Maria Catarina Silva, Ph.D.

Instructor in Investigation
Center for Genomic Medicine, Mass General Research Institute
Instructor in Neurology
Harvard Medical School
PhD Northwestern University 2012
B.Sc./M.Sc. University of Lisbon Faculty of Sciences 2005
alzheimer's disease; autophagy; frontotemporal dementia; ips cellular models of disease; neurodegenerative diseases; neurons; neuroscience; protacs; protein aggregation; stem cell biology; tau proteins; tauopathies
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.

  1. M.C. Silva, C. Cheng, W. Mair, Y. Huang, F.B. Gao, G. Coppola, D.H. Geschwind, A. Karydas, B.L. Miller, K.S. Kosik, J.A. Steen, S.J. Haggarty (2016) Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Aberrant Tau Levels and Mechanisms of Neuronal Vulnerability. Stem Cell Reports 7(3):325-40.
  2. M.C. Silva, F.M. Ferguson, Q. Cai, K.A. Donovan, G. Nandi, D. Patnaik, T. Zhang, H-T. Huang, D.E. Lucente, B.C. Dickerson, T.J. Mitchison, E.S. Fischer, N. Gray, S.J. Haggarty (2019) Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models. eLIFE 8:e45457.
  3. Silva, M.C., Nandi, G.A., Tentarelli, S. et al. Prolonged tau clearance and stress vulnerability rescue by pharmacological activation of autophagy in tauopathy neurons. Nature Commun 11, 3258 (2020).
  4. Bowles K.R., Silva M.C., et al. (2021) ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids. Cell 184(17):4547-4563.
Chemical Neurobiology Lab Publications
(617) 643-5444
Center for Genomic Medicine
Simches Building
185 Cambridge Street
room 5400
Boston, MA 02114