Teaching students and conducting Alzheimer’s research: It’s all part of the mix for Erin Reed-Geaghan, Ph.D., who joined Northeast Ohio Medical University in 2019.
Dr. Reed-Geaghan is the course director and primary lecturer for the Immunology and Biotechnology course in the College of Pharmacy. She recently received funding of $300,000 from the BrightFocus Foundation to support her investigation into the differences between men and women in the onset and progression of Alzheimer’s disease.
A good pairing
Teaching and research complement each other well, says Dr. Reed-Geaghan: “In the lab, we can get way down in the weeds, studying one cell type doing a specific thing. In the classroom, introducing students to the entire system forces me to take a step back and see the bigger picture, re-framing the research project or helping interpret the data. Teaching the fundamentals gets the science back to the basics and can open new ways of thinking about a problem. Plus, it’s always fun to share knowledge that I find fascinating with others!”
Supporting your own research
Dr. Reed-Geaghan came to NEOMED from the Harrington Discovery Institute at University Hospitals, where she helped academic researchers advance their basic science work through the drug development pipeline.
Her eyes were opened early as to the critical role of funding for research.
As an undergraduate at Colby College in Waterville, Maine, looking for summer research opportunities, she remembers, “I realized my ability to join a lab for the summer to gain valuable experience hinged on the ability of the investigator and/or myself to secure funding for me and the science. This became more apparent once I was in graduate school and a postdoc [at Case Western Reserve University in Cleveland], where obtaining my own awards permitted me to pursue questions that I found interesting but that my advisors did not have the resources to support.”
During Dr. Reed-Geaghan’s first year of graduate school, her advisor included her in the preparation of his own applications. After that, he and her postdoc advisor encouraged and helped her to navigate the process of applying for her own awards.
“I still rely on them and other more seasoned investigators, along with NEOMED’s Office of Research and Sponsored Projects, to help me know what to do,” she says.
Building a base
“Big, multi-year, lab-sustaining awards from the National Institutes of Health (NIH) can be very challenging to get, and especially so for newly independent investigators like me, due to a lack of preliminary data to validating the hypothesis and technical expertise,” says Dr. Reed-Geaghan.
“The BrightFocus Foundation, which specifically aims to address Alzheimer’s disease (AD), macular degeneration and glaucoma, offers smaller awards that do not require the same amount of technical or scientific validation as the big NIH awards. Their goal is to support investigators in testing their highly innovative ideas. Sometimes it doesn’t pan out, but when it does, it can produce key findings necessary to put forth a successful application to the NIH. As someone with an interest in AD, just starting my own lab, I didn’t have the data to back up my ideas for new ways to think about the disease, so my situation aligned really well with the mission of BrightFocus.
“It can be stressful not knowing if something is going to work, but having the support of the Foundation to test out innovative, high-risk ideas means that if it does, we’ve significantly advanced the field – and if not, that’s ok, too. It’s reassuring to know someone else is willing to take the risk with you for the sake of solving such a devastating disease.”
The BrightFocus Foundation provided $300,000 in support for Dr. Reed-Geaghan’s project, titled “Developmental Determinants of Sexually Divergent Neuroinflammatory Processes in Alzheimer’s disease.” Dr. Reed-Geaghan explains her research:
Alzheimer’s disease (AD) is the leading cause of dementia, with 5 million Americans currently affected and an anticipated increase of 138% over the next 30 years. While AD was first described more than 100 years ago, significant advances in understanding the associated pathology have only come relatively recently. One of the particularly enigmatic aspects of the disease has been its sexually disparate effects: Women make up approximately two-thirds of patients, are diagnosed later in life than men and have a more rapid rate of cognitive decline following diagnosis. My project seeks to identify the cause(s) for these differences in AD onset and progression between men and women.
In addition to the traditional pathological hallmarks of amyloid plaque deposits and tangled neuronal structural proteins, there is a robust inflammatory response in the AD brain. The cells primarily responsible for this inflammation are the brain’s resident immune cells – microglia. These cells take up residence in the brain early in development and are a very stable population, gradually replacing themselves over one’s lifetime. They are evenly spaced throughout the brain and are very active, constantly sending out and retracting “fingers,” sampling the entire brain every few hours. When they detect damage or something that shouldn’t be there through a variety of receptors expressed on their surface, they change their appearance and function in an effort to contain and eliminate the offending stimulus.
In the case of AD, microglia respond to amyloid plaque proteins, dead and dying neurons, and a variety of other signals. While this inflammatory response is meant to protect the brain by removing the offending stimulus, it ends up making things worse – driving additional amyloid protein production, preventing amyloid clearance, recruiting additional immune cells from the periphery, killing additional neurons, etc.
We hypothesize that the microglia in men and women are intrinsically different. In the normal, healthy brain, they appear the same; however, in AD, these differences become apparent when they respond differently to the various stimuli, resulting in divergent disease processes. At the most basic level, males and females differ in the complement of sex chromosomes (XY and XX, respectively), and gonadal sex hormones (testosterone and estrogen, respectively).
In the first set of experiments, we look at whether the expression of XX versus XY sex chromosomes affect microglia and their activity in AD. In the second set of experiments, we look at the role of sex hormones. One typically thinks of hormonal action following puberty, however, there are waves of estrogen and testosterone following birth that play important roles in brain development, setting the stage for later function. We are going to examine whether the neonatal exposure to estrogen or testosterone programs microglia so that they behave differently when challenged in the context of AD.
Ultimately, we hope that we can identify the biologic mechanisms that result in the sex differences we see in AD. These could provide the insights necessary to develop new therapeutic agents or to better use current therapies in a more productive way.