The extraordinary molecular and cellular changes that characterize Alzheimer’s disease and make it so debilitating also present a challenge for researchers trying to find a cure.
By the time someone dies from Alzheimer’s, their brain is so damaged and atrophied that untangling exactly how and why it got there has, so far, proven impossible.
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Nicholas Henkel hopes to play a role in changing that.
A student in The University of Toledo College of Medicine and Life Sciences’ M.D./Ph.D. program, Henkel is studying the progression of Alzheimer’s by taking a step-by-step approach that looks at the role of abnormal metabolic signaling in the brain.
Henkel has paired high-throughput profiling and standard biochemical analysis to study neurodegeneration. As brain function goes from normal to mild cognitive impairment, and then from mild cognitive impairment to Alzheimer’s, his research aims to build a clearer picture of how an enzyme called AMPK may play a role in the origin and progression of the disease.
AMPK has been implicated in Alzheimer’s before, but its role hasn’t been fully described.
Henkel’s work has already produced some intriguing results.
“In some ways it might feel like in the field of Alzheimer’s my findings may be incremental, but if what I think is happening is actually happening, it could be profound,” he said. “We might be able to explain what is responsible for driving cell death in a disease characterized by cell death.”
Based in part on his promising research project, Henkel was recently awarded a highly competitive F30 fellowship grant from the National Institute on Aging.
Reserved for especially promising students enrolled in a dual-doctoral degree training program, the F30 fellowship program provides funding to cover a student’s tuition and stipend expenses.
Henkel
The fellowship also pairs Henkel with a diverse group of faculty experts from UToledo and other nationally ranked universities who will mentor him and assist in his research.
“The F30 program is very competitive,” said Dr. Rob Smith, professor and chair of the Department of Neurosciences. “The most important ingredient for research is fire in the belly — motivation and hard work. Nick has worked at a very high level for a very long time to build the skill sets and develop the preliminary data in his project.”
Henkel, who is originally from the Cincinnati area, grew up knowing he wanted to be a physician-scientist. UToledo’s dual-degree program gave him that opportunity.
“I found the integration of medicine and research to be very powerful,” he said. “I’ve always wanted to do for others what others have done for me. I was in and out of the hospital as a kid, so for me, doing that meant going into medicine.”
Arriving at UToledo in 2017, Henkel didn’t see himself studying Alzheimer’s but was drawn to Smith’s lab, where a novel Alzheimer’s research idea was already percolating.
Henkel’s research has become far more meaningful over the past five years, as all three of Henkel’s living grandparents passed away from dementia — two from Alzheimer’s.
“Seeing that, the whole project became so personal. It has really fueled my passion for it and getting this NIH award validates my work,” he said. “This is a major accomplishment for me personally but also for the University. I hope this sets the way for future M.D./Ph.D. and will attract people who want to come here.”
The concept for Henkel’s research is rooted in taking a clean-slate look at the origins of Alzheimer’s.
“Given all the treatment failures there’s been over the past 20 years, we don’t really understand the pathophysiology of Alzheimer’s. We need a fresh look and Nick’s project is doing that,” Smith said. “It’s not relying on historical assumptions. We’re not necessarily saying others are wrong, but we are saying this deserves a fresh look.”
Rather than starting with animal models that don’t necessarily fully resemble the human disease, Henkel is working with human brain samples that have been donated for scientific research. Through a mentor at Emory University, Henkel also has access to adult stem cells from patients with Alzheimer’s, which provides unique research opportunities.
“Securing an F30 fellowship can add jet fuel to your career. Nick has now competed for extramural funding at a national level successfully. That’s a big deal,” Smith said. “On top of his research, he shows great promise as a clinician. He’s empathic, caring and very devoted to seeing patients. He’s developing as sort of a triple threat M.D./Ph.D. — clinician, educator and researcher.”
