Episode 1: Dr. Alberto Rascón

In this conversation with Dr. Rascón, Associate Professor of Biochemistry, we learn about his work and the research of his chemistry students. We also stretch beyond the world in the lab and discuss his journey as a first-generation student in the CSU.

Episode Transcript

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Vincent Del Casino: Did you go that students at San José State University are working with faculty to find solutions to the problem of dengue fever virus and Zika virus. Well, join me today on "The Accidental Geographer," where we'll learn about the work of Dr. Alberto Rascón and the research of his chemistry students. Alberto is a leading expert on biochemistry and a National Institutes of Health researcher, where he studies the processes within mosquitoes that lead to the spread of deadly diseases. In this conversation, we also stretch well beyond the world of the lab to talk about Alberto's journey as a first-generation student in the Cal State system. As well as his current collaborative research with scholars from the University of Arizona and UC San Diego. I'll be your host Vincent Del Casino, and you are listening to "The Accident Geographer."

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Vincent Del Casino: All right. Well let's get started. Alberto, thanks so much for being here on the show with me.

Dr. Alberto Rascón: Thank you for inviting me, it's a great pleasure.

Vincent Del Casino: It's exciting to have an opportunity to talk with you for a number of reasons. One of which, you gave a talk in the University Professor Lecture Series. You do some really fascinating work on issues related to health and disease and how we're going to combat some of that. But also you know you are a graduate of the Cal State system. You graduated from Bakersfield and from there you ended up going on in doing doctoral work. Tell me a little bit of how you got interested in chemistry and science, you know in those early days when you were heading off to college for the first time.

Dr. Alberto Rascón: Well it's actually a very interesting story that I really like to share, especially with the kids. You know, I've gone out to middle schools, and elementary schools, and high schools to talk about my own story. Because you know, I mean grew up, my family was pretty poor. You know, we were on welfare and people didn't realize how poor we actually were. You know, I was born in Los Angeles. I tell kids, you know I was an 80s kid during the crack epidemic and the gang violence that happened all through Los Angeles. And so we lived near the projects. You know, if people don't know what the projects are, you know they were housing developments for pretty much underrepresented people. You know very low income housing type of places.

And so if you're not familiar with the crack epidemic, I mean there's a lot of great specials out there. But you know I saw that my family and I saw that firsthand. And the thing that really got us not involved in you know gangs and all that kind of stuff was my mom. She was really tough on us. She said, I swear you do this and un chanclazo you know. She was always that lady. She was really, really strong willed. And she pushed us going through and staying into an education. And so I tell these kids these stories because you know, they're kids, right. They want to know. some of them have similar backgrounds.

And so usually I put up a slide showing NWA, which is a rap group from the 80s. Because we were pretty much, where we lived, we lived in Culver City, which was about maybe a mile and a half away from Compton when that all started. And these kids, right, they're like wait a minute, I know who they are, right. So I tell them the story and that way they could see that yeah, it was tough. But education really got me out of that. And really got my family out of that whole situation. And so from there, you know, my mom pushed us like hey education. The only way out is through an education. And it's funny because you know the only professionals that my parents knew were lawyers and medical doctors. That's it. You know like oh, mijo, if you know, you talk a lot maybe you'll be a lawyer. Oh, you like medicine stuff, maybe you'll be a medical doctor. And so that's pretty much all I knew. And so when I was in high school, you know, I did very, very well.

Surprisingly, with you know my parents only having a 6thgrade education. You know they try to help as much as possible, but pretty much I was on my own once I started high school. So that was really hard to navigate. But I did very well and surprisingly biology and chemistry was actually something that was very easy to me. And so I had a teacher in biology who kind of you know, kind of said hey, you know you're pretty good at this. But then I had a chemistry teacher who kind of said, oh, you know you're doing well in chemistry. And when I told her that I wanted to major in chemistry she's like oh you shouldn't do it because it's hard and you might drop out. So I'm like okay, challenge accepted. I'm going to be a chemistry major.

And then in college, that's where actually I learned about the cool things between chemistry and biology. And then you know I tell students you know I tell these kids, like yeah you may love something but then when you study it, you'll realize that there's more to it than just what meets the eye right. So I'm honest with my students. I tell them, look, there some portions of chemistry that I really, really don't like. Okay. And there's portions of biology that I really, really don't like. But then this is where I learned about biochemistry, taking the cool things that I really like from chemistry. You know catalysis and things like that. And then how they're applied in the biological system. And so I'm like you know what, if I take those two then yeah, this is something that I would love to do. But even then, though I still really wasn't interested in an actual science career.

And an undergrad, I had a great professor, his name is Ted Weinheimer. He was a biology professor. And he really motivated me. I mean he kind of switched my whole career around. You know he's the one who really motivated me to really learn how to read science, study science, but also more importantly how to write science. He was tough. I mean, he really made us work really hard. But that was a great experience for me. And still though I was like you know what, I'm going to medical school. I'm a med student, right. And I never figured that I would actually love science the way I do. And become a professor the way I did. And it was because of his influence that actually motivated me to apply to graduate school and get a PhD in biochemistry.

And so that kind of led me through, you know, this route and pretty much I haven't looked back since you know that decision. And you know one of the great things that I also share with my students is that great interaction of my professor at the Cal State level. And this is one of the reasons why I decided to become a professor at the Cal State level. Because if it weren't for him, I don't think I'd be here today. You know because of his influence, and even in graduate school, he was there during one of the most toughest times in graduate school. He gave me his phone number. We stayed in touch. And he really helped me out through not only undergrad, but while I was in graduate school. And he's completely changed my life. And so that's why I decided to then you know, become a professor myself.

Vincent Del Casino: Those moments of mentorship that you talk about in high school, and in university, they are the transformative moments. And I started as a chemistry major. I don't know if you know that. I loved chemistry too in high school. I had a fantastic chemistry teacher. I took AP Chem, I actually got a 4 on that exam. I was really proud because that's a hard exam. And I add a work my tail off for it, but I just got to college and I went some different directions. But what was nice is finding people that you know that kept me motivated and get me going.

It's interesting you talk about Los Angeles in the 80s because I think, you know, I hope students do listen to this podcast and an opportunity to share with the students on out campus. Because that was an unbelievable time in US, for those who don't know what crack is right. It's a kind of mix of cocaine and other things that became the smokable crystal. It was very cheap and easily accessible. And it became ubiquitous to a lot of neighborhoods in big urban areas. Aligned with the HIV epidemic and other kinds of things going on.

So I can only imagine what that was like. But you had mentorship. Obviously, your mother was there tightly as well. But other mentors throughout that early experience through the education that you have in Culver City and so forth. Why did you decide to go to Bakersfield then? Was that?

Dr. Alberto Rascón: So here's also part, another cool part of this story was that my dad and his brothers, they were actually painters. So they painted houses. You know they painted inside, outside. I mean they could do all sorts of nice paintwork. And so I don't know how they got involved but there was a lady. The only name I remember her by is Carol. But this lady she actually worked in the movie industry. So she was a set designer and things like that. And actually hired my father and his brothers to work on a couple of movies.

So they were like you know the painters behind the backgrounds and things like that. And one of the big movies that come up is actually "Dark Men." So "Dark Men" is a 1990s movie, was directed by Sam Raimi and it started Liam Neeson. So this is like kind of an antihero movie. And so my dad was actually on the set. And it's cool, because if you look at the credits you actually see Alberto Rascón in the credits. And so he got to do that kind of stuff while we were in in Culver City. And he and my uncles also painted the house of Carl Weathers, who was Apollo Creed from The Rocky movies. Well, it was during the filming of "Dark Men" that actually my dad was injured. And he hurt his back and he became disabled.

And so that's kind of where it all kind of went downhill for our family. LA was becoming very expensive; my dad was out of work. My mom, she was a homemaker. And so we pretty much lost our apartment, we lived in my uncle's truck for about two weeks. You know we were kind of homeless for about two weeks. And then, you know, there was an opportunity in Bakersfield. And so my parents moved us. And they actually were able to find a three bedroom apartment very cheap. At the time, I believe is it was a 420, three bedroom, two bathroom townhouse. But still it wasn't in the best neighborhood, you know.

But my parents did what they could, right. And they did a good job I think of just being tough on us. So that we didn't get involved in the whole gang problem. Because we went from the projects to now the barrio, right which is now where the Mexican and Hispanic gangs are. And so my mom was there too, you know, because every day my brother and I would walk to the store. And we would always have some people say, hey, so where you from? And like, nowhere, you know. And luckily my brother and I are only 11 months apart. So we were really close. And he was the scrapper of the family. So every time they try to fight us, you know, my brother would already jump to the gun and protect us from whatever. So that's kind of the story that kind of led us to Bakersfield, California.

Vincent Del Casino: That CSU is your home CSU then.

Dr. Alberto Rascón: Oh, yeah.

Vincent Del Casino: When you decided to go on and go to college.

Dr. Alberto Rascón: Definitely and that's what, actually you know and another thing that my mom was very supportive. But at the time when I was in high school, she said mijo, if you just graduate from high school that's going to be the best, you know gift you can ever give me. Because none of my parents, you know, they only went to sixth grade. And my family too, on my mom and my dad's side. I mean my dad's side; I think his brothers went through school in Mexico. But none of my mother's family ever got a chance to actually even go beyond I believe fifth grade. I think my mom was the highest education I think at sixth grade.

So she said just please go you know finish high school. And I'm like but mom, you know, I have an opportunity to go to college. You know, I went to campuses. I went to UC Santa Barbara, and things like that. But with the Mexican cultures, kind of, if you're the oldest, you don't really want to move far away, right, you have to be with your family. So that's why I decided to stay at Cal State Bakersfield.

And it's funny because when I got accepted, my mom was like so how much is it going to cost us? And I said, mom, nothing. You know, we were making for a family of six, our household income was about $12,000 a year. And my mom was the only one that was kind of working at the time. You know I got college paid for. And it's funny because even then, you know being a first gen student, going through all of this, I was a very good athlete too. You know, I played soccer. And I even got to play semi pro football in Bakersfield. So I figured, you know yeah, college will be there. I'm going to be such a good athlete that I'm going to be recruited by places.

Well, guess what, I tore my ACL during a fourth preseason my semi-pro career. And that ended that whole dream of me going on to pursue. And luckily still, I had college. And not only that, though the influence of the people around us in Bakersfield. You know, as I mentioned we were in barrio and a lot of our neighbors were people from el Salvador, from Mexico and they were all field workers. So they worked in the fields of Bakersfield, you know, cotton, grapes, almonds, things like that. And they would tell me, it's like mijo you have a great opportunity. Don't lose that. You know, you're Hispanic, you're a US-born person. Take advantage.

And so when I was in the hospital you know recovering from my ACL surgery that really hit me and I'm like you know what am I doing? You know this is great that I could you know, I'm glad that there's people out there that can make a living becoming an NFL player or basketball player. But how about the rest of us. How about the other 99.5% of the population, right. And so that really hit me really hard. And so that's kind of where I kind of switched you know my mentality and became a more serious student. And so from that point on, yeah going to Cal State Bakersfield really influenced my career. But also all these different experiences you know through my life kind of motivated me to get to the point where I am.

Vincent Del Casino: So if you think about then, you know, first gen, oldest, as you talk about needing to be close to home, that connection so important. you pick up and you go to Tucson, Arizona. You know, for graduate school. That must've. I can't even imagine the layers of emotion and kind of things that were going on both in your family. I mean probably very excited, incredibly excited, but just what was that transition like to go from Bakersfield, and CSU Bakersfield to let's say the University of Arizona. To this like massive chem-biochem department.

Dr. Alberto Rascón: Exactly what you said, it was a slew of a emotion. Because you know I had to convince my family that in order for me to grow and make all of us better, I had to leave. And it's funny because you know at the time you like I used to tell people, oh I got into graduate school at all these places. But then some people would kind of hate, and say well, why didn't you apply to schools in California? That actually was a conscious decision because you know my parents, I mean I love them to death. But they would always kind of you know, interfere. And not necessarily interfere. But the reason I'm saying this is because I also got married young. So when I graduated Cal State Bakersfield, you know, my wife and I got married. And we had our first child. And so that was also part of the thing that you know in my family, everyone was so excited because they wanted grandkids. And they want to grandkids fast.

And so, they were always over, I mean every day. Every day. You know, which is great. But then I tell them you know if I wanted to pursue higher education, you know, Bakersfield is not going to be the place to do it. And not only that too. You know, there's a joke that people say who are from Bakersfield, they say, well it's the armpit of California. Once you're stuck into this hole you will never leave. And I'm like, no, I don't want to do that, you know I want to make sure that I get better, not only for my parents, but also for my new family. For my wife and my kids.

And so believe it or not, I applied to 16 graduate programs, not in California. These were all over the place. From you know Yukon in Connecticut, Vanderbilt, Yale, Johns Hopkins, Arizona, Arizona State, Colorado. I mean you name it. All over the college. It's during the interview process, where I really enjoyed what the University of Arizona was offering for me. Not so much as a student, but so much as a person that I knew they were going to take care of me while I was there. That if I had any issues you know, and this is something also being a first-gen student getting the signs that I really didn't know what questions to ask. If I'm going to pursue a degree for you know 5 to 6 year, or now 6 to 7 years in biochemists, the biological sciences. I didn't really know what to look for. You know what do you look for in the program, not only science wise, but also to make sure that your 6 to 7 years, you know are going to be amazing and not feel like it's a waste of time.

Vincent Del Casino: It's a big deal. And you know the transition, especially when you're going straight into doctoral education from undergrad. It is a massive transition that a lot of people don't appreciate. And trying to explain it to undergrads, like this is another step here. And the expectations are very different, and so forth. But also what I found is that graduate students were critical. I always wanted to know what the grad students thought about a place. They knew as much as anybody like what it was like to work in a lab or in someones area. So were you attracted to the work that you're doing today at that point in time? Was that part of what you were interested in? Were you specific enough to know that? Or were you just passionate about biochemistry and the intersection of biology and chemistry. And wanted to go to a place that was doing that kind of work?

Dr. Alberto Rascón: Yeah, that's exactly what it was. For me, learning about biochemistry at Cal State Bakersfield, it really motivated me to pursue that realm. But more specifically, I thought I was going to focus mostly on entomology or protein biochemistry. And so when I was looking for graduate programs, I based it on the work that people were doing at these institutions at the time. Because again like I said right, I really didn't know how to navigate what to ask for and things like that. And so that's what I went after is the work. And so when I was interviewing, you know, I learned some like really important things that it's not really about the work. It's mostly about the people, right. People make a huge difference on whether or not a student should commit to a place.

And so I actually now have done, I think I've done, personally, I think I've done a good job with my students. Because a lot of my undergraduate and masters student, you know, they're very successful right now. And they always tell me, like, wow I'm glad we had this you know little fake interview and what to look for because I found a lot of places that were very suspect. And I'm glad I didn't choose-- to not go in that direction right. And it's something that I really didn't know until pretty much I think it was my fourth year of graduate school, you know I almost quit. I was quick graduate school. And it was because of a bad experience with my first mentor. And it's because there were so many red flags that I should've picked on during my rotation that I just didn't know what to look for at the time.

Vincent Del Casino: A lot of people don't know is a lot of people do not finish their doctoral program, it's about a 50% rate at a place like Arizona. And so it's hard to get there. And then you're right. Like, that connection to an advisor, it's critical for long-term success. So how did you navigate that challenge?

Dr. Alberto Rascón: At the beginning I thought I was alone. Because you know, again, being a first gen student no one tells you that you know there's a reason why you have a committee. There's a reason why you have these programs. There's a reason why there's you know people who are head of these programs that you can go talk to. I thought well, I'm stuck have nothing. You know, I'm going to have to see if I can suck it out. But it was really having a huge effect on me and also on my family too. Because I was so stressed. You know and also too in the first year of graduate school, then we had my son. So now we had two kids in graduate school. And that's something that you know I don't fault a lot of these mentors because they don't really, you know they're not used to seeing people like myself right who have a different background. We're not your typical PhD student. You know, we're kind of a different species altogether.

And so you really have to kind of understand and now science, I think, and I think this again my personal opinion is that we have to be a little bit more personable. Especially with our students, you know. Science could be cold. It could be a cold you know, field. And that's not what we want. We want to make sure that these students feel comfortable. And because everybody's different perspective and experience, will actually bring something different to the table. You know and this actually translates beautifully to why I've been successful at San José State. You know a lot of my students have been first generation students. A lot of students have had difficult backgrounds like I have.

And it's funny a lot of these students are not Mexican-American. They're usually Vietnamese, they're Indian, you know, they're even Caucasian, right. So we've had a very diverse students in my lab. And they all can relate to the difficulties right. Because something that I tell them is like, I can relate to when you were an undergrad. Sometimes as faculty, we forget, right. The older we get, the more busy we become, the more we move up in rank. And we forget about these experiences. And I want to make sure that my students know that, no, you know I had the same experience. I know what it was like. And I make sure that also my students in my class kind of have an idea too that, I know the struggle. You know, you're not alone. I'm here to help. But you need to come out and reach me, right.

And I say this because this then goes back to my undergraduate professor. When I was going through that difficult time in graduate school, you know, I called him up and I kid you not, I'm almost 6 feet, I used to push around 385 pound lineman, no problem. But I was crying because my PI you know was just, I just couldn't do it. You know I was afraid that I was going to do something that will make me a statistic, you know. Here's this big Mexican man from the barrio. He's going to be ghetto, and whatever. And I didn't want that to happen because then that would fail my family, not only my wife and kids, but my parents as well. And pretty much the whole community that I represented. And so when I talked to my undergraduate advisor, or my undergraduate professor. He said no, that's not the way it works. I'm like well, I don't know. I don't know how to navigate. And he's like, no you do not put up with this. Okay, this is what you have to do. You need to talk to whoever you can and let them know about the situation. And you've got to get out of there as soon as possible.

I'm like, but can you do that. And he's like, yeah, no. go talk to somebody. You need to go, your committee is there, go talk to them. And sure enough, I talked to one of the committee members. Well, actually, he got his PhD from Harvard University. He did a postdoc; I think at the same institution. And he's a great known inorganic chemistry professor. And I went to talk to him and he said you know what I switched labs in my fourth year too. And this burden right, this fear just lifted away. And I'm like what? Really? He's like yeah, it's common. You know, it happens. You just have to be amicable about it. And it's okay. It's okay. And that also kind of switched everything as well. Because at that point, I really hadn't talked to Roger yet. Because the Roger was giving a presentation believe it or not almost a week after I had this conversation. And Roger gave this presentation that he needed a graduate student, or somebody to help him with mosquito proteases. He said I need help with producing active proteases, write a grant and publish some papers. I really need the help. And so that's kind of where it led me to talking to Roger at that point.

Vincent Del Casino: So, this is Roger Miesfeld at the University of Arizona. And I say this because I know Roger. Because I was at Arizona. And when I got the job at San José State, he's like you've got to meet Alberto. He's just an awesome guy. He talks to highly about you. And clearly, because you're still connected intellectually, and research-wise with Arizona and people at Arizona. I mean you're doing big science across a number of different institutions. I mean your most recent grant from the National Institutes of Health, like 430,000 some-odd dollars right. You've got that lab now where you're creating the community that you talked about with your students. Did you know it was going to be mosquitoes for you or was it like Roger's working on mosquitoes and I love biology and chem so I'll go in on mosquitoes. And that's what the work will be.

Dr. Alberto Rascón: That's actually really funny because you know he was talking about mosquito proteases right. A type of enzyme that digests protein. And when I was an undergraduate student, we actually focused on a huge part of proteases. And I told my wife at the time, she was my girlfriend at the time, and I told my biochem professor, I'm like proteases, who cares about proteases . Well, fast-forward right. And working in Roger's lab. You know I really liked the challenge, especially because proteases are a type of enzyme. And so that really got me interested in that aspect.

And so when I went to go talk to Roger you know, he kind of laid it down for me. He's like this is what I want to do. This is why this is important. And so understanding that digestive aspect of the mosquito, you know, really interested me a lot. And that's kind of where my whole career, kind of, you know started. I was only in Roger's lab for two years, you know, it was an amazing thing. Because with Roger, you know he laid everything out for me. He's like look, I need to get this paper published. I need to write a grant. And if you can get two papers from the lab, I'll let you graduate. You know, you can move on from there. And you know you can get onto the next step.

From that point, I'm like okay, let's do this. And you know, with the work that they were doing, it was great. And again, you know mentioning how my perspective as a first gen student and my way of thinking is different from what they were doing. They were measuring these assays called an endpoint assay where you take your enzyme, you take a substrate, you let it incubate for I don't know 15, 20 minutes and then you measure the absorbance. And that's how they were detecting midgut activity. And I'm like no, you're actually dealing with a mixture of all these trips and enzymes. We could probably measure this real time at different time points during the blood meal digestion process.

And so, since the 50s right, everyone knows in the mosquito field that blood meal digestion is a biphasic process. But with the scheme that I came up with we were actually finally able to show this with the actual midguts using a chromogenic substrate. And you could see a nice curve of biphasic activity for every midgut at different time points. And because of this work, I earned a second authorship after being in the lab for maybe 6 to 7 months. Roger said okay, there's one. And I'm like, what? Really? You know this is something completely different from my previous lab. And so I'm like all right. So that really motivated me even more. And that actually also regained my love for science was, you know, that moment where it was like okay this is exactly what I wanted. This is exactly what, you know, you contributed something large to it. And sure enough we wrote an NIH grant. It didn't get funded. But we have a lot of data that turned out to lead to my solo publication from the lab.

Vincent Del Casino: So can I go back and ask a couple questions.

Dr. Alberto Rascón: Yeah, please.

Vincent Del Casino: Because you know, most people are going to be like biphasic, what do I mean here? Well, let me step this back just for a second, like why we're studying mosquito and these processes important? Because obviously right now your work today, it's actually really critical. Because we're in an involving climate situation. And mosquitoes, there's all different kinds of mosquitoes and so forth. So step us back a little bit. Talk about like what you were trying to accomplish in this lab. And how that leads to the kind of the questions you're interested in now. And what they mean for real world application. I mean this is like life and death kind of stuff you're working on in terms of, you know the impact on humans, right.

Dr. Alberto Rascón: Oh, definitely. And so you know we have to give credit to Michael Wells. He's a big-time entomologist biochemist who first identified some of the most crucial digestive enzyme in the mosquito. so the thing is, is that mosquito requires a blood meal from human host. And the species that we're working on and technically a few species of mosquitoes that only feed on humans. So you have the Aedes species, Aedes aegypti, Aedes albopictus. You have the Anopheles species that carry malaria. And then you also have Culex. So, there's about you know a handful of species that only feed on humans. And when they do, these mosquitoes release these proteases or these digestive enzymes to break down the blood meal proteins. And those are the nutrients necessary for egg production, but also gives the mosquito enough energy and other nutrients to lead to egg production.

And the thing is that these mosquitoes have evolved pretty much a synergistic effect with these viruses that they can pretty much transfer during the blood meal acquisition step. So the Aedes aegypti mosquito for example, and the one that we focus on carry dengue Zika, chikungunya, yellow fever. And they can be problematic to humans. And so there was this idea from Michael Wells' lab that well what if we can focus on these proteases. They're only pretty much released when a blood meal has been acquired by the mosquito. That's the only time these proteases are present.

So the idea was can we inhibit these proteases? And so they worked on this for very long time. But the problem is that a lot of them could not produce soluble recombinant protease. Meaning that you know it would take thousands and thousands of mosquitoes to try to isolate a very small amount of these specific enzymes. So with recombinant technology, meaning that you can take the DNA from the mosquito, the DNA gene from the mosquito and try to use a different system to try to express, or make more of this protein. And so one of the best expression systems in my opinion is bacteria. Because it's pretty fast. If you can clone the game properly, you could pretty much make a lot of recombinant proteins in four hours or so. It's a very fast system to produce these recombinant proteins.

But the problem was is that you know a lot of these bacterial cells would produce insoluble mosquito proteases. And so they tried for many years and even in graduate school myself, I could not actually produce a soluble or properly folded mosquito protease. So I had to turn to an alternative approach, where can you completely unfold this protein, and then try to re-fold it by removing, you know they call them chaotropic reagents. So this reagent kind of works to hide the hydrogen bonding effect of these amino acids and things like that to make a completely linear. But then once you start removing this high concentrated salt, the idea is that the protein should be folding back because now it has all this hydrogen bonding from the water. And it should be folding back into its proper confirmation. And sometimes that works great, and other times you know it's kind of a lost cause.

And I was just so lucky that for our system of proteases it worked. I was able to refold four of the most abundant proteases. And we were actually finally able to produce some recombinant protein to then really get a hold of what type of activity these enzymes have. Because in order to really put it into the big scheme of things, if you want to make it inhibitor against a specific enzyme, or you know in this case, protease you really need to understand its kinetics. You know what kind of substrate does it prefer. You know, can you actually inhibit it? What's the structure? What does the active site look like? And so if you want to make a specific inhibitor that only really goes after your intended target and no other secondary targets. Because proteases are found in every species you know in the human kingdom.

Vincent Del Casino: So you have to be really careful about what you do.

Dr. Alberto Rascón: Exactly. So that's why you know you really want to focus and you really want to make sure you go through a thorough biological study in knowing the enzyme specificity, the structural and things like that. To make sure that you don't affect anything else. And so that's kind of where the idea came from right. Because when I graduated from graduate school, I kind of, the project kind of ended. Because then the lab went in a different direction. Then when I was a postdoc, you know, I really wanted to learn more about Third World country diseases, and infectious diseases, and things like that. To kind of put everything into perspective. I really wasn't thinking about the mosquito project yet, right.

And so when I applied for post docs, I was also interested in doing a teaching, research postdoc. Where I could learn how to be an excellent science teacher, you know, not to hurt any of my science colleagues, but some of us cannot teach. Yes, we're great researchers, we're great presenters. But to actually teach science, some of us can't do that, right. So I wanted to make sure that I could be the best science teacher as well as a great researcher. And so that kind of led me to the UCSF where I not only did the teaching side of things, but also continued my research in infectious diseases and things like that.

Vincent Del Casino: Well, this is really interesting. You know, my background, I studied in Thailand. And I studied the HIV epidemic. And very different because it's not mosquito borne. But clearly, I lived in a part of the world that had a long history with malaria and other sorts of things, and dengue. And the mosquito you're talking about what's so interesting is there's a geography to these mosquitoes. So these are mosquitoes, because they feed on humans, they like high density urban areas. And, historically, the tropics. But these are real issues for us north of those boundaries now, right. Because we're getting climate. We're starting to see real cases of Zika in I think southern Florida, right,

Dr. Alberto Rascón: Oh yeah.

Vincent Del Casino: I think we've seen some of that. We've had reported cases of dengue in the United States, the continental United States. But so you start with this sort of tropical illness, that's urban based, but it's got real, it's spreading. It's got real impact on where it's going.

Dr. Alberto Rascón: Oh yeah, and that's the thing that during you know the Scholar Series Talk, you know I found an updated map showing how the mosquito pretty much has migrated from South America, through Mexico, through the southern states of Texas, Arizona, Georgia, Florida. And how they're moving north and in places that have been you know, historically pretty cold. And that's where the mosquito dies. But because of climate change, yes, we're having now the mosquito being found in places that were never found before. And so this could potentially be impactful in the United States now. Because before you know, when I first started in fall 2013, I had the map. You know and I would really recommend people to go see that Scholars Talk so you can look at the map.

Because when I first started, you know the boundary was not as, it was pretty low compared to the recent map now where it's higher. And the thing is that in that fall 2013 map, a lot of those cases were travel-associated. People went out to these countries and they were bitten by a mosquito, got sick, and then came back. But now, we're probably going to be seeing cases where now it's locally transmitted. As is the case with a lot of these southern states like Florida, where you see a lot of dengue, Zika. And so that could be problematic issue. Because all you need is one infected person and the mosquito. And once that happens.

Vincent Del Casino: And a little bowl of water, right, and a little bowl of water. Because mosquitoes are unbelievably prolific at breeding.

Dr. Alberto Rascón: Oh, they're yes.

Vincent Del Casino: They are amazing, right?

Dr. Alberto Rascón: A little tiny amount of water and she can lay up to 200 eggs.

Vincent Del Casino: And we're talking some serious illnesses. I mean dengue is bad and survival. But yellow fever. I mean you can die from dengue if you get it, you know--

Dr. Alberto Rascón: And that's the thing with dengue, you know, once you. The thing is that there's four different, and possibly five different serotypes, meaning that there's different types of these dengue virus. And the thing is that yes, the first time you're bitten and you get the dengue infection, you could pretty much survive it. But it's that secondary possibly tertiary could lead to the hemorrhagic stages where that's it. There's no more you can do about it.

Vincent Del Casino: And Zika as we know out of Brazil, I mean had dramatic effects on fetal development and these children were born with you know dramatically smaller brain sizes. I mean, these are some nasty sorts of illnesses. So now today, like you're working on, this kind of evolved into where you are. You've got your own lab. You've got lots of undergraduate and graduate students working on this stuff. And you're doing some really interesting work to try to resolve the question of how are we going to manage this. Because as you said if you muck the wrong way with the mosquito, we can actually transmit something that we don't know yet, right. Like we could have impacts on other species and so forth. So what are you working on now and what are you trying to accomplish with that work?

Dr. Alberto Rascón: Doing a postdoc at UCSF, it really opened my eyes on how really these are definitely neglected tropical diseases, right. But now that it's hitting our front door. I think a lot of people are going to be taking it a little bit more serious. And I think that's kind of where I was successful at the beginning with the NIH grant. Because I was able to convince them, like look, these numbers, climate change, we're going to see the mosquito is going to be a potential problem. And if we don't start doing something about it now, it's going to take us longer to figure out what's going on. And so with my training at UCSF, you know, I learned to do a lot of crystallography work on different enzymes, even other proteases.

And that kind of figured, hey wait a minute. I'm going to call Roger and ask him if that project is still going forward. And he's like no, and he gave me his blessing, you know and I took over the project. And what we're trying to really now do is really fit all the pieces of the puzzle together. Blood meal digestion is a very important process in the mosquito. But it's still unresolved. You know, in 2010 when I left graduate school, a publication came out with Colorado State where they identified other digestive enzymes.

And so now we're talking about maybe 10 to 11 different digestive enzymes. But how do they all piece together? How do they all collaboratively work to digest blood meal proteins. Because there's a possibility, then that maybe we can just make one inhibitor that targets all of them and nothing else. But in order for us to do this we need to really isolate and study each individual protease. We need to really know the differences and nuances between its digestive power if you really look at it that way. To see if it really will have an impact on the amount of eggs laid. Because the work in 2009, the publication that you know Aaron my [inaudible] from we did knock down studies of the three most abundant proteases and it resulted in not really a huge synergistic effect, right.

And so that's kind of what we have to piece all these things together to see if maybe knocking down all of them, or maybe others will lead to huge impact on the amount of eggs laid. Because then that could help minimize the mosquito population. And also in turn minimize pathogen transmission. And so that's kind of what we're focusing on now here at the San José State with a lot of my students. You know when I first started in 2013, I was tasked with teaching chem 131B which is our biochem capstone course. It's an entomology course, and they said okay here you go. Go do this. And I'm like but how do you want me to do this?

So it's like whatever you want as long as you cover what's in the catalog, you know all of that. I'm like you know what? I'm going to treat these kids as if they were in my lab, working on my research project. And sure enough, something that I could not do in graduate school as a graduate student, my students, my first semester, first year San José State found an article that they found these new bacterial cells that have a more oxidizing cytoplasm, that would help proteases, called disulfide bonds. So these are cystine groups, amino acid that come together to help properly forward and maintain the structure of the protease. So my students from that class found that article. And the next semester, we finally had those four most abundant proteases produced re-confidently, properly folded, with super high activity.

Vincent Del Casino: So what you're telling me is a group of undergraduate students at San José State pushed the science in a way that it had not been pushed before?

Dr. Alberto Rascón: That's exactly what I'm telling you. And that's exactly why they got published in 2018. If you read the article, you know, we have an acknowledgments section of students from chem 131B. And I believe three or four of those students are also authors on that manuscript too. Because this is something that you know as I mentioned earlier, the mosquito field was not able to do is produce soluble, active recombinant proteases. So now that we have the magic formula, I guess you could say, now we're actually going after all the other mosquito midgut proteases to see how they digest blood meal protein.

And the cool thing about this, and you know I don't really want to give too much because I don't want to get scooped, but we're learning so much that these proteases that were predicted to be their so-called activity. Let's say one of them is a trypsin like protease in our head is not a trypsin protease, it's some other type of protease activity. Which is great because now we can have a better understanding how it's not just a specific set of these digestive enzymes at work. It's a combination of these different proteases that have to come in to efficiently digest blood meal protein in a short amount of time. You know, you're looking anywhere between 30 to 40 hours for full blood meal digestion.

Vincent Del Casino: It's amazing. It's just so cool to imagine these students like walking into this lab experience, this class, this capstone. It's like we're going to actually address a practical question that has a real outcome. And that outcome, what's interesting about your research, right, it's a cross institutional. You're working with a number of different organizations and universities now, right, trying to address these concerns. Where else are you plugged into? Like what does your kind of network look like?

Dr. Alberto Rascón: You know it's really enhanced our understanding of these individual proteases. I have a great collaboration with UC San Francisco, with the Charles Craig group. His lab was actually the first lab to do any type of protease work, structural stuff on chymotrypsin and things like that. And so he's actually one of my collaborators in my grant to help us crystallize. So really solve the structures of these individual proteases to see what they actually look like in their active site. So we have hopefully you know during my sabbatical next year we'll get to do a lot of that work with his lab.

But also my former postdoc advisor, who actually left UC San Francisco, he's actually now the Dean at UC San Diego, I still have work with him. I actually publish with them still on a lot of work from parasitic enzymes and things like that. And also one of my good friends at UC San Diego who developed this great tool, a mass spec tool to detect the different substrate specificity of individual proteases. And you know, we actually have a paper in the works right now, you know I put it up on my CV, where he actually was able to detect different proteolytic signatures before and after a blood meal, using his technique. Which it's something that has never been shown before. You know everyone has always said that oh, yes, we detect protease activity after a blood meal. But what about beforehand?

And so mass spec is sensitive enough that we'll actually be able to detect that. I think it's going to be a great paper because with is work and then tying it to the recombinant proteases, we can actually profile each of these proteases and their different specificities. Because there are proteases in the mosquito that are similar in terms of trypsin activity right, overall trypsin activity. But when you get down to the nitty-gritty, they all actually have different specificities at different pockets which then improves our chances of making a specific inhibitor to target that specific protease.

And so with his work, in combination of course now with the University of Arizona and my friend June Easway [assumed spelling], and of course Roger Miesfeld, we can actually also do the biology side. If we do make in inhibitor for recombinant proteases, can we actually also then deliver this to the mosquito midgut and see what that effect is there. And then do the biological knockdowns and things like that to tie everything together and make sure that we are only, you know, one , focusing on the mosquito. But also seeing if there's an actual effect on blood meal digestion, and the amount of eggs laid. So yeah, it's a great collaborative effort. You know and I really thank them a lot all the time. Another thing too that I should mention is that they've offered my students a chance to go and learn these techniques, you know, once this whole pandemic is over.

Vincent Del Casino: You right now, obviously with everything going on, it must be just insane to just try to get some of the basic work done. But it is so interesting and it makes, you know really excited to hear about this work. Because you know those interventions. Because you're talking relative, toward the overall mosquito population, right, this is a relatively small group. And, again, it's a urban based. Because I know some people have concerns about knocking down certain species and so forth. But done in isolation, the importance relative to kind of overall human health and environmental health is critical. Because we don't even know you know where else things could potentially be passed over to.

Dr. Alberto Rascón: Definitely. And that's another thing that we get a lot of critiques from people that are not really you know involved in knowing the science with the mosquito and things like that. But there are thousands of species of mosquitoes. There's only a handful, and they live with us, they prefer humans. There's only an off chance that if they need a blood meal, they will bite another species. But if there's a human around, and of course being in an urban setting, there's always going to be humans around. You know and that could be the potential problem and disaster. And I hate to say it like this too, right and put some; but we should put some blame on us that we should be a little bit cleaner and make sure that we don't drop bottle caps or any little piece that can hold any type of water. Because then that will actually you know allow the mosquito to lay her eggs. And then become problematic.

Vincent Del Casino: It's an amazing piece of how important the human ecology is. And our trash behavior, our just ways of living. Because people don't think. Like a bottle cap, it's tiny. How could that possibly produce this, and then all the sudden, absolutely it can. And then it becomes very localized. They'll hang out right at that house, doing their thing right?

Dr. Alberto Rascón: And then not only this too, I should mention this because one of my students this semester in chem 131B, she gave a presentation on an article where they actually found that Zika survival in you know low pH sewage system is just as well as in you know, in the native settings. And it's just amazing how you know these things can actually you know lead to the survivability of these viruses too. Especially because the thing is that the eggs are laid in water. And if the virus can survive in sewage type of water, then there's a possibility that it might be able to infect eggs. I don't know this yet, but you know something to look into. But that presentation was just like eye-opening too, just to know also how relevant our work is becoming.

Vincent Del Casino: Well, it is so interesting, you know. And we're in a world now where people talk a lot about chronic disease, the post viral world. And yet COVID, every time we get arrogant enough to think that we've kind of knocked down the viral world, it comes back and hits us. It also hits us in a way that we should recognize our human role.

Dr. Alberto Rascón: Yes.

Vincent Del Casino: In the distributions and the networks that allow these things to happen.

Dr. Alberto Rascón: Yes.

Vincent Del Casino: That's what's fascinating, you know it's very, you know HIV very much took a lot of people's lives and so forth. It didn't need much to survive, because it could live 7, 8 years in a human. So that person could hold onto that. And it would take a long time to spread, but it survivability is intense. Even polio, still in some remote places we see it. And when the war breaks out and other things, we see flareups of these kind of things. To have a handle on this and doing the kind of work you're doing is critical.

Dr. Alberto Rascón: Thank you.

Vincent Del Casino: So yeah, Alberto, this is amazing. I could talk to you for three hours. This is absolutely awesome. I mean it's just so exciting what you bring to San José's state and to our students. But also to this broader scientific community that's trying to really tackle some deadly serious issues by thinking about things on a very small scale that massive impact and potential. So I just want to thank you so much for sharing your story. For being so open, but just for being a fantastic colleague. I just really appreciate the opportunity to pick your brain and learn a little bit more. So thanks so much.

Dr. Alberto Rascón: Oh, well thank you so much too. This was great and again I just want to shout out to all my students, right. They are the reason why I've been successful. They're the reasons why we've been able to bring in almost $1.3 million in grant money, you know. And I want to make sure that they understand that they're my colleagues too. They're starting out, but they're my colleagues. And I want to make sure that they know that. Because then that gives them that confidence. Something that I didn't have as an undergrad to go onto the next stage and be confident, like you know what I belong here. And it's something that I think is very powerful. Because I tell them even to this day, I'm a tenured professor with money and I publish. But I still sometimes don't feel like I belong here.

Vincent Del Casino: It's hard. It's a very humbling thing when you know when you're trying to tackle this stuff. I think that is wonderful. And it demonstrates as well just how valuable the research experience is to an undergraduate education. You've got to get in there and tackle some of these things. And when you do you realize you have the potential to answer some really wickedly big problems. You know, and that that's amazing. So, again this has just been a fabulous conversation. And thanks a ton. I really appreciate it.

Dr. Alberto Rascón: Yeah, thank you very much for having me.

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