Vassilis Aidinis Research Group

Fleming presents EL244, a dual ATX inhibitor/PPARγ agonist, developed through drug repositioning and innovative rational design. Inhaled EL244 attenuates pulmonary fibrosis in mouse and human models, suggesting EL244 as a promising clinical candidate.
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Fleming is happy to announce the establishment of DrugTrek, a micro small-to-medium enterprise (SME) spinoff of Fleming and Uni-Pharma, focusing on the research and development of antifibrotic therapies.
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Fleming researchers have uncovered a novel role for fibroblast-expressed Versican, a multifunctional ECM proteoglycan, as an autologous fibrotic brake that suppresses pulmonary fibrosis. [PubMed][Nat Commun]
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Fleming's Technology Transfer Office (TTO) is happy to announce the granting of an international (PCT) patent application, the very first of BSRC Fleming, on Autotaxin inhibitors for the treatment of Idiopathic Pulmonary Fibrosis (IPF) in Europe (to be soon followed by the US, Japan, Korea, China, and Brazil). This builds on an extensive related Fleming IP portfolio, including seven granted National (OBI) patents and one additional PCT application that has also entered the National phases. The TTO is actively pursuing the exploitation and commercialisation of the related IP through public and private funding and targeted actions.

The lab expands its experimental toolkit for studying fibrosis and the autotaxin–lysophosphatidic acid (LPA) signaling axis, bringing together tissue-based models, biochemical assays, and mouse genetics.
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Podosomes in lung fibroblasts stimulate extracellular matrix invasion and pulmonary fibrosis, suggesting pharmacologic targeting of podosome formation or organization as a very promising therapeutic option. [PubMed]
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Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions. [PubMed]
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Exploiting the vast transcriptomic information stored at Fibromine, all publicly available omics datasets on Idiopathic Pulmonary Fibrosis (IPF) were compared, and deregulated genes in most datasets were prioritized via machine learning, resulting in a list of genes with highly predictive statistical power. [PubMed]
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In our effort to discover new Autotaxin (ATX) inhibitors we have previously identified various hits [Pubmed] that led to six Industrial Property Organization (IPO) patents GR1010099, GR1010098, GR1010104, GR1010103, GR1010097, GR1010096. This effort was followed by a hit-to-lead potency optimization process employing Structure-Activity Relationship studies culminating in the finding of two new ATX inhibitors (with an active IPO patent GR1010268 and a Patent Cooperation Treaty (PCT) application WO 2022/003377 A1) now being at the stage of lead optimization [Pubmed].
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IMultiplex ELISA querying the phosphorylation of 27 phosphoproteins/signaling hubs and the secretion of 32 mediators (cytokines, chemokines and growth factors) revealed that Lysophosphatidic Acid (LPA) is a proinflammatory stimulus of renal tubular epithelial cells. Moreover, LPA responses were compared with other 175 biological stimuli, indicating that LPA clusters with other pro-inflammatory growth factors (e.g. TNF, IL1a).
[Pubmed].
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Enabling the study of microbiomics locally, a 16S rRNA deep sequencing pipeline has been created and was used to examine and compare the microbial communities of the gut, liver, and lung of obese and lean mice. [PubMed]
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Fibromine, a new database and data mining tool for target discovery in pulmonary fibrosis has been created to explore the numerous related publicly available datasets. [PubMed]
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Fleming researchers and clinical collaborators have reported increased serum Autotaxin Levels in Severe COVID-19 patients, correlating with serum IL-6 and endothelial dysfunction biomarkers levels, as well as with impaired functions of dendritic cells. [PubMed]
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A central role for TPL2 in the regulation of fibrotic responses in the lung. [PubMed]
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A new Frontiers E-book on “Pulmonary Fibrosis”, guest-edited by Fleming Researchers and distinguished leading experts, was recently published.
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Expanding previous work on the role of autotaxin in chronic inflammatory disorders that has provided the scientific basis for phase IIb clinical trials in idiopathic pulmonary fibrosis, Fleming researchers have now uncovered a role for this secreted lysophospholipase D in the pathogenesis of lung cancer [PubMed].
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In a collaborative study published in Nat Med, a Fleming Marie Curie Fellow revealed that aerosolized delivery of active Thyroid Hormone (TH) resolved pulmonary fibrosis in two mouse models through a mechanism that involved improvement of mitochondrial biogenesis and mitophagy in alveolar type II epithelial cells. [PubMed].
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Expanding previous work on the role of autotaxin in chronic inflammatory disorders that have led to phase II clinical trials in idiopathic pulmonary fibrosis, Fleming researchers have now uncovered a novel, major role for this secreted lysophospholipase D in the pathogenesis of hepatitis and hepatocellular carcinoma. [PubMed].
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Fleming researchers have revealed a major role for Autotaxin (ATX, ENPP2) and its bioactive lipid product lysophosphatidic acid (LPA) in the pathogenesis of rheumatoid arthritis [Pubmed1] and pulmonary fibrosis [Pubmed2]. Their work establishes the ATX/LPA axis as a novel player in chronic inflammatory disorders [Pubmed3] and as a promising therapeutic target. See also related highlights at Nat. Rev. Rheum, F1000, AJRCMB and TIS.
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Fleming’s researchers have discovered that embryonic expression of Autotaxin, a secreted lysophospholipase D generating lysophosphatidic acid, is necessary for vascular branching morphogenesis and neural tube closure. [PubMed].
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Pulmonary translational research at Fleming: Researchers at the institute of immunology in collaboration with various University hospitals have discovered an important role for gelsolin, an actin-binding protein, in lung pathophysiology [Pubmed].
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Inauguration of BSRC Fleming’s Expression Profiling Unit. The Unit is equipped with the most advanced technology on microarray experimentation and data analysis. The BSRC Al. Fleming’s Expression Profiling Unit provides expression profiling services to academic and research centers as well as the private sector.
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Researchers at the Institute for Immunology, utilizing comparative expression profiling, have discovered new genes and pathways involved in the pathophysiology of pulmonary fibrosis. Among them and through the utilization of tissue microarrays, HIF-1a was shown to have an early primary role in disease pathogenesis. [Pubmed].
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The MUGEN Mouse Database (MMdb) is a database of murine models of immune processes and immunological diseases. MMdb was developed in the context of MUGEN network of Excellence (MUGEN NoE) and serves as a use-case example of database integration and interoperability, in the context of CASIMIR, a co-ordination action on mouse resource integration [Pubmed].
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BSRC "Alexander Fleming" has recently published at PLoS One new work suggesting the use of soluble TNF inhibitors in the treatment of Idiopathic Pulmonary Fibrosis [Pubmed][F1000].
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