Melanie Simpson

Bio

Research Program Overview

The Simpson lab research program is focused on molecular mechanisms of prostate cancer progression. Our studies use a variety of approaches, including biochemical characterization of enzymatic activity and inhibitor function in purified protein, gene manipulation in cultured prostate tumor cells and quantification of effects at the molecular and cellular level, and a variety of techniques to examine tumor growth and metastasis in mouse models. We have two main projects. In one, our goal is to determine the role of steroid metabolizing enzymes in the control of prostate cancer hormone dependence and the potentiation of tumor response to drug treatments. In the other project, we are investigating how components of the cellular environment regulate growth and metastatic spread. Our lab has developed a unique set of molecular and cellular tools for these studies that allow us to dissect and quantify the respective roles of extracellular matrix synthesis and turnover in cellular processes underlying invasive progression. We further examine molecular receptors and signaling pathways that mediate cell-cell communication and alter tissue architecture during progression. An interesting new development in these studies is the implication of intracellular and extracellular vesicles such as exosomes, which are made and secreted by the tumor cells to facilitate cell communication and transformation. We are characterizing these vesicles to better understand their role in cell interactions that promote cancer.

Publications

• Impacts of Hyaluronan on Extracellular Vesicle Production and Signaling , Cells (2025)
• Phosphorylation of UDP-glucose dehydrogenase increases glycosaminoglycan biosynthesis and promotes tumor cell motility, spheroid growth, and therapeutic resistance , Matrix Biology (2025)
• Recent insights into the implications of UGDH mutations for human developmental disease , Biochemical Society Transactions (2025)
• Mechanisms of coordinating hyaluronan and glycosaminoglycan production by nucleotide sugars , American Journal of Physiology-Cell Physiology (2022)
• Altered glucuronidation deregulates androgen dependent response profiles and signifies castration resistance in prostate cancer , Oncotarget (2021)
• Integration of Sugar Metabolism and Proteoglycan Synthesis by UDP-glucose Dehydrogenase , Journal of Histochemistry & Cytochemistry (2020)
• Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy , Nature Communications (2020)
• Catalytically inactive Dnmt3b rescues mouse embryonic development by accessory and repressive functions , Nature Communications (2019)
• Hyaluronan Pericellular Matrix: Particle Exclusion Assay , Methods in molecular biology (2019)
• Molecular Pharmacodynamics-Guided Scheduling of Biologically Effective Doses: A Drug Development Paradigm Applied to MET Tyrosine Kinase Inhibitors , Molecular Cancer Therapeutics (2018)