Researchers at Washington State University’s College of Medicine have received $10 million in new research grants this fiscal year.
The grants will support research into a gene mutation linked to colon cancer; the relationship between sleep disturbance and autism; where people are exposed to air pollutants; and the ways the neurological system affects the immune system.
The funding covers a total of 21 projects.
“It’s a pretty broad spectrum of work. It’s kind of exciting,” said John Roll, the college’s vice dean for research.
The college was established three years ago, and its first class of medical students started classes this fall.
Roll said it’s taken some time for researchers to get proposals together and tweak them to receive funding.
“We’ve developed infrastructure to support this. We have outstanding faculty members who have been submitting grants and we’re starting to have some success,” he said.
The projects will also give graduate students on WSU’s Health Sciences campus a chance to work.
“When students learn in the context of ongoing cutting edge research then they’re exposed to brand new knowledge and a culture of inquiry,” Roll said.
Here’s a look at a few projects WSU’s researchers are working on.
Cancer, DNA repair and telomeres
Understanding how our bodies stop tumors from forming, and why that system sometimes breaks down, is key to stopping cancer.
Weihang Chai, an associate professor of medical sciences, is zeroing in on that question by looking at a gene mutation commonly found in colon cancer patients.
Chai’s grandmother died from breast cancer when she was young. Had she gotten ill today, her cancer likely would have been caught earlier and been treatable, thanks to advances in screening technology and treatment.
Knowing so many friends have loved ones fighting cancer motivates her work, she said. It’s a small piece of the cancer puzzle, but one she hopes will contribute toward better treatments.
“The cancer is like a common enemy to us,” she said.
Her work focuses on telomeres, a special section of DNA on the end of chromosomes, and the way they contribute to cancer development.
Telomeres work something like the aglets that prevent shoelaces from unraveling. They protect the rest of the chromosome and prevent it from fusing to other chromosomes or deteriorating.
As cells age and divide, telomeres get shorter. But most cancer cells have a way of getting around that process by activating an enzyme, called telomerase, that allow telomeres to keep growing. That’s part of what lets cancer cells keep growing uncontrollably.
When a cell is repairing breaks in its DNA, telomerase can sometimes copy portions of telomere DNA into the middle of a chromosome, where it doesn’t belong. Normally, the body stops that process so the DNA gets repaired correctly. Chai’s previous research suggests a particular gene, called MLH1, is involved in stopping the telomere DNA from being incorrectly inserted. But she’s not sure how that happens.
The MLH1 gene has mostly been studied for its links to colon cancer in another way. Its best-known job is to help with “mismatch repair” - fixing mistakes that happen when a cell’s DNA is copied so the cell can divide. That’s important to prevent errors in DNA, which can lead to mutations and eventually tumors.
But in people with mutations in MLH1, the gene doesn’t do its job, making it easier for tumors to form.
Chai believes MLH1 has another function: stopping telomere DNA from getting inserted in the middle of chromosomes. If the gene is mutated, it may not do that job, leading to more errors in DNA that can help tumors grow over time.
Her two-year grant from the National Cancer Institute is focused on developing a better experimental system to explore what happens when telomeres are inserted where they shouldn’t be, and understand why that insertion is happening.
“It allows us to obtain more data,” she said.
Autism and sleep disturbance
Having trouble falling asleep or staying asleep aren’t unusual. But autistic people are far more likely to have sleep-related problems than people who aren’t on the spectrum.
Lucia Peixoto, a neuroscientist and assistant professor of medicine, is trying to find out why.
Existing research suggests the severity of an autistic person’s sleep problems tends to correlate with how much support they require to live independently. People with worse sleep problems are more likely to be nonverbal, for instance, Peixoto said.
Her earlier research led her to believe sleep disturbance and autism develop through similar mechanisms in the brain when children are growing, though she’s not sure how.
Her grant, from the National Institute of Neurological Disorders and Stroke, will help her look deeper into the link.
Sleep depriving children to study them is frowned upon, so she’s working with mice. Some of those mice will be genetically modified to have a gene mutation common in autistic people that’s also associated with sleep disturbances.
In the lab, researchers keep mice awake for hours by gently brushing them with paintbrushes, which makes it difficult for them to sleep. Normal mice will doze off right away after the brush stops. But mice with the mutation will stay awake for hours after, even thought they’re exhausted. Peixoto hopes to better understand why through genetic sequencing.
She’s motivated to study sleep in part because it’s such an important part of living a quality life, she said. Whether it’s not being able to fall asleep or waking up many times during the night, sleeplessness impacts the person struggling with it, as well as their family.
“That means the whole household doesn’t sleep enough,” she said.
Uncovering the genetic basis for sleep disturbance could do several things, Peixoto said.
First, it can help better tailor therapies for autistic kids. Since sleep disturbance is a good predictor what someone’s autism might look like, understanding the link better could mean more relevant individual therapy at a younger age.
Second, researchers might get clues into what makes people fall asleep, a question that seems obvious, but which biologists haven’t yet been able to answer.
And finally, her work could lead to a better understanding of the causes of sleep disturbance, which could suggest fixes for both autistic and non-autistic people of all ages who struggle to sleep.
“Sleeping badly makes everything worse,” Peixoto said. “If you can make thing better than the quality of life is going to improve,” she said.
The overlapping lives of twins
Twins are something of a holy grail for medical researchers. Because they have similar or identical DNA, they’re a window into untangling the effects genes and environment play in a person’s health.
Glen Duncan, the chair of WSU’s nutrition and exercise physiology program, runs Washington’s twin registry, which registers pairs of twins who are willing to participate in research.
His latest grant, in collaboration with researcher Edmund Sato at the University of Washington, will look at air pollution by asking pairs of twins to wear small, portable devices that record pollutants in real time.
“We want to look at the effects of pollution and the exposure to these environmental toxicants on measures of health,” Duncan said.
Proving that exposure to a particular pollutant or toxin caused a particular health problem is nearly impossible in environmental health, since you can’t force a random group of people to inhale lots of particulate matter every day for years and then see how many of them develop lung disease.
Individual genetics affect how susceptible people are to chemicals that may cause illness. By using twin pairs, Duncan can get a better idea whether differences in health are linked to actual exposure to pollutants, not just common genes or environment growing up.
“We’re measuring this in twins who are identical so we can control for genetic influences and shared environmental influences on exposures,” he said.
The researchers will ask twins to wear a device measuring particulate matter and nitric oxide for two weeks, then mail them back with a questionnaire about health. The devices will also help scientists better understand where people are exposed to air pollutants, which could suggest ways to reduce that exposure.
They’re hoping to better understand how exposure to particulate matter is linked to inflammation and high blood pressure.
Keeping immune systems in balance
Human immune systems are a delicate balance. If your immune system is suppressed, you’re susceptible to infections and other problems. But an overactive immune system can also be a problem, causing the body to attack healthy cells and tissue. That’s the root cause of many autoimmune diseases, including rheumatoid arthritis and Crohn’s disease
“Not enough or too much are both not a good thing,” said Jingru Sun, a microbiologist at WSU.
Scientists are building evidence showing the nervous system regulates the body’s immune system, Sun said. But the way that works isn’t well known yet.
She’s hoping to tease out a specific chemical pathway using a species of roundworm that’s ideal for research. The worm’s immune system has several pathways found in humans, but the system is much simpler, making it easier to study.
“Each worm produces 300 offspring so you can get a good enough sample in a very short time,” Sun said.
Sun’s research is zeroing in on a neurotransmitter called octopamine that she’s studied before. Her prior work showed octopamine is released to suppress the body’s immune response, meaning it plays a role in regulating the system.
“Eventually it will bring the immune response into a balance,” she said.
Now, she’s hoping to learn how octopamine transmits a signal from the neuron that releases it to the immune system.
“What’s the nature of that signal? We don’t know yet,” Sun said.
Her five year, $1.91 million grant will look at the pathway in more depth, and study how the roundworm’s octopamine levels respond to infection with a pathogen.
By better understanding the exact way the immune system is regulated, her work could lead to therapies to help people whose immune systems are out of balance.
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