Eva Dale 0:00 From the heart of the Ohio State University on the Oval, this is Voices of Excellence from the College of Arts and Sciences, with your host, David Staley. Voices focuses on the innovative work being done by faculty and staff in the College of Arts and Sciences at The Ohio State University. From departments as wide ranging as art, astronomy, chemistry and biochemistry, physics, emergent materials, mathematics and languages, among many others, the college always has something great happening. Join us to find out what's new now. David Staley 0:32 Joining me today is Amanda Hummon, who is an Associate Professor of Chemistry and Biochemistry at The Ohio State University, College of the Arts and Sciences. Her research interests lie at the intersection of analytical chemistry and chemical biology with a focus on cancer biology. Welcome to Voices, Dr. Hummon. Amanda Hummon 0:51 Well, thank you very much, it's a real pleasure to be here. David Staley 0:54 Your lab studies colorectal cancer, especially using a technique called mass spectrometry. First of all, tell us what mass spectrometry is, please. Amanda Hummon 1:03 So, mass spectrometry is a very powerful technique where we weigh molecules, way molecules, when you first hear about it, it doesn't sound like it'd be all that powerful. But when you start thinking about it, everything has a mass. And we have instruments that can weigh these molecules very precisely, and be able to discriminate even slight differences in mass between different molecules. And those are there for diagnostic for the individual species. And so we can weigh all sorts of different molecules and figure out what they are by looking at not just their masses, but also if we break them apart, we can look at how they fragment and look at their fragment masses. And so in this way, we can look at all kinds of different species and be able to figure out not just what we have, but also how much we have. And so mass spectrometry has been used in all sorts of different applications. So for example, there's a mass spectrometer on the Mars rover that is being used to figure out molecules on Mars, my lab uses mass spectrometry a lot to look at molecules within the human body. So if we weigh different proteins in the human body, we can figure out the identity of those proteins, and how much are present for those proteins. And we can even look at where they're present in the body. So for example, if we take a tumor, we can use mass spectrometry to look at which proteins are there, how much is there, where they are, how they're interacting with different drugs, it ends up being a very powerful technique, again, because everything has a mass at the end. So, pretty much any molecule can be studied with mass spectrometry. David Staley 2:44 So, you have to help me with this. Are we talking about something like a scale, or is there some other sort of technology involved? Amanda Hummon 2:49 Yes, it's a scale where we take the molecules, we have to first ionize them and nebulize them. So, we have to make them gases, and we have to add charge to them so we can manipulate them in space and time, which is as cool as it sounds. Sounds very cool. It's very cool, yes. But at the end of the day, yes, they are very expensive scales. So, these instruments cost hundreds of thousands of dollars. But we can use them to look at all sorts of different species, and be able to learn a lot about different molecules. David Staley 3:19 Well, you've sort of made mention this already. What does weight tell us about the properties of different molecules? What does weight tell us? Amanda Hummon 3:27 At the end of the day, it can tell us the identity of a lot of different species. So if we take the example of proteins, proteins are commonly thought of as words that can be strung together into sentences. And those words, if we continue with our analogy are built of different letters and the letters in a protein would be the amino acids, each amino acid has a distinct molecular weight. So we can use mass spectrometry to figure out those different weights, which then help us figure out the proteins and because a lot of diseases, for example, are fueled by proteins, if we can understand the different proteins, we can understand a lot about human health, the evolution of disease, all sorts of real fundamental processes that control the human body. David Staley 4:12 Your lab is looking in particular at colorectal cancer: how do you use mass spectrometry to study that? Amanda Hummon 4:19 So, we use mass spectrometry to look at both the naturally occurring molecules that are present within a colon tumor. So if a patient develops a colon polyp, if we are given a sample of that tumor by a colon surgeon, we can use mass spectrometry to look at the different molecules that are present within the tumor. So we can perform specific chemical extractions to pull out, for example, the proteins that are present or the lipids, and we've done a lot of work characterizing those molecules that are present at different stages of the cancer. So for example, some will be more commonly observed in early cancer. Some are more commonly observed in later cancer. So we can Look at the naturally occurring biomolecules like proteins and lipids, we've also done a lot of work characterizing drugs. So there's a huge effort going on to try to develop better drugs to treat colorectal cancer. And so we have tumor mimics that we grow in cell culture, we can treat those tumor mimics with various different drugs and then use mass spectrometry to see whether the molecular weight of the drug is still there. And then what metabolites have been formed as well metabolites. So metabolites are the byproducts of the drug. So they're formed by metabolism. So as the drug is broken down by the body, it will be converted into metabolites that then interact with the cells within the body. And so it gives us a real sense of whether a drug is working as well as it's supposed to. David Staley 5:43 You talked about the role of proteins, you say that proteins can sometimes be a cause for these kinds of cancers, but I always sort of associated protein as a good thing, something my body needs? Amanda Hummon 5:53 Absolutely. Yeah, no, so proteins are a fundamental building block, and you need them, they're part of your daily intake, and absolutely essential for life. Unfortunately, in very rare cases, some proteins will go awry, they can, for example, fold in different ways. And so they have distinct functions that you want them to carry out within the cell for the cell to remain healthy, if unfortunately, something goes wrong. So for example, you get a mutation in your genetic code, that will result in a slightly different protein, and then the protein will not be able to carry out its original function. And in many cases, that won't be so bad. But in some rare unfortunate cases, those misfolded, or mutated proteins can lead to the development of cancer, and that's a lot of what my lab studies. David Staley 6:40 And so you're also looking at drugs and drug interactions, your work mostly looking at sort of causes or ways to treat cancer, or both? Amanda Hummon 6:49 So, we spend a lot of time right now developing methods to help evaluate how well a drug is going to work. So for example, we have collaborations with groups that are developing new drugs. So for example, we work with a well paced lab in the Department of Chemistry, his lab is developing a whole new class of cancer drugs. And they needed a way to be able to figure out how well those drugs would move through a tumor. So if you have a tumor, you don't want a drug to just treat the cells on the very outside of the tumor, you want the drug to be able to penetrate within a cell mass, move inside the tumor, and be able to treat all the cells in the tumor. And with our various mass spec methods, we can evaluate if a drug makes it all the way into a tumor, and if it's treating all the cells within the tumor, and so we spend a lot of time developing methods to help evaluate how well these drugs are working. David Staley 7:39 Presumably, you work as well with the OSU Medical Center. Amanda Hummon 7:43 Oh, absolutely. So in fact, my lab is located in the biomedical research tower, and I am a member of the molecular carcinogenesis program within the Comprehensive Cancer Center. So my lab, we divide our time, we are actually divided between three different entities. So we are in the Department of Chemistry and Biochemistry. We are also, as I said, members of the Comprehensive Cancer Center, and then we are also part of the foods for health discovery thing. So, we have our foot in many doors. David Staley 8:10 So one of the things I found fascinating in your research is that - and I want to make certain to get this right - tumors or cancers of the colon that form on the right side are distinct from tumors that form on the left side, such that maybe they are maybe even distinct diseases. Tell us about this. Amanda Hummon 8:28 Yeah, this is a wild concept, and I heard about this a few years ago, and it kind of blew my mind. Yeah, so the colon, it's a very big organ. I know most of us don't like to think about our colons in general, right. But it's, you know, it's also pretty important for life. And so the colon, it has three major sections, it has the ascending colon, which is the right side, it's got the transverse which is what cuts across your abdomen, and then it has the descending colon, which is the left side of the colon. And it turns out that colon polyps form on the right side and the left side, almost never on the transverse, which is bizarre, and I have yet to find a good reason in literature why that's happening. No one really knows why human beings don't get polyps in the transverse colon, it's just an area where they are extremely rare. So the vast majority of cancer will form either on the right side or the left side. And they're extremely different when you start looking at them from a genetic perspective. Or when you look at how they respond to different drugs. We have been working in collaboration with a number of colon surgeons to characterize the protein composition of these two try to get a better sense of what are the molecular underpinnings of these differences? I think a lot of it derives from basic embryology that the colon is formed from two different sides of the embryo that come together and fuse. And so the colon at the end of the day is probably two separate organs that are fused together, which is why the cancer is so very different. David Staley 9:51 And has this affected treatment? Amanda Hummon 9:53 Yes. So, just within the last year or so... David Staley 9:56 Within last year? Amanda Hummon 9:57 yeah, within the last year or so there have now been different says in the recommendations for clinicians recognizing the fact that if a colon polyp develops on one side of the colon versus the other, that the treatment path should be different for patients. David Staley 10:10 Does that mean different drugs, different...? Amanda Hummon 10:13 Yep. So, one side of the colon responds much better, for example, to immunotherapy drugs, where other sides will respond more to the classic small molecule chemo therapies. So we're now at a phase where the treatment recommendations are quite different depending on where the polyp develops, but we still don't understand entirely why that's happening. David Staley 10:31 Well, that was my next question. Do we know why this is the case? Amanda Hummon 10:33 No, no, yeah. That's a lot of what we're getting at. David Staley 10:36 And is there anything sort of analogous in the body, are there other areas where you have that sort of asymmetry? Amanda Hummon 10:42 Not that I know of off the top my head, as I said, the colon, when you think about the geography of the human body, it's a pretty big organ, right? And I don't know of any other examples of that. Eva Dale 10:54 Did you know that 23 programs in the Ohio State University College of Arts and Sciences are nationally ranked as top 25 programs, with more than 10 of them in the top 10? That's why we say the College of Arts and Sciences is the intellectual and academic core of the Ohio State University. Learn more about the College at artsandsciences.osu.edu. David Staley 11:18 I think this has answered a question I have, and this is maybe a naive question, but is cancer cancer, or are there different sorts of cancers; in other words, colon cancer is different from lung cancer is different from pancreatic cancer? Amanda Hummon 11:32 They're all quite different. There are some similarities that you start to appreciate as you study it more. So one of the main similarities is where many of the soft epithelial cancers will metastasize to so metastasis is when a primary tumor sets up a secondary location somewhere else in the body. So what will happen is a primary tumor will develop. So for example, a colon tumor will develop in the colon. And if a cell breaks away from that primary tumor makes its way into the blood supply, and then is able to survive being in the vasculature. If it's able to set up a secondary location in the body. That's what we refer to as metastasis. And that that is really the crucial point that determines survival for a lot of patients. Unfortunately, the good news is that only one in a million cells will survive that process. So it's actually a very inefficient process, which is obviously very good. But when you start looking at patterns of metastasis amongst a lot of the soft epithelial cancers, they're very similar. So there's this proposal that came out in the late 1860s called the seed to soil hypothesis 1860s 1860s. Yeah, Stephen Piaget came up with this hypothesis, because he was studying patients that had developed all these different types of cancers. And he kept on noticing that the same organs brain, bone, liver kept on coming up over and over, regardless of where the original cancer started. And so he came up with the seed to soil hypothesis, the seed being the tumor cell in the soil being a secondary location. And so there's a lot of interesting work going on now trying to figure out, are there ways that we can make those secondary locations less hospitable for the cells that have broken away, and that's work that I would be interested in getting into, we have not moved in that direction yet. But if you're talking about ways that can help people, that would make an enormous difference in terms of cancer survival, if we could make those secondary sites less hospitable in some way. David Staley 13:29 Well, one area that I know that your lab is working in is nutrient restriction. Amanda Hummon 13:33 Yes. David Staley 13:34 So tell us what this research is about, nutrient restriction. Amanda Hummon 13:37 So, this research came about I had a student a few years ago, who was extremely excited about not just analytical chemistry, but she was also very interested in all these very popular nutrient interventions that are going on. So undergraduate or graduate graduate strategy. So graduate student, she has completed her PhD and moved on, she's off working in the world now. But she was extremely interested in looking at the intersection between nutrients and cancer progression and studying by mass spectrometry. So there are a lot of popular dietary interventions that are out there right now. So for example, the five two diet, so the five two diet is where patients, people, not patients, necessarily or people can eat whatever they want five days of the week, and then two days of the week, they restrict their calories significantly. So on this program, you would eat only 500 calories on those two days a week. Wow. Yeah, so it's a severe restriction. So that would be an example. That's the five two diet I'm not advocating and just reporting these things. So that is one example of a popular dietary intervention that's been written up a lot in the press. And there's compelling reasons why people are moving towards these types of extreme changes. So caloric restriction in general just refers to restricting your calories. So neutral restriction, caloric restriction are kind of interchangeable terms. So if the daily recommendation for humans is about 2000 calories a day, from the federal government nutrient restriction be restricting that by about 60%. So really reducing it down to 600 calories a day or somewhere in that range. You're not talking starvation. Obviously, starvation is not good for your health. But there is accumulating evidence that restricting your calories can have all these other good health benefits. So everything from improved immune function to reduce cancer rates, living longer, and in general, being healthier. Now, the downside of this is that there haven't been as many rigorous studies done in human beings at this point, a lot of the work has been done in model systems. So yeast, C. elegans, there's a lot of mouse models. Oh, so C. elegans are worms. So yeast and worms and mice, who can't fight back when you take away their food, right? But studies with humans, there just haven't been as many that have been done, in part, who wants to participate in that kind of study, right? People love to eat. And when you really start thinking about eating five to 600 calories a day, every day, that's a hard one to do. Right? Eating is one of the joys of life. David Staley 16:10 So what explains this, what's the causal connection here between eating less or less caloric intake and these health benefits? Amanda Hummon 16:18 So, it's all traced back to an internal cellular mechanism called autophagy. So a toughie G, which was recognized in the last couple of years, it was recognized in 2016, with a Nobel Prize in Physiology and Medicine to Professor you shaming in Japan, a toffee G is an intracellular process, where the human cell, the mammalian cell, will sense that there's no external nutrients. So there's no calories coming in from the outside. And what will occur is it will trigger this process to essentially salvage debris that's floating inside the cell for survival. You think your your classic biology textbook where everything's very neat and tidy, you have all the organelles that are exactly where they're supposed to be. The inside of a human cell is actually really messy, like a lot of our lives, right? There's all kinds of random debris kind of floating around within the cell. And with the process of a toughie, G, the cell will trigger this program to consume that random debris that's floating around. So it's a survival mechanism. So if the cell is not getting food from the outside, it instead will harvest the floating garbage that's floating around inside the cytoplasm. And that's what the cell will do to survive. And it turns out that it's actually really good for you to have that random garbage vacuumed up and consumed. So in a human being, if you don't eat for 14 hours, your cells will start triggering a toffee G. And so it's believed that that is the mechanism, the molecular mechanism that is leading to these health benefits for human beings. David Staley 17:50 And there's a potential connection with cancer, colorectal or otherwise? Amanda Hummon 17:55 So, what we have looked at in my lab, so my previous graduate student, Monica, and the one who was so interested in nutrition, she wanted to look to see what would happen to the colorectal cancer proteins if we took away nutrients. So she started at the beginning part of her PhD, we took away sugar, we took away glucose, because cancer cells traditionally have very high sugar consumption. So we took away glucose from the cancer cells, and then we look to see what proteins changed. We did a series of other studies. And then her final study for her PhD was taking away the nutrients blocking the process of autophagy, and then adding chemotherapy drugs. And what we found was that the chemotherapy drugs worked better in our cancer cells, when we took away sugar. It was an extremely exciting result that we saw this improved drug efficacy with the nutrient restriction. The big caveat I should add to this is we have only done this work thus far with colon cancer cells. So we now need to repeat all these results with normal non cancerous cells and see if the same thing happens. Because if the same thing happens, then its utility from a clinical perspective is reduced. But as of right now, these are, I think, very exciting studies, because everyone needs to eat. This is a universal mechanism. And so, I think many cancer patients would be willing to eat less sugar, if it means that the chemotherapy would be more effective. David Staley 19:19 I'd asked about students in your lab, do you have undergraduates? Amanda Hummon 19:23 I do, yes. David Staley 19:23 What sorts of things do the undergraduates do in your lab? Amanda Hummon 19:26 So, the undergraduates work in tandem with the graduate students? So they also we'll go ahead and perform, for example, mass spectrometry analysis. They do a lot of cell culture. So I've mentioned our cell culture, or tumor mimics several times and so they are also right there in the lab, growing those tumor mimics and performing experiments on them. They have to work around their class schedule, so we have to be a bit more flexible in terms of their projects. But yeah, they are very involved in the whole process. David Staley 19:54 How does an undergraduate end up in your lab? What sort of qualifications must they have? Amanda Hummon 19:58 So I generally, we look for the students who are really motivated and excited. I like students who have, you know, some background in chemistry and have taken some of the lab classes, but I also recognize that you know, a lot of it is just getting to learn and developing those skills in the lab, I think it's absolutely crucial to have that undergraduate research experience, if you're going to go on for a career in research. That's how I got started. David Staley 20:24 Well, I was gonna say, what do most of your undergraduates in your lab, what do they tend to do after they leave your lab? Amanda Hummon 20:29 So many of them will go into medical school, obviously, a lot of them are attracted to my lab because of our focus on cancer. But then several have also gone on to chemistry graduate school. And that's really cool to see them moving on and progression in making that transition from student to scientist. David Staley 20:43 I was really struck when I was looking at the website about your lab that you listed the alumni of your lab, which I don't always see, and I was just struck by how many there were. Is that unusual for a chemistry lab? Amanda Hummon 20:54 No, actually, chemistry labs tend to be on the larger side. So I've been very lucky, there have been a number of students over the years who've wanted to work with me. So we've had a very vibrant and dynamic group over the years and a wide range of successes. It's interesting all the different fields, they go into that I don't predict at the beginning, but they know where they want to be. David Staley 21:13 Tell me about classes that you teach at Ohio State when you're not working in the lab. Amanda Hummon 21:17 So, I have taught three classes here at my time at OSU, I should mention, I spent the first eight years of my career at the University of Notre Dame. So, I was hired there as a new Assistant Professor in 2009, and then I moved here to Ohio State, let's see 2018, which has, it amazes me, I've been here almost two years now. David Staley 21:33 And you brought the lab from Notre Dame to Ohio State. Amanda Hummon 21:36 Yes, my lab moved with me from Notre Dame to Ohio State in 2018. So in my two years here, I've taught three different classes. So I teach a graduate class on proteomics and mass spectrometry. So using a lot of these techniques that we were just talking about, to be able to explore different types of cells and in teaching the graduate students and I should say also senior level undergraduates take that course as well. So teaching them a lot of the nitty gritty about how to go about this process. I also teach quantitative chemical analysis, I'll be teaching that this upcoming spring, and that is to junior and senior undergraduates. So the fundamentals of analytical chemistry, which is an important class, I have to say the class that I enjoyed the most was the one I taught this past fall. So I was given the privilege, I was a little nervous going into it, of teaching general chemistry to the majors, to General Chemistry at Ohio State is a big deal. That sounds like a big class. Oh, well, so 5000 students per semester, take general chemistry at Ohio State. I believe there's 12 sections of general chemistry, and I got to teach those students who are in the majors. So these are the freshmen who are coming to Ohio State. In fact, it was their first lecture their very first day of college, which is a amazing thing to get to say to them. Welcome to Ohio State, right. So anyway, these are the majors in chemistry and biochemistry, who are just embarking on this potential career path. And so it was an intimidating experience. But it's also a lot of fun. We have a wonderful chemistry demonstration team within the department. And so when you're teaching these big classes, you can request that they bring in demos that tie into your lecture material and kind of bring the the material live. So that was a lot of fun. In general, I enjoyed interacting with the students, we had a vote at the beginning of the semester, I wanted to bring in some fun element that was kind of, you know, off the wall, just to kind of make things a little bit more lively. So we had a vote of what could I possibly teach them from a cultural perspective that they didn't know about, given that I'm, you know, 20, some years older than all the students in the room, and we finally hit on the Muppets. So it turns out that I, I grew up in the 80s. And my mother taught me all about the Muppets, and I adore the Muppets, but they knew Kermit the Frog and Miss Piggy, and that's about it. And so throughout the semester, we learned chemistry, we did a lot of demonstrations, and everyday we did a Muppet of the day. So by the end of the semester, hopefully they learned chemistry and a little bit about the Muppets. David Staley 23:56 Well, I'm curious to learn why your research focus has gone toward colorectal cancer? Why that particular focus? How did you get to that stage? Amanda Hummon 24:04 So, colorectal cancer runs in my family, and yeah, and so I lost a member of my immediate family when I was a graduate student. And it occurred at a very critical point in my intellectual and professional development, because I was right at a point where I essentially needed to decide what I wanted to do with my life. You know, I was acquiring this education in chemistry that had all these possible avenues in front of me. So there's so many ways you can apply chemistry. And when I asked myself the question, what do you want to do with your life? Where do you want to apply this education, you know, what problem is most important to you? It was quite clear to me that it was colorectal cancer. David Staley 24:40 But before you got to that stage, how did you end up in chemistry? Why that major, why that concentration? Amanda Hummon 24:46 Because I liked - this is embarrassing. I like to organize things, and the day I learned about the periodic table, I thought it was the most beautiful thing I'd ever seen because you can organize the entire universe into a table. And I'm a nerd, I thought that was just amazing. David Staley 25:02 I had a similar sort of reaction when I first started exploring the periodic table in high school chemistry, now I don't have to become a chemist, but. Amanda Hummon 25:09 Yeah, no, I just I thought was so cool. And then when you get more into it, and you start learning about all the periodic trends, and there's such a systematic order to everything, and you know, life is, life is chaotic, and it's not always that easy. David Staley 25:21 You can predict the properties of undiscovered elements. Amanda Hummon 25:25 Isn't that cool? David Staley 25:25 Yes. Amanda Hummon 25:26 Yeah, no, I as a 15 year old, I thought that was amazing, and I still do to this day. So, I don't know if my students will agree with me, but yeah, they got to hear a lot about it this year in gen chem. David Staley 25:36 Well, you've got one person who totally gets it. So what's next for your research, what's next for your lab? Speaker 1 25:42 So we have been, as I've talked a lot about the tumor mimics. So we've done a lot of very exciting work, I think over the last 10 years developing these mimics and setting up all the tools to look at drug penetration. And we are now moving in to a more realistic model system. So since my move to Ohio State in the Comprehensive Cancer Center, I've been busy setting up a lot of collaborations with surgeons and clinicians. And so we've developed tools to be able to look at drug penetration and molecular changes with our model systems. But now we are getting patient derived organoids from surgeons. So these are organoid. Yeah, that's Yeah, so I was gonna say so an organoid is a sample of a person's biopsy that is then grown in culture. And so if, for example, you have a patient who has been diagnosed with cancer, and they're trying to figure out what drug treatment will work best for this patient, they can perform surgery, take a biopsy, then take that biopsy, grow it and culture and then give it to us to perform experiments so that we can report back to them yes, this drug works for you know, this drug doesn't work for you. And that, for me is really the evolution of everything that we've been working towards over the last 10 years to take this approach and hopefully use it in real time fashion to help some of the patients treated here at OSU. David Staley 27:01 So, rather than using a yeast or a mouse or something like that, or a worm, I think you said. Amanda Hummon 27:05 Right, yep, to actually apply this to human tissue. Yeah. David Staley 27:10 Amanda Hummon. Thank you. Amanda Hummon 27:13 Thank you so much. It's been a real privilege to be here today. Eva Dale 27:15 Voices from the Arts and Sciences is produced and recorded at The Ohio State University College of Arts and Sciences Technology Services Studio. Sound engineering by Paul Kotheimer, produced by Doug Dangler. I'm Eva Dale. Transcribed by https://otter.ai