Research:
In my laboratory, we focus on four fundamental topics in biology:
1) We study the role of mitochondria, the powerhouse of the cell, in cellular and organismal metabolism. Using an interdisciplinary approach, we seek to unveil the mechanisms that coordinate the function of the mitochondria with core metabolic pathways. In recent years we are focusing on the interplay between mitochondria and the mevalonate pathway, a metabolic pathway essential for cholesterol homeostasis and the activation of small G proteins. Impaired function of the mevalonate pathway results in the development of cancer and cardiovascular diseases, the two leading causes of death worldwide. Thus, our long-term objective is to translate our research findings of the link between the mitochondria and the mevalonate pathway into the development of therapeutic strategies to better treat these devastating diseases.
2) We investigate the beneficial and adverse effects of statins, a group of cholesterol-lowering agents that are the best-selling medications in history prescribed to more than 200 million people worldwide. Using C.elegans genetics and pharmacological studies, our work reveals critical mechanistic aspects of the effects of statins on different biological systems with specific emphasis on the nervous system. We expect that our findings will help to understand why some patients suffer from adverse side effects whereas many others seem to be unaffected by statins treatment. Ultimately, our discoveries will lead to improved treatment venues that will enhance the beneficial effects of statins, for example, their anti-inflammatory and anti-cancerous activities.
3) We study the evolution of metabolic networks with specific emphasis on cholesterol synthesis pathways in animals. Using bioinformatics approaches, we studied cholesterol synthesis across the animal kingdom and found that most animals on Earth, including arthropods and nematodes, lost the ability to synthesize cholesterol. Using genetic, biochemical, and metabolic approaches we have discovered in sterol auxotrophs a novel pathway that facilitates the conversion of dietary sterols to cholesterol. By the conversion of dietary sterols, this pathway supports the growth and reproduction of more than 80% of animals on earth. Current studies are focused on the study of cholesterol metabolism in the animal kingdom in order to deepen our rudimentary understanding of fundamental evolutionary processes such as the loss and conservation of metabolic pathways, the reconfiguration of metabolic networks, and the acquisition of new functions during evolution.
4) We explore the metabolism of animals that live in extreme habitats such as anoxic, hypersaline, or arsenic-rich environments. A growing body of evidence suggests that different species of nematodes dominate many of these extreme habitats. Therefore, our goal is to study nematodes life in extreme habitats as a model for the adaptations animals have developed to flourish in extreme habitats on the planet Erath. Currently, we are focusing on two unique and extreme ecological niches, the Dead Sea in Israel and Mono Lake in California, USA.
In my laboratory, we focus on four fundamental topics in biology:
1) We study the role of mitochondria, the powerhouse of the cell, in cellular and organismal metabolism. Using an interdisciplinary approach, we seek to unveil the mechanisms that coordinate the function of the mitochondria with core metabolic pathways. In recent years we are focusing on the interplay between mitochondria and the mevalonate pathway, a metabolic pathway essential for cholesterol homeostasis and the activation of small G proteins. Impaired function of the mevalonate pathway results in the development of cancer and cardiovascular diseases, the two leading causes of death worldwide. Thus, our long-term objective is to translate our research findings of the link between the mitochondria and the mevalonate pathway into the development of therapeutic strategies to better treat these devastating diseases.
2) We investigate the beneficial and adverse effects of statins, a group of cholesterol-lowering agents that are the best-selling medications in history prescribed to more than 200 million people worldwide. Using C.elegans genetics and pharmacological studies, our work reveals critical mechanistic aspects of the effects of statins on different biological systems with specific emphasis on the nervous system. We expect that our findings will help to understand why some patients suffer from adverse side effects whereas many others seem to be unaffected by statins treatment. Ultimately, our discoveries will lead to improved treatment venues that will enhance the beneficial effects of statins, for example, their anti-inflammatory and anti-cancerous activities.
3) We study the evolution of metabolic networks with specific emphasis on cholesterol synthesis pathways in animals. Using bioinformatics approaches, we studied cholesterol synthesis across the animal kingdom and found that most animals on Earth, including arthropods and nematodes, lost the ability to synthesize cholesterol. Using genetic, biochemical, and metabolic approaches we have discovered in sterol auxotrophs a novel pathway that facilitates the conversion of dietary sterols to cholesterol. By the conversion of dietary sterols, this pathway supports the growth and reproduction of more than 80% of animals on earth. Current studies are focused on the study of cholesterol metabolism in the animal kingdom in order to deepen our rudimentary understanding of fundamental evolutionary processes such as the loss and conservation of metabolic pathways, the reconfiguration of metabolic networks, and the acquisition of new functions during evolution.
4) We explore the metabolism of animals that live in extreme habitats such as anoxic, hypersaline, or arsenic-rich environments. A growing body of evidence suggests that different species of nematodes dominate many of these extreme habitats. Therefore, our goal is to study nematodes life in extreme habitats as a model for the adaptations animals have developed to flourish in extreme habitats on the planet Erath. Currently, we are focusing on two unique and extreme ecological niches, the Dead Sea in Israel and Mono Lake in California, USA.
