Building on a solid foundation

Dr. Ertekin-Taner is a physician-scientist, enterprise chair of the Department of Neuroscience and the Roy E. & Merle Meyer Professor of Neuroscience at Mayo Clinic. She sees dementia patients in her practice and is principal investigator of the Genetics of Alzheimer’s Disease and Endophenotypes lab at Mayo Clinic in Florida. The lab is made up of over 20 individuals and has been fully funded by the National Institutes of Health since its inception.

But she got her start at Mayo Clinic working in the lab of Steven Younkin, M.D., Ph.D. (PHAR ’95), emeritus professor of pharmacology at Mayo Clinic College of Medicine and Science in Florida, focusing her thesis on genetic factors that lead to Alzheimer’s disease. She was mentored by Dr. Younkin and Neill Graff‑Radford, M.D. (N ’89), a consultant in the Department of Neurology at Mayo Clinic in Florida and the David Eisenberg Professor, and had access to brain and blood specimens from deeply characterized patients who had been recruited by Dr. Graff-Radford and other Mayo Clinic physicians. 

“It was my luck that I was in this phenomenal environment with access to these biospecimens and the know-how from clinicians and scientists,” she says.

Building on Dr. Younkin’s and Dr. Graff-Radford’s analysis and foundation of knowledge of these specimens, she conducted a pioneering study for her thesis, introducing the use of plasma amyloid-beta levels as a phenotype in genetic studies of Alzheimer’s disease.

“I owe Dr. Graff-Radford and Dr. Younkin a debt as a mentee, and it’s impossible to fully pay that debt. But one way may be to try and be the best mentor that I can be,” Dr. Ertekin-Taner says. “Mentoring is hard work. It’s time consuming and it’s a lot of responsibility, but it’s also an aspect of my job that brings me a lot of joy.”

Dr. Oatman and Dr. Min have both benefited from this dedication and have already made important research findings that are “directly related to patients,” Dr. Ertekin-Taner says.

Bench to bedside

Dr. Min was drawn to study in Dr. Ertekin-Taner’s lab because of her fascinating and impactful research and her status as “the leading expert on Alzheimer’s disease and omics research,” he says.

He found Dr. Ertekin-Taner to be a consistent and dedicated mentor, willing to take the time to help him establish himself as a researcher.

Dr. Ertekin-Taner’s commitment to helping Dr. Min find his way paid off. Dr. Min found molecular changes in the brains of patients with progressive supranuclear palsy (PSP), an incurable brain disorder with symptoms that mimic Parkinson’s disease and dementia. The condition leads to rapid, progressive decline and death.

These were significant findings, as these molecular changes could act as potential treatment targets for PSP. But Dr. Min didn’t stop there. Thanks to Dr. Ertekin-Taner’s mentorship, he’s working to take his findings from bench to bedside.

“We’re developing actual therapy. It is amazing that working with Dr. Ertekin-Taner, we can continue the therapeutic development and hopefully bring it to clinical trials,” he says. “Her role as a physician-scientist and years of experience in this field helped me go from the basic science discovery to translation into a potential product.”

Dr. Min’s work also has the potential to make a broader impact across other neurological conditions.

“Because PSP shares similar biology with other neurological disorders such as Alzheimer’s disease, we hope our findings might also benefit drug discovery efforts in other neurological disorders,” he says.

The cycle continues

Dr. Oatman’s work also has important implications for treating patients. Her research is focused on connecting the pathological changes in brains with Alzheimer’s to molecular changes via epigenetics and transcriptomics.

“Stephanie’s work has helped unravel the complexity of the biochemical changes in a patient’s brain,” Dr. Ertekin-Taner says. “That’s essential for developing future therapies for patients with Alzheimer’s disease.”

For this work, Dr. Ertekin-Taner taught Dr. Oatman to handle the sometimes unwieldy big data involved in omics.

“There are a lot of ways to get really lost in all that data. Nilüfer has a really good way of taking a step back and seeing the important things,” says Dr. Oatman. “It’s making sure that you understand what you’re doing and why you’re doing it, rather than throwing the entire kitchen sink of data analysis at it.”

Dr. Oatman already had a chance to pass that knowledge along when she mentored then-high school student Kristi Biswas in benchwork and genome analysis as part of Mayo’s 10-week SPARK Research Mentorship Program. Dr. Oatman taught Biswas to focus her big data research and says it was rewarding to mentor Biswas so that she “really understood what was happening and why she was doing it.”

Biswas found that a genetic variant associated with brain levels of Alzheimer’s disease-related proteins also was associated with disease-related features, like the amount and location of tau and amyloid deposits. She ultimately placed in the Biomedicine and Life Sciences category at an international student science and engineering fair and says her time in the SPARK program was a “life-changing experience.”

“I wasn’t really a basic science person, but once I got into research, I realized how fun it is and really limitless,” Biswas says. “There’s no end to what you can learn.”