Exploring the Intersection of Surgery and Cancer Research with Dr. Dan Delitto

Dr. Dan Delitto is an assistant professor of surgery at Stanford University specializes in surgical oncology and holds a PhD in immunology. On this episode, Dr. Delitto reflects on his decision to pursue an MD-PhD pathway during residency and discusses the recent advancements in single-cell RNA sequencing technology that his lab has acquired. He explains the complex role of fibroblasts in cancer development, particularly in pancreatic ductal carcinoma, highlighting how these cells can both promote and hinder tumor growth.

The conversation includes a lightning round, during which Dr. Delitto shares his admiration for his mentor, Steve Hughes, and offers succinct advice on the importance of surgical experience. He also mentions his preference for trance music while working and shares his excitement about ongoing and future research projects in his lab, which include investigations into various cancers, such as sarcomas.

Link to Nature Cancer article: “Cancer-derived mitochondria fuel fibroblasts to become pro-tumorigenic.”  

Link to Cell Reports article: “Disruption of fibroblast MYD88 signaling promotes antitumor immunity in pancreatic ductal adenocarcinoma”

Rachel Baker: [00:00:00] Welcome to Scrubcast, where we take a closer look at the research happening at Stanford University's Department of Surgery. I'm your host, Rachel Baker. Today we're speaking with Dr. Dan Delitto. Welcome to the show.

Dr. Dan Delitto: Thanks, Rachel.

Rachel Baker: Thank you for joining us. Dr. Delitto, you are an assistant professor in our division of general surgery.

You are a general surgeon specializing in surgical oncology. You also happen to have a PhD in immunology. Uh, why did you decide to go the MD PhD route?

Dr. Dan Delitto: That's a great question, and I will say I didn't do it the traditional way where you do the MD and the PhD at the same time. I did my PhD in residency, because I met an amazing mentor there who I think really triggered a passion for science. And so we figured out how to do the training in a more formal way, and I think the [00:01:00] people that very much believe in the PhD pathway are great mentors. And so we decided to do a PhD in immunology during residency and then come back and pursue a research career.

Rachel Baker: Amazing. Is there a particular type of surgical oncology that you're drawn to? Are you like a Whipple person or a HIPEC person?

Dr. Dan Delitto: Yeah, it's a great question. I mean, I think, you know, initially when I got here, I thought I would be more liver and pancreas focused. I think there's a really nice breadth of surgery at Stanford and have since branched out to both sarcoma and a lot of stomach and esophageal cancers. And so I really have become more of a general surgical oncologist since I've gotten here, but still have a very, I think, strong foundation in a liver and pancreas surgery practice.

Rachel Baker: Makes sense. Well, so we do this new thing [00:02:00] now in the department where instead of seed grant funding, we do instrument funding, and your lab was one of the first recipients. You got an expensive gray box. Um, what is a chromium X and a G4 sequencer? and how are you going to use these things to further your research?

Dr. Dan Delitto: These have been pretty incredible resources to have. So the, the chromium x, the best way to explain it is science has come a long way in the last 10 to 15 years. I think when I was doing a PhD, it was focused on a very different set of technologies and now, what's become mainstream is actually sequencing the transcripts of the gene expression of each cancer cell individually or each cell individually in a sample. We call it single cell RNA sequencing. And to do that, it requires a lot of fancy instrumentation that can separate the cells and create a platform where you can sequence each [00:03:00] cell individually.

So to do that, you need both. The separator, if you will, the machine that emulsifies these cells in what we call gel bead emulsions and, and allows PCR within each gel bead and really gets at the results of what each cell is expressing. And then once you've done that, you need something to actually sequence everything.

And so the sequencer allows us to sort of do the reading of the preparation by the chromium max. Hopefully that makes sense.

Rachel Baker: I'm kind of getting flashbacks of the first Jurassic Park movie where they're like, here is a very long series of DNA and we're gonna let this work here.

Dr. Dan Delitto: So we are sequencing the RNA within each cell.

That's what sort of both of those machines allow us to do. And you know, in the past we've had to do it with the cores here, but there's a lot of demand. I think every lab coming out. Is [00:04:00] interested in this technology And so to have the ability to do that within the department, uh, has been a huge resource that I think has helped us a lot.

Rachel Baker: Awesome. Well, so you wrote a paper with Dr. Michael Longaker that appeared in Nature Cancer this past August. Here's the title “Cancer Derived Mitochondria Fuel Fibroblasts to Become Pro Tumorogenic.” Lots of big words. Um, mitochondria, we'll all remember from high school bio, uh, as the powerhouse of the cell. I like to break down these titles into like words that I know. Um, fibroblasts. We've all heard about them a lot on this show because we're usually in the realm of wound healing. How are fibroblasts related to cancer?

Dr. Dan Delitto: That is a great question. That paper was an editorial we did on somebody else's paper.

We were asked to sort of give a hot take on [00:05:00] it and it is a really interesting paper. They showed that cells can actually transfer these powerhouses or these mitochondria to other cells, and the mitochondria could be transferred. Two fibroblasts, which then promoted a sort of environment that was more permissive to the cancer.

So it was a really neat thing to look at how cells can interact with each other by transferring parts of the cell to another cell. And so it was a great paper. The question of fibroblasts, you know, how do they relate to cancer, I think is particularly relevant to what we study with pancreas cancer in that so much of these tumors is fibrosis.

When you look at 'em under the microscope, most of the bulk of the tumor is actually not cancer cells. It's fibrosis and so it's clearly important in the tumor. There have been a, there's been a lot of work because of that on fibroblasts. And I think we are in a very confusing time because a lot of groups have shown that if you get rid of the fibroblasts, the tumors just grow faster.

But a lot of groups have shown that fibroblasts contribute [00:06:00] to tumor development. So how do you reconcile those two things and, and that's, I think, been the big challenge of sort of the last 10 years in the field.

Rachel Baker: Word. Well, so actually you wrote an even more recent paper. It was in Cell Reports with Maria Korah, and you were looking at fibroblasts specifically as they relate to pancreatic ductal carcinoma, a particularly crappy disease. What is an MYD 88?

Dr. Dan Delitto: So this was, I think, a continuation of the work. I was fortunate enough to do a PhD under someone who was very interested in how sort of non-traditional immune cells like fibroblasts can set off the immune system and, and how they interact with the immune system. And so the offshoot that we took down pancreas cancer, since we knew that fibrosis was such a big part of it, was to ask, can fibroblast sense alarm signals?

In other words, how do they respond to pathogens? [00:07:00] How do they respond to signs of damage, cellular damage, which would normally trigger an innate immune system response?

Rachel Baker: Mm-hmm.

Dr. Dan Delitto: And what effect does that have downstream? Is there a machinery to respond to it the same as an immune cell? And if it's different, how is it different?

And really what we found is that. Fibroblasts respond to both pathogen signals and damage signals, but they respond to it in a peculiar way. They don't set off. The immune system like you would hope in a cancer, which would be to set the alarm and say, go kill this cancer. Instead, they create this environment of what we call tolerance or, or basically saying, everything's okay here.

We don't need any extra immune response. And when you do that with cancer, obviously that's a bad thing, you know? Yeah. You're basically laying down a curtain that says Everything's fine here, move along. And those little trainers. Yeah. So it, it's one aspect of their behavior that I think is detrimental for sure.

Rachel Baker: Have we tried educating them? [00:08:00]

Dr. Dan Delitto: Great question. I think the best question is how do you reeducate them or how do you, uh, reprogram them in a way that's gonna be beneficial for. Both the body and the tumor, and that's what we're working on now. I think shutting down these pathways in every cell is gonna be tricky, um, because the immune system needs them, but shutting them down in fibroblasts we've shown is very beneficial.

And so what can you do to sort of get at, how do fibroblasts, what in their response to these is different than the way immune cells respond to them? And maybe can we target something more specific?

Rachel Baker: Super cool. Cannot wait, but that sound means that it is time for our lightning round. On each episode of Scrubcast, we ask each of our guests the same three questions, and the first one is, who is a surgeon you admire and why?

Dr. Dan Delitto: Oh my gosh, so many. This one really, I think the answer goes to Steve Hughes. So Steve is a pancreas [00:09:00] surgeon now at the University of Florida. I met him when I was a medical student at Pittsburgh, and that was in probably 2009, I would guess, 2010, somewhere around there. It's a long time ago, but Steve saw something in me that I think really.

Inspired me to pursue this direction. He felt very strongly about being both a good surgeon and a surgeon scientist. He was one of the first surgeons to do laparoscopic Whipples, and that's what he made his practice on. But he also had a K08. He was very interested in tumor biology. And when I went out in the lab at the University of Florida, it was under his guidance.

And he, I think he's inspired me in a whole host of different ways. He's a wonderful person. Uh, he's a. Uh, very gifted technical surgeon, but he also is a great scientist and he places a lot of value in being both a good surgeon and a good scientist. And I have known him for, since that time. He came to our wedding, uh, when Andrew and I got [00:10:00] married in Pittsburgh.

Uh, we have a great picture there. Uh, and I've been very close with incense. We probably talk at least once a month about all sorts of things now that, now that, you know, I do surgery on the pancreas as, uh, you know, as faculty, um, it's funny you find, you end up just having more in common. So that would be my answer.

Rachel Baker: Awesome. I always love that question because I get to find out about all these very cool people. I love it. The second question is. The best advice you have received in 10 words or fewer?

Dr. Dan Delitto: Oh my gosh.

Rachel Baker: I know. We really put the constraints on there.

Dr. Dan Delitto: It comes from Steve. This is for surgery though. This is not for science.

He told me before I left. That should be 10 words or less. Experience and exposure. You need one. At least one. Uh, and, and that's, that's what I tell the residents here. Uh, you know, I think it's a [00:11:00] great mantra in surgery.

Rachel Baker: Fabulous. Uh, final question. What is your preferred or music.

Dr. Dan Delitto: Oh trance. I didn't, this is new. I mean, I do have a really good friend who spent a lot of time in Germany, but really the impetus from it came from doing the PhD and just realizing that if you listen to music for eight hours in a day, anything with lyrics will drive you crazy 'cause you, so that's the basis behind the answer.

Rachel Baker: So it's like.

Like EDM kind of stuff, or like any preferred artists. This is not in my wheelhouse. I did much better with Dr. Hyun, who is like country, and I'm like, oh

Dr. Dan Delitto: yeah, definitely. I, I think some wires get crossed in me with country, uh, within, within the operating room, you know, I mean. Armin van Buuren is probably, I think a, a great, easy [00:12:00] answer for that one.

Uh, he's okay. He's very famous DJ, but, but yeah, there's, I, I do like variety. And I think what's fun about particularly being in the OR here is, uh, you know, the circulators tend to put things on that they really like, and it's fun to hear the newer stuff.

Rachel Baker: Awesome. Well, it has been a pleasure chatting to you.

Before we go, one final question. What is next for Dr. Delitto?

Dr. Dan Delitto: Oh my. We have so much going on in the lab right now. I am very excited for both the trainees right now, and Deshka Foster, just joining the lab is, is just an incredible presence. She is an absolute force in science, um, and is gonna be a rock star. So, you know, there is a lot to do.

We probably have eight or nine, you know, major projects we're working on now and, and have branched out to some other diseases. Particularly sarcomas. And so we are very excited about what's to come over the next couple years.

Rachel Baker: Amazing. Well, [00:13:00] I'm looking forward to seeing everything that comes out. Love stopping by your lab and seeing what's going on. Thank you so much for coming on the show.

Dr. Dan Delitto: Thanks Rachel. Much appreciated.

Rachel Baker: And thank you to our listeners for tuning into this episode of Scrubcast. Until next time, stay sharp.

And that brings us to the end of another episode. If you like Scrubcast, we hope you'll tell your friends and subscribe wherever you get your podcasts.

Scrubcast is a production of Stanford University's Department of Surgery. Today's episode was produced by Rachel Baker. The music is by Midnight Rounds, and our chair is Dr. Mary Hawn.