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Health Sciences Research Fellowship 2024: Modulation of Microglial Response to Alzheimer’s Disease with Ultrasound Targeted Microbubble Cavitation in a Model of the Blood Brain Barrier

Hi everyone! My name is Mara Cicchetti and I am a part of the Health Sciences Research Fellowship this summer. My project in Dr. Villanueva’s lab focuses on Alzheimer’s Disease and a cutting edge therapeutic tool called Ultrasound Targeted Microbubble Cavitation (UTMC). This therapeutic can be used to disrupt the blood brain barrier, allowing for drug delivery to the brain parenchyma which is otherwise impossible for large molecules. UTMC is currently being tested in clinical trials. Because this therapeutic is being investigated as a tool to improve the drug delivery for Alzheimer’s treatment, my project investigates the effect of UTMC on microglia, the resident immune cells of the brain. Microglia can change their phenotype to be either neurotoxic or neuroprotective depending on how they are stimulated. A hallmark of Alzheimer’s Disease is an increase in the expression of the neurotoxic phenotype, which worsens disease progression. I have developed an in vitro (cell) model of the blood brain barrier with Alzheimer’s pathology. This model uses brain endothelial cells which form a tight barrier along the blood vessels in the brain. Among other things, Alzheimer’s Disease is characterized by a buildup of a neurotoxic protein called Amyloid-beta within the brain. My cell model utilizes aggregated Amyloid-beta to simulate Alzheimer’s Disease conditions at the blood brain barrier. My goal is to evaluate levels of inflammation and modulation of Amyloid-beta clearance with and without UTMC. My project is important because it assesses the safety of UTMC as a treatment used in Alzheimer’s Disease. Since microglia have such a complex role in the disease progression of Alzheimer’s, it is important to know their response to UTMC.

When it comes to my academic goals, I hope to graduate from Pitt with an undergraduate thesis and soon move on to start working on a PhD. I hope to complete a PhD in either neuroscience or immunology, but I am open to any kind of biomedical research! Research is definitely a passion of mine, and I am excited to be able to move to an academic space where I can focus all of my time and energy on it. This summer is helping me get a taste of that, and I am so excited to continue my research full time for the next few months. 

I am a neuroscience major with minors in chemistry and business. Something unique that I would like to share is that I spent the last semester studying abroad in Florence, Italy!

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