From Childhood Fascination to Life-Changing Research

In this episode of CU Anschutz 360, Angelo D’Alessandro, PhD, shares his fascination with blood science and how it led him into biochemistry, molecular genetics and metabolomics. A steadfast collaborator, D’Alessandro explains why multidisciplinary research is so important to science, especially in the area of personalized medicine. 

Transcript

Chris Casey:

Welcome to the CU Anschutz 360 podcast, where we highlight the research and innovation taking place at the CU Anschutz Medical Campus.  My name is Chris Casey, and I'm the Director of Digital Storytelling in the Office of Communications here at CU Anschutz. So, today we welcome Angelo D. Alessandro, who is a professor in the Department of Biochemistry and Molecular Genetics at the University of Colorado School of Medicine. He's the founder and director of the Metabolomics Core and the director of the Mass Spectrometry shared resource for the CU Cancer Center. He is a Boettcher Investigator and an affiliate investigator to the Vitalant Research Institute, the Linda Crnic Institute for Down Syndrome, and the Gates Institute for Regenerative Medicine. This October, Angelo will be inducted into the Association for the Advancement of Blood and Biotherapies Hall of Fame. Hi, Angelo, and thank you for joining us today.

Angelo D. Alessandro:

Thanks for having me.

Tom Flaig:

Welcome, Angelo. It's great to have you here. I'm very much looking forward to our talk today. My name is Tom Flaig. I'm the Vice Chancellor of Research here at Anschutz.

Chris Casey:

Angelo, I understand that you were quite an inquisitive child. You were born in Italy as, I believe, an only child, and you're one of those people who just clicked in at a very young age on what you wanted to do and that interest was around science, as I understand. And so, could you share that story and where your curious nature has come from?

Angelo D. Alessandro:

Well, I don't know where the curious nature came from, but I can tell you where it led me. Well, first of all, thanks so much for the correct pronunciation of my last name. That's unlikely.

Chris Casey:

Thank you.

Angelo D. Alessandro:

At a very young age I was really fascinated with a cartoon that was on TV. I think the translation for the product in the US is Once Upon a Time Life.

Chris Casey:

So, maybe comparable to our incredible journey film about the people miniaturized?

Angelo D. Alessandro:

Exactly with the difference there that, instead of little people going around the body, you had these little red blood cells that had, for all purposes, the shape of anthropomorphized little beings walking around the human body and one day visiting the brain, one day the heart, one day the liver, and exploring and explaining the process. And I was really excited about that. And there were cartoons, but it was a limited series. Probably, they didn't have much of a budget. And they also came with these little books that accompanied the little cartoons. And I remember I was four, something like that.

And I really wanted to read more. My mom was reading me these books, and one day she was so fed up with me asking to read more about these stories. She was like, "If you like it so much, just read it yourself." And I did. And it started like that. And, yeah, I soon knew I wanted to become a scientist. I have, as of this morning, written evidence from my parents. They sent me a photo of the diary. And, yeah, I started to write really early. I started to work really late. My mind was eager to know, but my feet were lazy. Yeah, and then, I ended up working exactly on red blood cells 20 years later.

Chris Casey:

And a little follow-up on your personal story. Well, you mentioned your parents finding a diary. So, you were a writer and a chronicler from a young age, and then you became a poet. You started writing poetry. How did you cultivate that interest? And how did that contribute into this application into the scientific field, which, I would imagine, is very much connecting the dots and advancing and adding to the body of knowledge. How did all of that flow into what you're doing now to your poetry interest?

Angelo D. Alessandro:

It started more as a game. Probably my mom, to keep me busy as a very inquisitive kid asking way too many questions, she started giving me words, random words, the most random ones and telling me to come up with a story. And I started writing up stories of all sorts. And then, at some point, some professor was like, "Oh, at a very young age you really like writing." And they started challenging me saying, "Oh, you think you can write poetry, but you really don't have any structure to your poetry." So, you need to study first if you claim that you can write pretty much without classic structure," iambic pentameter.

Then, in Italian, we have [foreign language]. Yeah, and they just gave me a chance to learn from the classics. We studied a lot of Latin and Greek in Italy starting from middle school and high school. And then, I grew fond of poetry, especially Italian, Middle Ages, Renaissance, all the way to UK, British poets of the 1600s, and French poets, and German poets, Romanticism, and learning my classic poetry, and then trying to work on it. And, yeah, I really love the structure of a sonnet. I wrote probably a few hundred sonnets. I was the youngest Italian sonnetist of the Academy of Sonnets in [inaudible] at age 16.

Tom Flaig:

If you think about scientists, two things that always come to mind are curiosity and the ability to communicate or write. And you've talked about both those things. Your curiosity from a young age of how things work and this ability to communicate at a young age. I think those are two really important attributes to scientists, people that are effective here. Let me shift just a little bit, Angelo, to talk about some of your recent work. You've been doing so many things and your publication record is truly amazing. One of your recent studies looked at the potential for this concept of lab on a chip or LOC technologies, and you've really focused on the assessment of our stored red blood cells, transfusional technologies, and so forth. Can you tell us a bit more about the study and maybe this technology underlies what you're looking at with that?

Angelo D. Alessandro:

Absolutely. This whole interest for blood storage started with Italian National Blood Center. As part of my PhD, I had a fellowship sponsored by Italian National Blood Center at the time. And it was around 2008, there was a paper that just came out in the England Journal of Medicine suggesting that blood stored longer than two weeks could be associated with increased morbidity and mortality in certain categories of recipients, like patients undergoing cardiovascular bypass requiring multiple unit transfusion. And they realized that the sicker the patient, unfortunately, the more likely they were to get multiple blood units and the more likely they were to get old blood. And there was a statistical issue there to make any sound conclusion, but that was sufficient to renew, in the field of transfusion medicine, the interest for the age of blood. How many days elapses since the time of donation are too long for the blood to be transfused without any complication in the recipients?

And we followed up on that work for many years, and we can have a whole two-hour conversation about that. But the long story short is that blood saves lives, and there's no doubt about that. And blood, like people, does not always age the same. And some donors, their blood actually stores really well. And, despite the fact that we only store blood for up to 42 days, some blood donated from some donors could actually be stored for longer. But blood from other donors still saves lives if you use it within a shorter narrow window, at least from [foreign language] standpoint. Coming from Italy, one aspect that was really striking to me is that you can go to a grocery store and get lost in the aisle where you have 50,000 different brands of cookies and beverages, not to mention any specific brand. But then, when you get transfused blood, you have just one product.

Right? And I feel like characterizing the product with different molecular approaches, among which anthropometrics, which is what we do on a daily basis in the lab, was a way to better understand how blood ages and how to maximize the quality of the product and how to extend the shelf life for some donor or shorten it for others. And in a personalized approach, tailor the product to the specific category or recipient. The need of a patient requiring transfusion could be a massive transfusion event for a patient who, unfortunately, just got a trauma with hemorrhagic shock, gunshot wound, or stabbing wound, or any other injury. A car accident, for example with a lot of bleeding.

Tom Flaig:

A major blood loss, right?

Angelo D. Alessandro:

Exactly. So, you have a massive transfusion protocol with a lot of blood being transfused in a short amount of time. And the need there is to restore as much of the blood volume that was lost in the shortest amount of time to both restore the blood and also the capacity to carry oxygen. But then, you also have some other categories of transfusion recipients that get blood regularly. For example, sickle cell patients, cancer patients that undergo chemotherapy/radiotherapy, and they become anemic over time and then they require blood as a support therapy. And in that case, their need is not the same as patient requiring massive transfusion.

So, understanding how blood ages, the donor characteristics, and to the extent these impact the qualities of their blood, and then the molecular characteristics of the recipients requiring transfusion, then you can match the donor, the product, the processing strategies, and the recipient in this personalized approach. And then, you can use, ideally, this Lab on a Chip approach to test the unit at the time of donation and now say, "This unit is better stored for 50 days, 60 days. But these other units are better transfused in 20 days to a patient that is more likely to bleed a lot," for example.

Tom Flaig:

So, tell us, this is fascinating. And it's really going from this one size fits all to say this donor's blood's going to have a lot more shelf life, so to speak, than this other. And so, this should be used earlier. Tell us more about how this actual Lab on a Chip works. What does it look like? How do you use it? How does it read out?

Angelo D. Alessandro:

Well, right now, it's not in the field, right? It's not implemented. We are working on this a lot with our colleagues. [inaudible] at Harvard University was a corresponding author of this article in PNS a few weeks ago, and it does look a lot like one of those COVID tests or pregnancy tests, but the approaches may be antibody based or just chemistry antibiotic reaction based. And all you'll have is positive or negative with a given range through a chronometric assay, for example. That can tell you, for example, how this unit fares with respect to specific markers that tell you how high the quality of the blood is. You can actually have those cheap and it has been patented, but there's still a long way to come to actually have the chips implemented on the bags so that you can do a real time monitoring of the quality of the unit.

If there is a failure on the freezers or something that goes wrong during the shipping, we are very lucky here in Colorado that we have one of the best blood donor communities around the United States, but there are other states that, be it for sparse population density, I'm thinking for example of Alaska, or poor donor base with respect to the demand for blood transfusion, they need to acquire units from other states. We are sending, for example, every month, as far as I know, units from Colorado to California or Alaska to help them meet their demand.

Tom Flaig:

So, it's really, I think, helpful to understand that technology and how it could be potentially applied in different settings. And I almost think of the lab going out into the field, right? You're able to move from in the laboratory, things are very controlled, you've got all this great environment. And this is being able to do the test real time, applying it either in this blood banking situation, or I guess you could apply it to other situations, as well, in the field.

Angelo D. Alessandro:

And that's part of the very interesting ramification of what we're doing. We generated this resource that allows us, from a blood drop, to see tens of thousands of things. Small molecule metabolite for example. Not much unlike what you do when you get your blood work done. If the doctor suspects that you can develop diabetes, you get your glycemia, your glucose level, tested. Glucose is no other than a small molecule metabolite, and we can measure that and, along with that, several thousands of these small molecule metabolites. But what you do when you find them, and ideally, you miniaturize all of this into a portable device that you can take with you in the field. So, we're now exploring different possibilities, one with the trauma research center, I'm lucky to be one of the MPIs along with Drs. Cohen, Moore, Solomon, and Hanson here at CU Anschutz.

In surgery, we identified some markers that predict whether a trauma patient, think people who require a transfusion, trauma patients who present, well, the ambulance gets to the field, the theater where a car accident, for example, has happened. And even before getting to the hospital, we should be able by looking at these small molecule metabolites with this Lab on a Chip device, be able to predict whether the patient is going to start bleeding uncontrollably in three hours from the injury, whether five days down the road, even if you save their lives within the first 24 hours if they stabilize, whether they're going to develop acute respiratory distress syndrome, not unlike to what happens, for example, a COVID patient whose lungs fail.

We found that there are very similar mechanisms that develop there, and we could predict whether these acute lung injury phenotypes, whether this lung filler could ensue days later. And that's one application. Other applications, for example, not to think only of negative things, pertain, for example, to the field of sports. We've been lucky in collaboration with Dr. Inigo San Millan to be working in close contact with elite professional athletes and monitor their performances in competition, which is something I never heard of until a few years ago.

Tom Flaig:

Pretty dynamic changes are going on, I bet, with those elite athletes as they're exercising.

Angelo D. Alessandro:

Exactly. And depending on the exercise and the kind of regimen of exercise, the intensity of exercise, and the duration, thinking for example of marathoners and ultra marathoners, Dr. Phil Khan in France, we've been working on the Ultra Trail du Mont Blanc, the longest and hardest marathon in the world. You need to qualify with ultra marathon to get to that one, to even be able to be allowed to run that. And people died running this marathon. It's intense. And I think it's happening this week, I think, August 24th through the 27th, or something along those lines, this year’s edition. And if you look their blood at the end of the 170 some kilometers, or over 100 miles, worth of run, not only long distance but also up and down the Alps in Switzerland and France, their blood looks a lot like somebody who has just been hit by a car, thinking of similarities.

Tom Flaig:

So, by the ability to go into the field, in this case, so these elite athletes running a hundred-mile race or something, you can understand how the body responds in a very dynamic way, and compare that to a blood-loss catastrophe or something along those lines and look for similarities, it sounds like.

Angelo D. Alessandro:

Yeah, both similarities and differences. What is really fascinating is that, for example, exercise, especially regular exercise, is really helping us improve our responses to stress, right? Be it, for example, oxygen stress by drugs or even accidents. Anecdotally, some of our best surgeons here in Colorado are some of the best in the world. For example, I'm thinking of Dr. Jim Moore here. He recalls an episode of somebody, a professional athlete, who got involved in a car accident and both legs got amputated and he lost a lot of blood. And despite that, he managed to make it through, despite the long time. And they think that, even this resiliency that you develop, by developing this resistance mechanism to stress, prolonged stress, induced by exercise, it gives you some endogenous defense to combat stress when you meet it in a pathological form.

Either disease, cancers, there is a program here on campus, Be Well, that is trying to use exercise to boost metabolism in a way to make your body help fight cancer along with chemotherapy and radiotherapy. Mentioning Dr. Cabos and Dr. Lanko here that are working on these research areas, and it's fascinating to think how some of this mechanism that you're learning from elite athletes can actually be translated into improving the care of cancer patients versus trauma patients.

Tom Flaig:

It's great to think through this line of reasoning. I'd say, as an oncologist, somebody that treats cancer patients, the idea that the patients who have control over some of this by their physiologic health and by the exercise they're doing, I think is a really positive thing, right? The idea that patients have that in their control to fight this disease, it's really great.

Chris Casey:

Absolutely.

Angelo D. Alessandro:

If I can add to that, blood donors are extremely generous. And going back to the blood donors as a population that has been historically leveraged to define health, right? And that piggybacks a good segue, from what Dr. Flaig was saying, is that it is interesting to understand the underlying physiology. And the blood donor population provides a window on the span of physiology, all the declinations of physiology, as it is defined by genetic and non-genetic factors. The genetic cards that you've been dealt at birth versus how much you exercise versus your exposures. Whether you drink coffee or whether you smoke cigarettes is going to make a difference in how your blood stores. So, now we've been involved in this study. It's called the Recipient Epidemiology and Donor Evaluation Study by Dr. Mike Bush of Vitalant involving over four different blood centers in United States and rather 10 research groups across the country, where over 14,000 blood donors were enrolled genotypes.

So, we have over 870,000 polymorphism in a full-blown personalized medicine approach, right? And then, we looked at the quality of their blood under this molecular magnifying lens, this mass spectrometry based approach that we use for metabolomics. And then, we find that donor sex, sex hormones, donor age, all factors that contribute to this durability of blood and how this blood performs upon transfusion in transfusion recipients. Now, this is relevant because, by studying this population, we can find genetic polymorphisms, but also non-genetic factors that contribute to how the body responds, from a metabolic standpoint, to stress, using blood storage as an example of real world medical intervention, iatrogenic intervention, right?

 That could be relevant. But also that same sets of genes or polymorphisms can inform how a cancer patient could respond to chemotherapy or specific additional mutation that they acquired during the last one. And whether you have specific polymorphism that boosts your capacity to promote a path that is called glycolysis, which is upregulated in most cancers, right? It depends on polymorphisms related to glycolysis, but then you acquire mutations that push glycolysis and whether those mutations are going to be little, or whether going to progress you to a more severe disease in a short amount of time, will depend on the genes that were regulating glycolysis in the first place. So, we cannot cross-pollinate this field learning from blood donors and moving on to cancer patients and back.

Tom Flaig:

Yeah, cross-pollination.

Chris Casey:

Yeah. Just to springboard off that topic, Angelo. In my introduction of what you've been doing, there's mention of Vitalant Research Institute, the Linda Crnic Institute for Down syndrome, the Gates Institute. Crnic and Gates being both here on the Anschutz campus. So, you are cross-pollinating and working with many other collaborators. I hear, and this is common knowledge to a lot of us when you look at medicine and science, often you are dealing with very brilliant people, but often many of them are working in isolation in their own silos. And you hear, to really advance the science, these people need to talk to each other, they need to collaborate, share what they're learning so that things can build and grow. And you seem to be a real silo buster. Can you just talk about why you see multidisciplinary collaboration so essential? And how you've gone about cultivating that here on the Anschutz's campus?

Angelo D. Alessandro:

Well, this campus has been an extremely collaborative environment for our lab. I like to think that I, well, first and foremost, I'm honored I get a chance to learn from a lot of smarter colleagues that work in their respective fields and learn something from one field that could be useful for another field, right? My lab started as a technology lab developing opportunities to see a lot of things in the shortest amount of time, high throughput omics. And I'm a biochemist by training, and, in biochemistry, there is a concept of catalyst, like an enzymatic reaction that is facilitated by a protein with enzymatic function. So, something that could happen anyway, but it would take millions of years to happen, it is facilitated by a small little niche [inaudible] that takes one piece, one ingredient, and takes it in proximity to the other one and facilitates that reactions and makes it occur.

I like to think that our lab has been a technology catalyst in that respect, providing the expertise and the instrumentation and the methods necessary to observe a lot of things in a lot of areas. And I am still a firm believer that, while science doesn't end with observation, it for sure starts with it. So, you need to observe to formulate specific hypotheses. There has been a stigma omics technologists for several years saying, "These are fishing expeditions. You're going out there, you don't know what you're looking for." In reality, we always come back with a lot of fishes. But that, also, is all true that once you make an observation and you formulate a specific hypothesis with a given field, thinking, for example, going back to trauma and hemorrhagic shock. A bleeding patient is an extreme case scenario of pathological hypoxia, right?

All of a sudden you lose a lot of blood and you don't have enough oxygen circulating in your blood and substrates, and that's the reason why we transfuse, to restore the tissue oxygenation capacity. And the lack of oxygen deprives your energy factory in the cell, mitochondria, from the main substrate required to make energy. So, mitochondria develop oxygen, and they generate these small molecules that is called, for example, succinate. Well, it just so happened that the same succinate activates coagulation complication and inflammatory complication. Now, that succinate will accumulate in response to, not necessarily pathological hypoxia, when you go for an intense run, like an ultra marathon.

That's one of the top marker that predicts how fast you accumulates succinate, even more than lactate, which was historically referred to as a marker of performance, predicts whether you're going to be running faster for longer, right? And that is true, for example, in animal models and in humans. But the same succinate, for example, if you're a patient with sickle cell disease or a patient developing pulmonary hypertension, can result in pulmonary fibrosis and complication in the lungs and kidneys. So, we see these connections on a daily basis because, again, we get to work with a lot of smart people in a lot of interesting fields, and then we tell each other, "Listen, this is something that you should be looking for."

Chris Casey:

Interesting. And so, personalized medicine, and you've touched on this quite a bit already, but I'm just curious, and this is a very open-ended question, but can you pinpoint or can you express where you think personalized medicine is going in just a macro sense? And what some of the key opportunities are within that?

Angelo D. Alessandro:

I'm beyond biased there. So, admitting the bias, first and foremost, I would like to say that the last 10 years, the innovation in, especially 15 years maybe, in genomics technologies democratize, they made available for everybody and affordable cost DNA oriented approaches. Thinking of commercial vendors that can tell you whether your grandfather was born in Finland. So, of last week, 99% Sardinian, according to 23 and Me, right? And that's great. But your genes are those at birth and, with some caveats, they remain pretty much the same through your lifespan. You can have twins who can one, develop obesity, one develop conditions that the other twin doesn't. And one reason for such phenomenon is because one, for example, goes for a run on a daily basis and the other doesn't. One likes to eat a lot of sweet food and sugar rich 45 beverages.

And so, that exposure you don't capture when you measure the genome, but you capture when you measure the metabolome, are there to be measured. Now, we have this technology that in an ultra [inaudible] fashion, we could theoretically run each and every sample from each and every Coloradan every year. We have the now output [inaudible] to measure millions of samples per year. Ideally, you would be able to longitudinally assess how, with the invariable genome match to the DNA component, how your small molecule signature in blood changes because of diet, exercise, because of pharmaceutical therapy, because simply of aging. And I think that that's the future of personalized medicine, and I think that, to some extent, that future is already here.

Tom Flaig:

How much of this development of personalized medicine do you think be driven by technologies, whether it's Lab on a Chip or something else that's coming along?

Angelo D. Alessandro:

Well, the arrays, gene arrays, for example, the one I explained before for the rats receiving immunology in the donor evaluation study, that had an array, precision transfusion medicine array, with 870,000 polymorphisms, right? Oh, okay.

Tom Flaig:

Oh, sorry.

Chris Casey:

That was, it was over here maybe? You may have to start that one over again.

Tom Flaig:

I have no idea what that was.

Chris Casey:

It sounded like a ringing.

Tom Flaig:

[inaudible]. It's not my phone.

Chris Casey:

That'll give us a nice audio take clip. We always like to have something clippable. So, that's our editable moment.

Tom Flaig:

So, I was just talking about the future of personalized medicine and how much this can be driven by technology.

Angelo D. Alessandro:

Definitely technology is a catalyst, to go back to one of the terms used before, to push forward this field. And technology in the space of a small molecule, metabolomics, has been limited in terms of throughputness, like how many samples can run in a given amount of time at an affordable cost. Now that those batters are falling faster than ever before, I think we are ready for the next stage, I think, of personalized medicine, which is nothing else but click up biochemistry on steroids, right? It's like, again, going back, instead of just measuring glucose and creatinine as a marker of kidney dysfunction, as we do these days in the clinics, we can measure all of this from a blood drop in 30 seconds, and do that for millions of samples, theoretically all the samples from any of the hospitals on campus.

And that could generate a treasure trove of information for, of course, research purposes, but also generational intellectual properties, novel companies, and then theoretically scale it down onto Lab on a Chip and have home testing devices. What you already have for a home device is the opportunity to collect samples without even a phlebotomist available at home. There are these devices you just put on your arm, push a button, and collect either a dry blood spot or liquid blood.

Tom Flaig:

So, a phlebotomist would be that traditional IV in your vein, and this would be something a patient could do themselves.

Angelo D. Alessandro:

Exactly. At home, completely painless, and you just push the button. Within 30 seconds to a minute, you have this little punch card, little piece of cardboard, that has these circles, and they get filled with a blood drop or two. You put that in the mail and mail it to us, and we can tell you 10,000 more molecules are in your blood the same way we did for professional athletes. And, again, disclosure here, but it's IP that we filed with the university, and in part we are developing now companies. We now have four different, three companies, and hopefully soon to open another one in this space.

Tom Flaig:

IP is your intellectual property you've developed around this idea. Wow.

Angelo D. Alessandro:

Correct.

Chris Casey:

Well, the metabolomics, we could talk about this all day. Actually, we could talk about a lot of these-

Tom Flaig:

And tomorrow.

Chris Casey:

... and tomorrow, and most of these subjects we could go on into the wee hours about. Just starting to move toward wrapping up our conversation here today, Angelo. This October, you'll be inducted into The Association for the Advancement of Blood and Biotherapies Hall of Fame. I always associate hall of fames for folks who are longer in the tooth in their careers. And here you are, not even 40, I believe,

Angelo D. Alessandro:

Yeah, correct.

Chris Casey:

... and you're going to be receiving this honor. I'm curious, how did this feat occur?

Angelo D. Alessandro:

You said it before, the way we look at science is it's a team effort, and there are social science and social media. We like to embrace science as a social discipline. And so, I've been lucky to have a lot of great mentors and great collaborators, and probably just lucky that pieces fell into place. I wasn't expecting that either, but I'm most grateful to ABB for the honor, and to be inducted in that company is an extreme honor.

Tom Flaig:

I mean, based on our conversation today, I'm certainly not surprised. And I can see why you were honored in this way. That's quite an accomplishment.

Chris Casey:

Yeah, congratulations on that. And, as Tom mentioned, you have an incredible record of publication and are always onto the next thing and expanding your field of collaborators. I'm still, as somebody who's spent a good period of my life in the wordsmith realm, I'm fascinated by this poetry bent that you have. So, I'm just wondering if you, as a scientist, is there poetry to be found in the lab?

Angelo D. Alessandro:

Well, yeah, this becomes a philosophical question in that area. I like to think of science as an attempt to get as close as possible to the truth. And I think I mentioned it before, but one of my favorite poetry periods is Romanticism. And thinking of Keats Ode on a Greek Urn, truth is beauty and beauty is truth. And I like to think of science as, again, one of those beautiful attempts, serendipitous attempts, to seeking truth.,Right?

Chris Casey:

That's a great way to put it.

Tom Flaig:

He answered you his poetry, Chris.

Chris Casey:

He did, and I fully expected it.

Tom Flaig:

He's a pro. That's a great quote.

Chris Casey:

That is a great quote. Well, it's, in some ways, and we could go into your personal story more Angelo, and it reads like a quintessential American dream type story, I'm sure. And that would be fascinating to perhaps take up on another podcast down the road or something because it feels like there's much to explore with your career and all the things you're studying. But thank you for all the work you're doing here at CU Anschutz, and thank you for giving us a window into all the fascinating research you're doing today.

Tom Flaig:

I just add it's a great conversation. Your model of collaboration, I think, is wonderful and really underlies a lot of your great success. The collaboration that you have on campus, off campus, it's really great. I really enjoyed our conversation.

Angelo D. Alessandro:

Likewise, thanks so much for the opportunity.

Chris Casey:

Thank you.