How to use engineering to address heart disease | Interview with Dr. Matthew Tirrell

0:00:14.1The many roles

Jed Macosko: Hi, this is Jed Macosko at Academic Influence and Wake Forest University. And today, I have an old friend, Professor Matt Tirrell, coming to us from Chicago, and I wanted to ask you, Professor Tirrell…

…how has it been being a teacher where you’re meeting with students and trying to give them information, being a researcher, where you’re trying to develop new things and being an administrator, trying to get an entire department or a group of people moving in a certain direction, so how have each of those things unfolded time-wise in your career, which ones you’ve done at different points, and how much, what different skills have they required of you and your enjoyment of each of those roles?

Matthew Tirrell: Yeah, well, I went from defending my PhD dissertation in the middle of August at the University of Massachusetts, drove to Minnesota and became an assistant professor two weeks later. And at the beginning, teaching and research are the entire job. And in fact, at major research universities, such as the University of Minnesota, there’s a big premium placed on allowing time for you to get your research career off the ground.

But you know, as I’ve progressed in my career, I realize that teaching and research aren’t as different as they might seem at first. In each case, you’re trying to teach somebody something. What we typically call teaching is classroom activity, where you lecture and interact with students in the classroom, but in your research lab, you talk and interact with students in the laboratory, and you try to produce results that teaches the world something about nature or about what nature can do with chemistry or biology or physics or whatever it is, and I think there’s a huge premium in both teaching and research on developing clear ways of explaining things.

And when I talk to students who are either coming into graduate school or coming out of graduate school into the next phase of their career, I always try to emphasize that, that whatever you’re doing, your ability to explain things to people clearly and concisely will be advantageous. You write good papers by writing clearly, you write good proposals by teaching the people who are reviewing them some new things. So in my view, the distinction between teaching and research isn’t that big.

Administration is a little different thing, and I worked at the University of Minnesota for 22 years. Just before I came there, a person, really, a giant of chemical engineering had stepped down as department head, Neal Amundson , who had been department head for 27 years, and then we had a couple of shorter-term department heads, and then Ted Davis, one of my friends and colleagues, took over for 15 years, so I saw some really excellent long-term stable faculty leadership. And then when Ted actually became Dean, I was asked to become a department head, so it wasn’t so much that I was angling for the job; if I really wanted to move quickly into administration, I probably would have left Minnesota, because there were such long-term people there.

But when you work at a place for a while, you start to feel a sense of responsibility. If people want to invest in you as a leader, and you’ve benefited from being at that place, I mean, that’s how it was for me.

I was honored, basically, by the request that I become department head. Having said that, and I don’t mean to turn this into too long of a monologue, but after I was department head for five years, I started to get recruited for deans’ jobs around the country. In 1999, 21 years ago, 22 years ago, I became Dean of Engineering at UC Santa Barbara, where I was for 10 years. And that really gave me a kind of a higher-level platform to try to guide the building of a faculty and hire people and so on.

And I think the thing that has driven me the most toward administration is that I’ve found that I seem to have a knack for convincing faculty members to do what I want them to do, persuade them to join my university or to engage in research initiatives, and things like that.

So, as you know, after 10 years at Santa Barbara, I think we might have almost crossed paths for a short time at Berkeley, where I became Chair of Bioengineering. And I did that for two years, and I expected I would still be there right now, except that after about two years, the University of Chicago contacted me saying they wanted to start their first ever engineering program, and I had the honor and responsibility of founding an engineering school, which we now call the Pritzker School of Molecular Engineering.

0:06:32.7University of Chicago

Jed: So tell us just a little bit before I want to move on to research, what led the University of Chicago, which has been around for a long time, to finally get into engineering and why hadn’t they done it before?

Matthew: Yeah. That’s an extremely interesting question. And the... I’ll answer the second one first. They had a long-standing, deep feeling of scholarship that you could perhaps describe as knowledge for the sake of knowledge or producing information for society, but that there were other places that could think about the applications.

But in 2006, a new President, who’s still our President, became President of the University of Chicago, his name is Bob Zimmer, Robert Zimmer , and he had been a faculty member at the University of Chicago since the ’70s. So he knew the University of Chicago’s traditions, and he himself is a pure mathematician, but he felt that the university was really missing out by not having engineering and applied science.

The way Bob described it to me when I first met him is that basic science is stimulated by engineering and applied science, and the University of Chicago had been missing out on that. The other factor, or one other factor, is that the University of Chicago manages Argonne National Laboratory for the Department of Energy, very much like the University of California manages the Lawrence Berkeley lab. And as we probably both know, the interactions between the campus and the lab at Berkeley are very strong. They hadn’t been so strong at the University of Chicago and Argonne, and we’ve put a lot of effort into changing that over the last decade.

Jed: Wow, that’s incredible. That gives me a better picture for what was going on. Just on that Argonne lab thing, was it partly because of the distance that you have to drive in order to get to Argonne National Laboratories, compared to just taking a shuttle bus up the hill to the...

Matthew: I’ve talked about that a lot. I think people say that. You know, Argonne is 20 miles away, but I went up the hill a lot when I was at Berkeley, and I’d walk from my office for five or 10 minutes, wait at the bus stop for five or 10 minutes, ride the bus for five or 10 minutes, and then walk from the bus stop up there to where I was going, so it would take 20 to 30 minutes to get from one place to another. I can be at Argonne in 30 minutes and there’s plenty of parking out there, so... So I think it was more attitude, Jed. More attitude and not seeing as clearly as people have at Berkeley the opportunity... Of course, the Berkeley lab historically grew out of the campus. It was Lawrence’s lab. So the history is different too, and that I think changed people’s attitudes.

Jed: Well, good, I’m glad you’re getting them together. I spent time at Wheaton University, and there was a little bit of collaboration between that really small school and Argonne National Lab, but it’s nice to know that the place that should have the most collaboration is finally getting a chance to do that. And I’m really excited that the University of Chicago has an engineering program now. I think it does add a lot to one of... You know, the top schools, certainly in the center of the country, it’s one of the top schools, so.

Matthew: And Chicago has supported this largely because it was the idea of the President in a phenomenal way. We have a brand-new building. I’ve hired about 35 new faculty members. We’ve made sure that many of them want to interact with Argonne. We now have 200 graduate students and an undergraduate program that has about 50 students a year in it, so it’s really gone from zero to 60 or something like that pretty quickly.

Jed: That’s great. So what’s next for you now that you’ve gotten it going and it’s pretty much the size that it needs to be, are you looking to yourself be a university president now that you’ve worked with Bob Zimmer and seen how important it is to have a good university president?

Matthew: If I was 10 years younger, the answer to that would be yes, but you know, I turned 70 last fall, and I’m really committed to this. I mean, the big news in the last year is that the Pritzker family gave a gift in 2019 of $100 million to the university to name our school. So we used to be called the Institute for Molecular Engineering. Now we’re the Pritzker School of Molecular Engineering. And because of that gift, the university has said we can double in size over the next decade, and they’re going to build another building for us, so there’s still a lot more to do here.

Jed: This is not the time to leave it yet. This is not the time to leave, no, I can see it, yeah.

Matthew: Yeah, exactly, exactly. This is going to be it for me...

Jed: Perfect. Wonderful.

Matthew: I don’t know how much longer, but there’s still at least a decade’s worth of work to do. I don’t know if I’m going to work till I’m 80, but I might.

[chuckle]

0:12:28.4The research

Jed: You look great, you really look great. And then has your research... You mentioned your research about nanoparticles that can get through the liver, go to places like your heart that are getting clogged up with plaque and help maybe get rid of the plaque.

Has that research been going along and when did it get started and where is it at right now?

Matthew: Well, this biomedical line that is a principal direction of ours really started back in Santa Barbara when we were working on some synthetic molecules that we call peptide amphiphiles, and the idea is to link a peptide, meaning a small piece of protein, with a lipid molecule, so that you could get the biological activity just of the peptide you want, not, not with the whole secondary and tertiary structure of a protein, but create a self-assembled nanoparticle by attaching a lipid tail to the peptide, so you get a lipid core with a peptide coat.

And interestingly, I got to know another... Well, a prominent molecular biologist, I guess you’d call him, Erkki Ruoslahti , I don’t know if that name means anything to you, but he’s the guy who discovered that RGD was the ligand that integrin molecules seek out. And we started a collaboration exactly on what I’m saying, using these peptide amphiphile nanoparticles to target atherosclerotic plaque.

And we showed that we could get these things to home to atherosclerotic plaque in mice. He’s gone on to do different things, and I’ve sort of moved this toward more therapeutic applications, what can you put in the cores of these nanoparticles that not only allow you to diagnose atherosclerotic plaque, but actually can carry some kind of therapeutic agent to them.

And without being totally mysterious, the kind of therapeutic agents that we’re bringing are anti-inflammatory compounds, because atherosclerosis is fundamentally a result of inflammation that caused... It’s either caused by lipid build-up in the endothelial lining or by disturbed blood flow and vortices, and so we’ve developed some interesting ways that actually are having some success, and I’ve said atherosclerosis, but there’s other conditions that it seems to work for too.

Jed: That’s so wonderful.

So do you think it could turn into a therapeutic that people with plaques in their heart and possible stroke, potential stroke victims might be able to use?

Matthew: Maybe. The problem with that exactly, and we’re still hopeful that it might, is... And this happens with any kind of drug or therapeutic is, who will you give it to and when and why, and atherosclerosis is such a slow-developing disease, it’s not clear, would you give it to every 50-year-old or something, or would you, just to check out what’s going on, or maybe those with a personal or a family history of some kind of heart disease. But this is where I’m very excited, exactly right now. We’ve discovered that these exact same particles that reduce the rate of growth of atherosclerotic plaques in mice work well for another much more immediate indication, which is something that happens in kidney dialysis.

When patients need kidney dialysis, an operation is done to speed up the blood flow and shorten the time that they have to be on the dialysis machine, called an arteriovenous fistula, an artery is connected to a vein. That is advantageous for reducing the dialysis time.

But this disturbs the blood flow, it creates vortices. And in 30% or more of the patients downstream of this fistula, the blood vessel starts to close off. It’s a different phenomenon from atherosclerosis, but it’s still caused by the inflammation of the disturbed blood flow. And we’ve found that our same nanoparticles can stop that so-called stenosis due to the arteriovenous fistula.

And the thing is that here you know exactly what patients need it, and this kind of problem develops in a month or two, not a decade or two, so it’s much more targeted. And then on the experimental side, we’ve done this work so far in mice, but the next thing we want to do is to use larger animals such as pigs. And from an experimental point of view, you can do four of these fistulas in one pig ’cause they have four limbs, and so you can get your data a lot quicker. So we’re kind of hoping to make some serious inroads and we’ve filed a patent for this, and I think that might be where this plays out most effectively.

So that’s another reason why I’m not looking for a university presidency. I’d really like to see this thing. One, I’ve been able, it’s been very satisfying to me to be able to continue to have an active research program while still having serious administrative responsibilities, so that’s a function of how I’ve decided to do the job and how the environment at Minnesota and Santa Barbara and Berkeley and Chicago has nurtured that as well.

0:18:54.7Sign off

Jed: Wow, that’s so great. I’m so glad to hear a little bit more about what you’ve been up to, it’s just been a wonderful pleasure to see you again. Thank you for spending some time on our show, we really appreciate it.

Matthew: Okay, thank you very much, Jed.