Sanford cancer researcher earns $1.9M grant

Dr. Michael Kareta, who leads a combination of stem cell and cancer research, has received a $1.9 million, five-year grant from the National Institutes of Health National Cancer Institute.

In particular, Dr. Kareta studies small cell lung cancer.

“We are studying the role of classic stem cell genes and investigating the role that they play in tumor initiation and this ability of a cell to change from a relatively normal state and change identity into this devastating state that we call cancer,” he said. “We would really like to start investigating some of the mechanisms that we’ve investigated in small cell lung cancer and apply it to other cancers.”

Stem cell and cancer research are important not only for Sanford Research, but for the entire scientific community.

“It can hopefully shed new light on how these cancers are arising, the general mechanisms that underlie them, and come up with new ways for us to develop new therapies for them,” he said.

Although the principal investigator gets the recognition, it was because of the hard work of the entire Kareta Lab that he was able to get this grant. Because of that, “we are able to put together a much larger network to understand how these cancers come about. We are not on a one-gene level, we are looking at the entire genome,” he said.

In this Q&A, Dr. Kareta discusses the grant he received and what it means for the future of his lab.

How did you end up at Sanford Research?

I am native to New England. I grew up in New Hampshire and Connecticut. Through the course of my studies, I spent time in Texas. Before coming out here, I spent 13 years in California. I was at Stanford before coming to Sanford, so that made it very interesting with the transition.

I saw the job opportunities that were here. I was on the job market and it was very difficult to get an academic job. I was interviewing all over the country, but when it was time to evaluate the job opportunities and the offers that were given, this [Sanford Research] was clearly the best in terms of the collaboration that was offered, the investigators, and how well everyone works together. A relatively young group that is trying to stay on the cutting edge was very attractive to me. So I packed up and moved to South Dakota.

What grant did you receive?

NIH is the National Institutes of Health, a governmental entity that is probably the major driver of funding for research nationwide. The R01 grant is their primary research funding mechanism. They have a lot of other mechanisms as well, smaller pilot grants, training grants, and the like, but the R01 is the major way they support research.

It is about $1.9 million for five years. These funds will obviously support our research, test tubes and things like that, but also the people who do the research. Really, the most important resource the lab has is the minds and the hands that are actually doing the work. It supports them and the technologies we will be using in the course of these investigations. We are trying to do some cutting-edge stuff to incorporate next-generation genomic studies to really understand what’s going on not just in the cancer as a whole but in one cell at a time. Unfortunately, these studies are not cheap.

How did you receive this grant?

This is a standard grant for the NIH. There are three times a year you can apply for those. I had applied for it a little after my first year here. I wanted to get the process started right away knowing it could take more than a year to work through the application. It took about a year and a half to get it all the way through.

It is a competition to a degree. The NIH will bring in independent investigators from all over the country and put them up in a hotel for a weekend. They will score all the grants that were acquired in that cycle and give a percentile ranking. The NIH will then look to see what their budget is because it is coming from Congress so it is always in flux. They look to see how much they can support, set up a percentile cut-off, and say they will support everything with a lower percentile than whatever the cut-off value is. This grant was right on the edge of that.

How did the reputation of Sanford Research help in the process?

There were a few things that worked in my favor. One of them is what the NIH refers to as an ESI – an early stage investigator. This is a program that they set up to try and help out people who are just getting their laboratory set up because it is sometimes difficult to compete with established investigators who have very large labs. They give a little leeway to these ESI investigators to help them get the ball rolling.

The other thing working in my favor is the fact we are in South Dakota. There is a recognition that the distribution of these governmental funds is not equitable across the geographic United States. There’s definitely concentrations of this funding that occur in the Boston area, California, and Texas. They are trying to make sure these funds favor the U.S. as a whole. There is also some leeway given to states that are underrepresented in this funding. We are getting a lot more of these R01 grants at Sanford.

When they evaluate a proposal, they do consider where the research is going to be done. Part of the score is based on where you work. I got some pretty good scores based on what we have here at Sanford. I know others that have been applying have got good scores. We have a very good support network, great core facilities, and access to fantastic equipment.

What does this grant allow you to do?

This will allow my laboratory to study these other cancers we haven’t had the resources to study. We will be able to cast a much broader net in terms of understanding some of the mechanisms that underlie the formation of these cancers. You can think of it as a clinical trial when you might run a trial on one patient and while it might be informative, benefit really comes when you start studying it in multiple patients.

Same thing; we are studying these mechanisms but instead of studying it in one cancer, we can start to see the applicability of these mechanisms in many cancers and start trying to find general mechanisms that could be driving these various tumors. The obvious benefit for that is if we could find the general mechanism that underlies at least this subset of tumors, then maybe we could develop new therapies that instead of targeting one cancer, it might be able to target a handful.

We do quite a bit of our investigations using mouse models of cancer because certainly when you are studying some of the very basic mechanisms, these are things we would not want to do in human patients. Some of the things we can do can be quite harmful, such as creating cancer. We use animal models for discovery purposes, so once we discover these mechanisms in these animal models, then we can make an application to human patients. That is a large component of the budget.

What does this grant mean to you, personally and professionally?

Professionally, it really gives us the opportunity to start expanding what it is that we study. When you start off, you’re a small lab. You’re focused. You’re really just trying to get noticed. You can’t take too many risks and you have to chase the sure shots. Now that we have the support, we can start asking riskier questions. We can start asking more questions, and I think that is where the science gets exciting.

Sometimes discovering something that is a foregone conclusion is not really that fulfilling, but when you take a chance on something that’s a bit out there and when it happens to work, that’s a great thrill. It helps put us on the map of investigators that are recognized nationwide. To be able to get recognized by the NIH in terms of being awarded one of these grants shows that we are a serious lab doing serious things. Now we have to make good on it, but that is the fun challenge of it all.

Personally, it shows that this was the path to take. It shows that we are asking the right questions and that we can do it. When you start off, there is a very high attrition rate in the sciences. When you look at people trying to pursue a career in the academic sciences, less than 10% are actually getting careers. Many labs, very good labs, have to close their doors because funding is so tight.

I don’t want to speak totally personally in terms of it being a validation of what we are doing because I say “we”. It is not entirely my achievement. It is the folks in the lab who are doing the work every day along with our collaborators. I think it does justify us as a group that we are doing good work and the well-known folks making the decisions are recognizing that we are asking the right questions and are willing to write a check to see it happen.

Research notes

Dr. Kareta’s grant was one of the numerous recent developments involving research, one of the key areas of innovation at Sanford Health. Some other research highlights include:

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