Mohd Jamal Dar, PhD
Professor, AcSIR (Biological Sciences)
Jammu, J&K-180001 India

Discovery of  novel JAK3 specific  small molecule inhibitor involved in promoting hair regrowth

11/07/2024 – ore 14:00

Abstract: 

Alopecia areata is an autoimmune disease that occurs when the immune system attacks hair follicles and causes them to lose the ability to enter the growth phase of the hair growth cycle, ultimately resulting in hair loss. Hair follicles were previously thought to be missing from the areas of complete baldness, however, recent studies have shown that even the bald areas of the human scalp contain hair follicles and hair follicle stem cells. Recently, pharmacological inhibition of JAK-STAT signaling was seen to enhance hair re-growth by awakening quiescent hair follicle stem cells (HFSCs). Thus, JAK-STAT signalling pathway has emerged as a promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 is an ideal target for drug discovery because it only regulates a narrow spectrum of gc cytokines. In a recent study, we reported the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter. During in-vivoefficacy assays, topical application of MJ04 on DHT-challenged AGA mice and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04exhibited a reasonably good pharmacokinetic profile and demonstrated a favorable safety profile under in-vivo and in-vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.

INFO : seminari.irib@irib.cnr.it

Dr. María D. Mayán

CINBIO – University of Vigo

Next-Generation Therapeutics: Extracellular Vesicles as Tools and Targets

02/07/2024 – ore 14:30

Abstract: 

In this talk, I will present our latest results in the study of extracellular vesicles in various age-related disorders, such as cancer and osteoarthritis. We have identified new targets to combat drug resistance in cancer and to address inflammation and disease progression in osteoarthritis. The use of EVs enables us to deliver specific peptides and mRNA molecules to target cells, aiming to halt disease progression in osteoarthritis and to overcome drug resistance in cancer. Additionally, these EVs can function as biomarkers, enhancing their applicability in nanomedicine for disease control and the monitoring of disease progression.

INFO : seminari.irib@irib.cnr.it

Dott. Massimiliano Alfano, PhD

Oxford Nanopore Technologies

Oxford nanopore technologies: technology update and applications

06/05/2024 – ore 14:30

Abstract: 

Oxford Nanopore Technologies (ONT) ha rivoluzionato il campo del sequenziamento del DNA attraverso l’introduzione di una tecnologia innovativa basata su nanopori. Le principali caratteristiche di questa tecnologia includono l’alta velocità di sequenziamento, la capacità di sequenziare frammenti estremamente lunghi e la possibilità di effettuare il sequenziamento in tempo reale. Queste caratteristiche rendono la tecnologia ideale per una vasta gamma di applicazioni, tra cui la genomica, la diagnosi di malattie genetiche, la microbiologia, la virologia, l’ecologia microbica e gli studi sulla metilazione del genoma umano. Durante il talk verranno discusse le sfide attuali e le prospettive future della tecnologia, evidenziando il suo potenziale impatto nel campo della biologia molecolare e della medicina.

INFO : seminari.irib@irib.cnr.it

Dr. Lucilla Mazzeo

Deal flow & Scouting Analyst
Scientifica Venture Capital

Dietro le quinte di un venture capital: dall’analisi del deal flow all’investimento in una start-up, i processi interni che misurano il valore di un progetto

21/03/2024 – ore 14:30

Abstract: 

Il webinar si propone di offrire una panoramica sul funzionamento di un venture capital, partendo dall’analisi del flusso delle opportunità di finanziamento fino all’investimento effettivo in una start-up. La presentazione si concentrerà principalmente sui processi interni che valutano il valore di un progetto, offrendo un’analisi delle metodologie e delle strategie d’investimento utilizzate.

INFO : seminari.irib@irib.cnr.it

Dr. Teresa Esposito

Senior Researcher, CNR-IGB

Identification of novel biomarkers for early prediction and progression of Parkinson’s disease through a multidisciplinary approach integrating omics data and in vitro modelling

29/02/2024 – ore 14:30

Abstract: 

Parkinson’s disease (PD) represents one of the most frequent neurodegenerative disorders for which genetic diagnosis is still challenging due to the high genetic heterogeneity associated with the disease and to the difficulty in interpreting test results. We have recently reported the identification of rare new gene variants in PD patients that support polygenic contribution to the disease. To better decipher the genetic complexity of PD and to identify novel biomarkers related to the PD etiology and severity we applied a multidisciplinary approach based on jointing ‘omics’ techniques (whole exome sequencing, proteomic, lipidomic metabolomics) with clinical data in circulating biofluids and cellular models. To address these objectives, we realized a Biobank for Parkinson’s disease which includes a large collection of PD samples (about 800 patients including familiar and sporadic cases) recruited at IRCCS Neuromed for which we collected and stored clinical information (neurological examination and drugs therapy), genetic data (WES) as well as DNA, serum, plasma, PBMC, fibroblast cell lines and induced pluripotent stem cells (iPSC).
Genetic analysis of the entire cohort discovered a significant excess of rare and deleterious variants in novel PD genes, highly expressed in human dopaminergic neurons, and involved in pathways potentially deregulated in PD including signal transduction pathways and endocytic recycling. In these genes, we identified both rare likely pathogenic variants, altering protein structure and dynamics, as well as frequent variants associated with PD risk. Moreover, we demonstrated that the co-inheritance of multiple rare variants (≥ 2) in a panel of 37 PD genes selected in this study, may predict disease risk in about 26% of patients, both familial and sporadic cases, with high specificity (> 90%; p = 3.23 x10-9). Furthermore, patients carrying multiple rare variants showed higher risk of manifesting dyskinesia induced by levodopa treatment (p=0.004), severe cognitive impairment (p=0.009) and an earlier age at onset of the disease (p=0.01).
Moreover, since PD is now considered to be a diverse group of disorders, rather than a single pathogenic disease entity, affecting both the peripheral and central nervous system, new approaches for the study of PD should be adopted by combining multiple omic layers of high-throughput sources to elucidate new biological information to a better understanding of neurodegenerative conditions. Lipids, metabolites, and proteins reflect the physiological and pathological status of an individual. Profiling these data types could be useful not only to highlight new pathways affected in PD condition but also to identify sensitive and effective markers for early disease detection and potentially effective therapeutic interventions. We applied this approach to investigate whether the presence of mutations in TMEM175 gene could reflect a characteristic lipidomic, metabolomic and proteomic signature of PD patients both at circulating and cellular levels. Preliminary data revealed a network of lipids and proteins associated to lysosomal and mitochondrial metabolism in Parkinson’s disease patients carrying mutations in TMEM175 gene.

INFO : seminari.irib@irib.cnr.it

Dott. Michele Migliore

Institute of Biophysics, National Research Council, Palermo

Cognitive functions and dysfunctions emerging from large-scale data-driven models of brain regions

15/12/2022 – ore 14:00

Abstract: 

Understanding the neural basis of brain functions and dysfunctions has a huge impact on a number of scientific, technical, and social fields. Experimental findings have given and continue to give important clues at different levels, from subcellular biochemical pathways to behaviors. However, most of the multi-level mechanisms underlying the cognitive architecture of the involved brain regions are still largely unknown or poorly understood. This mainly depends on the practical impossibility to obtain detailed simultaneous in vivo recordings from an appropriate set of cells, making it nearly impossible to decipher and understand the emergent properties and behavior of large neuronal networks. We are addressing this problem using large-scale computational models of biologically inspired cognitive architectures. I will present and discuss the main results and techniques we use to design and exploit full-scale models of neurons and networks implemented following their natural 3D structure, with the main aim to uncover the mechanisms underlying higher brain functions and helping the development of innovative therapies to treat brain diseases.

INFO : seminari.irib@irib.cnr.it