mark hannink

Summer ripens undergrad research interest

August 23, 2017 By Samantha Kummerer in Research Tags: mark hannink

By: Samantha Kummerer| Bond LSC

It takes a lot of time and patience to be a scientist. This is something that first-time researcher Natalie Hickerson quickly discovered.

“A lot of the time things are so small. I mean you’re using such tiny volumes of DNA that you can’t see anything happening,” said the undergraduate biochemistry major.

For some, this uncertainty pair with long lab hours and multiple trial and errors would be frustrating. Hickerson, however, put in the time and asked the questions, which led her to discover the rewards of research.

“You try something a few times and it wouldn’t work and then you change one thing and suddenly it works and you get results and it was just very exciting, like ‘wow what I’m doing is real,’” she said.

Hickerson attends the University of Miami but worked as a research intern in Mark Hannink’s lab in the Bond Life Sciences Center this summer. She said she chose the University of Missouri because the program was well rounded and fit with her major.

Hannink said while Hickerson entered the lab not understanding everything, she wasn’t afraid to ask questions and that helped her catch on fast.

“What makes a scientist different is that you are an active generator of new knowledge. Instead of being a passive consumer of existing knowledge you have to become an active producer of new knowledge,” Hannink said.

The Missouri native spent two months creating new knowledge on PGAM5, an important protein involved in many mitochondrial processes and cell death.

Hickerson began by intensely studying the protein at its most basic level to determine how and why it works the way it does. Part of this process was comparing different mutations of the protein.

Previous research shows how understanding the sensitivity of PGAM5 and its changes in the cell could help in nerve-degenerate diseases like Parkinson’s and ALS. Individuals suffering from those diseases experience a loss of function or mutation in some proteins.

Part of Hickerson’s initial research aimed at figuring out what signal activates PGAM5 in a cell. A better knowledge of that process will help scientists understand how pathways function and turn off during nerve-degenerative disease.

Hannink explained if a pathway is defective, activating a different pathway may function as a type of therapy.

After months of long hours, Hickerson discovered by changing the pH levels, PGAM5 can be switched from inactive to active.

“We had suspected it to be the case but the data she provided really helped demonstrate that was true,” Hannink said.

While Hickerson is headed back to Florida to continue her pursuit of biochemistry, her findings will continue to be advanced this fall in Hannink’s lab.

“There’s a lot more to be discovered with what we were doing,” Hickerson said. “A lot of the stuff we were doing this summer was new ideas and just developing deeper knowledge on things they’ve discovered in the lab previously. So, I was looking deeper into what they already started and we did find some new things so it was neat.”

She said her experience this summer inspired her to get more involved in undergraduate research.

“It definitely gave me a much better understanding of how to work in a lab and just basic lab techniques. The overall research project gave me a lot of good foundation for that,” she said.

As Hickerson continues to learn about research, Hannink said it’s an ongoing process that he is still a part of.

“I’m doing the same thing all the time that they are learning to do,” he said. “There’s this dynamic and that active learning process also challenges me to becomes a better scientist as well.”

The search for oxidative stress treatment continues

October 1, 2014 By Paige Blankenbuehler in Research Tags: Bond Life Sciences Center, drug, jeff sossamon, mark hannink, oxidative stress, reactive oxygen species, research, university of missouri science research

A yellow light indicates oxidant production in the tissue of a migrating fly larva. Source: Tobias Dick, German Cancer Research Center | Illustration by Paige Blankenbuehler Read more at: http://phys.org/news/2011-12-oxidative-stress.html#jCp — A yellow light indicates oxidant production in the tissue of a migrating fly larva. Source: Tobias Dick, German Cancer Research Center | Illustration by Paige Blankenbuehler

University of Missouri research characterizes a novel compound

By Paige Blankenbuehler | Bond LSC

Your body has an invisible enemy.

One that it creates all on it’s own called oxidative stress, long thought of as an underlying cause of some of humanity’s most insidious diseases – cancer, Alzheimer’s, Parkinson’s Disease, cardiovascular disease and diabetes.

Every day, our bodies are exposed to harmful free radicals known as reactive oxygen species as a result of our environment.

But, when something goes wrong with this energy extraction process, cells become inundated with reactive oxygen compounds that cause oxidative stress. The search for drugs to treat the problem have been ongoing, and with a complicated problem like oxidative stress, it’s all about finding the right combination.

Recent research by Bond Life Sciences Center investigator and Biochemistry Department Professor, Mark Hannink, provides a new approach for addressing the problem of oxidative stress and a starting point on developing a drug in pill form.

Mark Hannink and Kimberly Jasmer, a Ph.D. student in his lab, recently helped characterize a new molecule (called HPP-4382) that provides a novel way to treat oxidative stress. Their research was done in a partnership with High Point Pharmaceuticals, LLC, of North Carolina, where this new molecule was developed.

Oxidative stress can cause damage to the building blocks of a cell, resulting in excessive cell proliferation in the case of cancer or cell death in the case of neurodegenerative diseases like Parkinson’s.

Often, the majority of stressors are actually created inside our own cells as a byproduct of how our cells extract energy from the food that we eat and the air that we breathe.

Specimen of protein are prepared for an experiment in a lab at the Bond Life Sciences Center at the University of Missouri.

Understanding oxidative stress

Most simply, oxidative stress is an imbalance that happens when the body uses oxygen to produce energy.

Superoxide, a “promiscuous and nonspecific” compound produced as a byproduct of this process, is a highly reactive molecule that can damage DNA and other cellular components, Hannink said.

The superoxide molecule is a “free radical.” That means it’s especially promiscuous and reacts with many different types of cellular molecules, leaving destruction in its wake, he said.

That damage can lead to a long list of problems, including cancer or neurodegenerative diseases like Parkinson’s disease.

In response to oxidative stress, the cell produces protective “anti-oxidant” proteins, which help remove the harmful reactive oxygen species and minimize damage.

But a heavy anti-oxidant response could be dangerous, too. The bottom line: it’s about maintaining a fine balance between “oxidants” and “anti-oxidants”.

Search for right combination continues

A drug that corrects the imbalance of oxidative stress could one day have wide applicability.

Jasmer developed a test to measure how specific compounds altered gene expression. The genetic response to oxidative stress has both an “ON” switch and an “OFF” switch.

Using this test, Jasmer determined how each compound affected specific genetic switches and, in turn, how the response to oxidative stress is regulated.

This test helped identify which molecules might be promising candidates for treating oxidative stress, leading them to one in particular that seemed to have the desired properties: HPP-4382.

But creating effective drugs is a long process of trial and error. Once molecules have been identified that show efficacy in lab-based assays, scientists try different combinations to increase their potency and drug-like properties, and High Point is currently testing other molecules that behave like HPP-4382.

The compound serves as a good starting point for researchers who are interested in understanding how oxidative stress affects cellular processes, such as cell proliferation or cell death.“Now we have a better understanding of what this compound is doing,” Hannink said. “This compound can be used to test different ideas of how the balance between oxidants and anti-oxidants is achieved in healthy cells and how perturbation of this balance can lead to different diseases.”

This research was published in PLoS One in July and was funded by High Point Pharmaceuticals, LLC.