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MSU IQ researcher working toward new cancer therapies

Russ White
Jens Schmidt

Jens Schmidt is a professor of OBGYN in MSU's acclaimed College of Human Medicine, and he's also a part of Chris Contag's IQ team. IQ is the Institute for Quantitative Health Science and Engineering. 

At MSU, Schmidt’s laboratory uses a combination of cell biological and biophysical approaches to explain how human cells maintain their genomic integrity, which is an important barrier for cancer formation. 

Jens Schmidt:What I'm interested in is how human cells maintain their genomic integrity. What I mean by that is that all the cells in your body have their heritable information stored in the form of DNA and that's what we call our genome. What happens on a daily basis is that there is intrinsic and exogenous stress and damage that occurs to this genome. For the cells to grow and maintain the body and for you to grow from a single cell into a huge human being, the body has to make sure that the genome stays intact so that the heritable information is passed on to the next cell when a cell divides.

What I'm interested in is how cells do that. If you think about the health relevance of this, you have to consider that genomic damage leading to mutations in human cells is the main driving force behind cancer formation. What I want to figure out is how that happens and how the cells actually prevent these mutations from occurring in order to maybe figure out a way to improve this process or reverse the process to make sure that cancers don't form in the first place. That's one part of my research that I'm actually starting up here at MSU.

What I previously did during my post-doc was I worked on telomere maintenance. What telomeres are is basically, your genome is not one large piece of DNA, it's actually many smaller pieces of DNA called chromosomes. They're linear pieces of DNA, meaning they have ends. These ends actually shrink over time, and that's one of the main causes of aging, but also a trigger of genome instability. These things shrink and then things go wrong which can lead to genome instability. 

I'm trying to figure out how do these stem cells and most cancer cells use this enzyme called telomerase, that maintains the chromosome ends. If you don't maintain the chromosome ends, cells don't divide. Cancer cells divide all the time so they need a way to fix the chromosome ends and they use telomerase, just like stem cells and germ cells do.

Russ White:What if your research hits the mark or meets its goals, what benefit does it bring to humanity? What's game changing about it?

Schmidt:Ninety percent of all cancers use telomerase to basically give them the ability to keep dividing. If you stop telomerase in cancer cells they will stop dividing, meaning that would be a way to treat cancer. 
The only thing that we have to consider here is that there are also other cells in your body that have to divide, such as stem cells and germ cells. If you think about chemotherapy hitting all the cells that are dividing with the drug, for instance your hair falls out because your hair follicles can't properly function anymore.

What we really want to figure out is how does this process work quantitatively and are there maybe differences between how telomerase works in a cancer cell versus a stem cell. If we can figure that out, maybe there's a way to harm telomerase or stop telomerase in the cancer cells without effecting the stem cells.

It sounds a little pompous, but 90 percent of cancers require telomerase. So even if just a portion of those can be treated with telomerase targeted drugs, that would be a huge benefit to humanity in terms of cancer therapy.

In terms of the DNA damage response that I would like to study, there are actually already drugs that specifically interfere with the DNA damage response in cancer cells, because what happens in cancer cells, they get a lot of mutations. A lot of times they get a lot of mutations because the DNA damage machinery doesn't work properly. If we then break a broken process even more, those cells will cease to exist, and that can be done in a way that only targets the cancer cells but not the other human cells. They are just fine. 
That's really what we think about is, how can we study these processes to come up with new therapeutic approaches that target cancer cells but not all the other cells in your body.

White:When might we realize the benefit? How mature is the research?

Schmidt:The research in my laboratory is very basic biochemistry and cell biology, so we really try to get at the nitty gritty, the quantitative details of this process and it's a long term goal to translate that into therapies. That being said, I can put a realistic timeline on it, but as so often happens in science, a lot of times the really breakthrough discoveries are made in basic research without really having a specific translational goal immediately in mind. Then it goes very rapidly from there.

I like to tell myself that any day I go into the lab I can make a breakthrough discovery that can then lead to something that actually immediately benefits patients in the clinic. I myself am not a translational researcher. I do the basic science, I try to figure out the basic processes so that we can identify targets for the discoveries.

White:Jens, talk a little bit about this environment that Chris is developing where we're breaking down barriers and the collaborative nature of IQ, how it's different. I'm guessing that's part of what attracted you to MSU.

Schmidt:Yeah, absolutely. I think one of the really exciting things about the IQ is that you have a lot of researchers from different backgrounds that are all housed in the same building. A lot of times what happens is, as a researcher you can get really bogged down into what you're doing and live in your really small narrow world and you can only do what you can do. The barrier really is just going and talking to people and using their expertise to advance your research. What's really fantastic at the IQ is if you have something that you've never done before, there's probably somebody in the building that you can go talk to that about.

That's really I think a lot of times the activation energy barrier to starting a new project or to go into a direction that you haven't previously explored is being in touch with people and knowing people that know how to do that. That's really I think the strength of the IQ is that you have a breadth of different researchers there like computational biologists. That was something that I have no experience with, for instance. If there was a project where I wanted to do something computational, I could go down stairs and talk to the folks on the first floor about it.

If I wanted to build a device to carry out some of my experiments on my microscope that needs some special microfluidics, I can go onto the fourth floor and talk to those guys about how to do that. I think that the combination of expertise is really going to accelerate research in a way that's not possible if you don't have this collaborative, open design environment that IQ has.

White:How does your work benefit from this interface of engineering and medicine?

Schmidt:I think the main benefit for me is that I am trying to analyze cell biology from a quantitative perspective and that needs a lot of times sort of an engineering approach to it in terms of doing the math and figuring out all those pathways in the most descript way possible, doing modeling and things like that, which I don't have a lot of experience with myself. Having people in the building that do those kind of things, that helps my research a lot.

On top of that, there's a real focus in the IQ on imagining and a lot of the experiments that I do involve microscopy and large data sets. That is really a strength of the IQ is having a lot of imagining expertise ranging from small single molecule imaging. That's something I do. We actually watch individual molecules as they go about their business within a single human cell, all the way up to having folks that image brains and living animals and things like that. It's really that breadth there that really helps in terms of the imaging that's being done at the IQ.

White:Jens, humans are by nature people who stay within their own comfort zone or area of expertise, but how do you train this next generation of scientists to work at the interface of converging fields like is happening at IQ?

Shmidt:I think the most important thing is to not be afraid of trying something new. The approach that I always like to take is, a lot of times people say, "I'm a structural biologist." Or, "I'm a cell biologist." You kind of stay within that mold. I think what we need to be doing is we need to be not focused so much on one experimental or scientific approach, but much more trying to see what experiments can we do, whether that's something I'm good at or not, to best answer the questions that we're looking at?

Having a collaborative environment like the IQ fosters that kind of thinking in terms of having a graduate student or post-doc in the lab that you want to train in terms of answering a scientific question by whatever means is going to yield results the fastest or in the most productive way.

That's an approach I like to take and I like to see in my trainees as well. You can't be afraid of trying something new just because you've never done it before. Take advantage of the environment that you are in to basically drive research forward faster than the rate that it's currently been going at.

White:Summarize again your work and what you hope to do with it.

Schmidt:I'm trying to understand how human cells make sure that they don't incur genomic damage, which can lead to cancer, and trying to find ways to interfere, or specifically affect these pathways in cancer cells without affecting other human cells, so that we can come up with new strategies that can be used for cancer therapeutics or anti-aging disease.

That's Jens Schmidt, he's an OBGYN professor in the College of Human Medicine at Michigan State University, and part of the team at IQ. That's the Institute for Quantitative Health Science and Engineering and a lot more at IQ.MSU.edu.
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