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[EPISODE 24] Dr. David Berkowitz Talks Enzymes, Radiation, And The Lincoln Marathon

On this episode of Molecular Moments, Chad Briscoe speaks with Dr. David Berkowitz, Director of the Division of Chemistry at the National Science Foundation (NSF) and a Willa Cather Professor of Chemistry at the University of Nebraska-Lincoln, and co-lead of the Nebraska Drug Discovery & Development Pipeline. David shares how he got his early beginnings in science as an undergrad studying endocrinology at the University of Chicago, going to Switzerland with his Ph.D. advisor to work at a chemistry biology interface, and later attending Yale to understand how to make molecules better.

Chad and David also discuss the National Strategic Institute in Nebraska and David’s involvement with the program to research medical countermeasures for Acute Radiation Syndrome (ARS), the difficulty of testing drugs for prophylaxis treatments, and the importance of getting the most out of the NSF. They reminisce about when David was supportive of Chad’s pursuit of his Ph.D. at the University of Nebraska. David talks about some exciting work he’s doing with enzymes that came about as a result of talking to someone while waiting for a slow elevator, how higher learning has changed over the years, and running the Lincoln Marathon.

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Molecular Moments - David Berkowitz v1.mp3: Audio automatically transcribed by Sonix

Molecular Moments - David Berkowitz v1.mp3: this mp3 audio file was automatically transcribed by Sonix with the best speech-to-text algorithms. This transcript may contain errors.

Narrator:
Welcome to the Molecular Moments podcast.

Chad:
In today's episode, we sit down with our guest, Professor David Berkowitz. Dr. Berkowitz is currently the Willa Cather Professor of chemistry at the University of Nebraska. He's division director for the Chemistry Division of the National Science Foundation and a fellow of the National Strategic Research Institute at the University of Nebraska, where he's driving forward an exciting drug development program we are soon to learn more about. For normal people, these may be full time roles, but for Dr. Berkowitz, who has an academic pedigree, including the University of Chicago, Harvard, Yale, the Swiss ETH and the Max Planck Institute, this is all just another day. I'm certainly looking forward to hearing more about what all of this means is I hope you are. Also, we're going to talk science, as scientists do. So without further ado, here is another episode of Molecular Moments. Welcome to the podcast. Dr. Berkowitz I've known you for nearly 25 years now as professor friend and more recently, an industry collaborator. We have so much to explore today, and I'm delighted that you gave me your time. First of all, do you mind if I call you Dave today?

Dave:
Please do. We have known each other for a while and it's been a real pleasure.

Chad:
So what I'd like to do is start with us walking through the highlights of your career progression. And I'd love if you started at the beginning and we heard what motivated you to become a scientist.

Dave:
Yeah, I go back to really my undergraduate years that you mentioned, the University of Chicago, and I was taking a fair amount of science because I think you know that I kind of grew up around it and the world seemed like it. It needed science that somehow science drove progress in in humankind, really. But I didn't know where I wanted to plug in. And I think I go back to Bruce Ganim, who was a visiting lecturer at Nebraska from Cornell, who was my first organic chemistry teacher, and John Law, who was an organic chemist, sort of in disguise, teaching biochemistry at Chicago. And I had those courses back to back. And I realized that a organic chemistry wasn't memorization. It actually made sense. It was like playing chess. Once you knew how the pieces moved, you could kind of draw things out. You could strategize and you could invent new routes, new chemistry. And then when I got to biochemistry, I realized, wait a second, all delays. This is just organic chemistry, if I can understand it. Well, wow, there's an organic chemical logic to biology. So that really it was those two teachers who turned me on big time.

Chad:
Fantastic. We'll come back to the highlights of some of the areas that I talked about and what you're doing, but just kind of give me a walk through from maybe from getting into to graduate school at Harvard through where you're at now. Just the, you know, the three, five minute sort of path.

Dave:
Okay, Well, I'll start. Go back to undergraduate. And I took a course in, believe it or not, endocrinology as an elective, as an undergrad, which is crazy to think that that would be even offered. But it was there and it was like endocrine molecular. It was like molecular endocrinology. And it was taught by Joe Jarrett back at the med school because Chicago, he was crazy. He had gotten an MD and then he went back and got a PhD, which is in the old fashioned way. He got both degrees and he's teaching in the college as well as running rounds in the med school. And he had a lab in the basement of Billings Hospital. So as an undergrad I knocked on his door and I said, Could I work with you? I really love the subject of this class. And he said, Well, I guess so. He opened up a spot in his lab. He wasn't looking for undergrads, and I started working on enzymes as an undergrad. And then when I fast forward, I end up at Harvard. My advisor Steve Benner, moves to the in Switzerland. I'm in the library in Switzerland one day and I realized two paper papers were published in the journal Prostaglandins based on my undergrad research. Oh, wow. He was very kind. Joe Aerobic and got me in the lab as an undergrad and then kind of Steve Benner was a huge motivation as my PhD advisor and ended up taking me to Europe and we worked at this chemistry biology interface. I liked synthetic chemistry so much. I went to Yale to work with Sam Dana to understand how to make molecules better because that was really a passion that had not been satisfied in my PhD. And then and then when I came to Nebraska, I tried to set up shop right at that interface because of these influences that go back to undergrad, but sort of were pursued that way.

Chad:
So there's a few big things I wanted to touch on, but I'm really anxious to talk about what's going on right now with the National Strategic Research Institute at the University of Nebraska, and your involvement in that. So can you tell that story for us a bit?

Dave:
Yeah, sure. It's kind of a. Two things that are coinciding here. One is the University of Nebraska has four campuses and Lincoln, Omaha, and then the medical center also in Omaha and Kearney. There's a system and the system and the NYU Foundation had a competition for what they call big ideas. And Ken Bales and I can Bales, who's now the vice chancellor for research at UND emcee, sort of entered this contest, if you will, with a big idea that has come to fruition, which is the ND $0.03, which is the Nebraska drug discovery and development pipeline. So three D's in their drug discovery development and that has aligned with, as you mentioned, the NCAI, the National Strategic Research Institute, which is one of about just over a dozen university affiliated research centers, or you are around the country. These are DOD affiliated universities and it's a privilege of us at Nebraska, at the University of Nebraska, through Strategic command, to have a special relationship with the military. And you and I have rekindled our relationship through the possibility of working on a DOD funded project through NCAI in the general space of trying to come up with medical countermeasures for acute radiation syndrome. And we together, I think, had the idea that industry consultants, people who really understand what it takes to develop drugs, would be incredible resources to us in academia to try and bring in industrial chemists and academic chemists together around the planning table, around the research initiation table. And it's been now a few years and it's been it's been really exciting.

Chad:
Yeah. So can you talk to me a little bit about why are we moving forward with the acute radiation syndrome treatment and how is what we're doing different from what's been done in the past.

Dave:
So you think about radiation, you think, well, radiation, the whole population is going to think that this is going to be a potential hazard. And we think about certainly warfare. It's in the news every day now that there there might be a risk of either the tactical use of a nuclear weapon or as you hear about in Zap Korea, you see a nuclear energy facility that's in the midst of a battlefield. Or you think about natural disasters, as we saw in Japan. So and then there's just a lot of ways in which we might come into contact with radiation. Were we a civilian or were we perhaps even more so, part of the armed forces. So you see the danger. But then what about the thinking about this on a molecular level? Well, you and I have both learned a lot about something called acute radiation syndrome, which is a systemic malady that isn't so well understood. And the military clearly has an interest in the area. But so do you know, health and human services elements for the civilian population. So the problem working on is sponsored by DOD, but the implications are much broader. And the science here, because the systemic is really broad. So then you have to think about, hmm, is there a way we could protect or treat ours? And there's not a lot out there, particularly for preventing. So this is where this space is is not as well explored as you might think.

Chad:
And can you talk about this difference between protecting and treating and why the different motivation between, say, the military and health and Human services?

Dave:
Right, exactly. So if we are responsible for standing up a standing fighting force and we need to send that force to support the cause of freedom and national interest and international interests, and we may put them in harm's way, we have an obligation to all of those who choose to serve, to put them in the best position, both to be successful and to be safe as to protect them. But that's a different question scientifically. Then, once you suffer some of the consequences of radiation exposure, how might we best treat some of the the symptoms, if you will, or some of the mechanisms that come into play that are quite harmful, say, to your nucleic acids, to your DNA, oxidative damage and things like that, We're looking for something that prevents the damage in the first place. And these are scientifically two different questions and they're not necessarily the same agent. And those experiments on what we sometimes call prophylaxis are more limited than the ones in the literature on mitigating against radiation damage. And so that's why our scientific space is perhaps more challenging and more open.

Chad:
And how many drugs are on the market currently for the prophylactic treatment? Versus the post-exposure treatment.

Dave:
There are several that are for post exposure, but for prophylaxis, this is still there's still a need for an FDA approved drug in this space. And as you well know, this is a tricky space for drug development because we're under what's called the animal rule. We're obviously not going to run these kinds of experiments on humans. We need to find good animal models that are predictive. This is a this is a huge challenge for the ND $0.03 and for the NSR team.

Chad:
Right. And in fact, I just I just saw something in my in my day job about the animal rule where someone was was asking when when would you not do phase three studies on humans? And I think the other common example is, is when you're testing for something like anthrax or Ebola or something like that. Right. We're not well, maybe Ebola. You could if there was an outbreak, you could certainly test a drug. But but that's where the acute radiation syndrome comes in, right? We don't want to do phase three studies on humans because the phase three studies are all about patients who would get exposure. So instead we follow the we follow the animals and hopefully the biomarkers of the of the effect in that process. So what I think is really interesting about what's being done at Nebraska is the way that you and Ken Bales have assembled a team to investigate and utilize the researchers at the University of Nebraska to create somewhat of a pharma company in a in a university. I think that's a pretty unique model, and I'd love for you to tell us more about that.

Dave:
Yeah, right. So Ken and I like to call it a virtual pharmaceutical company. Of course we that's an overstatement. We know we're not a pharmaceutical company. We know it costs well over $1,000,000,000 to bring a drug to market. That's not what we're going to do. But we it's the spirit that's the spirit of what we're doing. The flagship campus of the University of Nebraska is in Lincoln, where you find a long standing program in chemistry that you know well, because it's your alma mater as well. Very proud to call you an alum. And many of our alums have gone on to the drug development space like you, and they range from synthetic chemists closer to my lab or medicinal chemists who are making small molecules, peptides, compounds that might be bioactive to analytical chemists like yourself who are thinking about how do we really make the proper measurements that are needed and get the key time points and as you said, quantitate biomarkers so we know how the drug is metabolized and how well it's how effective it is. So on the team we have in the chemistry department, we have synthetic chemists like Pat du Salt and we have analytical chemists who are in the omics space like Bob Powers. And omics is a powerful tool, both at UNL, the flagship campus and the medical center, you and M.S., where we have Bob Aguda and we also have Tom Hellicar from the biochemistry department at UNL, and the three of them constitute this omics core that takes everything from proteomics to metabolomics to rrna omics to get data points, key data points that give a complex pattern that's associated with a healthy cell versus a disease cell versus a healthy cell.

Dave:
We're trying to protect, say, from radiation and these molecular fingerprints that we get by using tools of mass spectrometry and AMR and systems. Biology and computational modeling are really the state of the art. And that that team has has changed the the nature of our science. And we have we have we are lucky to have those people on our team at UNM. See, then we have animal model people and we have in vitro model people, stem cell model people like Becky Deegan. And that is critical, as we discussed earlier, for a project like this, because there are different tissues in which, for example, you really notice the iris initially and you want to model those, be that bone marrow, for example. Then can you develop an in vitro model which is predictive? That's still an open question because this is a systemic problem. But having those biologists to work with the synthetic chemist, the analytical chemists and then having pharmacokinetics and pharmacodynamics people from you and MSI has really given us the multidisciplinary team. We need to be a mini pharma esque academic group. But having a group of eight of you who are our expert consultants who come a number from pharma or, you know, the drug development space in the private sector to people who have government experience at drug approval, to people from the military, that has been very special because we get a perspective academics don't normally get.

Chad:
I agree. And sometimes I like to think that we're trying to work smarter, we're working hard and they're working hard and smart at pharma. But sometimes I like to think of it again as as we're working smarter versus harder, or maybe we're working smarter because we don't have as many resources, but we have different resources that we're that we're working with, right? I mean, that's.

Dave:
Absolutely, you know, and we have a great c0r2. We get advice very well from our DOD lead. And I think you're right. The resources we're throwing at this are much smaller than you would typically find in pharma. You've got to start somewhere. And if we can seed a good compound or two and we know that combination therapy may be the ultimate solution here, we're probably going to need to partner with someone bigger to really develop something depends, right. What that winning compound or two or or even biologic might be.

Chad:
So someone listening to this podcast so far might be sending themselves, well, a drug takes 12 to 15 years to get on the market and and $1,000,000,000 and these guys at a university or nuts and there's an immediate need for for for these treatments or these prophylactic acute radiation syndrome drugs how are we going to do it? How can we do it faster than than 12 to 15 years and for less than $1,000,000,000?

Dave:
Exactly. Yeah. So, of course, we think about that and you know this well. So the group has surveyed the fields and the literature and interviewed members of drug development teams at small and large companies and really honed in on compounds that may already have had quite a bit of human exposure that have possibility. And of course, that would be a potential faster track to success here, where compounds that are relatively simple and that we can get at synthetically quickly and perhaps move up the development stage more quickly because they present less of a process chemistry challenge. We'll see where that goes. But as you know, we're pursuing kind of both avenues here.

Chad:
Yeah, it's exciting to see how we're looking at some of the drugs that are already approved for other treatments. Applying these omics and computational approaches and all know we're throwing a pretty heavy stick at it to understand how these things work, to see if they can work for acute radiation syndrome as well, either prophylactically or or for treatment. So that's that's really exciting and can't wait to see where that keeps going. I want to talk about your work at the NSF, your chemistry division director. This is a big deal. It really is. It's exciting. It's exciting to know somebody in this kind of a role. The Nzdf is something I think almost everyone is probably heard of, and unfortunately, it's probably not something nearly enough. People really know what it does, even though it touches us all. And I'm in that camp as well. So tell us about the Nzdf and why it's so important to our lives.

Dave:
And absolutely happy to do it. Yeah, I'm very privileged to be the chemistry division director here in Alexandria, Virginia, at the National Science Foundation. We are the voice of science, fundamental science for the United States. Our mission is sometimes called health, stealth and wealth. If you go down to the lobby of the building here, you'll see a much more eloquent expression of that. But that is in 1950, we we're created by an act of Congress to look out for the scientific mission, the scientific interests of the United States, and keep us competitive as a nation. Vannevar Bush had the vision for the National Science Foundation. We're not mission driven other than what I just said, but really, we're in Virginia. We're in the greater metro Washington metro area. It's called the DMV over here, D.C., Maryland, Virginia. The NIH is in Maryland. Right. And they're in Bethesda. And they have the health mission. We have the fundamental science mission. We're at about $10 Billion agency just under. And we cover all science under one roof. Here we are organized into directorates. One is bio, one is geo, one is engineering. Chemistry is in mathematics and physical science. One is computer science, one is education, one is social, behavioral and economic sciences. Each floor of the building is is a directorate like that. So we're a $260 dollar operation in chemistry. I oversee 40 plus people and nine core programs and a centers program and instrumentation to mete out funding to keep us competitive across the country. Anyone can apply who's at a university, and we have a huge number of universities who get their basic funding through us. It's really exciting, actually.

Chad:
Yeah. Yeah, without a doubt. Without a doubt. So let me ask a really basic question. How did you get that gig? How did you land in that in that role as a professor in Nebraska?

Dave:
Right. So here's the other nice thing about NSSF. You too can work at NSSF. I might say to everyone out there, well, we're different from other funding agencies in that about half of our people maybe just under rotate in and out from universities around the country and to the rotator program. It doesn't really exist at NIH or DOE or EPA, but it certainly it's alive and well here. The head of the entire agency is appointed by the president and approved by the Senate. His name is Ponch Sethuraman. Ponch Jonathan. He was appointed by President Trump and he served. Under President Biden. That's very common. We're apolitical here. That turns about six years. Division directors are often like I am rotators from universities. Heads of directorates are also often rotating in and out, and program directors who run the individual programs do that. I started out as a program director in 2010. I was funded by NSF. My program director called me up. You said, Hey, have you ever thought of being a rotator? And I said, What's that? And then why would I want to do that? Yeah. He said, Oh, well, you keep your research going on the side. We fly you back to Nebraska, you go back and forth and back and forth. Really, I don't have to become a bureaucrat. You mean I can keep my research going? And he said, Yeah. And I said, Wow, this sounds kind of interesting. So it's actually a wonderful opportunity and it keeps fresh ideas coming in and out of the foundation that we have people rotating in and out like that.

Chad:
That's cool. So one of the things I realized when I was doing some background research for the for this podcast is that the NSF supports the research experience for undergraduates. Right? And so again, on that theme that we don't realize sometimes how the NSF touches us. So I did an REU semester at Pacific Northwest Lab back in 1993, and that was my first real work with mass spectrometry. And since since then, mass spectrometry became a core of everything I've done scientifically. And if I think everyone, when they ask you sort of what you are at your core as a scientist, I'm a mass spectrometer. So. So the NSF in that way really, really touched my life. And was the trigger and the thread running through everything I've done in my career for almost 30 years now, I guess going on 30 years. So so that's, that's cool. So I'm excited to see that. And it was before your involvement with NSF, but thank you.

Dave:
I did not know that before. Chad That's really cool to hear and panel is an amazing place. So that's that was very special to you. You had.

Chad:
Yeah, it was. I was very fortunate, without a doubt. And I didn't know it till I got there. And I know it more and more as I as I age and get further in my career. So. So as you mentioned, taxes pay for for the nzdf. And when I think about our taxes paying for something, I think, wow, we should we should know what we're getting. But we should also take advantage, right? It's like if you have a library down the street, you never go there. You're paying for it. You ought to go take advantage of that library. So what can we do to to take advantage of of the nzdf being out there to get the most out of it as scientists and citizens?

Dave:
Well, a couple of things. First of all, we're open for business. The pandemic kept us remote for a while, but I am talking to you from my office here in Alexandria, Virginia, and we welcome visitors. You do need to let us know in advance. We have security and all that, but we can if you want to visit and talk science with us, whether you're from a university, if you're a scientist or from the private sector, or you're a citizen advocate for science and you want to know what's going on, don't hesitate to contact us. We also have OPA, which is the office of Legislative and Public Affairs, and it is their job to communicate with all of our wonderful representatives and senators and citizens who who really want to hear the the outside voice of the the NSF. The other things you can do is get involved in NSF projects. You mentioned the ROO program. There are use sites all across the United States in all fields. University of Nebraska has one in chemistry. It has many actually. In other fields. We have something called NPS High where if you're a high school student, you can be supported in a lab that's NSF funded. If you're in high school and you're interested in science, talk to your science teacher and they can reach out to a university nearby. And anyone who's funded in these general mathematics and physical sciences means our floor is chemistry, physics, math, division of materials, research and astronomy. Believe it or not, so cool. Yeah. So high applies to people in all of those disciplines. And we have programs going on and on. Later in your career we have a brand new postdoctoral fellowship program all Ascend and a research initiation grant called Leaps. These are also designed to increase excellence through diversity. We'd like our scientific workforce to look like the population of the United States because, you know, in biology, diversity breeds excellence in business, diversity breeds excellence, and in science, diverse ideas coming at a problem can really kind of get you into out of the box ideas and really move the science forward quicker.

Chad:
Wow. I mean, like I say, there's so much there that that people don't even know to take advantage of. I love hearing about the the High School Reach Out program. When we think about building opportunities in STEM, I think, you know, things like that or fuel that can ignite someone in the sciences so that's that's so fantastic so. How much longer do you expect you'll be in this current role as division director?

Dave:
This is you know, when you work for the federal government, you serve at the pleasure of the taxpayer. But it's a year by year gig. Chat is.

Chad:
Okay.

Dave:
I won't speak for my boss on that one, but I've really enjoyed the ride and hopefully we've done some things that have been exciting for the community.

Chad:
Well, fantastic. Fantastic. Well, we'll keep up the good work. I mean, you and everybody at the NSSF, thanks so much. I definitely want to talk about what you're doing at the University of Nebraska. As I said in the intro, you've got sort of three full time jobs that you take on. And I want certainly want this to be about you and what you do. But I, I told you the story before, but I'll I'll recount it here. I got my PhD at Nebraska, as you mentioned. I did it in an unusual way while I was working full time. And maybe not too dissimilar from what you told about your professor. I just went and knocked on their door and said, I want to do research with you. I went around and just sort of shot myself around to professors and I knocked on their door and just said, Hey, I'm thinking about doing this unusual PhD program, and I'm just looking for professors who would kind of support the idea. I wasn't even looking to join the group and you were one, and it was at some sort of a gathering or something that I went to. And and you said, Chad, that's a that's a cool idea.

Chad:
You absolutely you ought to do it. You ought to go forward with that and say you're one of the early supporters of me coming back and getting my PhD in this unusual way. And then you served on my committee. And and when I asked you to be on my committee, my wife, who had you as a undergraduate organic chemistry professor, said, Are you crazy? You're asking? Dr. Berkowitz? And I said, Yeah, you know, he's supporting me. And I said, I think he'll be tough. And you were tough. You asked me you asked me some some challenging questions throughout the years. But but you're also a supporter, and I really appreciate that. And I didn't work and do organic research as we as we discussed. I work for David Hedge, of course, which which is a guy who's interested in chromatography and mass spectrometry is a great path to go down. It was you know, he's he's also had a fantastically esteemed career and I probably should bring him on a podcast. But anyways, enough talking about me and what I've done. Tell me about your research program at the University of Nebraska.

Dave:
Yeah, well, first of all, Chad, I have to say, I do remember this was when I was the admissions chair and I remember you.

Chad:
Yeah, that's why. Yeah.

Dave:
And you were I think you got a master's from.

Chad:
I had a master's from University of Michigan.

Dave:
Yeah, right. And you were really interested in applicant because your path was a little bit different and you were obviously very, very talented. And yeah, we wanted, we wanted to recruit you hard and we wanted to. And you had unusual ideas, and that's even better. So yeah, it's been really fun to watch you from an applicant come over. And Dave Hage is a wonderful colleague who's soft spoken but carries a huge stick when it comes to chromatography and science. A wonderful program he's built. So yeah, it's it's an interesting path to to watch you progress. So I've been at Nebraska, gosh, three decades. It's crazy. But I set up independent shop. You know, when we drove cross country with my wife from New Haven, Connecticut, we were expecting our first child and our two girls were born in Lincoln. So they're the true Nebraskans in our family. But I'm I'm in Nebraska. And because I've been in Nebraska more than anywhere else, and it's been a great run, we operate at the interface of synthetic organic chemistry and mechanistic enzyme ology. Those are fancy ways of saying we're kind of at this space that's related to drug development, but perhaps more fundamental understanding how small molecules interact with proteins, enzymes, how can we tweak them, especially if they're really important enzymes in biology, and we specialize in vitamin B six dependent enzymes. And initially we were, oh, we understand how this vitamin works as a CO factor. We understand the electron pushing chemistry. We're going to develop detour molecules that are harmless, but once they get into the target active site, they'll be Trojan horse inhibitors. The enzyme will think it's doing performing catalysis and all of a sudden we've rigged the substrate so it will lead to a reactive intermediate and attach itself to the enzyme. We've done a lot of fun work in this area, but we at some point decided to stop just doing fundamental science and and have an application. And it came when I had was waiting for the elevators in Hamilton Hall. As you may remember, elevators used to be really slow.

Chad:
Yes, they.

Dave:
Were. Yes. And instead of cursing the elevators, what you could do was talk to the person next to you who was waiting for the elevator. So one day that happened with a guy named Brad Charette, who was like a transfer undergraduate. And I didn't know this guy at all. And we got to talking and he was interested at this interface. He came back to my office. He was a guy who was sort of. Extremely bright. Hated class, but loved research. And he had been reading. He started reading more about vitamin B six dependent enzymes. And he said, you know, have you ever heard about Serine Rasmus? And it's an enzyme that makes a D amino acid in the brain. It's a peel enzyme or a vitamin B six enzyme. And Dave Nelson, who was a grad student in my lab, was also very interested in getting into molecular biology. The two of them convinced me to get into chemistry in the brain. So now we're working on pulp enzymes that are important in neuronal signaling. And this and we are one of the few labs in the world working on this enzyme. Syrian James that makes D serine, which is a really important co agonist of the N'DIAYE receptor and its levels are clearly low in schizophrenia. This D amino acid, we used to think all amino acids in human biology were L we're one handedness, but this has the opposite handedness.

Dave:
Most people don't know this. It's not in your introductory courses. It needs to get there. Yes. And this is elevated in all timers in ischemic stroke. This enzyme is elevated and h2s, which you think of as hydrogen sulfide, as a toxic chemical is a is a gaseous hormone that we make with a different vitamin B, six dependent enzyme. That's also important in neuronal signaling. And we work with both cbz the enzyme that makes h2s and hsr human Sirin maximus, the enzyme that makes D serine. So we've come to a kind of neurobiological theme that's related potentially to drug development again, right, Starting with fundamental science, having some students who pointed their advisor in the right direction. Right? I love that waiting for an elevator. But it those guys were a huge influence on the group and and they've gone on off to do better things and we have a paper I hope will be coming out very soon. We have several papers on this new enzyme I was telling you about, but one that's in major revision, like sent in the 30th of November. I hope the next time you see me, I can give you the reference for that one that has a new assay for this enzyme that uses NMR and has some fascinating new inhibitors that we found and some mechanistic information. So that's a teaser for our next paper on human and resumes.

Chad:
Yeah, you blew my mind on a lot of levels. I haven't read, I've probably read a few of your papers way back in the day, but you know, I don't read your research regularly, but, but I think your teaser caught me. I think I'm going to I'm going to look for that one for sure. So that's good. That is that that's really cool. So how is being a professor change and thinking about a science professor, a chemistry professor changed from when you taught? My wife as an undergraduate organic chemist, probably 92 or something like that until now, right? It's been a few years. So how have you seen that evolve?

Dave:
Well, of course, you know, I think generations have evolved. The student is different today than the student we saw. Very different. And you can talk, you know, Gen Z and all that stuff. I mean, the good side of this is the way we get information is so different. I have all these filing cabinets in my space that I don't use anymore. I used to copy papers and file them away and now we do everything electronically. And that's good and bad, right? And we can get information at a moment's notice whether we're using sci fi and or scholar or Google or Google Scholar or whatever it might be. And and Wikipedia is good and bad, but the key is know your sources and bank that stuff. Do we bank it? So how do we bank information? Because it's good to have ideas, bank principles banked in different areas so you can connect them. Talking to other people, as we discussed earlier, with diverse points of view, like if I'm a chemist, I'm talking to a biologist, I'm talking to a computer scientist, maybe even an astronomer. I'm going to get might get some out of the box ideas that are really important.

Dave:
But how do I myself create ideas? Or if I'm a student, how do we teach creativity? Right? That's the most important things critical thinking and creativity. People bank less. They don't really take notes as much as they used to, physical notes or even iPad notes. It's not something people do because they know they can Google something. So then if we ask you to draw something on the board, you better have it banked. If you're Googling every time you try to construct an idea, you're handicapped. So we try to we try to build a repertoire of useful knowledge, thinking skills, chemical intuition, biochemical intuition into the students. And more than ever, I think that interactive chalkboard experience, we can use slides, we use Zoom when we're when we're in the same room, because it's a better way of sharing information. And then we can have people outside the rooms. The technology's made it much better and the access to data has made. Much better. But it's the retention that banking part that's the bigger challenge, I would say.

Chad:
That's really interesting. Have you changed the process or has the process changed or evolved at all in sort of the requirements to get your PhD and and how you get there?

Dave:
Yes. Yes, I did my my tour of duty as department chair, the chemistry department. Right. A few years ago. And one of the things we asked was exactly that we set up a committee of the youngest faculty members, the newest faculty members, and we said, look at our graduate program and tell us what's broken and what's working great, Right? And they looked at it and all these folks came in and they said, You have cumulative exams. That's so passé. So passé. We all became really creative PhDs and we didn't have cumulative exams.

Chad:
I did them.

Dave:
Well, you and I are not just saying that. Right, right, right. And so we the senior people were like, what do away with killing? You can't. That's anathema. You cannot do that. And they said, well, what about if we replace it with something more meaningful? So we had this meeting of the generations there and they won. And we, we we changed the program. So we asked for a a more advanced research meeting. I remember we used to call it the research update interview. Yeah or no, it was called the Research Preparedness Interview. And now it's called the research update is the RPI, and now it's the UI. It has a written component as well as a verbal component that has been enhanced. And we have them give seminars, the seminar program we change. We used to have organic, inorganic, physical, analytical and biological. We had five divisions. Now we have three. To really emphasize, the interdisciplinary nature of our.

Chad:
Science makes sense.

Dave:
So it's organic. Chemical biology is one. An analytical bio analytical is one. And then PYM physical, inorganic and materials is what? Which is kind of cool. So you get cross-disciplinary in the seminar program and we have them talk about their research as well as the literature in that program as well. So they get not just to talk about the research of their committee, but their their peers. Those are some of the changes we made to emphasize research and cross disciplinary research, more and traditional pedagogy less.

Chad:
Yeah, so I was probably right at the tail end of the really traditional approach, which which worked right. But it's good to see that we continue to evolve because we need to do that and everything we do. I wanted to ask you a fun question. I guess it could be fun. So if you hadn't become a chemistry professor, what would you have done with your with your life?

Dave:
Oh, my goodness. Yeah. Well, I'll tell you what I would have wanted to do, but I don't think I could. I love sports. So this is going to corny, but it's true. So I grew up in the Chicago area. Actually, I'm still a huge Cubs fan. I was never a very good baseball player. I tried and I played basketball and I'm pretty short, so I made the freshman B team in high school. But sophomore year I got cut. I couldn't make the cut. And I had a teacher who said, You should go out for track. He called me Burke. He said, Burke, you should go out for track. It'll keep you in shape, you'll love it. And I had long jumped, believe it or not, in junior high school and actually gotten a medal. Okay. So I said, okay, let me do that. So I did, and I loved it. And I was and again, I wasn't spectacular. Then I had a friend who said, Oh, you should go out for cross country. He was captain of the cross country team. This is Hinsdale South High School. So I did that. So I've been running ever since is the short answer, and I don't think I could ever have done it professionally. So it remains an avocation and it's a little hard to keep it going when you get senior. Right. But the Lincoln has an amazing song Marathon, the Lincoln Marathon, and it was always my goal to get up to marathon. And in 2014 I qualified for Boston Lincoln Marathon. So that's something I didn't choose to do. Not professional. So not quite in answer to your question, but it's actually is huge in my life. Yeah. The running part and we have I'll tell you another story related to this literally is yesterday's news in D.C. There's something called the cherry Blossom ten mile run every time the cherry blossoms bloom. First week, April. Right. I've been going on for it's hard to get into it, but there's a special category. So it's a lottery to get in, right, Called federal agency or government agency teams.

Chad:
Okay.

Dave:
And my first tour of duty in around 2011, a guy named Mike Scott, who's a really good inorganic chemist and who is a rotator from University of Florida and a really good runner, said, We need a team in chemistry. So we put he stood up a team. And he's now a dean at in the San Francisco area. Mike Scott Good. He'd be a good podcast guy. Yeah. He's put up a team and it had to be co ed and you took your first three and you could have. And we just found the results yesterday from the 2011 Cherry Blossom run. We knew we placed we were fifth. We were called NSF chemistry cruisers. Guess who the number one team was among federal agencies for the Cherry Blossom ten mile run in 2011. You got to pick your agency who should be the fastest federal agency.

Chad:
Secret Service.

Dave:
You got it? I got it. You nailed it. Yeah. And so if you go on their website, you can see the actual three Secret Service agents that write Lewis out of the water. But my name is there on the fifth place team, along with Mike Scott and Amy Jacobson, and we're the proud fifth place team that year, so we're going to try and do it again. Yeah, I have an NA person, Tonya Whitmer, who's a rotator from Ohio State, and she's captain of our team for 2023.

Chad:
Well, that's fantastic. So good luck to you, Dave. Is there anything else you want to share with us? I feel like I could talk to you for another hour or two. I'm confident. But is there any other is there any other big things you want to you want to share while we have the time together?

Dave:
I think the only thing I would say is we as scientists, first of all, thank you for doing this, because I think one of the things we're a little nerdy sometimes is scientists. And I think, you know, to me, what's one of the most inspiring things of the last few years is how science has so quickly gotten us out of the pandemic. It's just unbelievable. And this is very close to what we try to do in the ending $0.03 But to stand up a viable mRNA vaccine that quickly was remarkable. I don't think any of us thought it would happen that quickly. You know, HIV, we still don't have that vaccine really, Right. Look how quickly that happened and that you need a methylated pseudo uracil to get the right mRNA vaccine. That's chemistry. You need the right lipid to deliver that drug. So to me, science is all pervasive and we need to get the message out to the community. That's why I appreciate you doing this. I don't think everybody appreciates the beauty of that story and how important it is to all of us. Today's news in China is trying to relax restrictions, but they don't quite have the right vaccine yet.

Dave:
They're right and they really need it. Humanity needs it. And so I'm a little concerned, but at the same time, I'm just bringing this up because it's actual it's right now. And we need as a society to not only invest in science, very thankful here at NSF for taxpayer funds, as you say, to keep us going. But we also need to invest as teachers and as students. We have the best nation in the world, in my opinion, still for doing science. And we need young blood. We need the next generation. It's a great living. You can there are many pathways. Chad and I are both enjoying what we do and we both done a few different things. Chat It's been so fun to watch you as you move from company to company and moved around the world and been such a leader in the drug development space. So I hope you as a leader will continue to inspire. And I know you will. Young generation and to the young people out there bother us, you know, bug us. I'm sure Chad and I would both like to talk to you about the journey and how it could be interesting for you.

Chad:
Completely agree. And thanks so much, Dave. That's all for this episode of Molecular Moments. If you enjoyed today's episode, be sure to subscribe on Apple Podcasts, Spotify, or your favorite podcast app so you never miss a conversation. If you'd like to hang out with us outside of the podcast, we have many webinars and other presentations available for your enjoyment and education. Visit bio analytics to see what's coming up and how you can stay in touch. And in today's episode, I'd add, go visit the NSSF website and see what you can do with the NSSF. Don't forget to keep an eye out for more episodes coming soon. We're looking forward to some great guests from across the Bioanalytical Field, Pharmaceutical Development and other hot science areas. Thank you so much.

Narrator:
Thanks for listening to the Molecular Moments podcast.

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