Postdoctoral Fellow

Florencia Lucia Herbstein

Profile

 I earned my degree in Biochemistry from the University of Buenos Aires (UBA), where I also trained in physiology teaching and have been active in university education for over a decade. I completed my PhD at IBioBA–Max Planck Society Partner Institute, supported by the National Scientific and Technical Research Council of Argentina (CONICET), investigating cellular senescence and inflammatory signaling in pituitary tumors. For my postdoc at IJC, I will explore metabolic genome regulation in leukemia.

Project description

Acute myeloid leukemia (AML) is an aggressive and diverse form of cancer, marked by frequent relapses and low survival rates. The improvement of current therapies and their outcomes is a major unmet need. It is well known that leukemia-persistent cells undergo metabolic reprogramming that enhance their survival. The observation that metabolic enzymes are enriched on chromatin in AML cells suggests that there might be a direct link between nuclear metabolism, chromatin regulation and cellular adaptation to therapy-induced stress. Here, I propose a fundamental research project in which I plan to dissect to which extent metabolic genome regulation contributes to AML. Specifically, I plan to extend existing proteomic data on chromatin-associated metabolic enzymes and test their relevance for leukemia cell survival and proliferation. Preliminary results indicated that these would include enzymes responsible for ROSdetoxification. By leveraging innovative perturbation methods specific for the nuclear compartment, I will determine the contribution of the nuclear pool of selected enzymes to leukemia-relevant cellular parameters including senescence and the response to current treatment schemes. Finally, I will dissect the molecular mechanism of action. First, I will determine if enzymatic activity is essential for the phenotype. In parallel, I will explore if the enzyme has alternative functions as metabolite sensor or scaffolding protein. Finally, I will test the hypothesis that chromatin-associated metabolic enzymes act at least in part through gene regulation. In conclusion, I propose a fundamental research project that will provide unprecedented insight in the metabolic aspects of genome regulation. To make this challenging project feasible, I will apply my expertise in cell fate transitions and be able to leverage the expertise of the European NUCLEAR network that will start its activity in 2025. This network is coordinated by the host lab and includes my key collaborators Sara Sdelci and Jan Zylicz.  Thus, I am confident of bringing together the right people, resources and skills that will allow me to succeed in my endeavors.