Where Ideas Grow

Nerve Regeneration

ABOUT

We are interested in characterising pathways that control axon growth during development, and axon degeneration and regeneration following injury and disease. We have a special focus on studying the axonal cytoskeleton organisation and dynamics, and axonal trafficking.

 

RESEARCH

Neurons, one of the most striking examples of polarization in eukaryotic cells, are dependent on cytoskeleton dynamics and trafficking to establish their distinctive cell shape and function. Understanding the basic neuronal cell biology is crucial to unraveling the causes of neurodegeneration, and to developing strategies to promote axon regeneration.

Research in our group has currently the following main topics:

  • Characterize the biogenesis and function of the axonal membrane periodic skeleton;
  • Identify determinants of the central-peripheral polarity of dorsal root ganglia neurons;
  • Understand cytoskeleton dynamics and trafficking during axon (re)growth and degeneration;
  • Understand the mechanisms allowing the spiny mouse to spontaneously regenerate the CNS.

Our work brings together in vitro neuronal cell culture systems, microfluidics, and in vivo rodent models, including the model of spinal cord injury and models of rare neurodegenerative disorders (Globoid Cell Leukodystrophy and Amyloid-related neuropathies). These models combined with genetic strategies, cell biology and biochemical approaches, and state-of-the-art microscopy, allow us to advance our knowledge on the mechanisms that regulate axon growth, degeneration and regeneration.

Team

Selected Publications

Brites P., Sousa M.M.,
Neurons contribute to pathology in a mouse model of Krabbe disease in a cellautonomous manner. PLoS Biology20(7):, 2022. [Journal: Article] [CI: 1] [IF: 9,8]
DOI: 10.1371/journal.pbio.3001706 SCOPUS: 85134360903

Nascimento A.I., Da Silva T.F., Fernandes E.C., Luz L.L., Mar F.M., Safronov B.V., Sousa M.M.,
Sensory neurons have an axon initial segment that initiates spontaneous activity in neuropathic pain. Brain145(5):1632-1640, 2022. [Journal: Article] [CI: 7] [IF: 14,5]
DOI: 10.1093/brain/awac078 SCOPUS: 85131702538

Nogueira-Rodrigues J., Leite S.C., Pinto-Costa R., Sousa S.C., Luz L.L., Sintra M.A., Oliveira R., Monteiro A.C., Pinheiro G.G., Vitorino M., Silva J.A., Simão S., Fernandes V.E., Provazník J., Benes V., Cruz C.D., Safronov B.V., Magalhães A., Reis C.A., Vieira J., Vieira C.P., Tiscórnia G., Araújo I.M., Sousa M.M.,
Rewired glycosylation activity promotes scarless regeneration and functional recovery in spiny mice after complete spinal cord transection. Developmental Cell57(4):440-450.e7, 2022. [Journal: Article] [CI: 19] [IF: 11,8]
DOI: 10.1016/j.devcel.2021.12.008 SCOPUS: 85123830565

Pinto-Costa R., Sousa S.C., Leite S.C., Nogueira-Rodrigues J., da Silva T.F., Machado D., Marques J., Costa A.C., Liz M.A., Bartolini F., Brites P., Costell M., Fässler R., Sousa M.M.,
Profilin 1 delivery tunes cytoskeletal dynamics toward CNS axon regeneration. Journal of Clinical Investigation130(4):2024-2040, 2020. [Journal: Article] [CI: 20] [IF: 14,8]
DOI: 10.1172/JCI125771 SCOPUS: 85082814702

Costa A.R., Sousa S.C., Pinto-Costa R., Mateus J.C., Lopes C.D.F., Costa A.C., Rosa D., Machado D., Pajuelo L., Wang X., Zhou F.Q., Pereira A.J., Sampaio P., Rubinstein B.Y., Pinto I.M., Lampe M., Aguiar P., Sousa M.M.,
The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction. eLife9:, 2020. [Journal: Article] [CI: 37] [IF: 8,1]
DOI: 10.7554/eLife.55471 SCOPUS: 85082635132

Nascimento A.I., Mar F.M., Sousa M.M.,
The intriguing nature of dorsal root ganglion neurons: Linking structure with polarity and function. Progress in Neurobiology168:86-103, 2018. [Journal: Review] [CI: 69] [IF: 10,7]
DOI: 10.1016/j.pneurobio.2018.05.002 SCOPUS: 85048777484

Leite S.C., Sampaio P., Sousa V.F., Nogueira-Rodrigues J., Pinto-Costa R., Peters L.L., Brites P., Sousa M.M.,
The Actin-Binding Protein a-Adducin Is Required for Maintaining Axon Diameter. Cell Reports15(3):490-498, 2016. [Journal: Article] [CI: 76] [IF: 8,3]
DOI: 10.1016/j.celrep.2016.03.047 SCOPUS: 84962762309

Ongoing Projects

Exploring axonal microtubule and mitochondrial transport defects in Transthyretin Amyloid Polyneuropathy (ATTR-PN)
Reference: Pfizer GRG 2021-Tracking#67463999
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Pfizer, Inc
From 01-JAN-22 to 30-JUN-24
Cytoskeletal and membrane adaptations of stretched neurons: from tension-induced growth to traumatic brain injury
Reference: DRI/India/0336/2020
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 14-AUG-22 to 13-AUG-25
Translating Acomys Regenerative Capacity
Reference: Premio Melo e Castro - SCML 2022 - TARGET
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Santa Casa da Misericórdia de Lisboa
From 01-JAN-23 to 31-DEC-25
Finding and validating the molecular map that enables axon regeneration in mammals
Reference: 2022.06613.PTDC
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-FEB-23 to 31-JUL-24
GLYCOswitch: Exploring ß3gnt7 as an enabler of axon regeneration in mammals
Reference: MCPF- Research Grant 2022 - GLYCOswitch
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Morton Cure Paralysis Fund (MCPF)
From 01-OCT-23 to 30-SEP-24
Exploring the proteoglycan signature as a roadmap for mammalian axon regeneration
Reference: AOS-Startup-23-033
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: AO Foundation
From 01-SEP-23 to 01-DEC-24
A human sensory neuron model to explore the pathophysiology of Transthyretin Amyloid Polyneuropathy
Reference: Pfizer GMG 2023-Tracking#87074543
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Pfizer, Inc
From 01-JAN-24 to 31-DEC-25
Exploring the biogenesis, assembly and dynamics of the membrane-periodic skeleton (MPS) in fixed and live systems.
Reference: 2023.00048.RESTART
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 23-DEC-23 to 22-MAY-25