Cell Signaling and Metabolism in Disease

Maria Teresa Cruz

Ph.D., Principal Investigator

This research group, now re-named "Cell Signaling and Metabolism in Disease" integrates researchers with extensive know-how in cell quality control mechanisms, mitochondrial metabolism and dynamics, endothelial dysfunction and inflammatory processes, which will allow a more in-depth perspective of the scientific questions. The objective of the group is to investigate the molecular mechanisms associated with brain and inflammatory disorders. We aim to identify the molecular mechanisms involved in neurodegenerative processes and inflammation-related diseases with potential applications in the diagnosis, prognosis and targeted therapy, using mitochondria, cell lines, primary cell cultures, mouse models of disease and human samples as experimental models. Basic research is used for biomarker identification and drug development, which is indicative of the translational value of our research group.

In the 2013-2017 period, the Group aimed to clarify the involvement of mitochondria, inflammation, quality control mechanisms and microbiome in aging and age-related neurodegenerative pathologies, namely Alzheimer´s disease (AD) and Parkinson´s disease (PD), as well as in other age-related diseases, including the mechanisms underlying diabetes-associated central and peripheral damage. We also investigated the role of sex in the development of AD-like pathology. Our objectives are to clarify the mechanisms involved in mitochondrial trafficking and signaling pathways and the crosstalk with other organelles such as the endoplasmic reticulum (ER) in the aforesaid diseases. The mechanisms of protein quality control present in these organelles and in the cytosol, and their role in inflammation, are another focus of our research. In addition, we aim to explore the role of autophagy and intercellular communication in the maintenance of brain homeostasis.

Group Members

Group Members

Group members are: Teresa Cruz (PhD, Group Leader), Ana Silva (PhD), Isabel Ferreira (PhD), Mylène Carrascal (PhD), Ana Isabel Sebastião (PhD student), Daniel Ferreira (MSc, Technician), Ana Isabel Jesus (PhD student), Rita Lavrador (Master student), Ana Duarte (Master student), Adriana Tavares (Master student), Daniela Mateus (PhD student), Cláudia MF Pereira (PhD), Ana Catarina Pereira (PhD student), Patrícia Moreira (PhD student), Tânia Fernandes (PhD student), Paula I. Moreira (PhD), Cristina Carvalho (PhD), Sónia Correia (PhD), Susana Cardoso (PhD), Armanda Santos (PhD), Sandra Morais Cardoso (PhD), Ana Raquel Esteves (PhD), Diana F Silva (PhD), Emanuel Candeias (PhD), João D Magalhães (PhD student), Ana Raquel Santos (PhD student), Beatriz Guedes (MSc student), Inês Melo-Marques (BSc student).

Selected Publications

Calmeiro J, Mendes L, Duarte I, Leitão C, Tavares AR, Ferreira DA, Gomes C, Serra J, Falcão A, Cruz MT, Carrascal M and Neves BM. In-depth analysis of the impact of different serum-free media on the production of clinical-grade dendritic cells for cancer immunotherapy. Front Immunol. 2021 Feb 5;11:593363. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893095)

PFerreira I, Silva A, Martins JD, Neves, BM and Cruz MT. Nature and kinetics of redox imbalance triggered by respiratory and skin chemical sensitizers on the human monocytic cell line THP-1. Redox Biol. 2018 Jun;16:75-86. (https://pubmed.ncbi.nlm.nih.gov/29477863)

Marques AP, Resende R, Silva DF, Batista M, Pereira D, Wildenberg B, Morais S, Macedo A, Pais C, Melo JB, Madeira N, Pereira CF. Mitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder Patients. Biomedicines. 2021 May 7;9(5):522. doi: 10.3390/biomedicines9050522

Fernandes T, Resende R, Silva DF, Marques AP, Santos AE, Cardoso SM, Domingues MR, Moreira PI, Pereira CF. Structural and Functional Alterations in Mitochondria-Associated Membranes (MAMs) and in mitochondria activate stress response mechanisms in an in vitro model of Alzheimer's disease. Biomedicines 9(8):881. DOI: 10.3390/biomedicines9080881

Correia SC, Machado NJ, Alves MG, Oliveira PF, Moreira PI. Intermittent Hypoxic Conditioning Rescues Cognition and Mitochondrial Bioenergetic Profile in the Triple Transgenic Mouse Model of Alzheimer's Disease. Int J Mol Sci. 2021 Jan 5;22(1):461. doi: 10.3390/ijms22010461.

Cunnane SC, Trushina E, Morland C, Prigione A, Casadesus G, Andrews ZB, Beal MF, Bergersen LH, Brinton RD, de la Monte S, Eckert A, Harvey J, Jeggo R, Jhamandas JH, Kann O, la Cour CM, Martin WF, Mithieux G, Moreira PI, Murphy MP, Nave KA, Nuriel T, Oliet SHR, Saudou F, Mattson MP, Swerdlow RH, Millan MJ. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020 Sep;19(9):609-633. doi: 10.1038/s41573-020-0072-x.

Resende, R, Ferreira-Marques M, Moreira P, Coimbra JRM, Baptista SJ, Isidoro C, Salvador JAR, Dinis TCP Pereira CF, Santos AE (2020) New BACE1 chimeric peptide inhibitors selectively prevent AβPP-β cleavage decreasing Aβ production and accumulation in AD models. J Alzheimers Dis. 76: 1317–1337. DOI 10.3233/JAD-200381

Coimbra JRM, Baptista SJ, Dinis TCP, Silva MMC, Moreira PI, Santos AE and Salvador JAR. (2020) Combining Virtual Screening Protocol and In Vitro Evaluation towards the Discovery of BACE1 Inhibitors. Biomolecules vol 10, 535. doi:10.3390/biom10040535

Esteves AR, Munoz-Pinto MF, Nunes-Costa D, Candeias E, Silva DF, Magalhães JD,Pereira-Santos AR, Ferreira IL, Alarico S, Tiago I, Empadinhas N, Cardoso SM (2021) Footprints of a microbial toxin from the gut microbiome to the mesencephalic mitochondria. Gut. 2021:326023

Silva DF, Candeias E, Esteves AR, Magalhães JD, Ferreira IL, Nunes-Costa D, Rego AC, Empadinhas N, Cardoso SM (2020) Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation and Alzheimer’s disease features in cortical neurons. Journal of Neuroinflammation. 17(1):332.

Selected Projects

Skin allergens: molecules with an improbable therapeutic application for Alzheimer’s disease. POCI-01-0145-FEDER-029369 (PI: M. Teresa Cruz)

The ups and downs of cellular stress: the “MAM hypothesis” for Bipolar disorder pathophysiology (2018_2022) , CENTRO-01-0145-FEDER-028214 (PI: C Pereira)

Zfra 1-31: an early intervention in T2D-associated neurodegeneration (EXPL/MED-FSL/0033/2021) Fundação para a Ciência e a Tecnologia (PI Cristina Carvalho)

"Tackling Alzheimer’s Disease with a new peptide inhibitor of BACE1" projecto financiado pela Fundação para a Ciência e Tecnologia (PTDC/NEU-SCC/1351/2012) e desenvolvido entre 15 Junho 2013 e 30 de Novembro de 2015. (PI: Armanda E. Santos)

Gut-Immune-Brain axis in Parkinson’s disease (2021-2023) Project PTDC/MED-NEU/3644/2020, FCT (€248.992,50) (PI: Sandra Morais Cardoso)

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