Calvin VanOpstall and Brendan Looyenga collaborate on research. The two are using the tissue culture hood and incubator, which were paid for with funding from the NIH grant.
“With every answer, you have five new questions. You never come to a final solution, there’s always more to investigate. You see God’s creation in a new light. It’s unfathomable. For every stone you turn over, there are ten more under. It’s never ending excitement.”
Biochemistry professor Brendan Looyenga doesn’t hide his enthusiasm for research.
“It’s like you’re a detective, trying to solve a problem, answer a question. You can’t solve a problem if you can’t conjure up what the answer might be. You have to pick the right experiment. You have to think of all the possibilities.”
Taking the cases
Looyenga teaches biochemistry and conducts research with undergraduate students at Calvin College, and also conducts Parkinson’s Disease research at the Van Andel Institute in Grand Rapids. His research interests are in some of the unusual genetic connections between cancer and neurological disease, which he says are often thought of as two opposite conditions: “In one disease [cancer], cells are growing out of control, whereas in the other [Parkinson’s Disease], they are dying out of control.” Looyenga hopes that insights into how both diseases can arise as the result of the same genetic mutations may allow medical doctors to “kill two birds with one stone.”
Looyenga recently received a $295,939 grant from the National Cancer Institute at the National Institutes of Health (NIH-NCI) for the project “Cooperative Cellular Transformation by LRRK2 and MET in Renal Neoplasms.” The three-year project involves a host of students conducting research that could provide useful insights into both neurology and oncology.
His research team is digging deeper into the interaction between two proteins—LRRK2 and MET (a growth factor receptor)—that he previously discovered were often overexpressed in some forms of cancer, including that of the kidney. Interestingly, both of them are also clearly implicated in neurological diseases including Parkinson’s Disease and autism. This new study will seek to understand how these two enzymes cooperate to turn a normal kidney cell into one that grows out of control to form tumors, but may also yield insights into how they malfunction in neurological disease.
Identifying the suspects
Looyenga hypothesizes that increased LRRK2 activity—due to its genomic amplification or mutation—modifies how MET growth factor receptors get moved around inside the cell. When MET normally binds to growth factors on the cell surface, it rapidly gets internalized and inactivated to avoid overstimulating cells. In this case, the research team will track what happens to MET when LRRK2 is hyperactive. They expect to see changes in where it goes or how long it remains in the cellular “sorting system” before being inactivated.
“A cell in some ways is like the U.S. Postal Service,” said Looyenga. “You need to sort what’s junk mail, what to keep and what needs to be sent back out. When that sorting system gets messed up, there are problems.”
And with research like this, he and his co-investigators are able to hone in on a specific gene for a specific cancer and better understand its molecular underpinning and the role it plays within the cell.
Digging in deeper
“It’s difficult to cure diseases if you don’t know how the disease works,” said Looyenga. According to him, 20-25 years ago chemotherapy treatments would just kill off any fast growing cells—both good and bad—with the hopes of killing the cancer before the person. He said basic research—like he and his students are doing now—hopefully will provide insights into why these cells are growing fast, which will allow researchers at the next level (translational research) to develop targeted treatments for pre-clinical trials. These more focused approaches to therapy often have far fewer side effects, and directly attack the actual cause of cancer at the molecular level.
“When you see the results, it’s really satisfying, that something so small that’s being altered can have such a big impact,” said Calvin VanOpstall, who graduated in December and is working on Looyenga’s research team at Calvin. “If we can somehow target that [protein] it can have a great impact if it goes into some translational research, looking at treatments, improving patient life.”
Helping crack the case
For Looyenga and his students it’s not just the wonder of learning more about God’s creation that drives them in their research, it’s also about the possibility of even just one patient benefiting from their new understandings.
“Cancer is not a disease, it’s a whole spectrum of diseases. You can’t treat breast cancer and colon cancer the same way, you can’t even treat two cases of breast cancer the same way,” said Looyenga. “Cancer is not faceless. Every cancer is unique just like every person is unique. Your mother is a specific person, you don’t treat her like a breast cancer patient, you treat her like your mother.”
Training up detectives
And this new NIH grant isn’t just benefitting future patients; it’s also benefitting current and future students. Looyenga, who was the first intern at the Van Andel Institute in 2000, is now opening doors for his students.
“The training that I’ve received from him [Looyenga] as someone who is so excellent in his field and knows his techniques, has a solid background, good connections, that’s been helpful to me. I couldn’t have asked for a better mentor. The training I’ve received is excellent,” said VanOpstall.
And Looyenga credits his success in research to his colleagues in the science division at Calvin, who over the past five years have obtained $30 million in grants for research.
“A lot of us are funded by NSF, NIH or other places,” said Looyenga. “It’s a shared dedication to excellence. Students benefit from their professors being research-active, more current in their field.”
VanOpstall and Looyenga agree that the liberal arts education that frames the research experience is crucial.
“You can get all the science anywhere, the language of biochemistry, but liberal arts helps you communicate that to the world better in a way they can understand,” said VanOpstall.
“What you do doesn’t matter unless you can [clearly] tell other people about it,” added Looyenga.
