On the Edge of Breakthrough: The long game of cancer genomics: John Carpten, Ph.D., on building precision oncology that reaches patients

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.

 

 

On the Edge of Breakthrough: All Episodes

Full Transcript

Dr. Monty Pal:
I'm Dr. Monty Pal from City of Hope, and this is On the Edge of Breakthrough: Voices of Cancer Research. Each episode, we bring you the minds behind the science, the stories behind the data, and the breakthroughs that could change everything. Let's dive in. Welcome back, everyone. Our title is On the Edge of Breakthrough, of course, and I have to tell- tell you today I'm a little bit on edge because I'm here with the Cancer Center Director of City of Hope, the chief scientific officer, Dr. John Carpten. John, welcome to the program.

Dr. John Carpten:
Good morning, Monty. It's great to be here.

Dr. Monty Pal:
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? And tell us about that.

Dr. John Carpten:
Yeah, I had a interesting upbringing. You know, my father was in the Marine Corps. Um, I was born in Hawaii, uh Bay Marine Corps- Oh, okay. ... based and, uh, after I was two, he was sent to Yuma, Arizona, which is just barren 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. <laugh>

Dr. Monty Pal:
Oh my gosh. Okay. I'm sure mom was thrilled about that, right? Mom

Dr. John Carpten:
Was thrilled about that. <laugh> Um, and, uh, after my father retired, you know, the decision was to move back home, quote, quotes, uh, air quotes, which was the Mississippi Delta. Both of my parents were from the Mississippi Delta. So they packed us up and, uh, we moved, uh, to, um, Leland, Mississippi, small town. It's famous for Jim Henson who founded The Muppets.

Dr. Monty Pal:
You're kidding. Okay. Oh. So there's a

Dr. John Carpten:
Creek that runs through my town, Deer Creek, and that's- that was the, uh, inspiration for him creating the Muppets.

Dr. Monty Pal:
That's a fun fact.

Dr. John Carpten:
Yeah, it's a fun fact. And so I 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.

Dr. Monty Pal:
Okay. Right?

Dr. John Carpten:
Um, and so instead of being in a desert, I'd be in the cotton fields.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
And, um, you know, I was the weird kid who thought that Caterpillars was the most beautiful organism on the planet, right?

Dr. Monty Pal:
Better than scorpions.

Dr. John Carpten:
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.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
Requisite.

Dr. Monty Pal:
Right.

Dr. John Carpten:
Run, throw, catch, hit, didn't matter, right? Okay. I just had some natural abilities, 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.

Dr. Monty Pal:
And ultimately, you- this took you to Lane College, is that right? It

Dr. John Carpten:
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.

Dr. Monty Pal:
Okay. <laugh>

Dr. John Carpten:
Right? And they were dueling. Okay. Sure. Constantly doing. And, uh, um, you know, I had a great, um, uh, biology, you know, professor and, you know, Samuel Braxter, who's just a fantastic mentor and, you know, really helped, um, um, helped me navigate, right, through college and, you know, biology, what do I wanna do, and how do we tweak and tune your curriculum to, you know, get you into med school or graduate school? But again, there was football.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
And, um, you know, I was excelling on the football field as well. No

Dr. Monty Pal:
Kidding. What position, if I may ask?

Dr. John Carpten:
Um, I ... By the time I got to college, it was sort of a linebacker safety hybrid.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
If that makes sense.

Dr. Monty Pal:
Okay. Yeah. Two very different positions, I guess.

Dr. John Carpten:
Yeah. Last line of defense. If they get by John, it's a touchdown. <laugh> That

Dr. Monty Pal:
Was the-

Dr. John Carpten:
The typical saying. And, uh-

Dr. Monty Pal:
Okay.

Dr. John Carpten:
Um, yeah, I played- played- played defense.

Dr. Monty Pal:
Awesome. Okay. Yeah. Yeah.

Dr. John Carpten:
So, you know, that's a short version.

Dr. Monty Pal:
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?

Dr. John Carpten:
I had a term paper I had to write for literature. 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.

Dr. Monty Pal:
I remember those, yeah. It's something

Dr. John Carpten:
That 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.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
And I went over and looked and it said something like genetic engineering, the wave of the future.

Dr. Monty Pal:
Okay. Or

Dr. John Carpten:
Something, right? And I sat down and I opened it and I started reading through this article and I said, "That's what I want to do. "

Dr. Monty Pal:
No kidding.

Dr. John Carpten:
Like, I swear to God.

Dr. Monty Pal:
Well, and I- I remember that timeframe because back then, genetic engineering, it was sort of a pipe dream, right?

Dr. John Carpten:
This was 86, maybe?

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
87.

Dr. Monty Pal:
So it's almost the same way that people talk about flying cars now, right? Yeah, exactly. Yeah.

Dr. John Carpten:
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 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 a medical school, we're a dental school, and the room is getting smaller and small, fewer, fewer people, and I'm the only one sitting here.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
This guy Paul first walks in, "Are you John Carpen? Molecular genetics." <laugh> I was like, "Yeah, that's me. " <laugh> So there wasn't a van, it was his car, right? Okay. I was the only one who signed up for the Department of Molecular Genetics. Okay. And 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. Ro- Roy Tassova who was studying, uh, wound healing and lizards and amphibians and, um, Phil Pearlman who was studying the genetics of yeast. I mean, it was just amazing, right? And I said, "This is what I wanna 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 wanna do with my life.
I- I'm going to Ohio State, call my mom, we had a conversation." That was it. That's how it happened.

Dr. Monty Pal:
I packed

Dr. John Carpten:
Up my car and drove to Columbus.

Dr. Monty Pal:
Amazing. <laugh> But 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 bill, but it's just ever happened. It's hilarious, yeah. Uh, but tell us about your PhD work. What were you focused on during the PhD?

Dr. John Carpten:
Yeah, it's interesting. Um, um, 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 summer 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." <laugh> Yeah.

Dr. Monty Pal:
It's a

Dr. John Carpten:
Biochemical, and it just clicked.

Dr. Monty Pal:
Okay. Right?

Dr. John Carpten:
Um, and so I began to think about it from the perspective of chemistry. And then there was another epiphany where, you know, I began to approach it from the perspective of, if I close my eyes, can I imagine what's going on inside of the tube, right? And these were my sort of, uh, approaches to help me better understand, um, and not- not just was hap- what was happening didactically, but what was happening- happening practically in the laboratory. And it was at that moment that I put the two things together. After getting out of that 500 level class,

Dr. Monty Pal:
It

Dr. John Carpten:
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 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, uh, began his, uh, faculty and his professional career, uh, at Ohio State, and I was one of the students that joined his lab.
And w- subs- subsequent to that, uh, during one of the molecular genetic 701 courses, there was a presentation on a new, um, uh, methodology, uh, for human genetics called geest 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 Clark 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. <laugh>

Dr. Monty Pal:
Yeah, in- incredible. A- and it's amazing that you can pinpoint this all to looking at that journal cover, right, in the library.

Dr. John Carpten:
At that journal covering the library. It just was a red, I looked over, huh, sat down, opened it up, that's what I wanna do. It's

Dr. Monty Pal:
A real turning point. You can see sort of a through line to, you know, all these other major accomplishments.

Dr. John Carpten:
That was it. That was it.

Dr. Monty Pal:
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.

Dr. John Carpten:
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 Frances 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, as about, I don't know, maybe a 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. 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?" And, uh, one day the phone rang in Arthur's office and he said, "Hey, it's the genome center. They wanna talk to you. " And it was Jeff, Jeff Trent.

Dr. Monty Pal:
Jeff Trent. Uh, and just for our audience, Jeff Trent presides over TJ and 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, uh, in the field of genetics research. Is that a fair statement?

Dr. John Carpten:
Absolutely. And he's a wonderful human being.

Dr. Monty Pal:
I, I've got to agree with you there, yeah.

Dr. John Carpten:
And so he gave me 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, right? Uh, Francis was leading, uh, a series of national and international studies to identify genes linked to diabetes. And, uh, one of the studies was in Africa, and another study was in Finland. He was working with, working with Mike Binky at the University of Michigan. And, um, so the, the agenda was to meet with all of the various faculty members. It was a veritable who's who in genome research at the time. And, uh, and I remember the moment, uh, I went to meet with Francis, he and Larry Brody. Larry Brody was one of his postdocs. Um, and, um, the gene for, the BRCA1 gene had just been published-

Dr. Monty Pal:
No kidding. ... like

Dr. John Carpten:
A week or two before my interview.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
And I walked in the conference room and Larry and Francis were holding autoradiographs up to the light looking at the mutations in their BRCA families. When I walked in the cam- when I, I opened the door, I walked in and they're like this, "Oh, you're John Carpenter, 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 l- reviewed your CV. It looks great. You have all of the appropriate skills, but I just don't have room." So I have five postdocs already and I, you know, uh, 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'd it go with Francis?" I said, "Well, he doesn't have room." You know, I'd already started thinking about next steps, right?

Dr. Monty Pal:
Of course, yeah.

Dr. John Carpten:
And he said, "Great. I, I have a, a, a postdoc for you. " Oh,

Dr. Monty Pal:
You're kidding. He

Dr. John Carpten:
Said, "We're, you know, they just cloned the bra- the breast cancer gene." He said, "I'm working with, um, some investigators at Johns Hopkins to identify the gene that might cause hereditary prostate cancer." Okay, prostate cancer. What's that, right? <laugh> Of course. I, right, had no, no real background or understanding of cancer. It just wasn't something that I had really focused any, um, of my attention on. Uh, and I thought about it and we sat there and talked for about 30 minutes and said, "This actually sounds pretty cool, right?" Especially all of the press that the breast cancer gene got.

Dr. Monty Pal:
Around what timeframe was this?

Dr. John Carpten:
94.

Dr. Monty Pal:
94, okay. Yeah. I

Dr. John Carpten:
Called Jeff back and said, "Sign me up, right? Um, what are the next steps?" So I joined Jeff's lab. We moved to Maryland, I believe in October.

Dr. Monty Pal:
Wow. And

Dr. John Carpten:
That's when it all began. And we created a group called the Prostate Investigation Group or the Pigs. <laugh> <laugh>

Dr. Monty Pal:
Okay.

Dr. John Carpten:
And it's funny because Jeff got flack, I think, from some of the NIH leadership. We hear that there's some group, you can't use that term as an official, like, come on, man. It's just a, you know, it was a fun thing for us to

Dr. Monty Pal:
Do. I, I know for the clinical trial space, the NCI, they don't love acronyms. <laugh> So that's, that's the one thing I've heard about them.

Dr. John Carpten:
Yeah. They, they did not like that acronym, uh, 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, uh, 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- <laugh> ... And, uh, eat pop tarts and drink espresso. <laugh>
Okay. And just-

Dr. Monty Pal:
Operts and espresso, huh?

Dr. John Carpten:
Man. Okay. Yeah, 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-

Dr. Monty Pal:
Tell us about that paper, if you don't mind.

Dr. John Carpten:
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 hereinterior prostate cancer. So it was that first step to get to the actual gene and the mutations, right? And,

Dr. Monty Pal:
And I just hope our audience appreciates how challenging this type of work was at the time right? I mean- There was no genome.

Dr. John Carpten:
There was

Dr. Monty Pal:
No human genome. Yeah. And 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, uh, heavy duty manual labor, if I may say, right? Yeah. You had to

Dr. John Carpten:
Piece it together.

Dr. Monty Pal:
Okay. It

Dr. John Carpten:
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.

Dr. Monty Pal:
Right. So this kind of leans on that experience.

Dr. John Carpten:
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 megabases of human genome real estate. And 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, right?
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.

Dr. Monty Pal:
That, that's so Jeff, you know, to kind of preside over things, but in a very sort of non-dominating way-

Dr. John Carpten:
Exactly. ... right?

Dr. Monty Pal:
You know, just to give you a lot of creative direction I've- The

Dr. John Carpten:
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 popcorn-

Dr. Monty Pal:
Popcorns and espresso, right?

Dr. John Carpten:
Right. Bob Marley blasted on the speakers and, um, I was sitting at my desk in front of my computer and we were, uh, you know, analyzing genotype data and I had this s- I don't know, it's like a bubble, right? I wonder how many of these families are African American.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
Right? Yeah. I, I mean, it was just a, just a question- Yeah. ... that popped into my head. Looked over to Jeff Smith, said, "Hey, Jeff, do you know what the racial background of the families are? " He said, "No, never even thought about it, John." <laugh> I said, "I wonder if they have that information." He said, "Reach out to, uh, Bill and Sally at, at Hopkins." And I did, they said, "We had about a hundred families that they had recruited into the study." I'm thinking, I don't know if you've ever been, visited Johns Hopkins, but where it resides in the city of Baltimore-

Dr. Monty Pal:
Sure, sure. <laugh> Yeah. ...

Dr. John Carpten:
I'm thinking there's, it's gotta be a substantive percentage or, or a proportion of the families- Yeah.

Dr. Monty Pal:
... and it was

Dr. John Carpten:
Like two of them.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
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?

Dr. Monty Pal:
So I'm just registering this now, the, the study, the 100 families that you'd had, only two- Only

Dr. John Carpten:
Two.

Dr. Monty Pal:
That's so interesting, from Hopkins. I mean, that's- Moskin. ... that's bizarre. And it, it really speaks to the issue that we have even today, right? Even today, clinical trial accrual and enrollment and so forth, but, but carry on.

Dr. John Carpten:
And so I went to Jeff and Francis with an idea and a concept. I said, "I'd like to re, uh, recapitulate this study, but focused on African American families. So I need to recruit families. I wanna create a coordinating center to help me do that, pull that off. All of the genetic research would be done here." And, uh, Francis said, "You know, John, this is a great idea." Um, and Jeff said, "I concur. Uh, what do you need?" Francis came to me and said, "Hey, there's an, a scientist or a researcher at Howard University, which is a historically black college in the DC area, uh, Georgia Dunston, and she wants to do something similar with breast cancer." And so one day Georgia knocked on the door in the lab and we talked about it and she said, "Oh, I, I know some urologists that see, you know, large numbers of African American men in their clinic, um, and they're all part of this, uh, the National Medical Association." Monty, I don't know if you know the

Dr. Monty Pal:
AMA- I, I do. Yeah, I know indeed, yeah.

Dr. John Carpten:
So they have a urologic, uh, uro- um, urological section.

Dr. Monty Pal:
Okay. So I,

Dr. John Carpten:
Isaac Palll was the chair. Okay.

Dr. Monty Pal:
He

Dr. John Carpten:
Was a urologist, African American urologist who was in Detroit

Dr. Monty Pal:
At

Dr. John Carpten:
Carmettos.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
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 <laugh> from, from the campus to Dulles, and we had a meeting room in Dulles.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
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." <laugh>

Dr. Monty Pal:
You know, I, I did a little bit of homework ahead of this podcast. And 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- It was- ... 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? That's

Dr. John Carpten:
Fair to say. I would say among the first. If there was another, uh, similar study, I would probably say Fumiola Pty at the University of Chicago-

Dr. Monty Pal:
Oh, sure. Okay.

Dr. John Carpten:
... was beginning her work in Africa. And, you know, Monty, it was bigger than that for me. Um, it was about the community.

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
And so how could we also ensure that, you know, African Americans were involved in the study design, c- uh, recruiting the family, the nurses, the physicians, um, the coordinating center was at Howard University, the, the study coordinator was Rick Kittles. I hired Rick- Oh, gosh. ... we hired right out of graduate

Dr. Monty Pal:
School- Oh, wow. ... because

Dr. John Carpten:
Study ... Yes.

Dr. Monty Pal:
I guess you know Rick well during his time at City of Oak. Of course. Yeah. Uh,

Dr. John Carpten:
So Rick became a part of the team. Um, and Agnes Bafubani, who had trained as a statistical geneticist with Joan Bailey Wilson at the end, um, at the, at NHTRI became this ... So it was a African American led study team to focus on a disease that was significantly impacting our community. 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.

Dr. Monty Pal:
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, the, 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.

Dr. John Carpten:
Absolutely. Everyone deserves access, right, to innovative care.

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
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.

Dr. Monty Pal:
Awesome. Yeah, you know, we've only gone through a part of your journey so far. So you did your postdoc at the NIH. 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?

Dr. John Carpten:
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. So there was a couple of different opportunities, right? One was Ohio State.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
But Jeff and Francis both wanted me to stay at Genome, but, you know, the decision among all the faculty was we're not gonna give him, um, uh, a, a faculty slot. He's gotta compete for it. 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.

Dr. Monty Pal:
... maybe

Dr. John Carpten:
2000. I played baseball in college too, high school and college. And little did I know when I interviewed with Jeff, uh, 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?" <laugh> Little did I know he was trying to recruit me to softball.

Dr. Monty Pal:
Are you telling me Jeff Trent played some Softball.

Dr. John Carpten:
Jeff is uber competitive. He formed this softball team and we played in the Navy League and the Army League. You know, business, business people play golf and do business.

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
Well, Jeff, we play softball and we talk science, talk shot. 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 really, I really wanna apply the genome to human health. I just can't figure out how to get it done here."

Dr. Monty Pal:
Okay.

Dr. John Carpten:
Um, he says, "So I'm thinking about leaving, right?" And I'm like, "What?" <laugh>

Dr. Monty Pal:
This is during a softball game. Yeah. Okay. Yeah.

Dr. John Carpten:
Things are going really, really well.

Dr. Monty Pal:
Right.

Dr. John Carpten:
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 to Arizona." 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 Dorance and some of the major benefactors.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
And so Jeff introduces us and asks us to give a little spiel on what we were 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.

Dr. Monty Pal:
" Okay.

Dr. John Carpten:
Um, my wife's like, "Dude, I'm not moving to Arizona." <laugh> Uh, you get that out of your head. Okay. And, uh, so it was a really, really tough decision. And, um, I think it just boiled down to the opportunity for a new build.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
So when we got there, there was no building. Wow. Okay. 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 TJ building and we moved in.

Dr. Monty Pal:
So you get out there to TJ- Absolutely. And what's it like, you know, just starting this practice first in a Quest laboratory, then in this, you know, beautiful new facility, and what were some of the major accomplishments in those first couple of years out?

Dr. John Carpten:
Jeff is a very entrepreneurial-

Dr. Monty Pal:
Mm-hmm.

Dr. John Carpten:
... scientist. Um, and, you know, he, 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. Right. Right?

Dr. Monty Pal:
Oh yeah. Indeed.

Dr. John Carpten:
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.

Dr. Monty Pal:
And with all due respect, that's a very different focus from the NIH, right? I mean, it's- It's

Dr. John Carpten:
Very different focus.

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
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

Dr. Monty Pal:
Hoff. Oh, Dan Von Hoff. Okay, great. He's another big part of this story, I think, right?

Dr. John Carpten:
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 zeal-

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
... to help patients

Dr. Monty Pal:
And

Dr. John Carpten:
Save lives, especially for a tough disease like pancreatic cancer, right?

Dr. Monty Pal:
Indeed.

Dr. John Carpten:
Um, and so this translational platform that we were building, it wasn't about research, it was translational research. And I believe TJN was the first organization to use the word translational in its name.

Dr. Monty Pal:
Hmm. Okay. Yeah, I did, actually, I didn't dig that up, but that's probably absolutely true. That's interesting.

Dr. John Carpten:
If someone shows me something different, I, I'll take a look at it- Yeah. ...

Dr. Monty Pal:
But I believe

Dr. John Carpten:
We were the first to use translational- Awesome. ... 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?

Dr. Monty Pal:
I, I love that. Y- you know, just for the audience who may not know Dan Von Hoff, uh, maybe I'll just give him a- Yeah, please. ... 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. And

Dr. John Carpten:
This was the, the foundation of precision medicine. How do we utilize genomics, right, to, uh, improve the practice of medicine? And that was the focus of our work at TGIN, 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 Bittner, had created one of the first micro array technologies when we were in Bethesda.

Dr. Monty Pal:
No kidding. Okay. So

Dr. John Carpten:
They were pr- printing genes on glass slides.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
Uh, Pat Brown and David Botstein were doing the photolithographic printing of oligos- Wow.

Dr. Monty Pal:
... which

Dr. John Carpten:
Was the AFIMETRIX, became the AFIMetrics-

Dr. Monty Pal:
Oh, I remember the AFI chip,

Dr. John Carpten:
Yeah. Jeff and Michael's became Agilents- Okay. ... technology. And when we moved to T-gen, Dan had the idea, why don't we clinically validate this assay- Okay. ... 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.

Dr. Monty Pal:
So this

Dr. John Carpten:
Was the beginning and foundation of precision medicine.

Dr. Monty Pal:
Wow.

Dr. John Carpten:
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 nine, had a knock on my door, and it was David and one of his colleagues, and he said, "Hey, we see you're using this ABI 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?"

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
So we sat down and they were using Illumina, uh, sequencers. I was using ABI 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 Dorance, who's one of the major benefactors of TGen, who's a, 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.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
And that was the clinical laboratory that was developed by David and I at TJ. Y-

Dr. Monty Pal:
You know, I have to tell you, my clinical practice- <laugh> ... I was one of the highest end users of the Ashay on platform. I loved it. You know, whole exome. I thought it really, you know, did a lot of good for my patients. Around this same time, I wanted to call attention to a paper that I actually think has really had a transformative im- impact. You know, this is a, a nature paper that you'd first authored, uh, identifying AKT, right? Which, y- you know, I, I wanna underscore for the audience what a dramatic impact this has had to this day, right? We have clinical trials targeting AKT different elements along the, what we call the PI3K, AKT signaling axis. And, you know, I think your work was really foundational there, right?

Dr. John Carpten:
Yeah. You know, that was probably 2005, I think, uh, we began collaborations with Eli Lilly. One of the things that Lilly 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 Bittner, and the other was more of a functional genomic study that was led by spiromusces, one of the other faculty members at TGEN where he was using, uh, siRNA to knockout genes and, and perf- and, uh, create perturbations in cells and then see how those cells would, um, the, the behavior and biologyal 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, Elio, Eli Lilly acquired about 600 tumor samples and the question was, let's profile and sequence and perform 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.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
Um, and then we would PCR the tum- 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 AKT family.

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
And there are two major regions in AKT. One is the plext homology domain, the other is the kinase domain. Lilly really wanted us to focus on the kinase domain. And I said, "No, I wanna do the plexigen hormone. I wanna do the whole thing."

Dr. Monty Pal:
Okay.

Dr. John Carpten:
And lo and behold, right, this mutation, um, E17K 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-

Dr. Monty Pal:
Hmm.

Dr. John Carpten:
... credentialed AKT as a bonafide oncogene in human cancers. And so it was really, really amazing work and that was published in nature.

Dr. Monty Pal:
Incredible.

Dr. John Carpten:
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 Mateesh Borad and Allen Bryce, uh-

Dr. Monty Pal:
Oh, okay. Allen Bryce who now had City of Hope Phoenix.

Dr. John Carpten:
Exactly. Where we identified mutations in the EGFR pathway and oncogenic fusions in FGFR2 in cholangiocarcinoma. Oh,

Dr. Monty Pal:
Gosh. Oh, wow. That had

Dr. John Carpten:
Never been discovered. And, and th- those mutations are now changing the practice of medicine for how cholangios are being treated.

Dr. Monty Pal:
You know, it's funny, I'm, I'm a big fan of this literature because I treat bladder cancer as well and FGFR3 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 AKT, did not know about your work on FGFR2, which is- Yeah. ... also, I mean, transformative when it comes to oncology care.

Dr. John Carpten:
Yeah. So a rural shinein at Michigan and our group sort of came out with those discoveries around the same time, um, where we identified oncogenic fusions. So FGFR2 was fused, right, to, um, um, uh, other partner, uh, fusion genes, and they were oncogenic fusions. And, but the difference was we actually treated patients. Mm-hmm.

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
Um, and, uh, 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, 2015, 2014, 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 FGFR2 inhibitors, EGFR 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. That's

Dr. Monty Pal:
Incredible. And, and it requires a lot of patients, I would imagine, right? Because you, you 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 a case of cholangio, some of these pivotal phase two trials, right?

Dr. John Carpten:
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 or 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.

Dr. Monty Pal:
Oh, no kidding. So I, I have to tell you, it seems like you're on a role at T-Gen. Frankly, you're on a role- Agile going well. Age were going well. Um, but, you know, what was it that sort of, uh, pulled you over to the USC role?

Dr. John Carpten:
I think there were probably two main, um, pools, Monty. 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 two, um, was the relationship with, um, what was LA County Hospital- Okay. ... 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.

Dr. Monty Pal:
Yeah. And, and not to all to fast forward through the USC experience, but, you know, you were doing great at Tejin, 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. Yeah,

Dr. John Carpten:
That, that's ... Yeah. Um, I think a couple of things. Um, I ... Mike Calageria was one of my mentors as well.

Dr. Monty Pal:
Okay. And

Dr. John Carpten:
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 they're going national. That's pretty cool. And then three, the relationship with TJ. Mm-hmm. Right? Sort of, you know, full circle, right?

Dr. Monty Pal:
It does seem like a trifecta in some ways, right? Absolutely. I mean, gosh, 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. Yeah. Indeed. Indeed.

Dr. John Carpten:
So again, I think when I look back on my career, Monty, I've been a builder.

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
I joined a lab, um, in grad school that didn't exist. So someone fresh out of their postdoc building their first lab, and we literally built the lab. Yeah. 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 built something from the ground up. Then USC recruits me and says, "We wanna build a department in the medical school, and I went to USC and built a department that did not

Dr. Monty Pal:
Exist."

Dr. John Carpten:
Mm-hmm. So every, every stage has been a build stage. And then City of Hope, which provides a very different challenge because it's an exceptional organization already. I mean, it's unbelievable. You're exceptional, you're, you know, top five, top 10. I mean, right? Right.

Dr. Monty Pal:
So

Dr. John Carpten:
This isn't a new build, but it is a new build, right? I think the phrase has been said, we're an amazing established organization trying to become a startup. <laugh>

Dr. Monty Pal:
I like that. And,

Dr. John Carpten:
Right? Yeah. And so it's a different kind of build now.

Dr. Monty Pal:
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? Yeah, for sure. 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, 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 in getting some of our research out to those areas. Is that fair, just based on previous experience? That's

Dr. John Carpten:
Definitely fair. You know, I think, you know, this 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 Newnan and you're in South Georgia, right? Mm-hmm. And you think about that population, the demographics- Yeah. ... 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 license 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? Absolutely. And so that's, that to me is just such a unique opportunity.
I feel so lucky to be a part of it.

Dr. Monty Pal:
Oh, that's awesome. You know, we've talked about, you know, uh, this, this national model that we have. I, really, 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, selected group.

Dr. John Carpten:
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.

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
You know, when someone says he wants you to chair, then you're thinking he, right? <laugh>

Dr. Monty Pal:
Incredible.

Dr. John Carpten:
President of the United States.

Dr. Monty Pal:
And I imagine- It's

Dr. John Carpten:
Funny, I missed the phone call the first time.

Dr. Monty Pal:
<laugh> Did you really? Oh, God. Tell us that story, if you don't mind.

Dr. John Carpten:
It's, it's a bizarre story, but I, I, I missed it. I saw the 202 and it said White House. I'm like, this is definitely a scam right now.

Dr. Monty Pal:
You're kidding. It said White House on your phone. White House. Okay. But I would think of that as a scam call. Is that fair?

Dr. John Carpten:
Uh, that is fair.

Dr. Monty Pal:
Okay. Okay. <laugh>

Dr. John Carpten:
And, uh, then I listened to the message and I said, "This sounds like it could be credible." Okay. <laugh> Right? Um, and, uh, and then Francis called me- Oh, wow. ... said, "Hey, did you get this call?" And I was like, he said, "You need to respond to this call." <laugh> So I called them back and, uh, yeah, and that, that was, that was that. And, but it's been a great experience, you know, to work with the, um, directors of the National Cancer Institute and, you know, to, um, you know, work with them on the agenda for cancer research, uh, to help advocate for funding for biomedical research and, uh, to make sure, um, that, you know, the, the institute is, is, is providing the type of impact that we know it's supposed to provide.

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
And to be, you know, a part of that discussion.

Dr. Monty Pal:
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, who you'd mentioned previously and others. Any particular bits of work you'd like to spotlight from your current research portfolio?

Dr. John Carpten:
Well, yeah, it's, it's interesting, Monty. It's, yeah, I'm a scientist, right? That's, that's who I am.

Dr. Monty Pal:
Indeed.

Dr. John Carpten:
We had a paper that came out in nature 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 stud- 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. Okay. So triple negative breast cancer, ovarian cancer, and endometrial cancer.

Dr. Monty Pal:
Okay.

Dr. John Carpten:
So we have spatial biology, uh, projects running in all three of those cancer types.

Dr. Monty Pal:
Brilliant. And, and this is really, am I understanding this correctly to sort of understand the tumor microenvironment- Yes. ... where immune cells sit in relation to cancer-

Dr. John Carpten:
Cancer.

Dr. Monty Pal:
Yeah.

Dr. John Carpten:
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 in, uh, Black women.

Dr. Monty Pal:
Yeah, 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-

Dr. John Carpten:
Collaborating with Lorna Rodriguez and some of the other folks, uh, the gy- uh, on our gynec team, uh, really excited about the prospects.

Dr. Monty Pal:
Oh, gosh. 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. Carpton?

Dr. John Carpten:
How are we going to incorporate technology into every aspect of our organization?

Dr. Monty Pal:
I love that. So really bringing all these discoveries in the lab, you know, sort of to the patient.

Dr. John Carpten:
And how are we gonna implement, implement AI and machine learning to help, um, accelerate discovery, right? Help get it into the clinic faster. What does 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 Rocney, Dave Craig, you know, Vidahi, 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 wanna be at the bleeding edge of, of, of that transition.

Dr. Monty Pal:
I love that. 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.

Dr. John Carpten:
As I look back on my career, there was bioinformatics and, you know, it was how do we genotype? How do we, you know, three 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 <laugh> because ultimately, how do you ask AI a question?

Dr. Monty Pal:
Brilliant. You know, with, with, yeah, with your own words. You

Dr. John Carpten:
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?"

Dr. Monty Pal:
Yeah, yeah. Right?

Dr. John Carpten:
And so how can we do that, right, in 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?

Dr. Monty Pal:
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. Yeah. It's an incredible story.

Dr. John Carpten:
Right moment, right time. I, I can't take any credit for it.

Dr. Monty Pal:
We, we've promised me you'll do this again. We've got to come back here in a year or two.

Dr. John Carpten:
For sure. We'd love to, Monty. This is fantastic. Thanks for the opportunity to share.

Dr. Monty Pal:
You got it. Thanks for tuning in to On the Edge of Breakthrough. See you next time for more insights from the front lines of cancer research and care.

Subscribe to our
CancerCenter Newsletter

Thank you

Keep an eye on your inbox for the latest City of Hope news and research breakthroughs. If you have previously subscribed to receive email communications, your preferences have been updated.