Homes for Receptors

Graduate student Kate Lansu searches for what activates orphan G protein-coupled receptors – a group of molecules that many scientists think could be good targets for new, more effective medications for a host of conditions, including chronic pain.

Kate Lansu, photo by Max Englund/UNC Health Care

About 40 percent of FDA-approved drugs target cell surface molecules called G protein-coupled receptors – or GPCRs – which take outside signals and trigger a cascade of responses inside cells. These drugs treat ailments from acid reflux to schizophrenia, and a recent avenue of receptor research has opened in the cancer field.

There are orphan receptors that researchers are still trying to understand. The lab of Bryan L. Roth, PhD, is one group at UNC trying to understand what activates these orphan receptors, how they function, and how to design drugs to treat a variety of conditions.

In this student profile, we meet Kate Lansu, a graduate student in Roth’s lab who recently won a poster award for her research presentation before some of the best GPCR researchers in North America.

Name: Katherine Lansu

Nickname: Kate

Hometown: Chicago, IL

Education: BS in biology, Creighton University. PhD student, pharmacology

Goal: To understand how orphan receptors in the spinal cord work in relation to pain

Mentor: Bryan L. Roth, PhD

Hobbies: running, reading novels, cooking.

History:

“I was always into science when I was little. I still have my very first microscope. It’s so dinky that I can’t even see anything through it. But when I went to college it was really hard for me to decide on a major because I liked English a lot, too. I thought about becoming a writer. But I figured that, with science, there were just so many questions. Also, I realized I could always read and write in my spare time, whereas science is really hands on and involves a lot of training. You can’t just do science without focusing really hard on it. And I really liked that part of it.

“Although I earned a degree in biology, I was kind of confused about what to do next. I got a job working as a technician in a pharmacology lab at the Loyola University Medical School in Chicago, and that’s when I first did experiments with cells and began to understand how something from outside the cell can make so much happen inside a cell. It was just amazing and a lot of fun.”

Undergraduate research:

“My undergraduate research was more in toxicology, specifically how frogs may have been exposed to pesticides in Nebraska and whether the exposure caused deformations in their development. We looked at histology and we did staining experiments to see if their morphology was the same as in normal frogs.

“I thought this was interesting because it brought in basic physiology – how cells grow and change but also this outside effect of drugs – or in this case, pesticides used throughout the Midwest.

“We determined that atrazine – a widely used pesticide in the Midwest that had been linked to developmental abnormalities in amphibians – did not have an effect on the development of male reproductive organs of northern leopard frogs in northeastern Nebraska.”

Post undergraduate work

“At Loyola, we studied potassium channels in cancer cells. This was kind of a weird combination because usually we think of potassium channels in cardiology, which is a strong field at Loyola. We studied how potassium channels regulate cancer proliferation and survival in breast cancer.”

Why UNC?

“When I was applying to graduate school, I looked for programs that had a real strength in cell signaling – [how cells communicate to carry out various functions]. I found out that UNC had a great pharmacology department. I remember looking at toxicology, pharmacology, and neurobiology programs here and thinking I could definitely find something very interesting to work on 

“I also worked with people at Loyola who had either gone to UNC or knew about it; they all said it was a great school. I applied but didn’t think I’d get in. When I did, I was really excited. When I came here for interviews, I immediately I loved this place.

“The people were so excited to be doing science. At some other places, some of the students thought it was such a drag to still be in school or thought the work was too difficult. Here, you could just sense there was an excitement, and people were collaborative. And I’m like that, so I felt at home here right away.”

Why The Roth lab?

“I was actually nervous about rotating into the lab of someone so well-known in his field. But when I took pharmacology classes during my first year, Bryan gave a lecture that turned the traditional notion of what we know on its head. His lab uses a screening approach so he could see how one drug could hit every receptor in the entire genome. This was kind of mind-boggling. He was working on different ways to understand these cellular pathways we think we fully understand.

“I was really excited because instead of looking at one signaling pathway, he wanted to look at a whole variety of pathways all at once to see how a drug affects them all. I thought that was really progressive.

“I also knew that he had a bunch of great papers and people I could learn from. One of his recent grad students, Kate White, encouraged me to rotate into the Roth lab because she thought I’d be a good fit.”

Your research:

“I’m still in my second year, my first in the Roth lab full-time. I joined the lab in May. It’s been great. The main focus in the lab is on the functions of G protein-coupled receptors – [a large group of proteins that sense outside molecules and trigger a cell’s response].”

GPCRs are involved in many diseases, and because they are relatively easy to target, they are the targets of about 40 percent of FDA-approved drugs.

“I study a family of orphan G protein-coupled receptors that are involved in pain and are localized in the spinal cord. They’re called orphan receptors because, so far, no one has really been able to show what activates them or how they function. But in the Roth lab I’ve been able to begin figuring out how they work. The first paper I’ll be a co-author on is in preparation.”

Your poster presentation:

“I was lucky enough to attend the Great Lakes GPCR Retreat where a bunch of really good Canadian and U.S. GCPR researchers present all kinds of findings.

“Anyone could present a poster – professors, students, post docs. There were 88 posters, and presenters had to give a five-minute explanation of their posters to judges, who then picked eight people to return the next day to give a one-minute synopsis in front of 15 really good scientists. I was really nervous. I had only been in Bryan’s lab for five months at that point. But I was one of four winners. 

“That poster was on our screening work. Some receptors have had no known ligands – [molecules that trigger particular responses in a cell]. I presented some newly discovered characteristics of these ligands and how these might explain what those orphan receptors do and how known drugs might be hitting them. This work might help explain the side effects of drugs people are already taking.”

What’s the big picture?

“One important thing to remember is that a lot of FDA drugs already target G protein-coupled receptors, but there’s this whole unknown group of orphan receptors, and we don’t know what they do. They could be useful in treating different diseases or they could be better targets for diseases that already have established treatments.

“We hope that because the receptors I study are expressed in the spinal cord that they might be involved in pain. Some current medications for pain disorders have really unpleasant side effects. We need better ones. Even the medications that work well usually cause severe side effects.

“Think about morphine, which can make people feel very dissociative; they can’t focus on what they want to focus on. We’re trying to find other things related to the same pain process but don’t have the same effect on cognition.

“Maybe there are alternative ways to treat some types of pain. I think we’ll find out.”

The future:

“I definitely want to run my own lab. I really like academia. I like the feeling of sharing information. The openness. It might sound cliché but I love this spirit of science – discovering things worthy of sharing. And the education piece is really important to me. I think I might like to stick with studying G protein-couple receptors, because I think they’re really interesting. There are a lot of different ways you can approach studying them – what happens to them or what happens upstream or downstream of the receptors themselves.” 

“It’s too early to say if I’ll stay with pain research, but we’ll see. Right now, I’m learning a lot and I love being here.”

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