We investigate mechanisms of neurodegeneration and conduct studies towards the development of therapeutics for neurodegenerative diseases.

We have been focusing our research primarily on the fatal polyglutamine disorder Machado-Joseph disease (MJD), also known as Spinocerebellar ataxia type 3 (SCA3).

We are also interested in expanding our research programs to other neurodegenerative diseases. 

Our lab is currently interested in:

  1. investigating mechanisms that regulate the abundance of the mutant ATXN3 gene products in MJD/SCA3.
  2. developing therapeutic approaches for MJD/SCA3 and other polyglutamine diseases.
  3. understanding the function of native and mutant polyglutamine proteins.

To conduct our research we use mouse models, control and disease human cell lines including human embryonic stem cells (hESCs) and induced pluripotent cells (iPSCs), human brain and retina tissues, drug and genetic screens, biochemistry, and molecular and cellular biology techniques.

Here’re some examples of our models:

human mutant ATXN3 (green) nuclear accumulation in pontine neurons of YACMJD84.2 transgenic mice.

SCA3 hESC-derived midbrains neurons expressing beta-TubulinIII (red). Tyrosine-hydroxylase (TH)-positive neurons are labeled in green. Cell nuclei are detected with DAPI (blue). unpublished

SCA3 hESC-derived astrocytes expressing GFAP (purple). Cell nuclei are detected with DAPI (blue). unpublished

Human mutant ATXN3 (green) accumulates in the phoreceptors (PhR), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL) and ganglion cell layer (GCL) of YACMJD84.2 transgenic mouse retina. Cell nuclei are detected with DAP (blue). Adapted from Toulis et al. 2022

Accumulation of negative electrodense particles in the nuclei and soma of ganglion cells of YACMJD84.2 mouse retina. Adapted from Toulis et al. 2022


02/10/2023 – Ebony Johnson and Becky Harris from Eversight visit the Costa lab to hand in person the certificate for the Eversight Center for Vision & Eye Banking Research Award to Carmo. The goal of the one-year funded project (January-December 2023) is to define the interactome of the polyglutamine protein ATXN3 in the human retina.

11/11/2022 – Ana Ferreira defends her PhD thesis – Ana is now a Doctor in Biology from the University of Azores. Congrats Ana!

01-04/11/2023 – Carmo presents a flash-talk (Barget et al. (a)) and two posters (Tsimpanouli et al.; Barget et al. (b)) at the International Congress for Ataxia Research in Dallas, TX, USA

08/19/2022 – the Costa Lab (academic partner) and Enzerna BioSciences start a Small Business Innovation Research (SBIR) program funded by the National Institutes of Health (NIH) to develop an allele-specific protein-based therapeutic targeting the pathogenic RNA associated with Spinocerebellar ataxia type 3. This is a milestone program for three years.

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