Laboratory of Cell Biology and Applied Pharmacology

Macroarea: Pharmacology

Settori ERC: LS1_10 Molecular mechanisms of signalling pathways;  LS3_5 Cell signalling and signal transduction, exosome biology; LS4_4 Fundamental mechanisms underlying ageing; LS5_7 Neurological disorders (e.g. neurodegenerative diseases); LS7_4 Pharmacology and pharmacogenomics (including drug discovery and design, drug delivery and therapy, toxicology)

Keywords (max 5): 

Cell signaling, stress response, ageing, cytoprotection, retina

Lab Manager: Marialaura Amadio (PA)

Scientific Consultant: Stefano Govoni (Prof. Emerito)

Research lines

The main interest is for cellular and molecular pharmacology, especially for the Nrf2 factor and the RNA-binding ELAV proteins (both gene expression regulators, acting at transcriptional and post-transcriptional level, respectively). The aim is to understand the role of these proteins in physio-pathological contexts. The research includes the pharmacological modulation of Nrf2 and ELAV as potential therapeutic targets in ocular pathologies and beyond.

With regard to Nrf2 pathway, the study of the well-known Nrf2 activator dimethyl fumarate focuses on highlighting new possible therapeutic applications in contexts characterized by oxidative stress, inflammation, protein clearance impairment; these studies are related to pathologies of the retina and other body districts.

Linked to these two research lines, a new study of the biological signature and effects of retinal pigment epithelium-derived extracellular vesicles, a potential cytoprotective multichannel message among specialized eye cells, is also ongoing.

The research lines are here synthetized:

1.         Study of the role of the transcription factor Nrf2 and the RNA-binding protein HuR/ELAVL1 in physio-pathologic contexts by in vitro cell cultures under stress stimuli (e.g. oxidative stress, autophagy dysfunction, altered protein homeostasis)

2.         Study of the role of the HuR/ELAVL1 protein in ocular pathologies, such as age-related macular degeneration and glaucoma –in vitro, in vivo studies

3.         Pharmacological modulation of Nrf2 and HuR/ELAVL1 as potential therapeutic targets for pathologies of the eye and other body districts –in vitro, in vivo, ex vivo studies

4.         Study of the potential repurposing and therapeutic use of dimethyl fumarate in pathologic contexts characterized by oxidative stress, inflammation, dysfunction in protein turnover

5.         Study of extracellular vesicles in in vitro cell cultures 

• Machowicz J, Mróz K, Pacwa A, Gąsiorek A, Rodak P, Lewin-Kowalik J, Amadio M,
  Smędowski A. Serotonin Signaling Pathway Modulation Affects Retinal Neuron Survival in
  Experimental Model of Retinal Ischemia. Life (Basel). 2025 Nov 8;15(11):1726. doi:
  10.3390/life15111726. PMID: 41302150; PMCID: PMC12653536
• Bresciani G, Manai F, Felszeghy S, Smedowski A, Kaarniranta K, Amadio M. VEGF and
  ELAVL1/HuR protein levels are increased in dry and wet AMD patients. A new tile in the
  pathophysiologic mechanisms underlying RPE degeneration? Pharmacol Res.
  2024;208:107380.
• Manai F, Smedowski A, Kaarniranta K, Comincini S, Amadio M. Extracellular vesicles in
  degenerative retinal diseases: A new therapeutic paradigm. J Control Release. 2024 Jan;
  365:448-468. doi: 10.1016/j.jconrel.2023.11.035. PMID: 38013069
• Bresciani G, Manai F, Davinelli S, Tucci P, Saso L, Amadio M. Novel potential
  pharmacological applications of dimethyl fumarate-an overview and update. Front
  Pharmacol. 2023 Sep; 14:1264842. doi: 10.3389/fphar.2023.1264842. PMID: 37745068;
  PMCID: PMC10512734.
• Pacwa A, Machowicz J, Akhtar S, Rodak P, Liu X, Pietrucha-Dutczak M, Lewin-Kowalik J,
  Amadio M, Smedowski A. Deficiency of the RNA-binding protein ELAVL1/HuR leads to the
  failure of endogenous and exogenous neuroprotection of retinal ganglion cells. Front Cell
  Neurosci. 2023 Feb; 17:1131356. doi: 10.3389/fncel.2023.1131356. PMID: 36874215;
  PMCID: PMC9982123.
• Manai F, Govoni S, Amadio M. The Challenge of Dimethyl Fumarate Repurposing in Eye
  Pathologies. Cells. 2022 Dec; 11(24):4061. doi: 10.3390/cells11244061. PMID: 36552824;
  PMCID: PMC9777082.
• Manai F, Amadio M. Dimethyl Fumarate Triggers the Antioxidant Defense System in
  Human Retinal Endothelial Cells through Nrf2 Activation. Antioxidants (Basel). 2022 Sep;
  11(10):1924. doi: 10.3390/antiox11101924. PMID: 36290650; PMCID: PMC9598343.
• Koskela A, Manai F, Basagni F, Liukkonen M, Rosini M, Govoni S, Monte MD, Smedowski
  A, Kaarniranta K, Amadio M. Nature-Inspired Hybrids (NIH) Improve Proteostasis by
  Activating Nrf2-Mediated Protective Pathways in Retinal Pigment Epithelial Cells.
  Antioxidants (Basel). 2022 Jul; 11(7):1385. doi: 10.3390/antiox11071385. PMID: 35883876;
  PMCID: PMC9312215.
• Catanzaro M, Lanni C, Basagni F, Rosini M, Govoni S, Amadio M. Eye-Light on Age-
  Related Macular Degeneration: Targeting Nrf2-Pathway as a Novel Therapeutic Strategy
  for Retinal Pigment Epithelium. Front Pharmacol. 2020 Jun; 11:844. doi:
  10.3389/fphar.2020.00844.
• Felszeghy S, Viiri J, Paterno JJ, Hyttinen JMT, Koskela A, Chen M, Leinonen H, Tanila H,
  Kivinen N, Koistinen A, Toropainen E, Amadio M, Smedowski A, Reinisalo M, Winiarczyk
  M, Mackiewicz J, Mutikainen M, Ruotsalainen AK, Kettunen M, Jokivarsi K, Sinha D,
  Kinnunen K, Petrovski G, Blasiak J, Bjørkøy G, Koskelainen A, Skottman H, Urtti A,
  Salminen A, Kannan R, Ferrington DA, Xu H, Levonen AL, Tavi P, Kauppinen A,
  Kaarniranta K. Loss of NRF-2 and PGC-1α genes leads to retinal pigment epithelium
  damage resembling dry age-related macular degeneration. Redox Biol. 2019; 20:1-12. doi:
  10.1016/j.redox.2018.09.011.

Main national collaborations out of the DSF

Dept. of Biology and Biotechnology “L. Spallanzani”, University of Pavia; U.O. Oftalmologia Pediatrica, Meyer Children's Hospital IRCCS, Firenze, Italy.

Main international collaborations

Medical University of Silesia, School of Medicine, Dept. of Ophthalmology, Katowice, Poland; University of Eastern Finland, Dept. of Ophthalmology, Kuopio, Finland.

Pharmacological consulting. Cellular, molecular biology and pharmacological assays - in vitro, cell culture