would say, in the South, right? I mean, tell us about that.
Speaker 2:Yeah, I had a interesting upbringing. You know, my father was in the Marine Corps. Um, I was born in Hawaii, uh, con Bay Marine Corps
Speaker 3:Oh, okay.
Speaker 2:Base. And, uh, after I was two, he was sent to Yuma, Arizona, which is just Baron Desert, but there's a Marine Corps base there. So I spent a short, uh, stint of my childhood in Yuma, uh, probably five or six years there. Um, sort of, you know, getting into first grade, uh, in, in Arizona. And I think that was when, you know, I really began to, um, um, express my interest in life science. It was just natural, you know, I was the kid out in the desert trying to catch scorpions and spiders and bringing them home
Speaker 1:Okay. I'm sure mom was thrilled about that.
Speaker 2:Right. My mom was thrilled about that
Speaker 1:That's a fun fact.
Speaker 2:Yeah, it's a fun fact. And so, uh, may have been seven years old when we moved to, to Mississippi. I think I, I sort of expanded right on my interest in life science there, because now I'm out of the desert and I'm into essentially what was a jungle at one point. Right. You've got, you know, we're four or five miles from the Mississippi River, so it's the richest soil in the world. And, uh, so there's a lot of life. Okay. Right. Um, and so instead of being in the desert, I'd be in the cotton fields.
Speaker 4:Okay.
Speaker 2:And, um, you know, I was the weird kid who thought that caterpillars was the most beautiful organism on the planet.
Speaker 1:Right. Better than scorpions,
Speaker 2:Better than scorpions man. so yeah, I've always had this interest, this innate just natural interest in life science. Growing up in Mississippi, the other thing is sports. Okay.
Speaker 4:Requisite. Right.
Speaker 2:Run, throw, catch, hit, didn't matter. Right. Okay. I just had some natural ability. So I was able to, you know, use that as another way to sort of, you know, become more social, engage, be a part of the community, a part of all the kids in the community growing up. Uh, and you know, there, there's not a lot of opportunity in the Mississippi Delta. Right. Small town in the middle of the cotton fields. Right. and, you know, from a young age, I sort of figured, you know, I wanna parlay this into something, uh, professional. Right. Um, research Right. Medicine, something to that degree. But then there were the sports. Right. And I was excelling in sports as well.
Speaker 1:And ultimately, you, this took you to Lane College, is that
Speaker 2:Right? It did. It took me to Lane College, and I think by the time I got there, I was this weird creature. I was a nerd surrounded by a jock. Okay.
Speaker 4:Okay. And, um, you know, I was excelling on the football field as well. No kidding. What position, if I may
Speaker 2:Ask? Um, I, by the time I got to college, it was sort of a linebacker safety hybrid. Okay.
Speaker 1:If that makes sense. Okay. Yeah. Two very different positions,
Speaker 2:I guess. Yeah. Last line of defense, if they get by John, it's a touchdown, you know,
Speaker 4:That was the,
Speaker 2:The typical saying.
Speaker 4:And, uh, okay.
Speaker 2:Um, yeah, I played, played, played defense.
Speaker 4:Awesome. Okay.
Speaker 1:Yeah. Yeah.
Speaker 2:So, you know, that's a short
Speaker 1:Version. So, and, and then, so this interest in the sciences in college, ultimately, how did that sort of take you to Ohio State for your PhD?
Speaker 2:I had a term paper I had to write for literature, and I can't remember, I think it was my junior year. And this was when we had libraries, meaning you had to go into the building.
Speaker 1:I remember those, yeah.
I'll never forget because it was such an important moment in my life. I walked into the library and there was a little lobby area where there was a, you know, a few chairs and a sofa, and there was a table, and then they would have a few periodicals just sitting there. Um, and I can't remember if it, I think it was a life magazine. Um, and the cover was red. That's what caught my eye.
Speaker 4:Okay.
Speaker 2:And I went over and looked and it said something like, genetic engineering, the wave of the future
Speaker 4:Okay.
Speaker 2:Or something. Right. And I sat down and I opened it, and I started reading through this article, and I said, that's what I wanna do.
Speaker 3:No
Speaker 2:Kidding. Like, I swear to God.
Speaker 1:Well, and I, I remember that it's bananas time frame, because back then genetic engineering, it was sort of a pipe dream,
Speaker 2:Right? This was 86, maybe.
Speaker 1:Yeah.
Speaker 2:87.
Speaker 1:So it's almost the same way that people talk about flying cars now, right? Yeah. I mean, it's
Speaker 2:Exactly.
Speaker 1:Yeah.
Speaker 2:Genetic engineering. And, and, uh, and so a few months later, one of our faculty members took, um, a group of us, uh, on a, a graduate school visit to Ohio State. And Ohio State would hold this, um, graduate and professional school fair where they would invite, you know, juniors and seniors from college to expose them Right. To, you know, medical school, law school, graduate school, just to meet professors and meet faculty and meet some of the students and, and just get an idea of what it's like Right. To be in that environment. And, um, and it was interesting. It was a massive room full of kids and individuals from, uh, faculty members or administrators from the different colleges. And were would come by, you'd sort of sign up what you wanted to do. And so I'm sitting there and, you know, oh, we're the law school. Bunch of kids get up. We're in medical school, we're dental school, and the room is getting smaller and small, fewer, fewer people. And I'm the only one sitting here. Okay. This guy Paul first walks in, are you John Carton Molecular Genetics? I was like, yeah, that's me.
Speaker 4:And Okay.
Speaker 2:He drove me over to the, um, building and, you know, I met the chair and some of the faculty members, and they talked about the research that they're doing. Wrote Roy Sava, who was studying, uh, wound healing and lizards and amphibians and, um, Phil Perlman, who was studying the genetics of yeast. I mean, it was just amazing. Right. And I said, this is what I want to do. And I remember having to go back and, uh, a bunch of my teammates were going to New Orleans for tryouts for, um, a couple of Canadian league football teams. Um, I had, you know, run for some scouts and, you know, but when I got back, I said, that's what I want do with in my life. I I'm going to Ohio State, called my mom. We had a conversation. That was it, that's how it happened.
Speaker 1:That's amazing. You may
Speaker 2:Be packed up my car and drove to Columbus.
Speaker 1:Amazing. Right. You may be surprised to hear this, but I, I've never had that conflict between football and, and science, just, you know, given my build. It's just never happened. Uh, tell us about your PhD work. What were you focused on during the PhD?
Speaker 2:Yeah, it's interesting. Um, I'm, I guess I'm a little embarrassed, but, you know, it's, it's my story. Um, you know, I had never had any experience in like real laboratory research. I'd done some work in high school. So the US Department of Agriculture has an experiment station outside of my hometown. It's a massive research facility where they study things like the, um, uh, migration pattern of the cotton bowl, worm moth. Right. I mean, things of that nature. Right. But I actually had some jobs out there and, uh, had projects that took me to the state science fair, but it wasn't molecular research. Right. In college, it was dissecting a frog or a rat, or things of that nature. I didn't have the, um, the experience. Some of the kids who were in my graduate school class, you know, had done internships during the summer at universities and actually knew what a pipette was.
Right. Uh, so when I got there, I had no idea what I was getting myself into. so I was a little behind and I found myself on academic probation. My advisor basically, um, said, we're gonna put you on a 500 level, uh, biochemistry class. Right. I said, okay. Uh, so I took that step, and it was funny. It was a week. I said, oh my God, it's just biochemistry. You know, DNA is a chemical
Speaker 3:And
Speaker 2:After getting outta that 500 level class, it just exploded. I was the second person in my group to, to defend. Right. Everything just clicked. And so I joined the laboratory of someone who was fresh out of their postdoc, Arthur Burgess. He had just finished his postdoc. This was his first faculty position. I was his second graduate student. And, um, he had worked, um, in the lab, one of the laboratories that helped identify the gene that caused muscular dystrophy, the Duchenne's Muscular Dystrophy. And his, uh, goal was to be a part of the team that identified, uh, the gene that caused another rare pediatric disorder, spinal muscular atrophy, which was another type of, uh, muscular dystrophy, um, um, uh, muscle wasting, you know, innervation, uh, innervation of the muscles. Again, the kids get these diseases and it's, it's just horrible. Um, and so Arthur began his faculty and his professional career at Ohio State, and I was one of the students that joined his lab.
And sub subsequent to that, during one of the molecular genetic 7 0 1 courses, there was a presentation on a new, um, uh, methodology, uh, for human genetics called yeast, artificial chromosomes, where you could take large pieces of human DNA and clone them into a vector and transfect that vector into yeast cells, and then propagate that large piece of human DNA. And so you could imagine you're, you can generate a library of these clones that would essentially represent all of the DNA across the entire genome. And then if you could, if you could sort of amplify the ends of that, you could generate PCR products and find contiguous pieces of DNA that would represent a long stretch of human DNA. And so, Arthur's lab had identified a region on human chromosome five that likely, uh, contained the gene that would cause that disease.
And so my role in the, in the lab was to build out the physical map of that region of human chromosome five that would allow us to map new genes to the region and help us identify the mutations in the families that caused that disease. And so this was essentially the beginning of the genetic revolution. So Francis Collins and, uh, Mary Claire King, they were trying to identify the breast cancer genes at that time. Uh, cystic fibrosis had just been cloned. Right. So it was, it was just great timing. I got in the right field at the right time. And here we are.
Speaker 1:Yeah. Incredible. And it's amazing that you can pinpoint this all to looking at that journal cover Right. In the library
Speaker 2:At that journal covering the library. It just was a read. I looked over, huh. Sat down,
Speaker 1:Opened it up. That's what I want to do. Just a real turning point. You can see sort of a through line to, you know, all these other major accomplishments.
Speaker 2:That was it. That was it.
Speaker 1:You know, you'd mentioned Francis Collins, and I know that he's been a, a mentor to you of sorts over the years. Uh, I know that your journey took you from Ohio State to the NIH Right. For Postdoctoral Fellowship. So tell us about that continuum and how that, uh, came about.
Speaker 2:Yeah, it's interesting. Again, genetic revolution. Uh, Jeff, uh, Francis Collins and Jeff Trent, uh, had worked together at the University of Michigan. And, um, the National Institutes of Health was looking for new leadership for, at the time, what was the Center, national Center for Human Genome Research. Uh, and Francis accepted the job. So Jeff and Francis became the director and scientific director for the National Center for Human Genome Research. And I was finishing up my, uh, dissertation. Uh, it was about, I don't know, maybe little under a year out from defending and thinking about the next steps. And Arthur and I had been talking about things, you know, on one hand it was industry, you know, go make some money, get married, and, you know, have a regular life or do this academic thing. Right. Um, and Arthur knew that I was a huge fan of Francis. Like Francis was my, my hero. Right. I had heroes in football, and I had heroes in, in science. And Francis was probably my biggest hero. Um, Ohio State's Cancer Center at the time was really small. There might have been five or six people doing cancer research at Ohio State at that time,
Speaker 1:Just five. So
Speaker 2:And Arthur encouraged me to send my CV into the Genome Center. He said, you love Francis. You know, why don't you at least send your CV and see what happens? One day the phone rang in Arthur's office and he said, Hey, it's the Genome center. They want to talk to you. And it was Jeff, Jeff Trent.
Speaker 1:Jeff Trent. And just for our audience, Jeff Trent presides over tj, the City of Hope affiliate. And you know, I have to tell you that Jeff is one of the most accomplished and also understated guys in the field of genetics research. Is that a fair statement?
Speaker 2:Absolutely. And he's a wonderful human being.
Speaker 1:I, I've gotta agree with you there. Yeah.
Speaker 2:And so he gave him a call and he said, Hey, you know, see, you've done positional cloning and, you know, physical mapping. You know, we're gonna do a lot of that work here at the Genome Center. You've got all these skills. We'd love to invite you out, you know, um, and, uh, talk about a postdoc position. Wow. So I jumped on a plane, flew to Bethesda, and of course, I wanted to work for Francis mm-hmm
Speaker 1:No kidding.
Speaker 2:Like a week or two before my interview.
Speaker 1:Okay.
Speaker 2:
And I walked in the conference room, and Larry and Francis were holding auto radiographs up to the light, looking at the mutations in their BRCA families. When I walked in the ca when I, I opened the door, I walked in, and they're like, this, oh, you're John Carton. Yeah. Have a seat. I'll be with you in a few minutes. Like it, like one of those moments, right? This is Francis looking at SSCP gels Right. In the light. Um, and, um, and so we sat down and he said, well, John, I reviewed your cv. It looks great. You have all of the appropriate skills, but I just don't have room. Said, I have five postdocs already. And I, you know, to, you know, as a postdoc, you need your own thing. You, you have to have a project of your own. That's really the, the only way you'll be successful. And I just don't have room. So, of course, I was disappointed. So I circled back with Jeff. At the end of the end of the day, Jeff was my official host. He said, how did you go with Francis? I said, well, he doesn't have room. You know, I had already started thinking about next steps. Right, of
Speaker 1:Course. Yeah.
Speaker 2:And he said, great. I I have a, a, a postdoc for you.
Speaker 1:Oh, you're kidding.
Speaker 2:He said, we're, you know, they just cloned the bro, the breast cancer gene. He said, I'm working with, um, some investigators at Johns Hopkins to identify the gene that might cause hereditary. Okay. Prostate cancer. What's that? Right.
Speaker 1:Around, what timeframe was this? 94. 94. Okay. Yeah,
Speaker 2:I called Jeff back and said, sign me up. Right. Um, what are the next steps? This
Speaker 1:Wow.
Speaker 2:And that's when it all began. And we created a group called the Prostate Investigation Group, or the pigs
Speaker 1:To do. I, I know from the clinical trial space, the NCI, they don't love acronyms. So that's, that's the one thing I've heard about them.
Speaker 2:Yeah. They, they did not like that acronym.
Okay. But we rolled with it, and, you know, Jeff was great, and so it was me. And, uh, there was another postdoc, Jeff Smith. And, uh, we began, uh, a lot of work genotyping, DNA samples, um, um, from families that had multiple men who had been diagnosed with prostate cancer at a relatively early age. Um, sort of the indicators that the cancer might be, uh, inherited. So first degree relatives, a father and multiple sons, or a grandfather, then the father, then the sons. Right. So, first degree relatives, multiple first degree relatives diagnosed with prostate cancer, collected blood samples. The blood samples, uh, at this, that work was done at Hopkins. Samples were sent to us, to our lab, and we did all the genotyping in the laboratory. And so Jeff Smith and I had this lab in Building nine, which was one of the older buildings on campus. And we had these massive speakers, and, and we were like the only lab in the building. And we just turned the music up,
Speaker 1:Just Pop Tarts and Espresso.
Speaker 2:Huh, man. Okay. Sounds, that's how you get 14 to 18 hours, like, you know, every day, uh, for multiple years. And we, we just did it. And before we knew it, there was a science paper. And, um,
Speaker 1:Tell us about that paper, if you don't mind.
Speaker 2:Yeah. It was the first paper that, uh, reported, um, on a region of the genome that likely harbored, uh, a gene that would be associated with hereditary prostate cancer. So it was that first step to get to the actual gene in the mutations. Right.
Speaker 1:And I just hope our audience appreciates how challenging this type of work was at the time. Right. I mean,
Speaker 2:These days there was no genome, there was no human genome.
Speaker 1:Yeah. I mean, these days you pop something into a sequencer and boom, you've got your answer in a couple of minutes. Then it was a lot of really, I mean, heavy duty, manual labor, if I may say. Right.
Speaker 2:Yeah. You had to piece it
Speaker 1:Together. Okay.
Speaker 2:It was like building, it was like a puzzle, building a puzzle. Now, the, the cool thing was, of course, Francis was also leading the Human Genome project. And so as we mapped out this region of the genome, my laboratory led the efforts to build out the yeast artificial chromosome map, which I had done as a graduate student. Right. So this kind of leans on that experience. Exactly. And then there were higher resolution clones, right. To build out a more detailed map. And so we, we did that work and then mapped the genes to the region. Now, the cool offshoot of that was, was that we built out this 25, I think it was 25 mega bases of human genome real estate.
Speaker 3:And
Speaker 2:So we were able to engage with the Human Genome Project to say, we've mapped out this region of the genome, why don't you use our clones as part of the Human Genome Project for that region of the genome? So I began, um, to become more involved in the actual human genome project, and was one of the human chromosome one leaders. So there were different teams working on different human chromosomes. And Jeff really gave me the freedom to operate Right. As a postdoc, to build the lab, build the team, lead the team, um, lead the projects. He oversaw it, he resourced it. Um, he would join our lab meetings, but he allowed me to take the lead on everything. Um, and so it, you know, really opened a lot of doors for me. Monty,
Speaker 1:That's so Jeff, you know, to kind of preside over things, but in a very sort of non dominating way.
Speaker 2:Exactly. Right.
Speaker 1:
Exactly. To give you a lot of creative direction,
Speaker 2:
The creative direction and the, uh, the opportunities to innovate and think outside of the box. And, um, I believe it was 97 when I had another epiphany, um, in the lab with Jeff Smith. And, you know, we were standard, you know, uh, espresso pop tart day
Speaker 1:
Pop cards and espresso. Right,
Speaker 2:
Right. Bob Marley blasting on the speakers. And, um, I was sitting at my desk in front of my computer and we were, you know, analyzing genotype data. And I had this, I don't know, it's like a bubble. Right? I wonder how many of these families are African American?
Speaker 4:
Okay.
Speaker 2:Right. Yeah. I mean, it was just a, just a question. Yeah. I popped into my head, looked over to Jeff Smith. Hey, Jeff, do you know what the racial background of the families are? He said, no, never even thought about it. John
Speaker 4:Okay.
Speaker 2:And I'm like, wow. And so, you know, from that moment, it was like, how can I create a study similar to this, but focused on African Americans, given the fact that black men are two and a half times more likely to be diagnosed with prostate cancer, maybe two or three times more likely to die from the disease? Shouldn't we have a study? Right. That sort of helps us understand what the potential role of biology and genetics might be.
Speaker 1:So I'm just registering this now, the, the study, the a hundred families that you'd had only two, were only two. That's so interesting. From Hopkins. I mean, that's, that's bizarre. And it, it really speaks to the issue that we have even today. Right. Even today, Martha, in clinical trial accrual and enrollment and so forth. But, but carry on.
Speaker 2:And so I went to Jeff and Francis mm-hmm
Speaker 5:Indeed. Yeah.
Speaker 2:So they have a urologic, uh, ur uh, urological section. So I, Isaac Powell was the chair. Okay. He's a urologist, African-American urologist who was in Detroit at Caros. Okay. And so, Francis and I reached out to Ike, and he said, I'll pull the entire group together. They flew to Dulles Airport. We drove Francis' old minivan,
Speaker 5:Okay.
Speaker 2:And we met with them, and we laid out our, our, our project plan, and they endorsed it and said, we're, we're in to help. We can get you a hundred families in no time.
Speaker 1:You know, I, I did a little homework ahead of this podcast, to my knowledge, I can't think of any other setting in which, you know, there was a sort of focused exploration within an ethnic group. Is that fair to say? Within oncology? I think this was really the first example that I could come up with of, of looking at, you know, hereditary patterns, you know, genetically based, uh, within oncology. Is that fair to say?
Speaker 2:That's fair to say it. I would say among the first, if there was another, uh, similar study, I would probably say Fola Potty at the University of Chicago
Speaker 5:Sure. Okay.
Speaker 2:Was beginning her work in Africa. And, you know, Monty, it was bigger than that for me. Um, it was about the community.
Speaker 3:Yeah.
Speaker 2:And so how could we also ensure that, you know, African Americans were involved in the study design, uh, recruiting the family, the nurses, the physicians. Um, the coordinating center was at Howard University. The, the study coordinator was Rick Kittle. I hired
Speaker 1:Rick. Oh, gosh. Kidding. We hired Rick, you're
Speaker 2:Kidding. Right. Outta graduate school.
Speaker 1:Oh, wow.
Speaker 2:To become a study. Yes.
Speaker 1:I got to know Rick Well, during his time at City of Hope. Of course.
Speaker 2:Yeah. So Rick became a part of the team. Um, and Agnes Babani, who had trained as a statistical geneticist with Joan Bailey Wilson at the end, um, at the, at N-H-G-R-I became the, so it was a African American led study team to focus on a disease that was significantly impacting our community. Amazing. And, um, it, it, it's to this moment, right. One of those achievements, you know, where you just say, okay, you know, I, I've, I've, I've impacted my community Right. In a very, very positive way. And there's still individuals being trained by me or Rick and, you know, some of the urologists who participated. So even though the study is completed Right. It lives on
Speaker 1:Yeah, indeed. You know, I've, I've, I've read this story, it's so different hearing it, and I will say it explains so much of our focus, you know, city of Hope expands into Chicago and Atlanta and Phoenix. I mean, one of the many awesome elements of this expansion is that we can actually capture diverse populations in our research and really try to address this problem.
Speaker 2:Absolutely. Everyone deserves access. Right. To innovative care. Yeah. And, um, that's one of the things I feel that's a responsibility of mine. So, you know, it's not just about the job, it's not just about sort of the work, it's responsibility and purpose. That's how I, that's, that's what gets me up every day.
Speaker 1:Awesome. Yeah. Know we've only gone through a part of your journey so far. So you did your postdoc at the N-I-H-I-I, I think it's really curious, you know, sort of the path that emerged from this, I mean, this illustrious experience Right. Founding this group working with Francis Collins, you know, doing this very foundational work. Where did this take you next?
Speaker 2:So Jeff and I had had some conversations about my next steps and, um, and, uh, I had to compete for an open, uh, tenure track slot. Okay. Uh, it was, so there was a couple of different opportunities. Right. One was Ohio State.
Speaker 4:Okay.
Speaker 2:But Jeff and Francis both wanted me to stay at Genome. But, you know, the decision among the faculty was we're not gonna give him, uh, uh, a, a faculty slide. He's gotta compete for it. And I competed for it. And, and I earned that, that faculty slot. So I joined, uh, the Cancer Genetics branch and as a faculty member, I think this was 99. Okay. Maybe 2000.
Speaker 2:Played baseball and college too, high school and college, and little did I know when I interviewed with Jeff, you know, he was sitting there and he was looking at my cv. I'm waiting for him to ask me a question about science. He said, I see you played baseball in college. Right.
Speaker 1:Are you telling me Jeff Trent played softball? Jeff played
Speaker 2:Jeff is uber competitive. he formed this softball team, and we played in the Navy League. And the Army League.
Speaker 2:You know, business, business people play golf and do business. Yeah. Well, Jeff, we play softball and we talk science talk shop in the dugout or before the game, throwing the ball around. So one day, I think it was in 2001, um, he approaches me, he said, Hey, you know, I, I really, I really want to apply the genome to human health, and I just can't figure out how to get it done here.
Speaker 5:Okay.
Speaker 2:Um, he says, so I'm thinking about leaving. Right. And I'm like, what?
Speaker 1:Is during a softball game. Yeah. Okay.
Speaker 2:Yeah. Things are going really, really well.
Speaker 1:Right.
Speaker 2:I've been talking to some people in the state of Arizona about creating a new research institute, Arizona. I'm like, no way. I'm not moving here, son,
Speaker 2:And then one day I was in my office and said, Hey, I've got this group of people from Arizona coming, and they're gonna be in a conference room in a few hours. I need you to, you know, come in, you know, and I have baseball hat on, and, you know, it's just regular day. So I go into the conference room and contingency of individuals from the state of Arizona, the mayor of Phoenix, and, um, uh, Bennett Dorrance and some of the major benefactors. Okay. And so Jeff introduces us and asks us to give a little spiel on what we're working on in the lab. And it wasn't, there was no formal presentation. Jeff did a presentation, but we all just introduced ourselves and went back to my office and didn't think much of it. Um, and a few months later, you know, Jeff said, Hey, I'm gonna take this position in Arizona. Uh, I'd love for you to come with me.
Speaker 4:Okay.
Speaker 2:Um, my wife's like, dude, I'm not moving to Arizona.
Speaker 2:It was a really, really tough decision. And, um, I think it just boiled down to the opportunity for a new build
Speaker 4:Okay.
Speaker 2:When we got there, there was no building. Wow. There was no foundation. There was, there was a, a empty lot in downtown Phoenix. And before we knew it, a couple years later, there was the teaching building and we moved in.
Speaker 1:You get out there to tj tj and what's it like, you know, just starting practice first in a Quest laboratory, then in this, you know, beautiful new facility. What were some of the major accomplishments in those first couple of years out?
Speaker 2:Yeah. There were a few things. I think, um, it began to, Jeff is a very entrepreneurial
Speaker 3:Mm-hmm
Speaker 2:Scientist. Um, and, you know, he respects the academic mission, but understands that to drive things into the clinic to really impact patients Right. It requires the development of products.
Speaker 1:Right,
Speaker 2:Right.
Speaker 1:Oh yeah,
Speaker 2:Indeed. And so, you know, it really allowed me to begin to think differently about science and how we do science and what the, what the outputs of our science should be geared towards.
Speaker 1:And with all due respect, that's a very different focus from the NIH. Right. I mean, it's,
Speaker 2:It's very different focus.
Speaker 1:Yeah.
Speaker 2:And this is, I think, one of the reasons why he wanted to sort of move on. And then there was Dan, so Dan von
Speaker 1:Hoff, h Dan von Hoff. Okay, great. He's another big part of this story, I
Speaker 2:Think. Right. And yeah, so that partnership was just something I had not really understood or experienced where you have Jeff with the technology, the innovation, uh, the entrepreneurial spirit, and then you've got Dan with this missionary ill to help patients and save lives, especially for a tough disease like pancreatic cancer, right? Mm-hmm
Speaker 1:Hmm. Okay. Yeah. I did actually, I didn't dig that up, but that's probably absolutely true. That's interesting.
Speaker 2:If someone shows me something different, I I'll take a look at it. Yeah. But I believe we were the first to use translational
Speaker 4:Awesome.
Speaker 2:In the name of the organization. Um, and so the two of them, and it probably within the first six months, I just got it right, Monty, it was really about, you know, how do we innovate the technology? How do we accelerate and advance the research? How do we ensure that the research that we're doing is focused on outputs that have the potential to impact the lives of patients?
Speaker 1:I, I love that. You know, just for the audience who may not know Dan Von Hoff, uh, maybe I'll just give him Yeah, please. A quick spiel. You know, Dan has just had this transformative impact in oncology. And he remains very much involved in sort of paving a path for now application, I think, of precision medicine, right? Yeah.
Speaker 2:And this was the, the foundation of precision medicine.
Speaker 5:Yeah.
Speaker 2:Right. How do we utilize genomics Right. To, uh, improve the practice of medicine? And that was the focus of our work at TEN. Right? What are the discoveries that we can make, um, again, where the results right. Could impact the, the practice of medicine and improve the lives of, of cancer patients. Jeff, uh, uh, and Jeff's um, uh, collaborator, Michael Bitner, had created one of the first microarray technologies when we were in Bethesda.
Speaker 5:No kidding. Okay.
Speaker 2:So they were pre printing genes on glass slides. Okay. Uh, pat Brown and David Botstein were doing the photo lithographic printing of Oligos. Wow. Which was the afis became the Atrics technology. Oh,
Speaker 5:The afi, yeah.
Speaker 2:Jeff and Michael's became Agilent technology.
Speaker 5:Okay.
Speaker 2:Uh, and when we moved to T Gen, Dan had the idea, why don't we clinically validate this assay, and then we'll test the tumors gene expression profiles, and then we'll make the treatment decisions based on the profile of the tumor. Got it. So this was the beginning and foundation of precision medicine.
Speaker 3:Wow.
Speaker 2:David was really focused on, uh, data science and bioinformatics. On the other side of the hall was my group, the Cancer, uh, genomics program. And we were using different sequencing technologies and different approaches, but trying to ask similar questions. It may may have been 2008 or oh nine. I had a knock on my door and it was David and one of his colleagues, and they said, Hey, we see you're using this a BI solid next generation sequencer. We'd love to, you know, grab some of your data to develop tools to identify variants and mutations. I said, awesome. Right.
Speaker 5:Yeah.
Speaker 2:So we sat down and they were using Illumina, uh, sequencers. I was using a BI sequencers, and we were, we were seeing and observing what Dan and Mike and those guys were doing. We said, we should be doing this with sequencing. And so that was the foundation of creating a next generation sequencing based clinical laboratory. And so David and I set out right to build a lab based on next generation sequencing. And I remember going to Bennett Dorrance, who's one of the major benefactors of tj, who's a, a philanthropist with the idea. And I remember going to his foundation and presenting the idea, and they funded me, I think a million dollars a year for five years. And I built a lab and we called it a Cheyenne Analytics. Okay. And that was the clinical laboratory that was developed by David and I at tej.
Speaker 1:I wanted to call attention to a paper that I actually think has really had a transformative impact. You know, this is a, a nature paper that you'd first authored, uh, identifying a KT. Right. Which you, you know, I wanna underscore for the audience what a dramatic impact this has had to this day. Right. We have clinical trials targeting a KT different elements along the, what we call the PI three KAKT signaling axis. And, you know, I think your work was really foundational there, right?
Speaker 2:Yeah. You know, one of the things that Lily wanted to do was to identify new targets for therapy for cancer. And so we devised a study where, um, and there was, there were, uh, two major components. One was a large molecular profiling study that I led with Mike Bitner.
And the other was more of a functional genomic study that was led by Spiro MUEs, one of the other faculty members at TJ n where he was using, uh, sir a to knock out genes and, and per and, uh, create perturbations in cells. And then see how those cells would, um, the, the behavior and bowels you cells would change under different, um, uh, pharmacological conditions, right. So that there was that functional genomics. And then we performed, which to some degree was, um, sort of a pre TCGA type study where, um, Eli Li, Eli Lilly acquired about 600 tumor samples, and the question was, let's profile and sequence and performed microanalysis on these tumors to identify novel therapeutic targets. They wanted to focus on kinases. And so my laboratory created PCR primers to, um, PCR up the genes.
Speaker 5:Okay.
Speaker 2:Um, and then we would PCR the DNA from the tumor samples. Right. And then we would perform the analysis and look for new mutations. Um, and I remember during the design of the study, um, we were looking at some of the major cancer oncogenes and including the A KT family. Yeah. And there are two major regions in a KT. One is the plex and homology domain, the other is the kinase domain. Lily really wanted us to focus on the kinase domain. I said, no, I wanna do the whole plex and homo, I wanna do the whole thing.
Speaker 4:Okay.
Speaker 2:And lo and behold, right this mutation, um, E 17 K popped up and, uh, Jim Thomas at Li at Lilly was super, super excited about it. And so we went ahead and did all the biochemistry and showed that it was an activating mutation that credentialed a KT as a bonafide oncogene and human cancers. And so it was really, really amazing work. And that was published in Nature.
Speaker 3:Incredible.
Speaker 2:Um, and I, I think there was one other paper though, Monty, that I don't know if it's gotten as much, um, uh, publicity, but I also see it as one of the major, um, accomplishments. And that was the study with Maesh Borad and Alan Bryce. Um,
Speaker 1:Okay. Allen Bryce, who now heads City of Hope Phoenix,
Speaker 2:Exactly where we identified mutations in the EGFR pathway and oncogenic fusions and FGFR two in cholangiocarcinoma.
Speaker 1:Oh gosh. Oh, wow.
Speaker 2:That had never been discovered. And and th those mutations are now changing the practice of medicine for how cholangios are being treated.
Speaker 1:You know, it's funny, I'm, I'm a big fan of this literature because I treat bladder cancer as well, and FGFR three as opposed to two, you know, plays more of a pathogenic role there, but there's some cross reactivity between these drugs. Right? Absolutely. So, I, I knew about a KT did not know about your work on FGFR two, which is also, I mean, transformative when it comes to oncology care.
Speaker 2:Yeah. So ARU nine at Michigan, and our group sort of came out with those discoveries around the same time, um, where we identified Oncogenic fusion. So FGFR two was fused right. To, um, um, other partner, uh, fusion genes, and they were oncogenic fusions. And, but the difference was we actually treated patients
Speaker 4:Mm-hmm
Speaker 2:Um, and that showed that, you know, the drugs were, were, um, um, uh, efficacious against those tumors that harbored those, those, those oncogenic fusions. Really, really exciting work. I believe it was published in plus genetics, um, 20 15, 20 14 15. But it's interesting going to oncology meetings and going to the cholangio or the, the hepatic sessions and hearing the oncologist talk about the utilization of FGFR two inhibitors, eeg, FR inhibitors, um, EGFR pathway inhibitors to treat patients with cholangio, and they're trying to move it up closer to, um, uh, first line. So it's really exciting to say, wow, we were a part of that.
Speaker 1:That's incredible. And, and it requires a lot of patience, I would imagine, right? Because you, you've made these discoveries two decades ago, and it's really only now, right? That we're starting to see this clinical impact through phase three trials, or in the case of cholangio, some of these pivotal phase two trials, right?
Speaker 2:Yeah. So it was just the application of genomics and, you know, and, and again, just that, you know, when we think about precision oncology, precision medicine, you know, those were the beginnings then the foundation, right. Of what we now, you know, call precision medicine, precision oncology. And we kind of served as the precision medicine engine for a lot of groups. So Pat LaRusso Group in Detroit, we had a, um, stand up to Cancer Dream team with Pat. Uh, we did a lot of the clinical sequencing for Mayo Clinic in Scottsdale. We did a, and, and we worked with Steve Gruber when he was the cancer center director at USC.
Speaker 1:Oh, no kidding.
Speaker 1:So I, I have to tell you, it seems like you're on a roll at T Gen, frankly, you're on a roll at the NIH too. Um, but, you know, what was it that sort of, uh, pulled you over to the USC role?
Speaker 2:I think there were probably two main, um, pools. Monte, I think one was the opportunity to be in an environment where there was a hospital with patients. And, and the opportunity to sort of provide that innovative care, I think, too, um, was the relationship with, um, what was LA County Hospital,
Speaker 3:Okay.
Speaker 2:Which serves, you know, 70, 80% underserved patients, right? Patients from underserved communities. And again, for me, responsibility, purpose, ensuring that everyone gets access to this kind of innovation.
Speaker 1:Yeah. And, and not to all to fast forward through the USC experience, but, you know, you were doing great at Te Egen, doing great at USC, and then of course, you know, we at City of Hope come and try to entice you to come and run our cancer center. Tell us about that.
Speaker 2:Yeah. That, that's, yeah. Um, I think a couple of things. Um, I, Mike Cager was one of my mentors as well, and someone who, you know, I've always looked up to, uh, has always been there to, you know, plant those pearls. When Mike moved here, he and I connected and we talked about it. Um, he knew I had aspirations of one day becoming a cancer center director. City of Hope was doing something very different, and everyone was kind of hearing about it and seeing it, and like, how are they going national? That's pretty cool. And then three, the relationship with tj mm-hmm
Speaker 1:It does seem like a trifecta in some ways, right? Absolutely. I mean, mean the ability to like pull in your old partners from T Gen to run the cancer center to really capitalize on this, you know, sort of nationalized model vision. Exactly. Yeah. Indeed.
Speaker 2:Indeed. Yeah. So again, I think when I look back on my career mind to, I've been a builder,
Speaker 3:Yeah.
Speaker 2:I joined a lab, um, in grad school that didn't exist. So someone fresh outta their postdoc, building their first lab, and we literally built the lab. Like we put in cabinets, we put in benches, we built it from the ground up, and then moving to the genome center at NIH for Jeff and Francis, just showing up. And we built that center, which was later advanced to an institute, right? And then Jeff going to Arizona, nothing existed. And we build something from the ground up, then USC recruits and says, we want to build a department in the medical school. And I went to USC and built a department that did not exist. Mm-hmm
Speaker 1:I like that.
Speaker 2:And, right? Yeah. And so it's a different kind of build. Now,
Speaker 1:I, I see so many applications of the skills that you bring to the table, right? I mean, certainly I think at Duarte we've got things humming, right? Uh, we have a beautiful new hospital that just opened recently in Irvine. Um, and of course, these new facilities that are emerging in Chicago and Atlanta and Phoenix, which really, I would say world's authorities and respective areas of oncology at each one of those centers. I think that, you know, you're really gonna help us if, if I'm not forecasting too much here and getting some of our research out to those areas. Is that fair? Just based on previous experience?
Speaker 2:That is definitely fair. You know, I think, you know, it just offers a really, really unique opportunity that very few cancer center directors, right. Or, uh, research leaders get to, um, uh, be a part of. And I think, you know, on multiple levels, you know, when you, when you go to Atlanta, right? And you're in Nonan and you're in South Georgia, right? Mm-hmm
You go to Zion, Illinois, right? And you think about that population and those demographics in Orange County, right? Um, and, uh, of course here in Duarte and across our entire Southern California network that we can't, we can't forget about, right? The, the on licensed sites, right? All of our clinical partners, antelope Valley, I mean, uh, Upland, right? Just so many opportunities to get, uh, innovative care out to the masses, right? And so that's, that to me is just such a unique opportunity.
Speaker 1:Part of it. Oh, that's awesome. You know, we've talked about, you know, this, this national model that we have. I think really at, at this grand scale, you've, you've been shaping the direction of oncology for a long time, but now very formally through the National Cancer Advisory Board. Can you tell us about that role? It's a huge honor, right. To join that very, you know, sort of, uh, elective.
Speaker 2:Yeah. It's, it's been an unbelievable experience, you know, the appointment, uh, from President Biden, and not just the appointment, but to chair.
Speaker 4:Yeah.
Speaker 2:You know, when someone says he wants you to chair, then you're thinking he Right.
Speaker 1:Incredible
Speaker 2:President of the United States.
Speaker 1:Right? And I imagine,
Speaker 2:It's funny I missed the phone call the first time
Speaker 1:
Speaker 2:It's, it's a bizarre story, but I I, I missed it. I saw the 2 0 2 and it said White House. I'm like, this is definitely a scam. Right?
Speaker 1:Just you're kidding. It said White House on your phone.
Speaker 2:It's a White House.
Speaker 1:Okay. But I would think of that as a scam call. Is that fair?
Speaker 2:At That is fair.
Speaker 1:Okay. Okay.
Speaker 2:
Speaker 4:Okay.
Speaker 2:Right. Um, and, uh, and then Francis called me Oh gosh. And said, Hey, did you get this call? And I was like, he said, you need to respond to this call
Speaker 5:Yeah.
Speaker 2:And to be, you know, a part of that discussion.
Speaker 1:Well, y you know, you have such a massive role here at City of Hope, but, but it seems to me as though you're still maintaining a very sort of active research agenda with colleagues like David Craig you'd mentioned previously, and others. Any particular bits of work you'd like to spotlight from your current research portfolio?
Speaker 2:Well, yeah, it's, it's interesting, Monty. It's, yeah, I'm a scientist, right? That's, that's who I am. Indeed. We had a paper that came out in a genetics a month or two ago where we profiled, um, 500 triple negative breast tumors from, uh, that were derived from African American women. It's one of the largest stu genomic studies of African Americans and sort of, uh, detailed the molecular landscape of those tumors looks similar or different compared to, uh, women from other, um, uh, racial and ethnic backgrounds. So, really proud of that work and excited about, you know, the future prospects of those results. Uh, one of the things that we focus on a lot in my laboratory is around, um, uh, spatial biology. So trying to really understand, um, the tumor and immune microenvironment, uh, changes that occur in tumors, uh, with a focus on women's cancers. So triple negative breast cancer, ovarian cancer, and endometrial cancer. Okay. So we have spatial biology, uh, projects running in all three of those cancer types.
Speaker 1:Brilliant. And, and this is really, am I understanding this correctly, to sort of understand the tumor microenvironment where immune cells sit in relation to cancer? Yeah.
Speaker 2:Right. And, uh, fibroblasts and the interactions of these cells, the various cellular compartments. Um, for instance, one of the studies we're running in ovarian cancer, we're looking at ovarian cancers, um, from that were derived from patients who were treated with, um, immunotherapy, some patients who responded and some who didn't respond, and looking at the differences in the immune compartments right. In the responders versus non-responders, um, using spatial, um, uh, transcriptomic approaches and spatial prote pro protein approaches. And we're really excited about that new data we just generated. Um, so yeah, just really trying to understand the differences, um, that we see in the, uh, tumor and immune microenvironment, uh, where we're comparing across groups. It may be, um, groups who have been treated with therapy who responded or didn't respond in endometrial cancer. One of the things we know is that black women tend to, um, present with more aggressive disease and have poorer outcomes. So we're building an endometrial cancer cohort, uh, where we're collecting tumors from women across, uh, racial and ethnic groups, and profiling their tumor and immune microenvironments to see if we can, uh, glean any clues, um, uh, or extract any new knowledge that might help, um, us better understand what might be driving right. That more aggressive cancer and black
Speaker 1:Women. And that makes a lot of sense. We have a phenomenal force in gynecologic oncology here, right. Who I'm sure is, uh, serving as a great partner for that type of
Speaker 2:Work. Collabor, Lorna Rodriguez and some of the other folks, uh, the guy, uh, on our gyno team. Really excited about the prospects. Oh gosh.
Speaker 1:You know, we always wrap up these podcasts by asking maybe what I think is the toughest question of all, you know, our title is on the Edge of Breakthrough Voices of Cancer Research. What does on the edge of breakthrough mean to you, Dr. Carpen?
Speaker 2:How are we going to incorporate technology into every aspect of our organization?
Speaker 1:I love that. I love that. So really bringing all these discoveries in the lab, you know, sort of to the patient
Speaker 2:And how are we gonna implement, implement AI and machine learning to help, um, accelerate discovery, right. Help get it into the clinic faster.
Speaker 3:Yeah.
Speaker 2:what is our technology play really excited about? Our new leader, um, for our, uh, enterprise technology group si Simon Nazarian, uh, working closely with he and Marcel and some of the folks on our research, um, uh, team, uh, Russ, Rodney, Dave, Craig, you know, Vahe, uh, and just really trying to figure out how do we begin to incorporate technology right into everything that we do? Um, because, you know, technology is gonna change the way we do research, the way we do clinical care, the way way we engage with patients, and we want to be at the bleeding edge of, of, of that transition.
Speaker 1:And that's so, so appropriate for everything that we're seeing emerging from our labs right now, from our AI group. I think there's a, there's an excellent opportunity for us to really be leaders in that space.
Speaker 2:There was bioinformatics and, you know, it was how do we genotype? How do we, you know, 3 billion bases of the human genome, and you're looking at thousands of individual, all of these data points across all of these individuals. How do we manage that data, store that data, analyze that data, uh, you know, working with David, all of the work that they did in developing methods and tools and, and, and, you know, all of the, you know, working in r and working in Python, developing new informatics tools to now where, you know, I think one of the developers of, of, uh, AI was asked a question, you know, as we think about, you know, technology and coding, what's the, what, what, uh, computer language should people be focusing on? He said, the English language
Speaker 1:Brilliant. You know, with with, yeah. With your own words.
Speaker 2:You don't have to pull down some fancy tool off GitHub anymore. You just go to AI and say, Hey, here's a list of genes. What does it mean?
Speaker 5:Yeah.
Speaker 2:Right. And so how can we do that? Right. And a very efficient and effective way. How do we train our students and our fellows right, on how to use this technology again to accelerate discovery?
Speaker 1:I love that. Gosh, brilliant. I, I've talked your ear off here. We've gone probably way over time, but John, thank you so much for sitting down with me. Amazing, amazing history. I can't believe this all started by looking at the cover of a life sciences journal, you know, back there in that college library.
Speaker 2:Yeah.
Speaker 1:It's an incredible
Speaker 2:Story, right moment, right time. I, I can't take any credit for
Speaker 1:It. We, we've promised me we'll do this again. We've gotta come back here in a year or two
Speaker 2:For sure. We'll, love to. Monty, this is fantastic. Thanks for the opportunity to share. You got it.