Yann Grobs

Scholarships:

• 2021 Loretta Chu Memorial PH Research Scholarship

• 2022 Paroian Family PH Research Scholarship

• 2023 Paroian Family PH Research Scholarship

Research group: Pulmonary Hypertension and vascular Biology Research group, Laval University, Quebec Canada

Under the supervisor: Dr. Sébastien Bonnet

About Yann Grobs

Native from Montpellier (France), Yann obtained a bachelor's degree in health biology before specializing in microbiology and immunology during his master's degree at the University of Montpellier II. During an internship at the Research and Development Institute (IRD) on the genetic diversity of HIV, he developed a particular interest in translational research and, more particularly, in the physiology of the cardiovascular and respiratory systems. Pulmonary arterial hypertension (PAH) is one of the complications of an HIV infection. Yann enthusiastically joined the PAH group of Quebec led by Dr. Sébastien Bonnet and Dr. Steeve Provencher. Yann is currently working on his Ph.D. under the supervision of Dr. Bonnet.

Projects:

P300/CBP a potential therapeutic target to cure pulmonary arterial hypertension (2021)

Project description: Pulmonary arterial hypertension (PAH) is a deadly and incurable vascular disease. This disease affects the pulmonary arteries (PAs) that carry the blood from the heart to the lung. PAs are crucial for the reoxygenation of the blood. Like in cancer, cells of PAs wall multiply in an abnormal manner, i.e. faster than normal and conduct to PAs obstruction. This obstruction increases pressure in this vessel leading to fatal cardiac dysfunction. We identified P300 as a factor implicated in genes expression. In cancer, its overexpression induces an increase in cells proliferation.

Similarly, we believe that this factor is involved in abnormal PAH cell proliferation. We demonstrated that p300 is increased in PAH patients compared to non-PAH patients. In the PAH rats model, we showed that p300 treatment decreases PA cells proliferation and improves survival. We propose investigating further p300 function in general who will benefit several diseases and PAH development understanding. Interestingly, a P300 treatment is currently in clinical trials for the treatment of cancers. Therefore, our study has a high translational impact, potentiating the development of a novel treatment strategy from the laboratory to improve PAH patient quality of life.

ATP citrate lyase orchestrates metabolic and epigenetic modification in Pulmonary arterial hypertension (2022)

Pulmonary arterial hypertension (PAH) is a deadly and incurable vascular disease. This disease affects the pulmonary arteries (PAs) that carry the blood from the heart to the lung for reoxygenation. Like in cancer, cells of PAs will multiply in an abnormal manner, i.e. faster than normal and conduct to PAs obstruction. This obstruction increases pressure in this vessel leading to fatal cardiac dysfunction. The nucleo-cytoplasmic enzyme ATP Citrate Lyase (ACLY) has recently emerged as a key player and therapeutic target in cancer by favouring the Warburg effect, lipid synthesis and chromatin remodelling. We demonstrated that ACLY is overexpressed in PAH patients and PAH-induced animal models, respectively, compared to control patients and control animals. In PAH animal models, we demonstrated that ACLY inhibition prevents PAH development and improves survival in animals with PAH well-established. We propose further investigating ACLY function in general, which will benefit several diseases and the understanding of PAH development. Interestingly, ETC1002 (ACLY inhibitor) treatment is currently in clinical trials for the treatment of hypercholesterolemia. Our study has, therefore, a high translational impact, potentiating the development of a novel treatment strategy from the laboratory to improve PAH patients' quality of life.

Implication of APEX1 in Pulmonary Arterial Hypertension (2023)

Pulmonary arterial hypertension (PAH) is a deadly and incurable disease. Despite recent progress in our understanding of the pathophysiological mechanisms, lung transplantation is the only therapy in end-stage PAH. PAH is characterized by an obstruction of blood flow in pulmonary arteries (PAs) due to a vessel wall thickening, leading to vascular resistance and right heart failure. Cells from the wall of PAs feature a phenotype like cancer cells; in other words, they have a greater capacity to multiply rapidly. A protein called APEX1, involved in DNA repair and gene expression activation, is found to be overexpressed in PAH cells. Our research shows elevated APEX1 levels in both PAH patients and animal models, as well as a correlation with disease severity. This provides strong evidence implicating APEX1 in the development of PAH. Thus, we propose determining whether elevated APEX1 expression has a detrimental function. This research proposal is designed to advance biomedical knowledge, significantly impact our understanding of the pathogenesis of PAH, and increase our ability to treat the disease.