FunGP – Functional Genomics and Proteostasis

Margarida Amaral

The main goal of the Functional Genomics and Proteostasis Group is to understand human diseases and achieve drug discovery using functional genomics and systems approaches along with molecular and cell biology approaches.

FunGP is organized into five research labs, each headed by a PI. Each team explores independent scientific aims but with common interests and contributing to 3 out of the 4 major thematic lines of BioISI. Three of the groups have an international reputation in the frontline research of the competitive field of the monogenic disease Cystic Fibrosis, while the remaining two are leaders in signal transduction in cancer and pharmaco-resistance in malaria. The group also includes two Visiting Professors with double-affiliation to non-Portuguese institutions.

The major research topics of the FunGP group are focused on molecular and systems biology of Cystic Fibrosis (CF), cancer and malaria; studies of membrane proteins associated with human diseases; pharmacogenomics and drug development; biomarker identification; biodevices for point-of care medicine, diagnosis and prognosis.

Specific lines of interest include: 1) novel cellular epithelial models for CF studies; 2) molecular and cellular mechanisms of quality control of the endoplasmic reticulum and secretory traffic of the CFTR protein; 3) characterization of signal transduction pathways influencing oncogenic reprogramming of epithelial cells; 4) influence of host-pathogen genomes on the efficacy of drugs with a strong interest in drug transporter proteins; 5) identification of drug targets and drug screens target screens in cancer and chronic diseases

FunGP members are mainly associated with BioISI’s thematic line of Biomedicine but cooperative projects are being developed for integrative research within the thematic lines of Biophysics (for biodevice development) and Bioinformatics.

Team

Group Leader: Margarida Amaral msamaral@fc.ul.pt

PI’s: Carlos Farinha | Paulo Matos | Cláudio Gomes | Luka Clarke | José Pedro Gil

Technicians: Sofia Correia | Luís Marques

Recent Publications

Identification of novel F508del-CFTR traffic correctors among triazole derivatives

Bacalhau M, Ferreira FC, Kmit A, Souza FR, da Silva VD, Pimentel AS, Amaral MD, Buarque CD, Lopes-Pacheco M. (2022) Identification of novel F508del-CFTR traffic correctors among triazole derivatives. European Journal of Pharmacology, , . doi: 10.1016/j.ejphar.2022.175396

Drug Repurposing for Cystic Fibrosis: Identification of Drugs That Induce CFTR-Independent Fluid Secretion in Nasal Organoids

Rodenburg LW, Delpiano L, Railean V, Centeio R, Pinto MC, Smits SMA, van der Windt IS, van Hugten CFJ, van Beuningen SFB, Rodenburg RNP, van der Ent CK, Amaral MD, Kunzelmann K, Gray MA, Beekman JM, Amatngalim GD (2022) Drug Repurposing for Cystic Fibrosis: Identification of Drugs That Induce CFTR-Independent Fluid Secretion in Nasal Organoids. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(20), 12657. doi: 10.3390/ijms232012657

A Drug Screening Reveals Minocycline Hydrochloride as a Therapeutic Option to Prevent Breast Cancer Cells Extravasation across the Blood–Brain Barrier

Godinho-Pereira J, Lopes MD, Garcia AR, Botelho HM, Malhó R, Figueira I, Brito MA (2022) A Drug Screening Reveals Minocycline Hydrochloride as a Therapeutic Option to Prevent Breast Cancer Cells Extravasation across the Blood–Brain Barrier. Biomedicines, 10(8), 1988. doi: 10.3390/biomedicines10081988

Tetramerization of the S100B chaperone spawns a Ca2+ independent regulatory surface that enhances anti-aggregation activity and client specificity

Figueira AJ, Moreira GG, Saavedra J, Cardoso I, Gomes CM (2022) Tetramerization of the S100B chaperone spawns a Ca2+ independent regulatory surface that enhances anti-aggregation activity and client specificity. JOURNAL OF MOLECULAR BIOLOGY, , 167791. doi: 10.1016/j.jmb.2022.167791

Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus

Fernandes C, Palma E, Silva F, Belchior A, Pinto CIG, Guerreiro JF, Botelho HM, Mendes F, Raposinho P, Paulo A (2022) Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23, 7238. doi: 10.3390/ijms23137238

Severity of the S1251N allele in cystic fibrosis is affected by the presence of the F508C variant in cis

Cuyx S, Ramalho SS, Callebaut I, Cuppens H, Kmit A, Arnauts K, Ferrante M, Verfaillie C, Ensinck M, Carlon MS, Boon M, Proesmans M, Dupont L, De Boeck K, Farinha CM, Vermeulen F, Ramalho AS (2022) Severity of the S1251N allele in cystic fibrosis is affected by the presence of the F508C variant in cis. JOURNAL OF CYSTIC FIBROSIS, , . doi: 10.1016/j.jcf.2022.05.013