During my scientific training, I have been dealing mostly with pancreatic islets. They are part of our body and are essential to our health. The islets, named after Paul Langerhans (who discovered them in 1869), are miniorgans localized in our pancreas. They are present among other cells of the pancreas, the nerves, and the vascularization. The islets consist of cells which produce and release hormones. The major part of the islet is composed of beta-cells. Highly specialized nutrients-sensors, the beta-cells produce and release insulin. Discovered by Frederick Banting and Charles Best in 1921, insulin is the hormone that regulates the level of sugar (glucose) in our blood and allows the distribution of this sugar to various organs. If insulin is no longer available, or if its role is reduced, diabetes mellitus develops, giving rise to chronic hyperglycemia or high blood sugar (please see the page Diabetes on my site for further details). There are mainly two types of diabetes, type 1 diabetes, when insulin-producing cells within the pancreas die or type 2 diabetes, when insulin-releasing cells are not functional and/or insulin is not efficient anymore in distributing sugar in peripheral tissues and cells.
My main interest in my scientific research career is to investigate mechanisms that increase the release of insulin from beta-cells and prevent the death of these cells in situations of metabolic stress. In addition, I am also interested in the treatments of insulin deficiency, a condition where insulin is almost or completely absent from the organism.
Overall, my goal is to improve the quality of life of insulin-dependant and diabetic patients on a global aspect and to use my skills and knowledge to participate actively in disease control and prevention of further metabolic stress development.
Academic research projects
Dopamine is a regulator of insulin secretion from pancreatic beta-cells.
I fell into the field of metabolic diseases when I was doing a training in a lab at the Faculty of Medicine in Geneva for my Master degree in biochemistry. The first serious project I worked on was specifically focused on the crosstalk between neurosciences and metabolism and the effect of innervation of insulin-producing cells. In this study, we found that when treated with the neurotransmitter dopamine, murine pancreatic islets maintained in culture or isolated insulin-producing beta-cells showed a reduction in their insulin release. This is explained by the fact that dopamine binds to its specific receptors expressed on the surface of the pancreatic beta-cell and acts by slowing down the metabolism and the function of these cells. In fact, a complete dopaminergic signaling is present within the beta-cell, as for the neuronal cell, because pancreatic islets are highly innervated and receive multiple projections, including dopaminergic ones, revealing therefore a link between neurosciences and diabetes. Since then, as my Master training in this lab was also a very nice experience, I became interested in diabetes, and I decided to continue digging more deeply and investigating the mechanisms that underlie the development of this still very enigmatic disease as well as the treatments that can control it.
Group: Prof. Pierre Maechler
Mechanisms of insulin exocytosis from pancreatic beta-cells
During my PhD thesis at the University of Lausanne, I studied how beta-cells release the hormone insulin. A complex machinery works indeed in the cell to transport insulin-containing granules from their pool of formation to the close vicinity of the plasma membrane to liberate the hormone.
By mostly using imaging techniques and insulin-releasing tumoral cell lines, I observed and investigated the mechanisms that underlie insulin release from insulin-containing granules in beta-cells, a process specifically called insulin exocytosis.
Insulin exocytosis is a highly regulated process, involving various signaling pathways as well as protein complexes. I studied mainly two classes of proteins called Rab37 and RalA GTPases as well as their direct regulators. I found that these proteins are tightly implicated in two steps of the process of exocytosis, namely the docking (the insulin-containing granules is in the very near proximity to the plasma membrane, preparing the granules to the further steps of exocytosis) and the fusion (merging of the insulin-containing granules with the plasma membrane of the beta-cell in order to release their content into the extracellular environment) steps.
Group: Prof. Romano Regazzi
Crosstalk between survival and metabolism in the pancreatic beta-cells
After completing my PhD, where I was mainly working with cells and in vitro systems, I was interested to study metabolism and diabetes in a more physiological context and applied to obtain a Swiss National Foundation for Young Researchers grant to go to Harvard Medical School. I had the chance to get this financial support, and I spent three years in the Department of Cancer Biology of the Dana-Farber Cancer Institute in Boston. There, I was interested in the methods improving the pancreatic beta-cell mass in the process of pancreatic islets transplantation. Indeed, during this procedure, pancreatic islets suffer because of their transfer after their isolation from a donor pancreas to the environment of the recipient organism. In this context, I investigated the common factors between the survival and the function of pancreatic beta-cells. More specifically, I studied the role of the pro-apoptotic protein BAD and its link to the glucose-sensing protein glucokinase that is involved in the metabolism of glucose. It turned out that when modified (in this context phosphorylated), BAD becomes a pro-survival factor. After activating glucokinase, phospho-BAD increases glucose metabolism and stimulates insulin secretion. This result allowed me to test the best conditions that permit the improvement of both survival and function of pancreatic islets during transplantation in animals with insulin deficiency and type 1 diabetes. We were very pleased with the results of this work, which also enabled us to use small peptides mimicking the modified form of BAD and that successfully maintained the quality of cultured human and murine pancreatic islets during the process of transplantation in animal models. In fact, all our animals receiving the islets pre-treated with these small peptides corrected their hyperglycemia and glucose tolerance over time to normal level.
Group: Prof. Nika Danial
Life without insulin
In 2015, I joined a project where the interest was focused on a provocative question: can we live without insulin? Indeed, although insulin is the treatment of choice for diabetic patients (especially suffering from type 1 diabetes), when taken for many years, it can have damageable effects on the organism, including threatening the patient with severe episodes of hypoglycemia. To be able to maintain the positive regulatory effects of insulin on blood sugar while deleting the risks of this therapy, at the Faculty of Medicine in Geneva, our team has been working for more than four years, studying the effect of other hormones in the state of insulin deficiency (when there is no more insulin).
And guess what? Living without insulin may be possible, at least in animal models of insulin deficiency. This process is mainly involving the role of leptin (released by the fat cells) in mice models that completely lack insulin (in both genetically or pharmacologically induced insulin-deficient animals). When injected in their central nervous system, leptin increased circulating levels of S100A9, a protein implicated in inflammatory pathways, that surprisingly allowed the improvement of diabetes symptoms in those animals. Despite still hyperglycemic, when insulin-deficient animals expressed high levels of the S100A9 protein in the blood, their diabetic symptoms faded: the animals become normolipidemic, reduced their levels of ketone bodies (increased circulating ketones bodies being another hallmark of uncontrolled diabetes) and improved their metabolism. These ameliorated metabolic features allowed them to survive twofold longer as compared to insulin-deficient animals that do not expressed high levels of the S100A9 protein.
Group: Prof. Roberto Coppari
Translational Research/Clinical Research projects
Isolation and transplantation of human islets as a treatment of diabetes
One of the treatment of diabetes is pancreatic islet transplantation. In 2019, I had the great chance to join the most successful lab for human islets isolation and transplantation in Europe. I performed a lab-specific clinical training at the Geneva University Hospitals and the Faculty of Medicine, where I learnt the various steps of the clinical process of pancreatic islets isolation from a donor pancreas. During this great experience, I learnt many facts about the treatment of diabetes with pancreatic islets transplantation. After this procedure, a diabetic patient is able to reduce insulin therapy up to being sometimes completely independent of it. Having worked in the same team on projects related to pancreatic islet cells quality, I investigated the best conditions enabling the pancreatic beta-cells to be more functional before transplanting them in a patient.
Group: Profs. Thierry Berney and Domenico Bosco
Clinical trials in the field of hypertension and nephrology
Since August 2021, I have been working at the University Hospital Center of Vaud in Lausanne as a Clinical Research Associate and am currently participating in different clinical trials (Phase I to IV) in the field of hypertension and nephrology.
My stay at Geneva Biotech
When I came back from Boston in 2014, freshly having finished my Postdoctoral Fellowship at Harvard, I decided to dive into the industry world. Being very interested in entrepreneurship, I joined the start-up company Geneva Biotech, based within one of the University’s incubator: La Tulipe. The start-up provides a platform for synthetic signaling cascades and has the vision to develop a portfolio of viral and non-viral DNA delivery systems into cells. There, I worked as a Scientific Project Manager and the Head of Cell and Animal Models Department. While performing experiments, I had multiple roles, including installing all the infrastructure of the laboratory, organizing consortia, creating projects, writing grants, presenting my ideas and coaching Master students. During my stay at GB, I had excellent opportunities to develop my strategic mind and business ideas. I had the chance to write a project in the field of diabetes with the GB team and in collaboration with the University of Geneva, we got a CTI (Commission for Technology and Innovation) grant to develop an early-stage drug discovery program for the search of small molecules targeting specific receptors within pancreatic islets.
Supervisor: Dr. Daniel Fitzgerald