Labs

Dr. Hevener’s laboratory has made important advances in our understanding of estrogen action and estrogen receptor (ER) biology in metabolic tissues. Her research is focused on understanding the tissue-specific target genes of action, as well as the cellular processes controlled by ERs. Much of her research has shown that ERalpha plays a critical role in mitochondrial remodeling, oxidative metabolism, and quality control. Dr. Hevener’s research team interrogates the impact of ERalpha loss and gain of gene expression in a variety of cells and tissue types, including skeletal and cardiac muscle, adipose tissue, immune cells, and liver. Her laboratory has determined how impairment of estrogen action contributes to cardiometabolic diseases and certain forms of cancer, and has identified the beneficial effects of heightened ERalpha action in combating metabolic dysfunction and diet-induced insulin resistance. Similar to this work, her team has advanced the fundamental understanding of the molecular mechanisms that underlie the metabolic health benefits of daily physical activity.

To learn more, visit: Hevener Lab

The Shirihai lab is studying organellar biology with a focus on mitochondria, lysosomes and autophagosomes in the context of obesity and diabetes. In the past fifteen years the lab has focused on the study of the roles of mitochondrial dynamics in quality control, fuel preferences and energy expenditure. The lab is known for the development of key imaging approaches that allow for the quantification of mitochondrial dynamics, motility, mitophagy and turnover. Using these methodologies to study mitochondrial dynamics we described the life cycle of the mitochondria and the role of continuous fusion and fission dynamics in the maintenance of bioenergetic capacity and efficiency in the pancreatic beta cell. The lab played a pivotal role in the development of cutting edge technology for high throughput respirometry in collaboration with Seahorse Bioscience which lead to the development of higher throughput approaches for islet respirometry. The lab has provided training to over 80 different groups in the application of bioenergetics studies such as Respirometry and imaging. The lab has sustained active and fruitful collaborations with biotech and pharma over the years, in projects involving drug discovery as well as research and medical device development. The lab has trained over 14 postdoctoral fellows, of which six have been recruited as faculty in academic institutions, and two are founders of new biotech companies. Since 2016 I serve as the director of UCLA Metabolism Theme which facilitate team work and enable research by providing tools guidance to the members of the UCLA metabolism research community.

To learn more, visit: Shirihai Lab

The Tudzarova lab explores the role of transient glycolysis in the proliferative cell cycle of pancreatic beta cells and induced pluripotent stem cells (iPSC) with emphasis on the translation of the mitochondrial dynamics and cellular bioenergetics to DNA replication initiation. Dr. Tudzarova-Trajkovska recently identified the origin of the activation checkpoint (OAC), which monitors the activation of replicative origins and is sensitive to reduced CDC7 levels. OAC critically relies on multiple regulatory axes coordinated through the Forkhead transcription factor FoxO3a. SILAC-based high-resolution MS proteomics showed that the arrested phenotype of normal fibroblasts involves active rather than passive cellular and metabolic adaptation, and that the Cdc7-depleted proteome maintains cellular arrest by initiating a dynamic quiescence-like and catabolic response that promotes cellular survival. OAC's reliance on several tumor suppressor proteins commonly inactivated in human tumors provides a strong mechanistic basis for the differential killing of tumor versus normal cells after CDC7 inhibition/downregulation. The therapeutic targeting of the DNA replication initiation machinery thus constitutes one of the focuses of her research.

To learn more, visit: Tudzarova Lab