creating a
healthier future

Tumour and Microenvironment Interactions

ABOUT

The goal of the NeuroLipid Biology group is to understand how lipid synthesis and catabolism govern biological and functional processes in the healthy nervous tissue and in neurometabolic disorders. We are particularly interested in the role that ether-phospholipids play in neuron excitability, axon growth, and myelin synthesis. Using mouse models, we combine in vivo and in vitro studies to integrate physiological cell processes with disease states, and the development new therapeutic pre-clinical approaches.

 

RESEARCH

The impact of lipid dysregulation in neurologic disorders is evident by the number and severity of neurometabolic diseases. However, we are limited in understanding the function of lipids and how fundamental cellular processes and mechanisms are affected by lipid dysregulation, and thus mediate tissue pathology and disease. Previous work highlighted the consequences of branched-chain fatty acid accumulation in ataxia, and we identified cholesterol and sphingomyelin as novel myelin-associated inhibitors that affect axon growth and regeneration.

Currently, our research is focused on the study of plasmalogens, a class of phospholipids highly enriched in nervous tissue, whose deficiency causes a rare peroxisomal disorder, rhizomelic chondrodysplasia punctata (RCDP). Previous work allowed us to unravel the genetic basis of RCDP and attain an understanding of the pathology through the usage of mouse models. In line with our goal of understanding the fundamental processes and mechanisms governed by plasmalogens, we unraveled that these lipids are crucial for Schwann cell differentiation and myelination, as plasmalogens are essential for the initiation of the signaling cascade mediated by activation at the plasma membrane of Protein kinase B, also known as AKT. Our aim is to expand the understanding of how fundamental cellular processes are governed by plasmalogens, and how a dysregulation of these processes mediates the pathophysiology of RCDP and other neurological disorders (e.g. Alzheimer's and Parkinson's) known to develop defects in plasmalogen levels. The knowledge gathered in understanding the mechanisms behind the pathology is also used to design and validate effective pre-clinical therapeutic strategies.

Pseudocolored electron microscopy images of synapses in the central nervous system (CNS) and in the peripheral nervous system (PNS)

Team

Selected Publications

Blondeel E., Ernst S., De Vuyst F., Diósdi Á., Pinheiro C., Estêvão D., Rappu P., Boiy R., Dedeyne S., Craciun L., Goossens V., Dehairs J., Cruz T., Audenaert D., Ceelen W., Linnebacher M., Boterberg T., Vandesompele J., Mestdagh P., Swinnen J., Heino J., Horvath P., Oliveira M.J., Hendrix A., Demetter P., De Wever O.
Sequential orthogonal assays for longitudinal and endpoint characterization of three-dimensional spheroids. Nature Protocols20(10):2899-2941, 2025. [Journal: Article] [CI: 2] [IF: 16 (*)]
DOI: 10.1038/s41596-025-01150-y SCOPUS: 105002240171

Castro F., Pinto M.L., Leite Pereira C., Serre K., Costa Â.M., Cavadas B., Barbosa M.A., Vermaelen K., León S., Serrano D., Gärtner F., Calvo A., Gonçalves R.M., De Wever O., Oliveira M.J.
Chitosan/γ-PGA nanoparticles and IFN-γ immunotherapy: A dual approach for triple-negative breast cancer treatment. Journal of Controlled Release379:621-635, 2025. [Journal: Article] [CI: 12] [IF: 11.5 (*)]
DOI: 10.1016/j.jconrel.2025.01.042 SCOPUS: 85215603202

Moura S.R., Sousa A.B., Olesen J.B., Barbosa M.A., Søe K., Almeida M.I.
Stage-specific modulation of multinucleation, fusion, and resorption by the long non-coding RNA DLEU1 and miR-16 in human primary osteoclasts. Cell Death and Disease15(10):, 2024. [Journal: Article] [CI: 2] [IF: 9.6]
DOI: 10.1038/s41419-024-06983-1 SCOPUS: 85206064184

Oliveira S.M., Carvalho P.D., Serra-Roma A., Oliveira P., Ribeiro A., Carvalho J., Martins F., Machado A.L., Oliveira M.J., Velho S.
Fibroblasts Promote Resistance to KRAS Silencing in Colorectal Cancer Cells. Cancers16(14):, 2024. [Journal: Article] [CI: 1] [IF: 4.5 (*)]
DOI: 10.3390/cancers16142595 SCOPUS: 85199647438

Shanmugam S.T., Campos R., Trashin S., Daems E., Carneiro D., Fraga A., De Wael K.
Singlet oxygen-based photoelectrochemical detection of miRNAs in prostate cancer patients’ plasma: A novel diagnostic tool for liquid biopsy. Bioelectrochemistry158:, 2024. [Journal: Article] [CI: 8] [IF: 4.5]
DOI: 10.1016/j.bioelechem.2024.108698 SCOPUS: 85190731792

Torres Quintas S., Canha-Borges A., Oliveira M.J., Sarmento B., Castro F.
Special Issue: Nanotherapeutics in Women's Health Emerging Nanotechnologies for Triple-Negative Breast Cancer Treatment. Small20(41):, 2024. [Journal: Review] [CI: 26] [IF: 12.1]
DOI: 10.1002/smll.202300666 SCOPUS: 85151416951

de Souza W., Gemini-Piperni S., Ruivo C., Bastos N., Almeida S., Lopes D., Cardoso P., Oliveira M.J., Sumner D.R., Ross R.D., Jacobs J.J., Granjeiro J.M., Fernandes M.H., Rocha L.A., Melo S., Ribeiro A.R.
Osteoblasts-derived exosomes as potential novel communicators in particle-induced periprosthetic osteolysis. Materials Today Bio28:, 2024. [Journal: Article] [CI: 2] [IF: 8.7 (*)]
DOI: 10.1016/j.mtbio.2024.101189 SCOPUS: 85200971793

V. Lima B., Oliveira M.J., Barbosa M.A., Gonçalves R.M., Castro F.
Harnessing chitosan and poly-(γ-glutamic acid)-based biomaterials towards cancer immunotherapy. Materials Today Advances15:, 2022. [Journal: Article] [CI: 17] [IF: 10]
DOI: 10.1016/j.mtadv.2022.100252 SCOPUS: 85130370826

Brás J.P., Guillot de Suduiraut I., Zanoletti O., Monari S., Meijer M., Grosse J., Barbosa M.A., Santos S.G., Sandi C., Almeida M.I.
Stress-induced depressive-like behavior in male rats is associated with microglial activation and inflammation dysregulation in the hippocampus in adulthood. Brain, Behavior, and Immunity99:397-408, 2022. [Journal: Article] [CI: 41] [IF: 15,1]
DOI: 10.1016/j.bbi.2021.10.018 SCOPUS: 85120371740

Peirsman A., Blondeel E., Ahmed T., Anckaert J., Audenaert D., Boterberg T., Buzas K., Carragher N., Castellani G., Castro F., Dangles-Marie V., Dawson J., De Tullio P., De Vlieghere E., Dedeyne S., Depypere H., Diosdi A., Dmitriev R.I., Dolznig H., Fischer S., Gespach C., Goossens V., Heino J., Hendrix A., Horvath P., Kunz-Schughart L.A., Maes S., Mangodt C., Mestdagh P., Michlíková S., Oliveira M.J., Pampaloni F., Piccinini F., Pinheiro C., Rahn J., Robbins S.M., Siljamäki E., Steigemann P., Sys G., Takayama S., Tesei A., Tulkens J., Van Waeyenberge M., Vandesompele J., Wagemans G., Weindorfer C., Yigit N., Zablowsky N., Zanoni M., Blondeel P., De Wever O.
MISpheroID: a knowledgebase and transparency tool for minimum information in spheroid identity. Nature Methods18(11):1294-1303, 2021. [Journal: Article] [CI: 67] [IF: 48]
DOI: 10.1038/s41592-021-01291-4 SCOPUS: 85118431713

Cardoso A.P., Pinto M.L., Castro F., Costa Â.M., Marques-Magalhães Â., Canha-Borges A., Cruz T., Velho S., Oliveira M.J.
The immunosuppressive and pro-tumor functions of CCL18 at the tumor microenvironment. Cytokine and Growth Factor Reviews60:107-119, 2021. [Journal: Review] [CI: 47] [IF: 17,7]
DOI: 10.1016/j.cytogfr.2021.03.005 SCOPUS: 85104442722

Castro F., Leite Pereira C., Helena Macedo M., Almeida A., José Silveira M., Dias S., Patrícia Cardoso A., José Oliveira M., Sarmento B.
Advances on colorectal cancer 3D models: The needed translational technology for nanomedicine screening. Advanced Drug Delivery Reviews175:, 2021. [Journal: Review] [CI: 50] [IF: 17,9]
DOI: 10.1016/j.addr.2021.06.001 SCOPUS: 85108070633

Catarata M.J., Lourenço M., Martins M.F., Frade J., Pêgo A., Cordeiro C.R., Medeiros R.
Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome?. Pulmonology27(2):116-123, 2021. [Journal: Article] [CI: 6] [IF: 9,2]
DOI: 10.1016/j.pulmoe.2020.11.007 SCOPUS: 85098653319

Martins F., Oliveira R., Cavadas B., Pinto F., Cardoso A.P., Castro F., Sousa B., Pinto M.L., Silva A.J., Adão D., Loureiro J.P., Pedro N., Reis R.M., Pereira L., Oliveira M.J., Costa A.M.
Hypoxia and macrophages act in concert towards a beneficial outcome in colon cancer. Cancers12(4):, 2020. [Journal: Article] [CI: 9] [IF: 6,6]
DOI: 10.3390/cancers12040818 SCOPUS: 85082958618

Castro F., Pinto M.L., Pereira C.L., Serre K., Barbosa M.A., Vermaelen K., Gonçalves R.M., De Wever O., Oliveira M.J.
Chitosan/γ-PGA nanoparticles-based immunotherapy as adjuvant to radiotherapy in breast cancer. Biomaterials257:, 2020. [Journal: Article] [CI: 82] [IF: 12,5]
DOI: 10.1016/j.biomaterials.2020.120218 SCOPUS: 85088642097

Pinto M.L., Rios E., Durães C., Ribeiro R., Machado J.C., Mantovani A., Barbosa M.A., Carneiro F., Oliveira M.J.
The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer. Frontiers in Immunology10(AUG):, 2019. [Journal: Article] [CI: 169] [IF: 5,1]
DOI: 10.3389/fimmu.2019.01875 SCOPUS: 85071761383

Castro F., Pinto M.L., Almeida R., Pereira F., Silva A.M., Pereira C.L., Santos S.G., Barbosa M.A., Gonçalves R.M., Oliveira M.J.
Chitosan/poly(γ-glutamic acid) nanoparticles incorporating IFN-γ for immune response modulation in the context of colorectal cancer. Biomaterials Science7(8):3386-3403, 2019. [Journal: Article] [CI: 49] [IF: 6,2]
DOI: 10.1039/c9bm00393b SCOPUS: 85069760890

Castro F., Cardoso A.P., Gonçalves R.M., Serre K., Oliveira M.J.
Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Frontiers in Immunology9(MAY):, 2018. [Journal: Review] [CI: 991] [IF: 4,7]
DOI: 10.3389/fimmu.2018.00847 SCOPUS: 85046686322

Carvalho P.D., Guimarães C.F., Cardoso A.P., Mendonça S., Costa Â.M., Oliveira M.J., Velho S.
KRAS oncogenic signaling extends beyond cancer cells to orchestrate the microenvironment. Cancer Research78(1):7-14, 2018. [Journal: Review] [CI: 162] [IF: 8,4]
DOI: 10.1158/0008-5472.CAN-17-2084 SCOPUS: 85040196244

Pinto M.L., Rios E., Silva A.C., Neves S.C., Caires H.R., Pinto A.T., Durães C., Carvalho F.A., Cardoso A.P., Santos N.C., Barrias C.C., Nascimento D.S., Pinto-do-Ó P., Barbosa M.A., Carneiro F., Oliveira M.J.
Decellularized human colorectal cancer matrices polarize macrophages towards an anti-inflammatory phenotype promoting cancer cell invasion via CCL18. Biomaterials124:211-224, 2017. [Journal: Article] [CI: 115] [IF: 8,8]
DOI: 10.1016/j.biomaterials.2017.02.004 SCOPUS: 85013069713

Teresa Pinto A., Laranjeiro Pinto M., Patrícia Cardoso A., Monteiro C., Teixeira Pinto M., Filipe Maia A., Castro P., Figueira R., Monteiro A., Marques M., Mareel M., Dos Santos S.G., Seruca R., Adolfo Barbosa M., Rocha S., JoséOliveira M.
Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities. Scientific Reports6:, 2016. [Journal: Article] [CI: 162] [IF: 4,3]
DOI: 10.1038/srep18765 SCOPUS: 84954288518

Cardoso A.P., Pinto M.L., Pinto A.T., Oliveira M.I., Pinto M.T., Gonçalves R., Relvas J.B., Figueiredo C., Seruca R., Mantovani A., Mareel M., Barbosa M.A., Oliveira M.J.
Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y 1086, c-Src, Erk1/2 and Akt phosphorylation and smallGTPase activity. Oncogene33(16):2123-2133, 2014. [Journal: Article] [CI: 114] [IF: 8,5]
DOI: 10.1038/onc.2013.154 SCOPUS: 84899425243

Ongoing Projects

On the crossroads of Immuno-Epigenetics for targeting advanced Prostate Cancer
Reference: 2022.04809.PTDC
Proponent: Instituto Português de Oncologia do Porto FG, EPE
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-MAR-23 to 31-DEC-26
E-MAGIC: ExosoMes-derived rAdioresistance siGnature In breast Cancer
Reference: Gilead GENESE 2023 - Proj. 21483
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Gilead Sciences
From 01-JAN-24 to 31-DEC-26
ExosoMes-derived rAdioresistance siGnature In breast Cancer
Reference: Programa Pessoa - 2023.09861.CBM
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-APR-24 to 31-MAR-26
Targeting the Osteosarcoma Microenvironment using Non-coding RNAs
Reference: COMPETE2030-FEDER-00727500 - Projeto 16123
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 16-JUN-25 to 14-JUN-28
Uncovering the role of immune cells on rectal cancer radioresistance
Reference: COMPETE2030-FEDER-00707100 - Projeto 15942
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 16-JUN-25 to 14-JUN-28
Personalized Computational Forecasting of Prostate Adenocarcinomas
Reference: COMPETE2030-FEDER-00929300 - Projeto 14790
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-APR-25 to 30-MAR-28
ExosoMes-derived rAdioresistance siGnature In breast Cancer
Reference: COMPETE2030-FEDER-00696500 - Projeto 15852
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-SEP-25 to 30-AUG-28
Unlocking the Potential of KRAS Inhibitors in Cancer: Leveraging Chromatin Dynamics to Overcome Therapy Resistance
Reference: COMPETE2030-FEDER-00734600 - Projeto 16190
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 09-SEP-25 to 07-SEP-28
Engineering HybrID Extracellular vesicles For brEast caNcer vacCinE
Reference: 2024.15178.PEX
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-FEB-26 to 31-JUL-27
Epigenetic and Transcriptomic patterns associated with bariatric surgery response and functional genetic validation of biomarkers for personalized obesity treatment
Reference: 2024.16602.PEX
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 16-FEB-26 to 15-AUG-27