Investigator:
Michael Almeida, PhD
Name of Institution:
The University of North Carolina at Chapel Hill
Project Title:
The Role of CHIP Dysfunction in a-Synuclein Pathology: Mechanisms and Therapeutic Strategies for Parkinson’s Disease
Investigator Bio:
Dr. Almeida is a Postdoctoral Research Associate at the Pharmacology Department within the University of North Carolina School of Medicine. His research focuses on uncovering novel mechanisms of protein quality control in neurodegenerative diseases, with particular emphasis on Alzheimer’s and Parkinson’s disease. His translational work integrates molecular neuroscience, imaging, and cellular physiology to develop therapeutic strategies targeting disrupted protein homeostasis.
Dr. Almeida earned his Master’s degree at the University of São Paulo, Brazil, where he investigated the effects of physical exercise on brain health in models of aging and neurodegeneration, producing several impactful publications. He then obtained his PhD in neuroscience from the University of North Carolina Wilmington, where his research elucidated how environmental exposures, such as neurotoxins and blast injuries, impair synaptic function and identified pharmacological and plant-based approaches to protect against these insults by enhancing protein homeostasis pathways.
During his doctoral and postdoctoral training, Dr. Almeida developed expertise in advanced imaging techniques, including high-resolution optical and electron microscopy, and received further specialized training at Yale University, Harvard University, and the Marine Biological Laboratory. His current research involves engineering variants of the co-chaperone CHIP to enhance toxic protein clearance while preserving neuronal function, offering a precision-based strategy to relieve symptoms and potentially slow progression of neurodegenerative diseases.
Objectives/Background:
The pathology of Parkinson’s disease (PD) involves the harmful buildup of a protein called alpha-synuclein (aSyn), which clumps together and damages brain cells. Completely removing aSyn is not an option because it also plays important roles in healthy brain function. This project aims to decrease aSyn clumping by developing an improved version of a natural brain protein called CHIP. Normally, CHIP helps regulate aSyn by either breaking it down or recycling it, but in PD this process becomes less effective. The improved CHIP will be designed to better recognize and remove only toxic forms of aSyn while preserving its normal functions.
Methods/Design:
My project focuses on engineering a genetically modified, optimized version of CHIP, a natural brain protein that helps clear harmful proteins like aSyn. CHIP normally removes aSyn by sending it to be broken down or recycled, but in PD this process becomes less effective, allowing toxic forms to accumulate. I will design a genetically modified CHIP variant that better recognizes and removes only toxic aSyn while preserving its normal functions. Using gene therapy or small molecules to deliver this optimized CHIP into the brain, I will test whether it reduces toxic aSyn buildup, protects brain cells from damage, and improves movement and coordination in laboratory models of PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This research could lead to treatments that slow or stop disease progression, greatly improving the lives of people with PD.