Episode 68: Dr. Michael Pollastri on Drug Discovery for Neglected Tropical Diseases

Introduction

0:00Hi, you're listening to Let's Talk Chemistry, a podcast by Chemtalk. On today's episode, we interview Dr. Michael Palastri, Senior Vice Provost and Academic Lead of the Rue Institute at Northeastern University. Dr. Palastri works on developing treatments for neglected tropical diseases and shares with us the crucial role academic labs play in addressing gaps in global healthcare research. We hope you enjoy!

Host Introduction

0:30Hey there, welcome back to another episode of Let's Talk Chemistry. My name is Nina. And I'm Porvi. Today we'll be diving into our interview with Dr. Michael Palastri, a trained medicinal chemist tackling neglected tropical diseases. Whoa, that sounds like a serious job. Before getting into the interview, can you tell me a little bit more about what these diseases are? Yeah, for sure. It's great to start off with some context.

1:00Let me paint the scene for you. Imagine you're in a rural village in sub-Saharan Africa. Tiny insects like cc flies, sand flies, or mosquitoes can transmit parasites that lead to illnesses like sleeping sickness, leishmaniasis, or malaria. I've definitely heard of malaria before, but what about sleeping sickness and leishmaniasis? Great question. All of these are parasitic diseases that spread by insect bites. Malaria rapidly destroys red blood cells, causing high fevers and potential organ failure.

1:34Sleeping sickness starts with flu-like symptoms before progressing to severe neurological issues and disrupted sleep. Finally, leishmaniasis can cause skin sores or organ damage. Because its treatments are so specialized, recovery often depends on having the geographic and economic means to access specific health care centers. Ah, so if you're living somewhere like a rural village, the nearest clinic might be hours away by dirt road. And even when treatment is available, the high costs associated with treatment, like transportation,

2:07loss of income during treatment, and housing accommodations, can create a huge financial burden to the families involved. Exactly. And this lack of economic market is why we see neglected tropical diseases, or NTDs, receive far less research funding and attention from pharmaceutical companies compared to the diseases that affect wealthier countries. Okay, I see where the neglected part comes from now. And this is where scientists like Dr. Palastri come in to discover and help develop drugs for

2:40NTDs while making sure the treatment is accessible and can be accommodated by the health care infrastructure in under-resourced areas. Yes, Dr. Palastri's research is essential for providing forward progress to overlook diseases, and we'll be talking with him today about what it takes to develop treatments that can actually reach the communities that need them most.

Interview with Dr Palastri

3:04Let's jump into the interview.

3:14Welcome to the Let's Talk Chemistry podcast, Dr. Palastri. Thank you so much for joining us. Could you please start by introducing yourself and telling us a little bit about what you do? Sure. Sure. Yeah, my name is Mike Palastri. Um, I, my current job at Northeast Union University is that I, um, am the academic leader at our Roo Institute, which is located in Portland, Maine, which is a tech and life science, um, based institute. We're building the workforce in Maine in tech and life sciences.

3:45We're helping create jobs in Maine in that space. We have research programs in that space. Um, but before I came up here, I was a chemistry professor. Um, I, uh, I'm a medicinal chemist. Um, I basically started my academic career in 2009 after working in the drug industry for about 10 years, uh, and, uh, went to, moved to Boston University first and then to Northeastern. Um, and, um, our medicinal chemistry program focuses on, um, tropical disease, drug discovery

4:17or diseases of the developing world. Um, and, um, and yeah, and I teach arena chemistry. So.

4:26Awesome. Awesome. And before we dive more into the science, I'd love to hear a little bit more about your path into, like you talked about medicinal chemistry, what originally drew you to chemistry itself and how did your interests, I guess, eventually lead you towards drug discovery? Great question. Um, so I, um, I wanted to be, I wanted to be a chemist since high school. I basically, um, it was a class that I loved. I loved the labs and, um, the tech, the, um, the content really clicked with me in ways that

5:02most of many of the other classes had not. Um, so I, I, uh, basically went to college and majored in chemistry, um, and I was pre-med. Uh, and then after the first semester, I just switched into a straight chemistry major simply because it, I, my eyes had sort of been open to what careers in chemistry could look like. And, um, at the same time, I was also learning that I don't memorize things very well. And so I wasn't taking, I, I didn't think biology or medicine would work really well for me.

5:32Um, so I started doing undergraduate research, which changed the course of my, uh, the course of my, uh, college career in amazing ways, um, as a freshman. Um, and, uh, you know, did some, you know, organic synthesis work, got to present at the American Chemical Society meeting. And like, it was just an amazing experience. And then, um, when I graduated, I went to Duke university, um, into a PhD program in biological chemistry. Um, and then, um, for a variety of reasons, uh, I ended up leaving that program with a master's

6:06degree. Um, and I went to work at, um, at Pfizer. And so when I went to Pfizer, I, uh, I was a bench chemist and worked at the bench for about five years in, in the Groton, Connecticut facility, just making drug molecules, you know, drug molecules that would get tested in the iterative process that is drug discovery. Um, and a couple of years into my time at Pfizer, I decided that I really wanted to try to get my PhD again. Uh, and so I reached out to, uh, a faculty member at Brown university in Providence, which

6:40is about an hour away from the Groton camp, um, facility, uh, for the, the Pfizer facility in Groton, um, and we designed an industry PhD program. So basically I stayed working at Pfizer, um, and then over the next, uh, four years did a PhD project, uh, my PhD dissertation project, uh, with a faculty member at, um, uh, at Brown. Um, and when I finished that, I then moved to the Pfizer facility in Cambridge, Mass.

7:11Cause it just, they just, it just opened, it was called the, the, um, discovery technology center. They were hiring like crazy. It was around the time that, um, uh, we had acquired Pfizer had acquired pharmacia. And so there was all this reorganization going on and different campuses were being shuffled around. And then I moved there and ran a group that focused on chemical technologies. So technologies that could make drug discovery faster, easier, and then actually also organic

7:42synthesis, faster, easier, more technology driven. Um, so after I was there for like, I don't know, four or five, four years, um, I decided I wanted to become an academic. I was interested in working in drug discovery in the academic environment. Um, and, um, we can talk about sort of, you know, why I wanted to go to the active, go do the kind of drug discovery I wanted to do in the academic world. We can talk about that. Um, so I first then went to Boston university as a research faculty member, essentially helping

8:15them build a med chem facility. And, um, it's now called the center for molecular discovery. It's still there, um, uh, and then after a couple of years there, I moved to Northeastern into a tenure track position and then started my academic career now. So those 16 years ago, um, so that was the, that was the path I, uh, I, um, you know, I realized in grad school, uh, that really the interesting, some, a lot of the interesting

8:46questions in chemistry were at the interface of chemistry and biology. So if you look, think back to what I said about not being able to memorize biology and things like this, um, it's, it, it actually ended up being one of the more exciting parts of more exciting decisions I'd ever made because you could actually apply chemistry in a way that was very, um, translational in nature. You know, you could actually see a path for it to be something, you know, uh, it works in cells, it works in mice, whatever, that kind of thing.

9:16Um, and, uh, you know, and when it comes to human health, uh, you know, it seemed like a really impactful field. So I, so I, I, I enjoy collaborating with, um, biologists, um, and, uh, and others who are involved for the drug discovery process. Um, so, and that kind of informed how I built my research program at Northeastern. Yeah, it's awesome.

Academic Drug Discovery

9:40Awesome to hear about your background of your motivations. So you talked a little bit, how you spend over, I guess, a decade at Pfizer before moving into academia at North, Northeastern. Um, how would you say your time in big pharma shaped your approach to academic drug discovery? Oh, entirely. So, um, um, medicinal chemistry and drug discovery in general is really high risk, high reward. There's a lot of failure. The drug industry at the time was saying it costs, you know, you say it's a billion dollars

10:12to get a molecule from idea to, for into patients that billion dollars is not, doesn't really take a billion dollars for that one program, but it takes a billion dollars when you factor in all the ones that failed. So, um, as a result, these are, you know, companies that they have shareholders, they need to make a profit, et cetera. And so there was always interest in streamlining how we would do this iterative drug discovery process.

10:42So make a molecule, purify a molecule, screen, redesign, resynthesize a new one, purify, go through that loop. Um, and it actually instills a sort of discipline in the, in the, in the med chem in the drug discovery process. Right. So you, you have very clear milestones and marks you're trying to hit, whether it be for potency or selectivity or toxicity or solubility or like any number of drug metabolism properties and things like that. And so you measure all those things for every molecule so that you're making the decisions

11:15based on the whole molecule. They can do that because drug companies have a lot of money to invest in that kind of work. Academic drug discovery, uh, on the other hand is principally funded by, um, by government, federal funding, like, so NIH dollars and things like that. Um, and it just, there's just not the resource to do that under that kind of a scheme, like trying to get, um, you know, all that data for each molecule your lab makes. It's really expensive.

11:46Um, uh, and so why am I telling you this? I'm telling you this because when we would design molecules in my lab, we would always talk about what problem we're trying to solve, and then we would go and make sure we collected that data. Um, we were able to do it because, um, we had formed collaborations with a variety of different companies that were willing to do experiments for us, um, as a, as an in-kind gift. Like, so, um, AstraZeneca, for example, um, we would send them every

12:20compound we made and they would run the in vitro drug metabolism studies. They would give us solubility. They give us metabolic stability. They would give us protein binding data, all these things. I mean, they saved us over the decade or so that I was, you know, really running that lab, um, hundreds of thousands of dollars, I mean, without a question. And for them, it wasn't like, you know, it was, uh, it was some extra work for them, but, you know, they were so high throughput that the small numbers that we were sending

12:52them on a, on a weekly or monthly basis, weren't even a blip on their radar in terms of numbers of compounds going through their systems. So we had great collaboration with them. We had great collaborations with, um, uh, the, the database, a database company called collaborative drug discovery. They, uh, you know, we had, we had all this data and, uh, you definitely do not want to just keep track of your data and Excel spreadsheets, um, which is the cheap way to do it. Um, it's also very hazardous, uh, cause stuff gets corrupted easily, et cetera.

13:25Um, and so the CDD is a, is a, um, uh, a cloud-based database solution that we were able to use in the early days that they gave us some really good, um, you know, subscription cut, uh, price cuts because we were working in neglected diseases, um, and being able to collect all that data and then use all that data and then, you know, be able to go back and, you know, search compound and search data. Uh, it was, it, those kinds of things made it much more an industrial feel. We also got a bunch of equipment donated.

13:57So when I left the Pfizer site in Cambridge, um, a couple of years after that, they closed that site and there was all kinds of equipment that was then donated to our lab, high throughput purification, high throughput and high throughput analytics. Um, you know, uh, we got a mass spectrometer, an LCMS system, a pure purification system. We got a Genovac evaporator system. Like it, it, it, we, I would have never been able to afford that stuff without industry being involved. Um, so the mindset is everything.

14:28Um, and actually I should mention that that isn't always a mindset that is historically rewarded in academics. So it's a, it's a, it's a more of a discovery mindset as opposed to a, um, hypothesis driven science, you know, what I mean? So in other words, uh, you know, asking big science questions, having a big impact it's, you know, on the academic world, at least at the time, it was all about, you know, your scholarly impact and all the papers you write, the ones that you're the lead, that you, your

15:03lab did this and whatever in med chem and drug discovery, it was totally collaborative. I had, you know, every paper I had, had at least one other lab somewhere else in the world on the paper, doing the biology or doing, you know, some aspect of the project. Um, and it required us to me, it required me to like, and keep my leadership in my department and my college at Northeastern, um, understanding like, this is how drug discovery is done. And, um, you know, I, when you're thinking about my promotion and tenure, take that into

15:37account, right? Just cause I didn't do it all myself and in my lab and I have complete control over everything doesn't mean that it's bad science and something we shouldn't reward, I guess is what I would say. Um, long answer to a short question, um, but happy to go deeper if you like. Yeah. Thank you so much for going into some of the challenges about like drug discovery in academia. And it was really like hopeful to know that through the collaborations, you were able to overcome some of the economic issues and also like collaborating with labs all over the world.

16:09That was also really inspiring to hear about. Um, I was wondering about more about your research, um, that you do, you, you look into, uh, neglected tropical diseases, like, so what inspired you to focus on NTDs and how has your work progressed through this field? Well, um, when I was still at Pfizer in Cambridge, I, I started teaching a class in, um, in the bioinformatics program at Brandeis university.

16:42And, um, one of the faculty members in that program, um, was doing projects with his students, class projects with his students doing bioinformatics, uh, focusing on, um, the parasite because it's African sleeping sickness. So African trypanosomes, um, and the idea, his idea was basically, you know, what, what classes of targets do humans and parasites share so that we could use what we know about drug discovery in humans and apply it to the parasites.

17:14Anyway, he gave a talk in that program and I listened to that talk and I didn't know anything about these NTEs at all, but what I learned was, um, I learned a few things. One was, these are horrific diseases. Um, the drugs that were used at the time were also horrific, like arsenic kinds of compounds. Right. Um, and the third thing I would say was, uh, I learned that, uh, the drug industry, the, the drug companies and such, it's not a folk primary focus area because, you know, if they're selling

17:49drugs, they need to make a profit based on all the money they sunk in the research. Um, patients in Africa, sub-Saharan Africa can't pay for that. Right. And so there's no profit that can be had. Um, and then the last point is that med chem had not really been widely applied. It's sort of like people would take stuff off the shelf, test it. And then there was no iterative process. There was no optimization for toxicity. Like the, that arsenic compound that was used back then was like, it would kill like one

18:23in one in 20 people like that took it, but the disease is also fatal. So, you know, it's not a good choice. You don't have good choices as a patient. Um, that's actually what motivated me to move to academia, um, was basically to be able to do industry style drug discovery in an academic and non-profit environment where there is no profit motive. Um, uh, so we built this group, um, in, you know, starting in 2009 and, uh, you know, we

18:55got up to being around, I don't know, maybe 16 people or something like that. Excuse me. With a lot of, um, you know, we had, we were lucky enough to secure significant NIH funding to drive it. We secured industry funding to do it. We had all these industry collaborators, um, you know, a couple of the, my, my graduates went off and work in the drug discovery industry, not in NTDs, but, um, they have an awareness of NTDs that, that most people in industry didn't have. Um, and, um, and the lab is still running.

19:27It's joint, I joined, it's a joint lab that I have with a, another faculty member who actually started as a postdoc with me a while back. Um, and now she's a faculty member of her, in her own right. And we just share a lab space and, um, you know, she's keeping that program, those programs and her own programs pushing forward, um, pretty aggressively. So, um, there's a, you know, the, so the work continues, you know, I became an administrator. I'm not in the, I'm not in it so much anymore, but, um, uh, I'm, I'm really pleased to see

20:02that there are still, you know, students, postdocs, um, trainees working in this, working in this space, because it's really important.

Challenges in Drug Development

20:10Yeah.

Challenges in Drug Development

20:10Thank you for giving us some more insight. And I know we talked a little bit about the, since this is for nonprofit, there's some, like, uh, there's less funding, um, that goes into that drug discovery and academia. I was wondering, um, are there any other unique hurdles, um, for developing drugs for populations that, like, traditional pharmaceutical, that, that the traditional pharmaceutical market overlooks? Yeah, there are a few things. One is the cost of goods to make the drug, right?

20:43So most of the, most of the, um, drugs used in the, in the, in the developing world in these kinds of entities are funded by governments or the world health organization. Some are donated by companies. Um, and, but the, the, the lower, the cost of producing the drug, the, the easier it is to treat more people, right. With, with the chair, with charitable donations. Um, and so if you're making, if you have a drug that's like, you know, has a very complicated

21:14synthesis or has chiral centers on it, or there are all these different, like, you know, complexities, it's going to cost more to make it. And so you have to sort of be working with that in mind also. Like if I'm making a, if I'm making and testing a compound that is super complex and it took like 40 steps to make it, how likely is that going to be a successful NTD drug? So that's one, one part. To be clear, the, um, you know, the developed world drugs have the same pressure. It's just that payers could pay more, right?

21:46Um, in this case, there's a, there's a, there's a pressure. The second thing is, um, the infrastructure for doing clinical trials is, can be a little tricky. Um, sleepiness sickness in particular, um, it, it's been kind of cyclical in terms of the, uh, numbers of cases year to year. Uh, and there were, there are years where it's hard to find people who have it. Um, and so trying to run clinical trials means that, you know, you, you're finding people who are infected, you have to get to them, treat them, monitor them, et cetera.

22:21And in, you know, some parts of sub-Saharan Africa, that's, that is not an easy thing to do. Um, so there are real challenges. Now there are all kinds of, um, you know, uh, non-government organizations and, um, uh, you know, organizations like the drug for neglected disease initiative that all have built out a really impressive infrastructure to try to get to that, um, get to those patients. But those are a couple of the big ones. A third one is, um, cold chain.

22:53So if you're, if you're, if your drug requires refrigeration or it requires some kind of special handling, um, it's, it's, it's, can be especially challenging to get the drugs where people are. So you generally need to have drugs that can be formulated in a way that they can be just, you know, thrown into the back of a, back of a Jeep and taken where they need to be taken. Um, as opposed to things like, you know, monoclonal antibodies or, um, you know, these high-end

23:27sort of cell therapies and things like this that need special equipment, they, they're very bespoke for a, for a given patient, um, and they require a cold chain in a lot, in most cases. Um, so those are some of the challenges I would say. Yeah, that was super interesting to learn more about because usually when I think about like drug discovery, I think like the biggest challenge is actually making the drug, but then there's always so many more to like actually getting it to the people who need the drug. So thank you for that. Um, I wanted to also talk a little bit about like kind of the impact of your work.

24:01So what do you envision as a long-term impact of your research on neglected tropical diseases, um, in terms of improving global human health and also in underserved, um, underserved populations?

24:15Well, um, I would like to say that I expect, I expect us to have a drug in the clinic. Um, it's really hard to do that. Um, and if, if we, you know, obviously that's an ultimate goal, but if that's our like only ultimate, if it's our only goal, then, um, it'll be disappointing to look back. It could be disappointing to look back. Um, I think there are some secondary aspects that I find very powerful and rich and rewarding.

24:51One is that like every time I hear an NTD article on like NPR, or I see something about some disease that's being eradicated or, um, I, I actually like to think that we were part of this uprising of scientists who were really interested in working in these spaces back in the, in the early two thousands, um, and raising awareness and getting people so that they're thinking about these things and finding ways to finding ways to collaborate, to resolve it.

25:24Um, and that is through the media, it's through publications, it's through whatever, um, uh, helping to, it's helping to set funding priorities for government agencies, things like those. Um, I would say the second, a second thing is, you know, we published, I don't know, maybe 70, 70, 80 papers, um, in this space, um, you know, chemistry and chemist or drug discovery, like I say, is a team sport and, you know, sort of our, our, our, what we've learned and

25:59published can inform what other people do. Um, you know, there were some of our papers that are really nicely cited. There are people who think it's worth following up on. Um, uh, and then I guess the other thing I would just want to mention is one of the, I didn't, we didn't really talk about our, our general approach to drug discovery, but what we do is we'll design molecules for a particular parasite, right? To kill a particular parasite and the parasites that cause, um, African sleeping

26:29sickness and leishmaniasis and Chagas disease. They're all sort of cousins to each other. And so we started testing all of our compounds against all of those parasites, um, at the same time. So the idea would be, there would be divergent sort of structure reactivity relationships, um, as you're saying, well, okay, so, you know, we made a dozen compounds. This one's active against human trypanos, uh, African trypanosomes. These ones are against the, um, American trypanosomes.

27:00And now we have two projects, right? So that approach actually created a lot of parallel projects that, um, you know, move the ball on multiple diseases. I mean, and then we had stockpiled these compounds after we had, you know, done what we're going to do, someone says, hey, we're really interested in discovering drugs for schistosomiasis. Can we test some of them? And so we'd send them compounds and then start new projects and stuff. So you can see in the, in, in, in the work that I've, um, I've been part of in the publications. Um, and then some of the work that professor Lori Ferencz has published, um, you can see

27:34the similar chemotypes in classes of compounds finding their way into different kinds of pathogens, which is kind of awesome. It's so like inspiring hearing you talking about the collaborative aspect, I think for one, I am interested in like the future too. So we're seeing this massive surge in, you know, cell and gene therapies in various fields as a medicinal chemist. Do you believe like small molecules will still hold the throne for global health in coming years and specifically for NTDs, or do you think we'll see more of a shift towards those

28:07cell and gene therapies, or are there still some like underlying challenges preventing that pathway? Yeah. I mean, the, the way that those are produced are very intensive and very expensive. Um, they're customized for patient, um, and they require a cold chain, like I was describing. So I don't know that that's a near-term solution. Um, they're really expensive. I mean, really expensive. So, um, I think small molecules will remain being king with the exception, the biology in

28:38the biologics world. I think the exception are vaccines. So the more we can discover vaccines for travel diseases, the better, like African japanosomes, you can't immunize against it because they have this mechanism to evade the immune system. Um, so you can immunize against them, but they're going to escape. Um, so, uh, but you know, there was just a malaria vaccine approved. A couple of years ago, um, that, you know, that affects hundreds of millions of people every year. Um, so that's a, so if you, if you have an 80% reduction in that, cause it's, I haven't

29:15looked at this for a while. So I'm thinking it was, I think it was like 80, 85% effective. That's a 80, 85% of the big number is still a very big number. So think of the lives that are being saved simply by vaccination campaigns. Um, so I think that small molecules will, will remain the sort of the frontline. Um, you know, there, there may be sort of the midsize molecules that could be sort of, uh, pursued, right? Some of the, these so-called, um, like degrader compounds, these ones that sort of use the cell

29:48machinery to chew up essential proteins. And then, you know, therefore having a biological effect, that's really, again, you can basically make those molecules by standard organic synthesis and then they're, they're shelf stable. And so in principle, you could actually imagine that it's sort of a newer, newer class of chemotypes in the last say decade or so that are really have really started to, um, come to the fore that could actually be something that, um, is, is pursued. In fact, maybe it is being pursued. I, I actually, I'm not totally sure there's a huge place for technology in all this, by

30:21the way, like just with any kind of drug discovery, like I just talked about this, this thing around protein degraders, uh, applications of, uh, AI and drug discovery, right. We're still sort of feeling this out. It's not going to be a magic panacea, but it does bring a lot of interesting questions to the table about, can we do this in a different way? That is much more, that is better leveraging all of the information that we have as a, as

30:52a, you know, in the field to design the next generation of, of, of drugs or approaches or, or whatever. Um, I think that, I think it remains to be seen how effective that is in drug discovery writ large. Uh, it's, you know, it has its healthy amount of hype to it. Um, and, uh, but I, I, I think that there's just going to be, people are going to be using that toolbox more and more. And then once we start getting successes, it's going to accelerate all of this for everyone,

31:25not just for neglected diseases, but for cancer and diabetes and all the others things that drug companies work on. Thank you for talking a little bit more about the future and like future technologies that will play a big role into drug discovery. Um, you also describe yourself as like a medicinal chemist in an academic setting. Um, how does this identity influence you, how you mentor the next generation of students, um, compared to that of a traditional PI? Well, um, I think that it is no accident that most of the people that are trained with me

32:06have gotten industry jobs as opposed to going and becoming a faculty member somewhere. I mean, there are some, um, who have gone on to faculty roles, but most have gone off to industry. Um, and I think part of it is the, the approach we took with as an industry sort of feel of drug discovery, it's, it's, it feels very, it feels effective. Like it feels like you're making some headway. It's much more, you know, you're making a lot more compounds than you would if you were

32:39doing natural product synthesis or things like this. Um, that's, I think, and, and when people go and interview and they're looking for jobs, they can talk the language. Uh, so, um, you know, historically, uh, you know, sort of, uh, students or, or trainees kind of from a traditional med chem lab might not actually have the facility to talk deeply about drug metabolism properties or to talk about, um, physical chemical properties that a given compound would have, or what's the net effect of, um, you know, these kinds of,

33:15these kinds of, why do we use certain metrics? Like there are certain metrics that are sort of built into the language of industrial medicinal chemistry. Um, that if it's like a foreign language, if you're not, if you haven't been exposed to it, um, and a lot of academic labs don't necessarily spend their time on those things. So, um, so I think, I don't know, but I think that a fair, I think that where my students and trainees have ended up, I think is actually partially driven by that.

33:46They ended up in industry because they actually were trained in an industrial type, um, environment. They're also actually, interestingly, some, I've had a few students, um, actually, you know, they're, as they're finishing their PhD, they didn't be in their last year and they would be writing up their, their dissertation. They go to work for a drug company for a year while they're writing up. Also transformational, right. Um, because it provides a more experiential learning, right. They're working on a totally different type of projects in a totally different environment.

34:18Um, but it prepares them to then have a much broader basis to talk about drug discovery, whether they're working at Northeastern or Pfizer or Merck or whatever, and they can actually bring close skills and talents and experience elsewhere, which is kind of cool. Yeah. I think that insight will definitely be really helpful for anyone who's wanting to go into the pharmaceutical industry and like for what to focus on and to, in, to end this interview, what is the most important piece of advice you would give to a young chemist who wants to

34:50make an impact in science? Um, I encourage scientists, trainees to stay curious about what they're doing.

35:03Um, and, you know, often we get so married to our own hypotheses about this, you know, we, we observe something, we form a hypothesis and now that's the lens through which we see everything is really tempting to want to keep confirming your own bias, being able to, you know, encouraging researchers to step back and think about how else could I interpret this result? Um, or if this result is not, as I turned, it turned out that not as I expected, what

35:33is that telling us? What is that? What is that going to be? I mean, this is, this is just doing good science. Um, so part of it is to remind people to sort of keep an open mind and be creative. Um, um, the second thing is, and this is much more of a career path sort of thing, right? So my path through grad school the first time and Pfizer, then grad school a second time and then Pfizer and then BU, then Northeastern and now my role at Northeastern being like

36:07I was a chemistry professor and then became a department chair and then became an interim dean and now I'm in leading a campus in Portland. Um, it's about using your analytical skills that you learn as a scientist to do things that, um, you might not have imagined. I didn't imagine being an administrator or a leader in that, in this way at all. And what it comes down to is just saying yes to opportunities that sound even a little bit interesting because it really widens your, your, your horizon.

36:38Um, and so in that regard, um, you know, saying yes to a new collaboration, right? Even if you don't want to leave the bench, like if you want to be like, I want to be a bench scientist and I'm enjoying that keeping an open mind to like who you collaborate with, um, what types of, um, you know, what types of projects you would work on, where you want to work, just keeping your mind open to explore and potentially say yes to new things can unlock unbelievable experiences.

37:08I mean, I'm just thinking about the one time, uh, I've been to sub-Saharan Africa. Uh, I was invited by a colleague to visit, uh, Kenya and we went and we visited some clinics that treated leishmaniasis and at the time I was really nervous about it. Like I was, it was my first time actually in Africa. It was my first time in a public health environment. It was my first time, um, you know, traveling out into the far reaches outside of Nairobi to,

37:41to visit a clinic where there were actually people who had leishmaniasis and it made it real. Like it changed my whole perspective. And it was because I said, yeah, let's, let's go to, let's go to, let's go to Kenya. Right. So just keeping an open mind and, um, finding the opportunities to expand your, expand your horizons beyond what you think they should be.

Conclusion and Advice

38:02Yeah. Thank you. Very important words of wisdom. Definitely. Uh, thank you, Dr. Palastri for joining us today. It was really nice talking to you. Thank you very much. Thank you. It's awesome to hear the impact one person can have on improving treatments and awareness for NTDs through research. Yes. I'm really inspired by Dr. Palastri's commitment to this part of medicinal chemistry field where there isn't always a strong profit incentive. It makes sense that large pharmaceutical companies have to think about profitability and sustain

38:37future research, but it's great to see scientists like Dr. Palastri focusing on treatments for diseases that affect some of the most vulnerable populations. Exactly. And it kind of ties into our previous interview with Dr. LaMittina, where he talked about how developing a single drug can take billions of dollars and decades of research, not to mention the hundreds of drugs that fail before making it to market. It helps explain why companies have to be strategic in what they invest their time, research, and

39:07money in. But hearing Dr. Palastri's perspective really shows the other side of the equation and highlights why research on neglected diseases is so imperative. Yes, it really puts into context the hundreds of parameters that need to be accounted for when tackling a problem in healthcare, and really any field in general. We'd like to thank Dr. Palastri again for joining us and sharing his insights. And to all of our listeners, thank you for joining us today. We hope you learned something new about neglected tropical diseases or inspired you to.

39:41We'll see you next time. Thank you for listening to Let's Talk Chemistry, a podcast by ChemTalk. We hope you enjoyed it. For more information on today's episode and countless chemistry resources, please visit our website at www.chemistrytalk.org.