The perfect storm: it can erupt at any time if a variety of factors interact just right. Maybe it all starts out with a stressful day at work. Although you’re relieved to go home and get it off your mind, you can’t, leaving you with a fitful night of sleep. When you wake, you have a kink in your neck. The morning rolls on, and you juggle your schedule as well as the needs of your household. You step onto an elevator – part of your normal routine – and you take a whiff of a strong perfume. Your sinuses are stimulated, and you undergo a migraine attack.
In the world of Dr. Paul Durham, professor of cell biology at Missouri State and director of the Center for Biomedical and Life Sciences at the Jordan Valley Innovation Center, that is the perfect storm model. In the model, each factor plays a role in making the nerves more hyperactive and sensitive, until one of them just tips the scales.
“These nerves begin to do their job a little too well,” said Durham. “Instead of responding to a stimulus in a normal way and alerting you about it, it becomes not physiological, but pathological.”
In the early 1990s, during his post-doctoral work, Durham worked with a professor at the University of Iowa studying calcitonin gene-related peptide (CGRP) – a protein that causes blood vessels to dilate. As a cell biologist, he was intrigued that research was indicating CGRP levels increased in a migraine state; now he is an international expert on the study of the trigeminal nerve and orofacial pain.
The trigeminal nerve provides innervation to the head and face, so Durham studies the biological basis for migraines, headaches, temporomandibular joint (TMJ) pain (jaw pain), toothaches, gum pain, sinus headaches and rhinosinusitis among others. His work could have tremendous impact, as studies have shown that approximately 36 million Americans suffer from migraines.
In his lab at the Jordan Valley Innovation Center (JVIC), Durham researches why nerve cells become hyperactive, and why they cause pain. Nerve cells – spinal cord or brain cells – are grown in culture dishes, allowing him and his fellow researchers to see how cells react with certain drugs. They also have access to a vivarium in JVIC when the study calls for seeing what changes would take place in the attacked organism.
Over the past couple of years, his research team took it one step further: how and why does pain move from acute pain to chronic pain?
“What we’re finding with chronic pain patients is they get themselves in a vicious cycle,” said Durham. “Once they start having pain, they usually don’t sleep as well, which usually causes them more pain. Then they begin to stress about it, and then they get depressed about that. All of these things keep snowballing on top. Pretty soon you have a system that is almost out of control.”
Partially due to his involvement with organizations like the Society for Neuroscience, American Association for the Advancement of Science, American Headache Society, Inflammation Research Association, American Academy of Orofacial Pain and the American Pain Society, pharmaceutical companies often enlist his help in determining the viability and effectiveness of their products. Since JVIC opened in 2007, Durham has won more than $9 million in grants – in many cases, outsourcing the research phase of a pharmaceutical to researchers in his lab.
Youthful energy and innovative ideas
As you tour the Center for Biomedical and Life Sciences (CBLS) at the Jordan Valley Innovation Center, you may notice how young everyone appears. The approximately 20 researchers in the lab is a mix of full-time employees, undergraduate and graduate students – all homegrown from Missouri State, Durham noted. Durham is the only PhD in the lab.
“I’ve never looked at undergrads being any different than grad students,” he said. “If someone’s passionate about science and learning, and we put them in the right environment, then they just take off.”
Evan Clark, a senior working in Durham’s lab since 2011, said working in the CBLS lab has taught him about the design and setup of medical clinical trials, the importance of teamwork and organization, as well as research procedures and protocols. One project he led was a menstrual related migraine study.
“The experience was completely hands-on. I worked directly with the samples, organized a majority of the data, conducted the experiments, organized personnel to finish the study and finalized results,” Clark said. “I am truly appreciative of opportunity Dr. Durham has given me… His support has made me a better student and person.”
In the last 10 years, Durham has supervised more than 60 students’ research projects in the CBLS, and he is quick to say that this is one of the best parts about his job.
“The students play a key role in everything we’ve been able to do,” added Durham.
In the lab, at home, in the classroom or in his downtime, Durham lives to help people – especially youth. One of his current studies will help to calm the fears so many children have when they go to the doctor: the needle prick.
Over the past few years, he has studied human saliva to look for protein levels, understand the progression of disease and discern what each protein indicates. Now he’s researching the saliva of a group of neonatal babies and pediatric oncology patients in Utah, planning to develop a diagnostic tool to measure biomarkers in saliva that hospitals and doctors could use instead of drawing blood from children.
A place to break outside the box
Jordan Valley Innovation Center, a former MFA milling facility, is a seven-story state-of-the-art research and innovation accelerator. When it opened in 2007, it became CBLS’s new home, staying true to its commitment to the development and support of advanced biotechnology industries in the state. In addition to CBLS, JVIC is home to corporate affiliates in the medical, technology and defense industries and the Center for Applied Science and Engineering of Missouri State.
“We have the full complement of all the techniques and equipment that we need in one building, which is really unique,” said Durham. “Most people who visit are blown away by all of the resources that we have at JVIC.”
In addition to equipment, Durham said the ability to collaborate with scientists with other expertise has been a huge advantage of being housed at JVIC. One prime example was the development of a smart bandage that would deliver a drug to promote healthy wound healing.
Starting with a tent material that would decontaminate biological and chemical warfare agents – a product that was developed at JVIC as well – Durham and others at JVIC collaborated through several stages of development. And it was a success.
“It took electro-active polymer chemists to figure out how to put the matrix together, but then you have to have material science people working on how to make a bandage that doesn’t stick to the wound. Then you have to have the electrical current going to the bandage, so you have to have someone who can build an electric device that delivers the right amount of current,” he said. “We were actually able to, with the help of Crosslink, an affiliate at JVIC, work with their scientists to develop the product….and have it release the drugs that we wanted into the wound to promote healing. We all work together as a team to make it happen.”
Looking to the future
The worldwide scientific community collaborated to complete the Human Genome Project in 2003, sequencing the chemical base pairs of DNA to determine the significance of each gene. Since then, research has shown that the average person has 10 genes predisposing him to a major disease. Keeping that illness from becoming a reality is another area of research interest for Durham.
“Why are they still healthy? What it comes down to is diet, exercise and good environment and healthy sleep patterns,” he said.
On top of the DNA structure (the genome), is another similar structure called the epigenome, he explained. The epigenome is responsible for how the DNA is packaged and found in a cell, and these factors can be manipulated through diet, exercise and sleep.
“You could take a bad gene, a predisposition for a disease, and completely turn it off for your lifetime,” he said.
It’s a powerful thing – empowering patients with the knowledge that they have control over a disease. Durham sees nutraceuticals, compounds that would be found in fruits and vegetables and plants, as an emerging field over the next 10 years. These nutraceuticals will be key in a lifestyle plan to keep the epigenome from manifesting certain illnesses.
One nutraceutical that Durham has studied quite a bit is cacao, the cocoa bean, which was praised by early civilizations like the Aztecs and Incas due to its medicinal properties.
“We, five or six years ago, started looking at that and what would happen if you incorporate more dark chocolate in your diet. Would that actually protect you against these pain pathways?” noted Durham. “When you incorporate dark chocolate into your diet, you basically quiet those nerve cells. You allow it to modulate and respond to those stimuli in a normal way. So it’s blunting that perfect storm that’s developing.”
Migraine sufferers take heart – Durham and his team of researchers are working to find relief for this debilitating affliction.
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