Joana Miranda

Advanced Cell Models for Predictive Toxicology & Cell-based Therapies

We are composed of a multidisciplinary research team, with expertise in cell/tissue engineering, regenerative medicine, toxicology and cancer pharmacology, focused on the use of advanced (3D) in vitro models as tools for developing new cell-based therapeutics and studying drug metabolism and mechanisms of diseases (ex.: liver diseases, skin pathologies, lung cancer).

Microphysiological systems have emerged to provide an alternative to in vivo models in basic science and pharmaceutical research. In this group, we seek to understand how physical properties and biochemical cues work together to regulate and modulate cell functions. Ultimately, we aim to generate the grounds for more personalized/indication-specific treatments.

Alternative Cell Models in Toxicology (PI: Joana Miranda & Nuno Oliveira)

The poor predictability of human liver toxicity is still causing high attrition rates of drug candidates in the pharmaceutical industry. Herein, we strategically recreate the microphysiological (3D) environment for the development of relevant in vitromodels (e.g. liver) to study bioactivation and toxicity of xenobiotics, including drugs and environmental carcinogens.

Cancer Toxicology & Pharmacology (PI: Nuno Oliveira)

These advanced models are also explored towards improved efficacy and safety of antineoplastic drugs in cancer, particularly in NSCLC and breast cancer. The goal is the modulation of key cellular events induced by these drugs by resorting to DNA repair inhibitors and redox modulators.

Tissue Engineering & Regenerative Medicine (PI: Joana Miranda)

In this research area we explore 3D models of human stem cells for personalized cell-based therapy applications (liver diseases, skin regeneration, rheumatoid arthritis), and the development of new ATMPs. Cells-derived secretome/exosomes, and their paracrine effects, are also exploited towards cell free-based therapies.

Fernandez-Checa JC, Bagnaninchi P, Ye H, Sancho-Bru P, Falcon-Perez JM, Royo F, Garcia-Ruiz C, Konu O, Miranda J, Lunov O, Dejneka A, Elfick A, McDonald A, Sullivan GJ, Aithal GP, Lucena MI, Andrade RJ, Fromenty B, Kranendonk M, Cubero FJ, Nelson LJ. Advanced preclinical models for evaluation of drug-induced liver injury - consensus statement by the European Drug-Induced Liver Injury Network [PRO-EURO-DILI-NET]. J Hepatol. 2021; 75 (4): 935-959. DOI: 10.1016/j.jhep.2021.06.021
Cipriano M, Pinheiro PF, Sequeira CO, Rodrigues JS, Oliveira NG, Antunes AMM, Castro M, Marques MM, Pereira SA, Miranda JP. Nevirapine Biotransformation Insights: An Integrated In Vitro Approach Unveils the Biocompetence and Glutathiolomic Profile of a Human Hepatocyte-Like Cell 3D Model. Int J Mol Sci. 2020; 21 (11): 3998. DOI: 10.3390/ijms21113998
Proença S, Antunes B, Guedes RC, Ramilo-Gomes F, Cabral MF, Costa J, Fernandes AS, Castro M, Oliveira NG, Miranda JP. Pyridine-containing macrocycles display MMP-2/9 inhibitory activity and distinct effects on migration and invasion of 2D and 3D breast cancer models. Int J Mol Sci. 2019; 20(20): 5109. DOI:10.3390/ijms20205109
Miranda JP, Mauricio A, Camões SP, Rodrigues J, Silva I, Santos RD, Santo RC, Pedrosa S, Branquinho M, Santos JM. 2019. Compositions for use in the treatment of musculoskeletal conditions and methods for producing the same leveraging the synergistic activity of two different types of mesenchymal stromal/stem cells, Portugal: UPorto; PCT/IB2019/052006.WO2019175773.
Miranda JP, Camões SP, Gaspar MM, Rodrigues JS, Carvalheiro M, Bárcia RN, Cruz P, Cruz H, Simões S, Santos JM. The secretome derived from 3D-cultured umbilical cord tissue MSCs counteracts manifestations typifying rheumatoid arthritis. Front Immunol. 2019; 10:18. DOI: 10.3389/fimmu.2019.00018

Joana Miranda

Group Leader

Email: jmiranda@ff.ulisboa.pt

Phone: (+351) 21794600 (Ext. 14641/2)

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Faculdade de Farmácia da Universidade de Lisboa | Av. Professor Gama Pinto
1649-003 Lisboa | Portugal


Phone | +351 217 946 400
Fax | +351 217 946 470
Web | www.imed.ulisboa.pt
Email | imed.ulisboa@ff.ulisboa.pt

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