Carmo Costa, PhD

Assistant Professor
Pharmacology & Toxicology

Bio

The Costa laboratory investigates mechanisms of neurodegeneration and conducts studies towards the development of therapeutics for neurodegenerative diseases.

Colleges

• College of Human Medicine

Education

• Post-doctoral fellow - Translational approaches for neurodegenerative diseases, Department of Neurology, University of Michigan (2008-08-25—2012-12-31)
• Ph.D. in Life and Biomedical Sciences, School of Medicine/ Life and Health sciences Research Institute, University of Minho (2003-05-01—2008-05-26)
• Licenciatura in Biochemistry, Faculty of Sciences/ Institute of Biomedical Sciences Abel Salazar, University of Porto (1994-09-14—2000-02-15)

Funding

• Investigating the efficacy of aripiprazole related compounds as a therapeutic option for SCA3, National Ataxia Foundation (2024—2026)
• Development of allele-specific gene therapeutic targeting the pathogenic RNA associated with Spinocerebellar ataxia type 3, NINDS (2022—2024)
• Definition of the polyglutamine protein ataxin-3 interactome in the human retina. , Eversight Center for Vision & Eye Banking Research. (2023—2024)
• #1 Development of therapeutics for polyglutamine diseases/ #2 Elucidation of gain-of-function and loss-of-function mechanisms of polyglutamine diseases in the brain, Michigan Medicine, University of Michigan (2022—2023)
• NIK as a therapeutic target for Spinocerebellar ataxia type 3, Cayman Biomedical Research Institute (2021—2022)
• Molecular Mechanisms of Neuroprotection in Polyglutamine-Dependent Degeneration, NINDS (2019—2023)
• Identification of novel genes that modulate ATXN3 abundance, National Ataxia Foundation (2019—2020)
• Apoptosis-related genes BCL2, BAX, AND TP53 as biomarkers of Spinocerebellar ataxia type 3 (SCA3), National Ataxia Foundation (2018—2019)
• Exploring the therapeutic capacity of Aripiprazole and related compounds for Machado-Joseph disease, National Ataxia Foundation (2018—2018)
• Identification of therapeutic compounds for Spinocerebellar Ataxia type 3, Cydan Development Inc. (2017—2020)
• Aripiprazole as a therapy for Spinocerebellar Ataxia type 3, Michigan Institute for Clinical and Health Research (2017—2019)
• Identification of predisposing CNS-penetrant therapeutic compounds for Spinocerebellar Ataxia Type 3, Center for Discovery of New Medicines, University of Michigan (2016—2017)
• Mechanisms of Polyglutamine Neurodegeneration, NINDS (2015—2019)
• Defining pathways that regulate levels of polyglutamine disease protein in MJD/SCA3, National Ataxia Foundation (2015—2015)
• Unveiling pathways that regulate levels of polyglutamine disease protein in MJD/SCA3, Becky Babcox Research Fund, University of Michigan (2014—2015)
• Defining pathways that modulate levels of polyglutamine disease protein ATXN3 in MJD /SCA3, Protein Folding Diseases Initiative, Michigan Medicine, University of Michigan (2014—2015)
• Developing a SCA3 Therapeutic: Small Molecules that Reduce Levels of Mutant Ataxin-3, National Ataxia Foundation (2011—2011)
• Development of Therapeutic Strategies for Machado-Joseph Disease, Fundação para a Ciência e a Tecnologia (2008—2011)
• Study of the mouse homologue gene that causes Machado-Joseph Disease, Fundação para a Ciência e a Tecnologia (2003—2007)

Works

• Blood DDIT4 and TRIM13 Transcript Levels Mark the Early Stages of Machado–Joseph Disease. Annals of Neurology (2025-03-05)
• Blood and cerebellar abundance of ATXN3 splice variants in spinocerebellar ataxia type 3/Machado-Joseph disease. Neurobiology of disease (2024-02-27)
• Blood and cerebellar abundance of ATXN3 splice variants in spinocerebellar ataxia type 3/Machado-Joseph disease. Neurobiology of Disease (2024)
• Blood levels of neurofilament light are associated with disease progression in a mouse model of spinocerebellar ataxia type 3. Disease Models & Mechanisms (2023-09-01)
• Editorial: The role of posttranslational modifications in polyglutamine diseases. Frontiers in molecular neuroscience (2023-08-15)
• Tissue-Specific Vulnerability to Apoptosis in Machado-Joseph Disease. Cells (2023-05-17)
• Regional and age-dependent changes in ubiquitination in cellular and mouse models of spinocerebellar ataxia type 3. Frontiers in molecular neuroscience (2023-04-14)
• Regional and age-dependent changes in ubiquitination in cellular and mouse models of spinocerebellar ataxia type 3. Frontiers in Molecular Neuroscience (2023-04-14)
• Sleep Alterations in a Mouse Model of Spinocerebellar Ataxia Type 3. Cells (2022-10-05)
• Altered retinal structure and function in Spinocerebellar ataxia type 3. Neurobiology of disease (2022-05-21)
• Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)¹. Autophagy (2021-01-01)
• The Deubiquitinating Enzyme Ataxin-3 Regulates Ciliogenesis and Phagocytosis in the Retina. Cell Reports (2020)
• In Vivo Molecular Signatures of Cerebellar Pathology in Spinocerebellar Ataxia Type 3. Movement Disorders (2020)
• Recent therapeutic prospects for Machado-Joseph disease. Current opinion in neurology (2020-08-01)
• Druggable genome screen identifies new regulators of the abundance and toxicity of ATXN3, the Spinocerebellar Ataxia type 3 disease protein. Neurobiology of Disease (2020)
• Ataxin-3 Links NOD2 and TLR2 Mediated Innate Immune Sensing and Metabolism in Myeloid Cells. Frontiers in immunology (2019-07-19)
• Antisense oligonucleotide therapy rescues aggresome formation in a novel spinocerebellar ataxia type 3 human embryonic stem cell line. Stem cell research (2019-07-16)
• Selection of Reference Genes for Normalization of Gene Expression Data in Blood of Machado-Joseph Disease/Spinocerebellar Ataxia Type 3 (MJD/SCA3) Subjects. Journal of molecular neuroscience : MN (2019-07-08)
• Citalopram Reduces Aggregation of ATXN3 in a YAC Transgenic Mouse Model of Machado-Joseph Disease. Molecular Neurobiology (2019-05-04)
• Methods of Treating Neurodegenerative Diseases. (2019-03-16)
• A knockin mouse model of spinocerebellar ataxia type 3 exhibits prominent aggregate pathology and aberrant splicing of the disease gene transcript. Human molecular genetics (2017)
• Interaction of the polyglutamine protein ataxin-3 with Rad23 regulates toxicity in Drosophila models of Spinocerebellar Ataxia Type 3. Human molecular genetics (2017)
• Unbiased screen identifies aripiprazole as a modulator of abundance of the polyglutamine disease protein, ataxin-3. Brain : a journal of neurology (2016)
• Differential recruitment of UBQLN2 to nuclear inclusions in the polyglutamine diseases HD and SCA3. Neurobiology of disease (2015)
• Dominant negative effect of polyglutamine expansion perturbs normal function of ataxin-3 in neuronal cells. Human molecular genetics (2014)
• New hope for therapy in neurodegenerative diseases. Cell research (2013)
• Silencing mutant ATXN3 expression resolves molecular phenotypes in SCA3 transgenic mice. Molecular therapy : the journal of the American Society of Gene Therapy (2013)
• Toward RNAi therapy for the polyglutamine disease Machado-Joseph disease. Molecular therapy : the journal of the American Society of Gene Therapy (2013)
• Toward understanding Machado-Joseph disease. Progress in neurobiology (2011)
• Early changes in cerebellar physiology accompany motor dysfunction in the polyglutamine disease spinocerebellar ataxia type 3. The Journal of neuroscience : the official journal of the Society for Neuroscience (2011)
• Large normal and reduced penetrance alleles in Huntington disease: instability in families and frequency at the laboratory, at the clinic and in the population. Clinical genetics (2010)
• Absence of ataxin-3 leads to cytoskeletal disorganization and increased cell death. Biochimica et biophysica acta (2010)
• Ataxin-3 plays a role in mouse myogenic differentiation through regulation of integrin subunit levels. PloS one (2010)
• Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products. Neurobiology of disease (2010)
• Increased transcript diversity: novel splicing variants of Machado-Joseph disease gene (ATXN3). Neurogenetics (2009)
• Functional genomics and biochemical characterization of the C. elegans orthologue of the Machado-Joseph disease protein ataxin-3. FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2007)
• Exclusion of mutations in the PRNP, JPH3, TBP, ATN1, CREBBP, POU3F2 and FTL genes as a cause of disease in Portuguese patients with a Huntington-like phenotype. Journal of human genetics (2006)
• Population genetics of wild-type CAG repeats in the Machado-Joseph disease gene in Portugal. Human heredity (2005)
• The CAG repeat at the Huntington disease gene in the Portuguese population: insights into its dynamics and to the origin of the mutation. Journal of human genetics (2005)
• Nonsense mutation in TITF1 in a Portuguese family with benign hereditary chorea. Neurogenetics (2005)
• Towards a structural understanding of the fibrillization pathway in Machado-Joseph's disease: trapping early oligomers of non-expanded ataxin-3. Journal of molecular biology (2005)
• Neuroferritinopathy: missense mutation in FTL causing early-onset bilateral pallidal involvement. Neurology (2005-08-01)
• Genomic structure, promoter activity, and developmental expression of the mouse homologue of the Machado-Joseph disease (MJD) gene. Genomics (2004)
• Genotypes at the APOE and SCA2 loci do not predict the course of multiple sclerosis in patients of Portuguese origin. Multiple sclerosis (Houndmills, Basingstoke, England) (2004)
• Molecular diagnosis of Huntington disease in Portugal: implications for genetic counselling and clinical practice. European journal of human genetics : EJHG (2003)
• Identification of three novel polymorphisms in the MJD1 gene and study of their frequency in the Portuguese population. Journal of human genetics (2002)
• Improvement in the molecular diagnosis of Machado-Joseph disease. Archives of neurology (2001)

Employment

• Assistant Professor (tenure system), Michigan State University (2025-04-01)
• Research Assistant Professor , University of Michigan (2017-09-01—2025-03-31)
• Research Investigator , University of Michigan (2013-01-01—2017-08-31)
• Research Assistant, University of Porto (1999-10-01—2003-04-30)