Research

Biology of Degenerative Diseases Lab

We speculate that each of approximately 150 chaperone proteins could be a drug target for human diseases. Our lab is focused on chaperones capable of modulating the progression and toxicity of tauopathies, a group more than 15 neurodegenerative diseases (including Alzheimer’s disease) characterized by aberrant accumulation of aggregates of the tau protein. Our work has also explored chaperone involvement in other neuropsychiatric disorders including depression and PTSD. Our lab is involved in drug development and target validation for specific chaperone proteins, and we hope to someday soon translate these treatments and with the ultimate goal of developing a cure.

The Hsp90 cochaperone FKBP51 regulates tau structure and function

We are working to validate FKBP51 as a target for tauopathies, like Alzheimer’s disease, and explore the molecular landscape by which FKBP51 genetic variants create a vulnerability for neuropsychiatric symptoms. Neuropsychiatric symptoms are often co-morbid with Alzheimer’s disease and other tauopathies correlate with a faster decline in patients.

Aha1: A Promising Drug Target for Tau-Driven Neurodegeneration

This project focuses on understanding the role of a protein called Aha1 in Alzheimer's disease. We found that high levels of Aha1 increase tau aggregation and reduce neuronal survival and cognition in mice with tau-related diseases. Lower levels of Aha1 are associated with better cognitive stability in older individuals, and Aha1 has been identified as a tau interactor in human-derived neurons.

We aim to test whether reducing Aha1 can slow tau accumulation and improve neuronal survival. Our preliminary data suggests that reducing Aha1 may be beneficial, but we need to understand more about Aha1 biology and its pathways. We will use advanced techniques to study Aha1 and its interactions in the brain. By achieving these goals, we hope to develop therapies targeting Aha1 to reduce tau accumulation and improve cognitive function in Alzheimer's disease.

Controlling FKBP51 for the treatment of PTSD

Some individuals are vulnerable to develop PTSD, depression, and other neuropsychiatric disorders following stress exposure due to the presence of common allelic variations in the FKBP5 gene. We want to understand more about the mechanisms underlying this vulnerability and the best way to provide resilience towards this increased risk. We are also developing therapeutics. Our goal is to develop novel strategies to deplete FKBP5, while validating FKBP5 as a key regulator of susceptibility towards PTSD-like trauma. 

Support

You can support our lab through a donation to fund #250228 at Give to the University of South Florida :: Giving to USF.