Basic science research spotlight: Miguel Moutinho, PharmD, PhD

Nurturing a passion for biomedical research, Miguel Moutinho, PharmD, PhD, was introduced to research in Alzheimer’s disease and related dementias (ADRD) during his doctor of pharmacy training at the Faculty of Pharmacy at the University of Lisbon. Fascinated by the molecular and cellular mechanisms that regulate brain cholesterol homeostasis and neuronal function, Moutinho is particularly interested in understanding how disruptions in these processes contribute to neurodegeneration and how these insights can inform the development of new therapeutic strategies for ADRD.

Moutinho’s early experience in the field sparked a lasting interest in ADRD research, which led him to IU School of Medicine in 2017 as a postdoctoral fellow working under the mentorship of Gary Landreth, PhD. Moutinho accompanied Landreth, who relocated his laboratory from Case Western Reserve University to IU School of Medicine and the Stark Neurosciences Research Institute.

“From the beginning, I was excited by the vision of the Stark institute,” Moutinho said. “What stood out most was the exceptional environment and sense of collegiality. There was tremendous enthusiasm across the institute, with active recruitment of new investigators and a shared commitment to building something meaningful. It truly felt like we were part of the beginning of a major scientific enterprise with common goals and a promising future.”

Today, Moutinho, an assistant professor of medical and molecular genetics, is an independent researcher whose laboratory focuses on the molecular and cellular mechanisms that drive the development and progression of ADRD. His lab also investigates why specific genetic and environmental factors influence a person’s risk of developing these disorders. Moutinho’s research is supported by startup funding from the Department of Medical and Molecular Genetics and the Stark Neurosciences Research Institute, as well as grants from the Alzheimer's Association, the BrightFocus Foundation and the National Institute on Aging.

What are the potential implications of your research on future clinical care and treatment of ADRD?
Although our research is primarily conducted in cellular and animal models, these studies allow us to identify novel therapeutic targets and strategies that may ultimately be translated into clinical care. One example is our 2022 study showing that niacin treatment improved disease-related outcomes in a mouse model of Alzheimer's disease. Because niacin is already FDA approved, those findings provided the scientific rationale for an ongoing clinical trial at IU School of Medicine evaluating niacin in individuals with Alzheimer's disease. While the path from basic discovery to patient care is often long, this example illustrates how fundamental research can directly inform the development of new therapeutic approaches.

Do you have any recent developments or findings to share?
We have several exciting projects underway, and one area I’m particularly enthusiastic about involves the gut microbiome and its role in Alzheimer's disease. Our recent findings suggest that a specific pathway within the gut microbiome may contribute to disease progression, and that modulating this pathway can influence Alzheimer's disease-related pathology in preclinical models. Although more work is needed to validate these findings, they highlight the gut microbiome as a promising and potentially tractable target for future Alzheimer's disease therapeutics.

How has IU School of Medicine supported your research efforts?
The school has been instrumental in supporting the development of my research program. One of the most valuable aspects has been the protected research time during the first three years of my faculty appointment, which has allowed me to focus on establishing my laboratory, building collaborations and generating the preliminary data needed to compete for external funding. The school also provided dedicated laboratory space and startup funds, which were essential for launching my independent research program. In addition, I have benefited from outstanding mentorship and a highly collaborative environment through both the Stark institute and the Department of Medical and Molecular Genetics.

What are your plans for future research?
We are expanding our research program to better understand the biology of brain aging and the molecular mechanisms that promote resilience to neurological diseases. By identifying why some individuals maintain cognitive function despite underlying pathology, we hope to uncover new therapeutic targets and strategies to prevent or slow dementia, as well as age-related cognitive decline.

What do you find most rewarding about your work?
What I find most rewarding are the "Eureka" moments—those times when we uncover a new biological mechanism or finally understand how something works at the molecular level. I also enjoy the process of solving complex biological puzzles and contributing new knowledge that can serve as the foundation for future therapeutic approaches. Knowing that these discoveries, even if they begin as basic science, have the potential to improve human health is what makes this work so meaningful to me.