Maria Catarina Silva, Ph.D.

Our goal is to understand the fundamental molecular and cellular mechanisms associated with CNS proteinopathies and neurodegenerative diseases, caused by aberrant accumulation of proteins in the brain, then focusing on the translational potential of research into new patient therapies.

We work on the generation and characterization of patient-specific stem cell-derived cellular models of disease, with a focus on tauopathies such as Frontotemporal Dementia (FTD). We combine state-of-the-art methodologies for derivation of human induced pluripotent stem cells (iPSC) and iPSC differentiation into neuronal cells to model disease in patient-derived neurons. We have been investigating the etiology of FTD-tau by identifying early disease-associated molecular and biochemical changes and therapeutic targets in these patient-derived cellular models. Patient-specific neurons also represent a remarkable platform for testing small-molecule modifiers of disease-relevant phenotypes in drug discovery pipelines. We are working with several series of small-molecules that rescue tauopathy phenotypes, with the ultimate goal of identifying disease-modifying therapeutics. We work closely in collaboration with the MGH FTD Unit, the Alzheimer’s Disease Research Center and the Tau Consortium (Rainwater Charitable Foundation), which allows for remarkable training opportunities and research advance.

One of our projects is focused on phenotyping molecular and cellular abnormalities in tauopathy patient-derived 2D neuronal cells and 3D cerebral organoids. We continue to increase the collection of iPSC lines from FTD and Alzheimer’s patients, with confirmed tau variants and/or pathology, to characterize disease-relevant cellular mechanisms and therapeutic targets.
We also focus on small-molecule screening and drug discovery efforts. FTD and related diseases are still without effective treatment. We believe that progress requires integrative approaches, and so we have established collaborations with Dr. Brad Dickerson from the MGH FTD Unit, and with clinical colleagues and drug discovery experts within the Tau Consortium (Rainwater Charitable Foundation). 
We are privileged to work in the outstanding MGH/Harvard community and in close proximity with patient-oriented organizations such as the AFTD and the Tau Consortium that support our work and are global leaders in the effort to “making a difference” toward treating diseases such as FTD and Alzheimer’s.