My name is Steve MacLean, and I am a fourth-year graduate student in the department of physiology. I am originally from Beverly Hills, Michigan, and pursued my bachelor’s degree at Central Michigan University. I first came to the University of Kentucky in 2019 as a lab technician under John Gensel, PhD, where I worked for two years studying spinal cord injury. I then applied for the Integrated Biomedical Sciences (IBS) PhD program, which provided me with foundational coursework in genetics, biochemistry, cell signaling, bioinformatics, and statistics. After several lab rotations in the IBS program, I was happy to accept a position in the lab of Lance Johnson, PhD, in the department of physiology.
In the Johnson lab, we study Alzheimer’s disease (AD) with a particular focus on apolipoprotein E (APOE), the greatest genetic risk factor for late-onset AD. Of the three common forms of APOE, APOE4 severely increases risk for Alzheimer’s disease while APOE2 reduces Alzheimer’s disease risk. My project investigates the role of APOE derived from the liver, which is the organ that produces the most APOE in the body. Specifically, I am using a novel animal model that expresses the protective APOE2 in the liver while producing the risk variant APOE4 in the brain. The goal of my study is to test whether the APOE2 derived from the liver is sufficient to reduce Alzheimer's disease pathology in the brain. If successful, this could lead to a minimally invasive strategy to treat humans at risk for Alzheimer’s disease.
Preliminarily, my data suggests that APOE2 expression in the liver is not sufficient to reduce Alzheimer's pathology in the brain. Specifically, amyloid beta, a key pathological hallmark of AD is not reduced in animals that express APOE2 in the liver. These animals also did not improve in several tests for cognition and memory. While we are of course disappointed to learn that this approach was not efficacious, we have still addressed an important knowledge gap in the field that I hope will be informative to my fellow researchers and guide future therapeutic strategies. My time working in the Johnson lab has also helped me develop a set of scientific skills that I will continue to use after I graduate to further benefit scientific research. Specifically, I have gained experience in animal work, histology, microscopy, running biological assays, data analysis and scientific writing.
My time in the Johnson lab has also allowed me the fortunate opportunity to secure my own funding and to travel to conferences. In July of 2024, I was awarded with the Training in Translational Research in Alzheimer’s and Related Dementias (TRIAD) T32 training grant. This fellowship has connected me with a cohort of peers with similar interests in Alzheimer’s and related neurodegenerative diseases. I am also thankful for the opportunities this program provides to meet invited speakers and to present at the local Markesbery Symposium. Additionally, the funding from this fellowship allowed me to present my research at two conferences this year in Miami, Florida and Vienna, Austria. I am very thankful for Dr. Johnson, the Department of Physiology, the Sanders-Brown Center on Aging, and the TRIAD T32 for allowing me the opportunity to pursue my passion.
I have always been excited about science and have always been particularly fascinated with the brain. I am also passionate about helping people and have always wanted to have a career that can make a positive impact in the world. Alzheimer’s disease is a complex disease that can be very challenging for both patients and their caretakers. It is important to have compassion for this community because dementia can be difficult to predict and any one of us could eventually develop memory problems as we age. Community outreach is also very important. Last year, I participated in the Alzheimer’s Association’s Walk to End Alzheimer’s where I volunteered at an “Ask the Researcher” table. Working in a lab everyday can sometimes make it easy to lose sight of the bigger picture, but seeing the real people my research aims to impact rejuvenates my passion for science and helps me recognize that my work is important.