Research Focus Areas
PI3K Isoform Specificity and Oncogenic Mutations
Phosphoinositide 3-kinases (PI3Ks) are critical regulators of cellular signaling, controlling key processes such as cell survival, growth, and metabolism. There are several isoforms of PI3K, each with unique tissue distribution, functional roles, and regulatory mechanisms. Our research focuses on understanding the specific functions of distinct PI3K isoforms and their roles in cancer initiation and progression.
A major focus of our work is to investigate activating oncogenic mutations within the PI3K pathway, which frequently drive tumorigenesis across a wide range of cancers. By analyzing the molecular mechanisms by which these mutations promote uncontrolled cell proliferation and survival, we aim to identify isoform-specific therapeutic targets that could lead to more effective and less toxic cancer treatments. This research also explores the interactions between PI3K and other signaling pathways, providing insights into the complexity of tumor cell behavior and therapy resistance.
PI3K Drug Resistance Mechanisms
Although PI3K inhibitors have shown promise as cancer therapies, many tumors eventually develop resistance to these drugs, limiting their long-term effectiveness. Our lab investigates the molecular mechanisms underlying drug resistance to PI3K-targeted therapies, aiming to identify new strategies to overcome this challenge.
We use a combination of cell line models and xenografts to study the regulatory mechanisms underlying resistance. This includes identifying secondary mutations in PI3K and its downstream effectors, as well as alterations in other signaling activations that may bypass PI3K inhibition. Additionally, we explore combination therapies that target resistance mechanisms, including potential synergistic drug combinations that may restore the efficacy of PI3K inhibitors and enhance patient response.
PI3K-Regulated Cancer Cell Metabolism
The tumor suppressor PTEN (phosphatase and tensin homolog) plays a critical role in regulating the PI3K pathway. Loss of PTEN function, which is common across many cancers, dysregulates lipid signaling, leading to unchecked cell growth and survival. Our research focuses on understanding lipidomic changes in PTEN-deficient cancers and how these alterations contribute to tumorigenesis and progression.
Using advanced lipidomic profiling techniques, we investigate the specific changes in lipid metabolism, including alterations in phosphoinositides, sphingolipids, and other membrane-associated lipids. We also explore how these lipid changes affect key cellular processes and whether they may serve as potential biomarkers for early diagnosis or prognosis. This work may reveal novel lipid-based and lipid-regulated targets for therapeutic intervention in PTEN-null cancers, offering new avenues for personalized treatment approaches.