Daniel Lee, PhD, is an associate professor at the University of Kentucky College of Medicine Department of Neuroscience and a researcher at the UK Sanders-Brown Center on Aging, an internationally recognized Alzheimer’s Disease Research Center. He joined the UK College of Medicine in August 2019. He is also a member of the Faculty of Color Network and currently serves as co-director for the Research Education Component (REC) of the UK-ADRC.

For Alzheimer’s Awareness Month, Dr. Lee discusses his research on Alzheimer’s disease and other neurodegenerative diseases, what inspired him to pursue a career in neuroscience, and what advice he has for the next generation of researchers.

Q: How did you get started researching neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease?

A: My original PhD work was in Parkinson’s disease looking at lysosomal systems, autophagy, and clearance mechanisms in neurodegenerative diseases. During my postdoc, I switched over to Alzheimer’s disease. We looked at some of the commonalities and the divergent roles between Alzheimer’s and Parkinson’s.

From there, we started looking at the role of neuroinflammation. And then as I progressed to an assistant professor at the University of South Florida College of Pharmacy where I was before, we started looking at the role of simple metabolic processes known as amino acid sensing dysfunction. More specifically, there are biological processes that focus on arginine metabolism and how these simple biological processes are disrupted in neurodegenerative diseases.

Q: And what are you currently researching?

A: My current work focuses on the role of arginine metabolism in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases with aggregated proteins that accumulate with age. We’re trying to understand basic biological functions between these metabolic processes, arginine metabolism, and trying to tune those systems so we can start to clear out these aggregation-prone proteins.

In our lab we use animal models that exploit these different hallmarks such as amyloid proteins, which are associated with Alzheimer’s disease. We do gene therapy. We use cell culture models and recombinant protein systems. We employ various methods to answer specific questions regarding these neurodegenerative conditions that affect cognitive functions.

Q: What inspired you to study Parkinson’s disease and Alzheimer’s disease?

A: One of the big influences in my life was my grandfather. We both went to Lincoln University, which was an HBCU, a historically Black college and university. He put himself through medical school. He was a physician who came back to his community and started his own practice.

When I was in college, he started to develop Parkinsonism, Parkinson's-like phenotypes. And that led me to go and pursue my PhD in Parkinson's disease.

During that time when I was doing my PhD, he started to come down with dementia, cognitive impairment. It could have been Alzheimer's, or it could have been some type of mixed etiology with Parkinson's and dementia, so that led me in my postdoc and as an assistant professor to start looking at the role of Alzheimer's disease.

That's really what geared me toward looking at these neurodegenerative diseases, to understand how my grandfather, who's very smart, an MD, could come down with these debilitating diseases.

Q: What types of advanced technology do you use at Sanders-Brown that assists you in this research?

A: Actually, one of the things that drew me to UK was Sanders-Brown. Sanders-Brown allows me to integrate everything from the clinical aspect of human tissue down to the cellular level. Sanders-Brown has the designation as an Alzheimer’s Disease Research Center. They have international renowned scientists and a top-tier neuropathology and biomarker core. These resources allow one to test and study human tissue up close to confirm what we are doing in the lab and to make sure it is actually relevant to human conditions. In addition, they perform a lot of clinical trials.

Sanders-Brown has this clinical consensus consortium whereby they discuss a patient's history, disease onset, pathology, and final diagnosis. Some of these patients have come to this clinic more than 20 different times. Now that's a commitment that I've never heard of. To have 20 years of clinical history of a patient, along with the biochemistry, the biomarkers, and the neuropathy imaging is unmatched. And then to have physicians, neuropathologists, biomarkers, statisticians come up with the diagnosis, it allows people at Sanders-Brown to really start coming up with new hypotheses and diseases that haven't even been described yet.

Q: What is your overarching goal through your research career?

A: The problem with Alzheimer's is that there are a lot of different pathologies that emerge. We are still trying to understand basic biology of the disease. There are certain aspects of my lab that focus on this through arginine metabolism. In that respect, we believe that there is a route to treat those parts of the disease through arginine signaling.

We have to understand the basic biology so that we know we're hitting our target. We want to make sure that when we shoot on goal that we're hitting at least one of those targets in Alzheimer's disease.

Q: What advice would you give to students who are considering following a career path to neuroscience?

A: One of my big pieces of advice is don't be afraid to fail or to take risks. I think that's very important, as an educator, to take students out of their comfort zone and make them do things they're not accustomed to. This changes their perspective. You need to be put in situations you're uncomfortable with, grow from that, and see how you failed. I know it helped me to learn how the system actually works.

Also, I encourage students to develop good mentors. I think mentors are the No. 1 criterion for success. You need an advocate in this field. You need somebody to get you out of your own headspace and look at things from an objective point of view. I'm an associate professor and I still have four mentors here at UK. I touch base with them on a regular basis. And I think it's very critical.

One of my favorite quotes is from Winston Churchill. “Success is not final, and failure is not fatal.” Mentors help you navigate those successes and the failures.

Q: You’re a little more than a year into living in Lexington. What are things you enjoy doing outside of your lab?

A: I'd say 90 percent of my time outside the lab is focused on family. Every Friday, we have a movie night with the girls. My wife Maj-Linda Selenica, who is also an assistant professor here at Sanders-Brown Center on Aging, is Swedish. She has a custom known as “Fredags Mys” meaning “Friday-cozy.” It’s basically that one day of the week, usually on a Friday, the kids get to eat a bunch of junk food, candy, snacks, and we have a movie night. I get to hold that over my 6-year-old’s and 3-year-old’s heads all week. They love it.

We like to go to parks, too. We have seasons here in Lexington, so that's new to my kids. They saw snow in their backyard for the first time last winter.

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