I am an Independent Research Fellow in the Laboratory of Systems Pharmacology at Harvard Medical School advised by Peter Sorger. I use high-throughput functional genomics tools to answer questions related to cellular physiology, to mechanisms of drug action and to mechanisms of cellular resistance to chemotherapeutics. Recently, I have been focusing on CRISPR-derived technologies to perform genome-wide genetic screens in human cells (CRISPRi for gene knockdown; CRISPRa for gene overexpression). I have applied these methodologies to study the basis for the success of a combination therapy (RCHOP) in curing lymphomas. I am currently studying the mechanisms of small molecule (drug, nutrient, metabolite) import and export in and out of human cells.

I obtained my PhD in the lab of Kai Johnsson at EPFL in Lausanne (Switzerland) where I developed a yeast-based screen for the identification of the protein targets of small molecule drugs. I applied the methodology to the profiling of clinically approved drugs and I identified new off-targets for the anti-cancer drug erlotinib, for the cholesterol-lowering drug atorvastatin, as well as a novel target for the poorly understood antiinflammatory drug sulfasalazine. I showed that sulfasalazine inhibits tetrahydrobiopterin biosynthesis at physiologically relevant concentrations, a finding which explains some of the known beneficial and deleterious properties of sulfasalazine.

I then joined the lab of Erin O’Shea at Harvard University where I used haploid genetic screens in human cells to discover the mechanism of action of the potent anticancer natural product ophiobolin A (OPA). OPA shows strong cytotoxicity in vitro and displays promising anti-tumor activity in a mouse glioblastoma model, but the lack of known cellular targets has impeded any further development of the molecule. In my work, I discovered that genetic inactivation of de novo synthesis of phosphatidylethanolamine (PE) mitigates OPA cytotoxicity by reducing cellular PE levels. Through a variety of biochemical and chemical methods, I found that OPA reacts with the ethanolamine head group of PE in human cells to form pyrrole-containing covalent cytotoxic adducts and these adducts lead to lipid bilayer destabilization.