Researcher profile

Miguel Castanho

CV SUMMARY AIM The aim of Miguel Castanho Lab is to unravel the physical principles that determine peptide/protein-lipid interactions, with implications in viral fusion (eg HIV, Dengue, Zika, Measles), antimicrobial action, including biofilms, and CNS-targeting (translocation of the blood-brain barrier, BBB, in analgesia and neuroprotection). MAIN PARADIGM-SHIFT ACHIEVEMENTS AND DISRUPTIVE LINES OF WORK > Viral fusion – We established that viral fusion inhibitors for HIV and Measles interact with membranes as part of their mode of action and self-association events are key for their efficacy (eg JACS 2004, 126, 14758-14763; JACS 2008, 130, 6215-6223; J Virol 2017, 91, e01554-16; ACS Nano 2018, 12, 9855-9865). > Translocation over the BBB – Cell penetrating peptides from viral protein domain templates that use receptor-free routes are now used as efficient carriers to shuttle drugs and antibodies to the brain (eg Biochemistry 2005, 44, 10189-10198; Bioinformatics 2015, 31, 2252-2256; ACS Chemical Biology 2017, 12, 1257-1268). > Antibacterial action – We bridged molecular biophysics of antimicrobial peptides studies in artificial systems to microbiology as we found how to quantitatively estimate biological activity from biophysical parameters (eg Biochimica et Biophysica Acta -Biomembranes 2007, 1768, 1277-1290; Nature Reviews Microbiology 2009, 7, 245-250; J Biol Chem 2010, 285, 27536-27544; J Antimicrobial Chemotherapy 2019, dkz223). > Analgesia and neuroprotection – Endogenous neuropeptides were modified so they could traverse the BBB and be used in analgesia and neuroprotection therapies (eg British J Pharmacol 2011, 163, 964-973; Molecular pharmaceutics 2011, 1929-1940; Frontiers in aging neuroscience 2013, 5, 68; ACS Chemical Neuroscience 2017, 8, 1663-1667). > Quantifying and imaging drug-lipid interactions – We have developed tailored methodologies based on spectroscopic techniques, such as fluorescence emission, SPR, and light scattering with zeta-potential, and AFM to quantify retention of drugs in lipid structures and unravel the structures emerging therefrom (eg Analytical Biochemistry 2002,307, 1-12; BBA-Biomembranes 2003; 1612; 123-135; Trends Pharm Sciences 2010, 31, 449-454; Eur Biophys J 2011, 40, 481-487; BBA-Biomembranes 2015, 1848, 554-560; Frontiers in microbiology 2017, 8, 775). TRANSLATION TO INDUSTRY Encompassing the achievements in academic research, Castanho’s lab has engaged with industry for drug development in the fields of Pain (2 patents), neuroprotection (2 patents), and viral infection (1 patent). 3 out of the 5 patents were filed under agreement with industrial partners. M Castanho coordinated the consortia of 2 major academia-industry projects funded by the EU. Currently, he coordinates an EIC (European Innovation Council) FET-OPEN academia-industry consortium for antiviral drug development. SERVICE TO SOCIETY M Castanho, among other appointments, has been the president of the Portuguese Biochemical Society, and member of working groups in FEBS and PABMB. He has also contributed to the organization of major international meetings (eg FEBS2012, 14th IUBMB Conference, Chairman of the IUBMB-FEBS-PABMB 2021 congress). In addition, he contributes regularly to the general press and mass media with opinion articles as advocate for Science. Chief Editor for Pharmaceutical Innovations/Frontiers in Medical Technologies, and editorial board member of J. Peptide Sci, and Peptide Sci. INVITATIONS TO MAJOR INTERNATIONAL MEETINGS Invited plenary/keynote speaker for major international meetings in Biophysics and Peptide Science, such as: 33rd European Peptide Symposium, 22nd American Peptide Symposium, 9th European Biophysics Congress. BIBLIOMETRIC DATA https://scholar.google.com/citations?user=Fko-odYAAAAJ&hl=en&oi=ao