Research in the Mousssaieff laboratory
Research in the Moussaieff laboratory is focused on the profound link between metabolism and cell fate. Using a state of the art platform for metabolic profiling, we comprehensively characterize the metabolic content of biological systems. We use advanced cellular and in vivo models to study the involvement of metabolic perturbations in changes that occur during development and in the initiation and progression of disease.
The Moussaieff laboratory is focused on the profound link between metabolism and cell fate. Our data strongly suggest that lipid metabolism is central for this link, and we are studying lipid metabolism in:
Metabolic shifts during early embryonic development
We have been studying metabolism of the early developing embryo, with the following Aims:
Aim 1. Define the metabolic changes that occur during the exit of pluripotent cells (PSCs) from pluripotency, and unveil their role in the cell differentiation.
We studied of the glycolytic shift during early differentiation of PSCs, and its effect on cell fate via changes in acetyl-CoA concentration and histone acetylation (Moussaieff et al, Cell Metabolism, 2015).
Aim 2. Characterize the effects of maternal metabolism on the pre-implantation embryo.
For this Aim, we have been studying maternal and embryonic human samples, as well as the corresponding cell systems.
In collaboration with Dr. Assaf Ben Meir (Hadassah Medical Center), we have collected human maternal samples from over a hundred IVF patients: Follicular fluid, granulosa cells and blood samples. We are now in the process of metabolic analyses of the three sets of samples. We have also collected over a hundred samples from IVF embryo medium that will be associated with the corresponding maternal samples.
Aim 3. Elucidate the metabolic phenotype of the trophectoderm. The trophectoderm envelopes the embryo, and later becomes the placenta. It plays a critical role in providing the embryo the environment required for development. In the pre-implantation embryo, the totipotent embryo differentiates into two major cell populations: the inner cell mass that will for the embryonic cells, and the trophectoderm that would form the placenta.
We are studying the metabolome of trophoblast stem cells (TSCs), to provide the first description of their metabolic phenotype and of the metabolic micro-environment they provide for the embryo.
Cancer metabolic heterogeneity
By utilizing the protocol developed by Arik for the metabolic analysis of cell populations within a tissue, we study the metabolic profiles of different cancer cell populations in collaboration with professor Eli Keshet (HUJI).
Metabolic perturbations during aging and neurodegenaration
Changes in the lipid content of the plasma membrane have been known to play critical roles in aging, and especially with neurodegenerative processes. We therefore launched a project to characterize the lipid content in the brain of Alzheimer' disease (AD) patients in association with non-coding (nc)RNA expression, in collaboration with Prof. Hermona Soreq (HUJI).
Taken together, we propose here a new approach to address fundamental questions in development, cancer progression and aging, based on the metabolic shifts that are concomitant. The metabolic shifts will be utilized both as a powerful and sensitive readout for changes in cellular state and for regulating these changes.