Candidate. My sole career objective is to secure a faculty position at a majorresearch university or research institute. My undergraduate (B.A. in molecular and cell biology) and graduate(Ph.D. in molecular toxicology) research experience at the UC Berkeley under Prof John Casida focused onelucidating off-targets of organophosphorus (OP) nerve agents that are used as insecticides and chemicalwarfare agents. This yielded in 12 publications that 1) established a role for the unannotated serine hydrolaseKIAA1363 as the primary OP detoxification enzyme in the brain and 2) demonstrated that dual blockade ofmonoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) resulted in dramatic elevations inbrain endocannabinoid levels and robust cannabinoid behaviors, including antinociception. My postdoctoralstudies have focused on annotating dysregulated metabolic pathways in cancer. For the duration of mypostdoctoral tenure, I plan to hone my research and mentoring skills so that I am prepared for my independentcareer. Research Career Development Plan. The research group of Prof. Ben Cravatt is perfectly suited forthe continuation of my training, as his group has pioneered the development and application of diversetechniques at the interface of chemistry and biology that I will be able to learn and apply towards my research.This lab is also highly collaborative, allowing me to expand my scientific breadth. Prof. Cravatt and I will focuson my continued independent development of experimental plans, and my ability to present and defend theseplans and broader hypotheses, while I also participate in several training courses to further cultivate the skillsessential to becoming a successful investigator and attend several conferences to gain experience inpresenting my work and establish relationships with other scientists. Research. Lipid signaling moleculescontrol a wide range of cellular and physiological processes. Imbalances in major lipid signaling pathwayscontribute to the pathogenesis of chronic inflammation, cancer, and metabolic and degenerative diseases.Many lipid transmitters, their modifying enzymes, and their downstream targets are interconnected giving riseto highly integrated metabolic and signaling networks. This network connectivity allows for potential coordinateperturbation and control of lipid signaling pathways by targeting key nodal control points. My current researchhas uncovered that monoacylglycerol lipase (MAGL) is one such nodal enzyme that controls a diverse array of(patho)physiologically relevant lipid signaling pathways. In cancer cells, MAGL not only mediates theendocannabinoid 2-arachidonoylglycerol but also regulates a diverse fatty acid network that generates an arrayof protumorigenic lipid signaling molecules. In brain, MAGL controls endocannabinoids and prostaglandins-both important in neuroinflammation. This proposal will focus on dissecting the function and therapeuticpotential of MAGL in controlling lipid signaling networks in cancer and neuroinflammatory disorders. Thesegoals fall under the missions of the National Institute of General Medical Sciences (NIGMS).
Our preliminary results show that monoacylglycerol lipase (MAGL) is a nodal enzyme in cancer and in the brain where it controls multiple pathologically relevant signaling pathways. Our preliminary results show that blockade of MAGL causes diverse perturbation in lipid signaling molecules which lead to impairments in cancer malignancy as well as neuroinflammation. The results yielded from this study should not only clarify the role that MAGL plays in controlling multiple lipid signaling pathways in different disease contexts, but also shine light on this enzyme as a promising therapeutic target for cancer and neuroinflammatory disorders.
Showing the most recent 10 out of 20 publications
