Adama Sidibé & Biomedicine
Photo of Adama Sidibé by C. Henry
Born in Mali (West Africa), grown between Mali and Senegal,
adopted by France and Switzerland,
married to Audrey Ciccarelli,
father of Haby and Ana.
Have cousins from all continents...
Ask for a complete CV at :
adama.m.sidibe@gmail.com
The nature teaches us to face issues... Lions apply this...
Why not us in BioMedicine...
Snapshot of a bought canvas with a lion
Hi there! Welcome to my web pages,
I am a research scientist in Biomedicine for more than 15 years. I was appointed to a teaching and research position (Maître-assistant) in 2019 at the Faculty of Medicine of University of Geneva (Switzerland). My position was associated to the group of Prof. Bernhard Wehrle-Haller in the department of cell physiology and metabolism. I am a previous member of the laboratory of Prof. Beat Imhof in the department of pathology and immunology until the lab closure due to Prof Imhof retirement in 2017. As my carrer advances, I shift from one position to another, participate in different interesting research projects, all with the same aim: making significant contributions to diseases' biology to resolve key problems in medicine and propose new therapeutic solutions. Since some time now, I felt the need of making a digital space for myself and provide a clear view of my carrer development in this field. Thus I reserved adamasidibe.fr to serve this purpose. You are welcome to help me grow this website, or to get involved with me through collaboration or partnership.
Herein, I present a condensed view of my research interests from the beginning to now, my working projects as well as other professional matters in order to foster perspectives of productive collaborations towards an innovative and precise molecular medicine. By molecular medicine, I means therapies based on fixing issues related to the balanced functioning of the molecular components of our body. Here, I may also post some News about my carrer development, announcements, reference ressources of interest and publish fun movies of "cells in action".
I am a cell and molecular biology investigator specialized in the study of the physiology of vascular cells, their phenotypic and behavioral changes in health and chronic inflammatory conditions, the molecular mechanisms leading to those changes as well as using our insights to define therapeutic strategies that may improve patients' life in pathological situations such as fibrosis and cancers.
Working on vascular cells, the primary witnesses of all events...
Very early during my formation, I realized that understanding the molecular mechanisms supporting vascular cell physiology, vessel integrity and functions was primordial for an ambitious new generation medicine. Indeed vascular cells that constitute blood vessels coordinate their interactions to allow the transport of cells, gaz (oxygen and carbone dioxyde) and nutrients throughout the body as well as the supply of peripheral tissues. Vascular cells, specially the innermost cell layer called endothelium allow the spatially and temporally regulated extravasation of specific immune cells to sites of infection, injury, inflammation, necrosis, fibrosis and malignant cell growth. In principle, no tissue in our body grows beyond 2-mm of diameter without being perfused by new blood vessels. Vascular cells by their functions, density, locations in the body constitute ones of the first witnesses of all molecular and cellular events that occur in our organism. In addition they play major role in most of those events.
Identifying essential molecular components of vascular cells and understanding their roles in blood vessel physiology and pathophysiology allow the definition of therapeutic targets to ameliorate blood vessel phenotype and functionality in several chronic inflammatory diseases and related fibrosis. In case they are not the direct target, vascular cells and their molecular components can provide critical information and tools for an efficient targeted therapy in most diseases, from drug discovery to patients' treatment and disease curing.
Release of VE-cadherin fragments in rheumatoid arthritis
VE-cadherin phosphorylation, vessel leakiness in mouse ovary
VE-cadherin phosphorylation, edema and fibrosis in mouse uterus
VE-cadherin, the major protein of endothelial adherens junctions...
I was gratuated Ph.D in Cell Biology from University of Grenoble (Grenoble, France) in 2012 after three years of doctoral training in the laboratory Biology of cancer and infections (Commissariat à l'énergie atomique, Grenoble) under the supervision of Dr. Pharm.D. Isabelle Vilgrain. In fact, following my Master graduation internship on the post-translational modifications of the vascular endothelial (VE)-cadherin, a cell-to-cell junction protein, I was awarded a three years fellowship by the Foundation Arthritis to continue the work in the context of chronic inflammatory diseases and investigate eventual interest for the understanding of the rheumatoid arthritis. VE-cadherin is the major transmembrane protein of endothelial cell adherens junctions that is required for the homotypic contact formation, the integrity of endothelial layer and barrier function. We have reported that under inflammation, VE-cadherin of the "stressed" endothelial cells was phosphorylated by cytoplasmic kinases provoking changes to the protein conformation and thereby leading to cleavage of its extracellular fragment by the matrix metalloproteinases. Finding the shed fragment of VE-cadherin in the sera of rheumatoid arthritis patient and the correlation of its amount with the disease activity set the foundation idea of monitoring the blood circulating fragment of VE-cadherin, a consequence of the chronic inflammation, to guide during treatment (Sidibé et al Arthritis Rheum 2012). This work was awarded the prize of "UFR Chimie-Biologie 2012".
I also studied the relevance of VE-cadherin phosphorylation in vivo, specially in recurrent angiogenic organs in mouse namely uterus and ovary. I found in those organs that hormonal cycle induces a periodic phosphorylation of VE-cadherin at the tyrosine 685, a modification that I also found critical for the control of endothelial barrier function (Sidibé et al AJP:HC 2014a). Consistently, the female mouse carrying a mutation of VE-cadherin tyrosine 685 into phenylalanine, a structurally similar amino acid but non phosphorylatable, presented vascular leakiness and edema in uterus and ovary (Sidibé et al AJP: HC 2014b). This work contributed to set the stage for understanding how the different post-translational modifications of VE-cadherin were controlling its function, endothelial cell junctions and blood vessel functionality (Sidibé et al Nat. Immunol. 2014).
Angiogenic factors-driven inflammation for monocyte infiltration to tumors
I had a first post-doctoral experience in the laboratory of Prof. Beat Imhof in the department of Pathology and Immunology of the faculty of Medicine of University of Geneva (Geneva, Switzerland). I studied the molecular cascades of the extravasation of mononuclear phagocytes induced by tumor inflammation as well as their contribution to the pathological development of blood vessels in tumors. After a precise definition of the human pro-angiogenic monocytes, I found that these cells were particularly retained in the lumen of blood vessels during acute inflammation through mechanisms mediated mainly by endothelial cell surface-bound form of the chemokine CX3CL1 (fractalkine). The retention of proangiogenic monocytes allows the exclusive recruitment of inflammatory monocytes to site of acute inflammation. Interestingly, this retention is alleviated in tumors due to a strong downregulation of CX3CL1 expression by tumor-associated endothelial cells. This process is induced by synergistic actions of inflammatory cytokines and angiogenic factors expressed in the tumor microenvironment. This synergistic inflammatory condition was called ADIn (Angiogenic factors-driven inflammation). ADIn was absent in tumors presenting significant amount of the inflammatory cytokine interferon gamma (IFNg). We proposed a therapeutic regimen that combine IFN with anti-angiogenics to target at the same proangiogenic monocyte infiltration, pathological angiogenesis and foster anti-tumor immunity (Sidibé et Nat Comm 2018). This work was awarded the Alex F. Müller 2019 prize of clinical physiopathology of the faculty of Medicine (University of Geneva).
Imaging monocyte recruitment and transendothelial migration under flow
Combination of light and fluorescence microscopy (monocytes and endothelial cell monolayer in phase contraste, endothelial cell junctions highlighted by VE-cadherin staining in fluorescence (Credit: A. Sidibé)
Here, flowing monocytes are captured on endothelial cell surface, they crawl to endothelial cell-cell junctions where they transmigrate. See other videos here
Pyrazolyl-urea derivatives, drug candidates to target tumor angiogenesis
Concerned by the need of developing efficient anti-angiogenic drug to treat cancers, I participated in a collaborative study to investigate and supervise the evaluation of the potential of pyrazolyl-urea derivatives as anti-angiogenic compounds. Several of these compounds were found to present very interesting inhibitor profiles and few of them were potent blockers of pathological vessel development. The particularity of some of those compounds was the surprising absence of toxicity of those drugs even at very high doses demonstrating the great potential of pyrazolyl-derivatives in the anti-cancer drug development (Meta et al EJMC 2017 and Meta et al Oncotarget 2017). These works paved the way for a new field of investigation on the chemical synthesis methods of the best substituted forms of pyrazolyl-ureas to provide the most potent anti-angiogenic and anti-tumor drugs while presenting the lowest toxicity.
The pyrazolyl-ureas derivatives were synthesized by our collaborators (Prof. Olga Bruno and Prof. Chiara Brullo) from University of Genova (Italy), Department of pharmaceutical chemistry DIFAR.
Their Ph.D. student Elda Meta spent a year under my supervision on this project in the lab of Prof Imhof.
Modulation of integrins in endothelial cell migration and functions
Convinced by the importance of cell contacts with its environments mediated by neighboring cell-cell interactions and cell-to extracellular matrix (ECM) adhesions for endothelial cell physiology and vessel integrity, I joined the laboratory of Prof. Bernhard Wehrle-Haller in the department of Cell physiology and metabolism at the Faculty of Medicine of University of Geneva since 2017. We are exploring the molecular mechanisms of the modulation of integrin activity and functions as well as the influence on endothelial cell physiology. I am particularly interested in the ECM fibronectin-synthesizing integrin beta-1 and its post-translational modifications such as cell metabolism-dependent acetylation. Indeed, integrin b1 was recently found acetylated, a post-translational modification dependent on cellular metabolism and acetyl-CoA availability (Choudhary et al Science 2009). Despite the great potential, the implications of this integrin b1 modulations for endothelial cell physiology remains not well understood. At the molecular level, we are addressing several questions and issues related to the molecular mechanisms, technological tool development as well as clinical potential evaluation. I received a teaching and research (Maitre-assistant) fellowship from the faculty of Medicine of the university of Geneva (2019 - 2022) to work on these projects. I am thankful to several funding foundations for their financial supports.
I supervised few students during their mandatory graduation internship or when visiting my host labs. They include: Laurie Godart, Jéremy Rajanajatovo, Julie Creuzet, Elda Meta and Dilvin Semo.
From my Ph.D. training to the maitre-assistant appointment I participated in the following teaching programs:
Faculty of Medicine, University of Geneva - Geneva, Switzerland
-Cell growth and Aging (Problem-based learning, clinical cases in this module), for 2st year MD student, 2018-2023
-Oral presentation, for 1st year BIOMed students, 2017-2021
-Tumor vascular biology (Experimental pathology), for 2nd and 3rd year MD student, 2018-2020
-Chosen chapter for PhD student, 2018
-Angiogenesis (Cell-cell interaction) for 2nd-3rd year MD student, 2017
UFR Chimie Biologie, Joseph Fourier University (currently Université Grenoble-Alpes) - Grenoble, France
-Initiation to biology for 1st year Bachelor student, 2010-2011
-Supervision on exploration of mouse anatomy for 1st year Bachelor student, 2010-2011
Get involved with me through collaboration or partnership
If you feel that we may have common interest for science, research, drug discovery, project development or funding, or if you want to initiate a collaboration or just share some smart ideas with me, don't hesitate to get in touch with me by email at adama.m.sidibe@gmail.com .
I am very interested in interdisciplinary collaborations or partnership. For example, mathematics for life science and medicine, computational analysis methods, pharmaceutical chemistry and drug design. I am interested in partnership with oncologist clinicians, specialist of fibrosis and infectiologues.
I am tempted by the challenge of entrepreneurship, thus if you are looking for a potential partner with a profile close to mine, please feel free to contact me. If you hold an executive MBA, are specialist in fund raising for biotech companies, feel free to contact me.