 This is Think Tech Hawaii. Community matters here. And welcome to another episode of likeable science here on Think Tech Hawaii. I'm your host Ethan Allen here in the Think Tech studios. And with me today is Nathan Kanawa-Sunata. Welcome, Nathan. Thank you. Thank you so much for having me. My pleasure. Nathan is a PhD candidate in the College of Pharmacy at the University of Hawaii over in Hilo and happened to be on our island today and was able to come in and talk with me here. Thank you for being here. Yeah, of course. And Nathan earlier, he's a graduate of command male schools and then went off to Miami to get a Bachelor of Science and now is back doing his doctoral work, finishing up in, I should say, his bachelor's. He was a bachelor's in health science and a minor's in mathematics and chemistry. Very impressive. 18 classes helped a lot with that. You're in pharmacy and you've sort of taken an interesting path to get into your current line of research. You sort of started out, I guess, in sort of wanting to look at native Hawaiian plants and use them in sort of pharmaceutical ways, in medicinal ways. But you've taken another different shift now. Right. And so originally coming back from Miami back to Hawaii and specifically to Hilo, what drew me to College of Pharmacy was that I could actually explore some of our native plants, right? There's a lot of unique things. A lot of challenges also about going to school and doing research in Hawaii, but one of the unique things is that we can use our Hawaiian plants, right? As a foundation for sort of this unknown source of drugs, for drug sources, for natural products, for lots of things like that. And so my initial plan was to study that sort of line of work, right? As a Hawaiian myself, this sort of research to me is very important, right? It's kind of this translation from tradition to this Western sort of like mainstream being able to use this sort of thing. And so I thought that was kind of a really cool thing to do, sort of perfect for what I wanted to do. But as I kind of came along this thing, doing research is more about relationships and about people such as life, I guess in general. More than data, more than like getting results. I think that sense of life is about relationships. And so for whatever reason, that relationship with my mentor didn't work. In academia, it's very important that you're properly mentored. Absolutely. And so to me, I didn't get what I needed from that particular advisor. And so it kind of came full circle. I came back to my current advisor, who's Dr. Donna Lin Koh-Moh-Ling, who's actually who I wanted to have at first. She's the only Hawaiian on staff at the Plaza of Pharmacy. She has a lot of Hawaiian culturally outreach and things like that. And so I initially wanted her, but she wasn't able to have me at the time. And so it kind of came full circle. So I came all the way back to her and now we do cancer biology, which is very different than my initial start. But in some ways, we're more rewarding. Yeah. In a sense. And very interesting what you say about the relationships of being very important in science. You do need to be mentored. You need to have good advisors who can support you and who understand who you are and what you're trying to do just beyond just, are you good in the lab? Yeah. There is much more to a successful career than that. And also, especially being a minority, it's ideal to have someone to look up to. And being a Hawaiian in this STEM field, it's very difficult to find people to look up to. Oh, yeah. Pacific Islanders are terrible. That idols or anyone, even a success story, in my personal life, I don't know of any that have kind of navigated the steps that I have. And so to me, getting Donna now has been amazing. Let's jump in a little bit about this research. So you work on this neuroblastoma. It's a cancer of the nervous system, basically. Right, right. And furthermore, and rather an ugly way, it's a cancer that only affects, or primarily affects babies and infants and young children, right? Right, right. So actually it could be still slides two. So neuroblastoma is a cancer of the nervous system. So neuro refers to nerves. And blastoma refers to a cancer, but specifically a cancer of immature, undifferentiated cells. So graph on the right says neuroblast, which is a type of nerve cells, right, but young ones. And so eventually the neuroblast must mature into all these different types of nerve cells, like neurons, ganglion, all types of things. And so neuroblastoma occurs in between this transition step. And so that's why it occurs only in infants and children because they're still developing all of their tissues. And the neurons don't develop properly. The astrocytes fall apart, whatever. Right, exactly, exactly. And so this is a very difficult to treat disease. Also very difficult to diagnose because it occurs in infants and children, right? I'm not good at telling you what's wrong. Exactly. So the main, I guess you could say, the main diagnostic factor is like tiredness or like a swollen abdomen. And that's very difficult to diagnose in an infant because they're asleep all the time. They cannot vocalize like he said, right? What's wrong? And that just makes it very, very difficult to first find it. And then once you do have it, this is one of the most recurrent cancers just in general of all cancers. And so about 90% of patients actually died not from the primary tumor, but from the relapse tumor. And so our lab tries to treat this disease instead of, I guess, trying to reinvent the wheel, trying to find all these new sort of cancer therapies. Really, we're trying to understand what neuroblastoma is. What goes wrong with these cells? Well, I understand it better so that we can use, I guess, technologies that we already have. And so what we focus on is why does this tumor, is it so, why does it relapse so often, right? Why is it more than half of the patients always have a relapse tumor, a more aggressive, more cancerous, drug-resistant tumor, right? It's very similar to antibiotics, where after a while, antibiotics just don't work because you develop resistance. So cancer is the exact same way. Only you're using much more lethal forms of therapy. And so the resistance that it accumulates is very drastic and very sudden. And of course, infants are developing a nervous system very rapidly. Yeah, exactly. And the nervous system is everywhere. It's everywhere. It innervates literally everything in the body. And does this have a curve typically in one spot or another in the nervous system? Yeah, so it occurs most commonly in the adrenal gland and the nervous tissue above the adrenal gland. But again, like, this cancer metastasizes very quickly. So what that means is the cancer starts in the abdomen, but it can travel into the bloodstream anywhere, into the bone marrow, into the liver, into the brain anywhere. And that's really what really harms the patients, right? Because it's easy to treat it when it's a tumor. When it's everywhere, it's very impossible to eradicate it completely. And so again, all the more reason you want to catch it early, so you want to have a good diagnostic tool, so a lot of patients will tell you about it even if it's wrong, which infants can't do. Exactly, exactly. So you aren't picking it up too late in its course anyhow. Right, right. And so all these factors kind of makes it this difficult disease to treat. And so what we look at is how does it become this normal, this original neuroblastoma tumor and become this drug-resistant tumor. And we look at lots of different cellular signaling pathways, right? Yeah. Specifically, we look at calcium, which is a sort of fundamental signaling molecule in every single cell in the body, regardless of its muscle, skin, your eyes, anything really mobilizes calcium for anything, for a regulation of its life. So it can also kill itself based on its calcium, all these sort of things. So if you try to understand cancer in general, right? Cancer is a dysregulation of all these factors, right? For one, the main one is growth, right? That's what cancer is, right? Grows uncontrollably. But also all of its biology is sort of very, very aberrant. Right, right. Most cancer cells have very abnormal appearance. Almost exactly, exactly. And so calcium is just one of those pathways that's... But it's a very important one. But because it's so fundamental, that's kind of what we're choosing to look at. Okay. So maybe go to that next year, slide three there? Yeah, yeah, sure. So this is a schematic that I've made just, this is any cell in the body. So every cell contains calcium in it and your cell stores calcium in the endopasic reticulum, which is that kind of squirrely thing with the dots in it. And it stores it in here so that when it needs it, it can release it. And then that's kind of what triggers all these different effects. So essentially what we look at is everything colored in here, we measure all these pumps and channels. Types of receptors there. All these receptors, right? All these things, there's a whole global calcium signaling pathway. Right. So our goal in our lab is to figure out what is altered as the neuroblastoma develops drug resistance. And once we have targeted these things that contribute to drug resistance, and we then knock them down and revert it back to this original state where we can then treat it again with the normal sort of chemotherapeutics that work very, very well. And you've got some dynamic old videos here, I think that. Yeah. So the way that we measure calcium is we stain cells. So these are live cells. So this is just examples of different organelles in the cell which are different compartments. So this is the lysosomes which are just storage compartments. They're stained red. The calcium is green. This is the endoplasmic reticulum. When we apply a certain stimulus, you can see them sort of burst, right? And so that correlates with calcium releasing specifically at the ER level. This next one is the mitochondria, which are red, right? And then they'll flash through. And so really calcium signaling is very global in the cell. It affects essentially everything. Right, things are trading. Things are trading. Right, there's a lot of crosstalk between all these sorts of things. And this last one is just the nucleus. Again, there's a lot, a lot going on. There's a lot to unpack. Sure, sure. In the signaling pathway. But the way that we sort of extrapolate data from this is we take these figures, right? These live cell images that we've stained with color, and we can extrapolate graphs from it in real time. And so we can say that as we apply a certain stimulus to the cell, it will release calcium in this sort of linear sort of way, and it will kind of fade out. And this depends on the cell type, right? And as the cell develops from regular to drug resistant, this signaling kind of changes. So can we see figure, or the video for? So these are the figures that I'm talking about, right? So black and white would be differences between normal and drug resistant, right? And this kind of pairs with the graphic on the right. And so from the top graph, it's very obvious that there's a big difference in the right-hand side, right? There's a huge jump. The bottom graph is not so easy to see. But this is the kind of data that we kind of extrapolate to get and see. All right, there are definitely differences. So if we could negate those differences, can we then treat them normally again? And you would negate them by going back and either blocking receptors, or open them up or something, right? Right, so a cool thing about calcium signaling is it's very well understood. It's fundamental to all cells, so it's very, very well understood. And so there's lots of tools that we can use to inhibit, block certain things. There's a lot of ways that we can manipulate. But our key really is identifying. It's finding what should we target? Like what can we do to kind of help in this thing? And that's kind of the challenge, but also like the exciting part in it. Sure, and it's a very interesting point you're trying to move in. It's not looking at what makes a normal cell become cancerous, but it's what makes it through the first stage of the cancerous cells become really nasty. Right, because neuroblastoma is classified by risk, right? There's low risk and high risk, and 60% of the cases are high risk. And the high risk, there's almost no survival from them, right? I think the general survival rate for neuroblastomas in general is like 60-something percent, right? It's one of the lowest out of all childhood cancers. And so drug resistance is a huge part of that, because you can treat them very well initially. But when it comes back, they're just intolerable to throwing tantrums and everything in the body. It's very, very difficult. Fascinating to see this and, of course, huge applications for this. Once you learn that, these mechanisms that probably will inform other people with other forms of cancer, too, which also go through that same transition being reasonably amenable to treatment early on. And then at some point, they change and become truly metastatic and want to go all over the body and behave in much more aggressive fashion. Yeah, 100%. So I think the biggest finding that we've found so far is that they tolerate their calcium internally differently. So I've said that every cell stores calcium in the ER. But the drug-resistant cells, it's like they can tolerate more calcium in their cytoplasm, and so they don't store as much. And so when they do release it, they release less. And so they turn things on differently, turn the proteins on, turn everything on just a little bit differently, which has this cascade of all these different downstream effects and all these things and so on. Yeah. It sounds like very exciting work. I think you've got your work cut out for me. I'd say so. John security. That looks great. But there's a whole other part to your work that is you've really gotten where you are as you come in briefly early on. There are not many Hawaiians, native Hawaiians. Or Pacific Islanders in science and STEM. It's not a... There are many cultural aspects why this is so and all. And when we come back, we're going to talk a little bit about that. But right now, we need to take about a one-minute break. Nathan Sonata is here with me. I'm Ethan Allen, your host of Likeable Science. And we'll be back in one minute. Hi, I'm Rusty Kamori, host of Beyond the Lines on Think Tech, Hawaii. My show is based on my book, also titled Beyond the Lines. And it's about creating a superior culture of excellence, leadership, and finding greatness. I interview guests who are successful in business, sports, and life, which is sure to inspire you in finding your greatness. Join me every Monday as we go Beyond the Lines at 11 a.m. Aloha. Welcome to Sister Power. I'm your host, Sharon Thomas Yarbrough, where we motivate, educate, and power and inspire all women. We are live here every other Thursday at 4 p.m. And we welcome you to join us here at Sister Power. Aloha and thank you. Welcome back here to Likeable Science on Think Tech, Hawaii. I'm your host, Ethan Allen. With me today is Nathan Sonata from the University of Hawaii at Hilo. He's finishing up his doctorate in the School of Pharmacy there. We were talking in the first part of the show about the cancer research that you do. Very exciting stuff on neuroblastoma, rather nasty childhood cancer, all the complexities that you just give. It's a very nice summary of why it's so hard to work with what strides you're making. But there's been beyond sort of the academic, cognitive challenges of working in this area. You faced some other challenges, right? We commented earlier when we were talking, you graduated from Kamehameha School in a class of 450 people, I think you said. And you think there's a handful that was gone into graduate school. Yeah, as far as I can tell, very few of my classmates pursued graduate school and, of course, even less pursued PhDs. I know of a few in med school, right? I know of one PhD who's in mathematics, I believe. But there's a lack of, I guess, research-based sort of pathways that are being taken. And I'm not exactly sure why that is. I mean, I think there's cut a lot of factors, honestly. Yeah, I mean, certainly, I know Native Hawaiians and Pacific Islanders are grossly underrepresented in the whole STEM field, STEM education. At every step you look at all the higher levels. I mean, even bachelors and masters and doctors, the percentages keep dropping and dropping. And some of this, as we were talking before this show a little bit, may have to do with a whole cultural approach, right? Yeah, definitely there's a lot of cultural into that. I mean, especially just in Hawai'i, there's just that landlocked element, right? There's the family element, right? Your family depends on you for lots of things and so you can't leave in some senses, right? There's also the other aspect where you don't want to leave because this is so comfortable to you, right? There's also a part where it's not really pushed, where like, well, like I said earlier, we just don't have a lot of people to look up to, right? Right. We don't have a lot of people to say, oh, this is exactly how you can obtain this type of degree and this is exactly what's going to happen. And so without that, I mean, I think you have to use your imagination and if you're not comfortable doing that, then I think it's very difficult, right? So that's why I'm so lucky that I have someone like Donna who is done exactly what I did and she's a woman, right? Right. So she's a Hawaiian woman in hard STEM science and so that to me is very, very inspiring, right? And she's given me lots of great mentorship, but I think in general just for the kids, I think, you know, like, science should be pushed a little bit further maybe. Right, right. But part of it is, as you say, we've procured the islands, right? We don't have a thriving pharmaceutical or biotech industries right here very much in Hawaii. We're getting a little bit now, but it's been very slow coming. So it haven't been that many opportunities for anyone, much less Native Hawaiians or Pacific Islanders, to be in those positions, be STEM leaders, be STEM role models. As for the universities have been pretty slow when picking up Native Hawaiians and Pacific Islanders into the faculty positions. Right, right. They are underrepresented there. If you're going to be successful in this type of field, I think you kind of have to go away. And then if your plan is to come back, you have to come back only after the fact. You have to gain some experience. Like you said, there's just not that much opportunity here for at least research-based sort of programs. And there are wonderful efforts now to contract that trend. I do some external evaluation for the EPSCOR, the National Science and Education EPSCOR project, I keep eyeing with Hawaii's groundwater and one of their goals is to get more Native Hawaiian students involved in doing this fundamental water research. And that has enough for interesting and sort of culturally appropriate pull. The water has been very central to Hawaii and so studying the water makes some sense to a lot more students and it's actually interesting to see. So I think that's a good point you made though where it's about interest. And how do you generate interest in the Trojan? Because I mean, at least when I was growing up, it wasn't cool to be a nerd. It wasn't cool to like science and like math like I did. I like picking rocks and looking for bugs and stuff like that. And I love science and I love that sort of thing. And it's not as... I think it's more accepted now, right? This generation is so much more up with technology, with being able to do all these different sorts of things that my generation didn't have. But again, how do you sort of channel that into careers, right? Not just like, oh, I'm good with my phone. I'm good with social media. I'm good with my computer. How do you channel that into, oh, I'm good with tech. I'm good with coding. I'm good with like doing some sort of like real science. So I think that's become the issue, right? Where like everything's at the tip of everyone's fingertips now. Right. But it's integrating that into like a way that's like motivating, I guess, for the younger generations. Yeah. As you say, it sort of does open up some doors and windows. I mean, for instance, this program that we're producing now will allow you to sort of be an image or role model at least on some superficial level to a gazillion people, right? And that wasn't around 10 years ago, 20 years ago at all. So these channels have opened up but still, even if children grow up and see sort of one video or whatever some role models when they get to an actual university, they're still going to find... Right, they're still going to be minorities. They're still going to not have as much support as the rest, but I think to your other point, I think isolation too is a big factor. Right. Just being in Hawaii in general. Right, it's just very isolated from everything else. It's broken up into a, you know, small islands that are separated from each other. I mean, education is hard. There's a lot of travel in the hall, which is expensive and difficult. Right, so just from what I've seen on the research side, it's difficult to be out here by ourselves, right? Especially when we have the pharmacy school in Hilo and we have the medical school and the rest of the facilities on Oahu, it's very difficult to sort of collaborate and share. And also when we collaborate with other PIs, like for example on the mainland, right? When we have to exchange information back and forth, that gets hard just by the hourly, but you can work through that. But when you have to ship goods, like sometimes we ship cancer cells, sometimes we ship drugs, treatments, like that has to go overseas and has to be on ice, right? It has to be all these sort of things to make sure that it lands okay. And so that creates its own set of challenges too. Yeah, but they're, you know, again, we have technologies now that are overcoming them. I've been interested to see this, the so-called cyber-accountability now, how it connects Hilo and Manoa here, campus is very neat with these big, huge, multi-screen events so you can really get people, essentially almost in the same room, even if they're separated, you know? As that continues to grow and develop, presumably that's going to help address some of these issues. Yeah, absolutely. We're going in the right direction, absolutely. I mean, it's just a matter of time where, I mean, I think, as a whole, kids are more excited about science than they used to be, I think just as a general rule of thumb. But again, it's not where it needs to be, especially in specifically the Hawaiian community. It's just not that... Again, there's no role models. Right, right. So they would rather, I think, better role models in the Hawaiian community are other types of leaders, not necessarily academic leaders, right? I think they look to lots of other figures about scholarship. If we had a good representative of our field, I think that would make a big difference. But again, being a Hawaiian and being a minority is not strictly negative. I think it depends a lot on how you look at it, right? So it's all some of the benefits and advantages. So very easily the biggest benefit is scholarships, right? Being a Hawaiian has afforded me so much opportunity just by being Hawaiian, right? Just by going to community schools and having some of this culture like it, it's very beneficial, right? And it makes me very attractive as an applicant. So as I... Since I'm applying for research grants and all this sort of thing, incorporating minorities into your grants and stuff is very powerful. And so I'm able to get funding based on, I guess, just my ethnicity, just that sort of thing. And so if you look at it from that perspective, then being a minority is really cool. It's really unique. And really, in some ways, it's the first thing that separates me and then it's my merit, right? Because on a sheet of paper, everyone looks the same except that sort of thing. And so, yeah, I've never really viewed it as that much of a crutch. It's just like another barrier you have to pass through. Right? It's like, if I was going to quit, I would have quit a long time ago, right? Just being that is not really enough of a factor, I think. You can't spin anything to be positive as long as you want to. Right. Your attitude is going to determine that. Again, this gets us back to earlier discussion about why you need good mentoring and good support from an advisor because that helps sort of put the whole attitude around you and the attitude of the lab that you're in is very important. I always knew that fact, but I think being in this program has really solidified that for me it's very independent my whole life. I can always do things by myself. I could always figure it out, but there was a point in this program where I couldn't. And that was very humbling for me because there's a point where I need help. And I'm not very good at accepting help or asking for help. I think a lot of people aren't like that. And so that was very humbling for me and once I kind of opened it up it's like this sort of relationship kind of evolved through it but amazing. Yeah, science particularly now is becoming increasingly collaborative and it's got the very clear to you in the cancer research. You've got to have all kinds of different people from clinicians to basic bench scientists and everyone's sort of in between and electronics wizards and chemists working with you and all these different kinds of groups helping out and putting their expertise together in a coordinated fashion to make this all work. We look at one ion in the cell right, calcium. And so it's very easy for us to get tunnel vision and kind of forget about the big picture. Sure. The old saying is that's what graduate school teaches you to look more and more about less and less until you know everything there is to know about nothing at all. Yeah, exactly. Exactly. The programs are trying to get around that now. They are actually making efforts to broaden out and help in broader perspective. But that's why it's always good to... students of Hawaii advanced research program has afforded me a lot of opportunity to go to conferences once a year. And so at these conferences I've interacted with lots of different types of health professionals. So not only researchers like me, but medical doctors and nurses and parents of patients. You kind of get this total perspective on everything and that's very important when you're... because the bottom line is about patients. This disease not like publishing papers or getting recognition. The point is the patients. Without understanding all of the factors you're only doing... You slice that but it's a big pie. There's no point in finding a novel drug when you have to apply this... You have to give the patient a lethal dose There's no point. You have to look at it Absolutely. This has been fascinating but we have come to the end of our time here. Nathan Sonata, PhD candidate at University of Hawaii in Hilo School of Pharmacy there. Thank you very much for being here. I hope you'll come back and join us on another episode of a likeable science next week.