GradAttack Podcast #10 Judith Simcox

Podcast #10 – 08/04/2016

Fat, Proteins, and the Pursuit of Knowledge

Judith SimcoxJudith Simcox

Judith Simcox is a postdoctoral fellow in the Department of Biochemistry at the University of Utah, and also the vice president of the U.’s chapter of SACNAS, the Society for Chicanos and Native Americans in the Sciences. She stopped by to tell us about the exciting research she is doing into type-2 diabetes treatments, and about the factors that motivate people going into difficult fields in the hard sciences.

Download the file here: Fat, Proteins, and the Pursuit of Knowledge with Judith Simcox

PATRICK HADLEY: Hello and welcome to the University of Utah’s GradAttack podcast. Today we are speaking with Judith Simcox, who is a postdoctoral fellow here in the department of biochemistry. And Judith, why don’t you tell us a little more about your research?

JUDITH SIMCOX: So, we actually do research fat cells. Fat cells are really interesting. Originally, when people think of fat, they always think of it as just this inert storage depot that kind of sequesters fat away. But that’s not exactly what it does. In about the 1980s they found that fat was not just a storage depot, but it’s actually an endocrine organ. And what I mean by that is that it’s an organ that’s sending signals on the nutritional state of your body. And so what we study in our lab is things that regulate the fat cell for its maintenance of health. And we also study things that are secreted from the fat under these really stressful metabolic conditions. And so, for the first part of that, the way we find things that affect fat, we’re mostly looking at proteins. So, a cell is made entirely of just three things: It’s made of fat, or lipids; it’s made of carbohydrates, or sugar moieties; and it’s also made of proteins. And so what we do [is] we identify proteins that have no known function – and I think that’s kind of a misclassification. Everybody kind of thinks that we know everything about cells and how they work, but what’s surprising is how little we know about cellular function. So, only about 60% of the estimated proteins have a known function, and a lot of these are contested. So there’s a huge amount of proteins that we don’t know what they’re doing, where exactly they’re expressed, and how they’re functioning. And so we kind of identify things that are specific to fat, and we find their role and see if they could be a good drug target for type 2 diabetes. A lot of drugs, including the popular diabetes drugs metaformin, are activating proteins to change fat programs.

PH: So, if I’m understanding correctly, basically, we don’t know what a lot of proteins do; your research finds the proteins that could be used to treat diabetes, and then tries to activate them?

JS: Right. So it depends – you an activate or shut down the protein. It just depends on what it’s doing. But no, that’s exactly what we do.

PH: Okay. Excellent. And can you give me an idea of the importance of this research – you mentioned the possibility of using it to develop new drugs for type 2 diabetes in a very lay-friendly manifesto on your research that you sent me, but can you give us an idea of how far off those drugs may be, and what kind of an impact they might have on the general health of the nation or maybe, you know, on anyone suffering with type 2 diabetes.

JS: Right, so, some of the problems with the current type 2 diabetes drugs; they work really well, however – so, metaformin acts on a protein called PPar gamma. It activates it. The problem with PPar gamma is it’s present in a lot of other tissues rather than just fat. So if you activate PPar gamma in fat alone, it improves diabetes without any problems. However, when you take the drug, it’s taken in and it means that this protein is active throughout all the various tissues. And so metaformin has been associated with cardiac issues; it’s also been associated with uptake of fluids from your kidneys, so it can cause edema, is one of the common side effects of metaformin. So the idea with the proteins that we’re identifying, we’re looking at things that are really highly expressed in fat cells and only expressed in fat cells. So, maybe through identifying these proteins and then identifying drugs that are able to affect them, you can improve diabetes without all of these really difficult side effects that can be fatal. So – I think the original question was how far off are we from these drugs, and drug testing is a really long and arduous process. So, first we have to identify proteins, and then it has to go through clinical trials, there’s multiple phases of it. So anything that we would develop now would be, at least – I mean, some things are expedited – but at least ten years down the pipeline. But the importance of this is that drug companies will identify drugs that target known proteins, but they don’t have – I mean, they do have the resources – but they’re functioning based on the ability to make profits, because they are profit-based companies. And so these drug companies are hitting known targets because there are known risk factors. But you kind of need basic research to identify the drug targets because these companies aren’t gonna pour a bunch of research into it…

PH: Especially not if they already have a functioning pill.

JS: Right. And so what you get fro university research is, one, you get research that is completely unbiased, in the sense that we are funded by the federal government through NIH, and so we are asking questions that are important and we’re asking questions that we’re interested in, because we think that they’re going to help society down the line, and we don’t have a profit goal at the end of it. And so we’re asking these questions not entirely altruistically, but somewhat. And the second thing that we’re doing is we are able to probe these questions that are seen as too risky by profit-based  companies.

PH: And in what ways is it risky? Just because there wouldn’t be an immediate return on investment?

JS: So, I mean it can be risky in the sense where you identify a protein that looks great. So we’ve identified proteins through different ways, you can do large base screen assays, but with these random assays, you can identify proteins that seem like everything is going to work out great, and then in the end when you take it to the mouse model, maybe it doesn’t have the same effects in the mouse as it does in the cell culture. So when we start this, we start at the protein level, and then we start in cell culture, and then we move to mice. And then after we validated it in mice, we couple with clinical researchers to then go on and do drug studies. But at that level of the mice, it can be scary – I mean, you can spend years working on a protein that doesn’t have any effects on glucose, or the effects aren’t as strong as what you saw in the cell culture. Maybe even if you get past the point and you design a drug, maybe you can’t take it by mouth, maybe you’d have to inject it, which is not attractive as a type 2 diabetes drug. So there’s a lot of risk in the sense that we’re identifying unknown things and we don’t know what they do. And you can’t ask the question by saying, “I’m gonna start by curing diabetes.” You have to start smaller than that, and you have to say, “Okay, I’m going to start on the small scale, and then I‘m going to move to a broader question.” And it’s really important to do in the context of helping society, but it’s also important to do it from just a questioning basis so that you do performed unbiased research.

PH: Okay. So you’re funded through the NIH, though a postdoctoral fellowship. And you did your doctoral work here at the U., as well. Can you give me some idea of what that whole experience has been like? What I mean is, you’ve already given us an idea of what the advantages are for you as a researcher working under the auspices of a very nice grant from the NIH and being able to do unbiased research, but what are some of the difficulties that you’ve faced in this environment? I mean, what is it like to go through this whole process here from beginning to end.

JS: That’s a very complex question.

PH: It was in too many parts. I should’ve cut it down. What are the difficulties of working in these circumstances.

JS: I’m gonna start with the positives because I always think – I think a lot of people have the ability to focus on problems and negatives without necessarily focusing on solutions. And sometimes, when focusing on the negatives, you forget the really awesome things about it. But I will say that the things that I have found here, both in my graduate work and in my postdoctoral work are supportive communities, both at the departmental level in biochemistry, and then at sublevels. So we have different interest groups that meet to discuss research that is similar. Because in biochemistry there’s really a broad array of research. Some people are looking at HIV and the proteins in HIV infections. Some people are looking at fats. Some people are looking at actually computer animations of these processes. Some people are looking at iron homeostasis. These are all really diverse pathways, and what’s great is, you can come together during research in progress, and you can discuss your research and get feedback. And that’s the biggest part about these questions: the questions are so big, they’re so complex, that you need as many diverse points of view to ask the right questions and get you to think about them critically as you can get. I would say the best part about being up here is the community, At the departmental level, in Biochemistry, it’s amazing – we have so much support staff.  We also have people that are so invested in your growth as a scientist – it’s amazing. I mean, the famous saying “it takes a village to raise a child”? I feel like it takes a university to raise a scientist. So, I have the support system through the department. I also have another support system through what’s called Seminars In Metabolism. It’s for people who focus on metabolism research, and it’s really interesting. It brings together doctors from the diabetes center, and we have one of the best-established diabetes centers in the Northwest. And so, it brings about doctors, scientists, all of these different people to come and ask questions, and from multiple departments, not just Biochemistry, but also from Endocrinology, Nutrition, all of these really great things. And so, the best part has really been the support. And continuing from my PhD to my postdoc, everyone has been spectacular. There have been challenges – I think it’s challenging because you start out asking what you think is a pure question, and then you realize all of the road blocks that stand between you and the answer: There’s problems in methodology, there’s problems in research, there’s all these different things that you have to overcome. And having a sense of community both in your lab and in your department, all of those things are absolutely necessary to get through with a positive attitude.

PH: And speaking of that, you actually were introduced to me by Daniela Chavez, who is the president of the SACNAS chapter here at the U., of which you are yourself vice-president. So that’s the Society for Advancement of Chicanos and Native Americans in Science. Can you give us, then, some idea of how your membership in this organization has contributed to you research and your experience, and how you hope to use that in the future?

JS: Yeah, so, there’s a few things. It’s helped me grow as a scientist in the sense that we have a monthly SACNAS meeting, the last Wednesday of every month at noon in the fourth floor conference room of EJMRB. But we before these meetings do a short science talk, and so all of our members are able to give a talk, and that’s important because you need to be able to communicate science to a diverse group. And so, our SACNAS members, some of them are undergraduates, some are graduate students, but even the graduate students are in different fields: some people are computation biologists, some are biochemists, some people are geneticists, and so SACNAS has helped me grow by allowing me to communicate my research to a broader audience and make it come alive for them. And that’s really important because a lot of the members have led me to resources that I would’ve had no idea about without them. And it’s also a great opportunity to kind of broaden your speaking, because some of our members went on to the SACNAS national conference, because it is a national organization – including Daniela – and they won presentation awards for their excellent oral presentations. And I think that a huge part of this is the fact that we present in our meetings. And it’s also made me realize my own potential. So, I think that one of the most surprising things in my development as a scientist is that I came to it really late. I didn’t really become passionate about science until college. I kinda thought I was gonna be a doctor because my mom was a nurse and I’d always been good at school, and so I thought, oh, I’ll just be an MD. And research was one of these things that I just had to check off of this list. So I went into this research lab, and I was so lucky to go in with this guy named Jerry Shields. And Dr. Shields was so passionate about science, he had been in science for what seemed like forever then, but he still loved it, and he still – any time you had a question that you would ask, he would say, “That’s a good question. We don’t know the answer. How would you answer it?” And so, as I started thinking about going to med school, I kinda realized I was really dreading it, and dreading the idea of just becoming a funnel for information instead of producing the information and asking the questions and guiding that path. And so at that point I decided to take a bit of a break, worked at a company for a while, and then I applied for grad school at the University of Utah, where I didn’t exactly know what I wanted to do and…

PH: Can I ask you, based on my own position as sort of a figure from the university – I assume my bosses would want to know what made you want to apply here?

JS: [Laughing], Free admission? Free application? No – so, where I come from, family is really important to me, and Montana is actually quite close to Utah in the sense where, if there were an emergency, I could go home. And so some of the reasons I first became interested in science: my sister has both type 1 diabetes, but she also has Downs Syndrome. And there’s a really high correlation between the two, because people with Downs Syndrome have trisomy of the 21st chromosome, And the 21st chromosome encodes a lot of things, including beta amyloid protein, and that’s the protein that’s really important in Alzheimer’s, so they are more slated toward the development of early onset Alzheimer’s. And it’s also kind of a hub for a lot of immune genes, and so people with down syndrome are slated towards autoimmune diseases, including Type 1 diabetes. And so, she was the first thing that got me interested in science, but family and community are really important to me, and so the ability to go back home when my sister needs me or my mom needs me. So I guess that geographic default was the first thing that brought me here.

PH: But you were also mentioning some scientists…

JS: But there were also some really fantastic scientists. I mean, there are research institutes closer to my family, but the University of Utah is really excellent. We have leaders in the study of HIV in my own department, even; we have leaders in cancer research up at the Huntsman Center; we have leaders in epigenetics. All of these different fields, Utah is really at the cutting edge. And when I interviewed here, people were so friendly – and it kind of reminded me of walking into Dr. Shields’ lab for the first time. Everyone was really excited about what they did, ad they were really excited about what I was doing, because they were just excited about science and excited about questions.  And it just seemed like a unique place to cultivate both that and love of life. Because I think people become so focused on how a scientist should be or what you need to do to be something, and, really, you’re given a lot of freedom here to be an individual and still be a scientist.

PH: DO you think that’s typical of science departments across the country, or is it more unique to the U.?

JS: I have found it at other science departments across the country, but I think that the way that we foster it is really unique. And I think that I’ve been able to appreciate it more through the development of SACNAS. So, the SACNAS chapter was founded three years ago by a few people who had been involved in it as undergraduates and seen the power it had in them with networking, because networking is such an important part of finding a future career. But we didn’t really have that, especially for minority students here, and so what I’ve been surprised by in starting that, is how supportive people have been. My professor, Claudio Villanueva, ended up being the faculty advisor to SACNAS. He is Nicaraguan and has a really rich history as both a minority in science and an excellent researcher. But, so what I’ve been surprised with is how much support we’ve had in the community through developing this organization. We’ve started things called SACNAS talks, and so many people – from the first one, where I think maybe 30 people went, now we have packed rooms, where people are standing outside, and a huge part of that is that the different departments have given us money, they’ve given us resources, like the ability to reserve conference rooms and things like that. And so I think what’s unique here at the University of Utah is the ability to be an individual and a scientist.

PH: So, thank you so much for being with us today, Judith Simcox. It’s been a real pleasure, and we wish you the best of luck in your continued studies.

JS: Well, best of luck to you, as well.

PH: Thank you.