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.
Education
B.S. Biochemistry University of Minnesota 1992
Ph.D. Biochemistry, Molecular Biology, and Biophysics University of Minnesota 1997
Publications
- Mechanisms of coordinating hyaluronan and glycosaminoglycan production by nucleotide sugars , AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2022)
- 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)
- Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling , MATRIX BIOLOGY (2018)
- Inhibiting Hexamer Disassembly of Human UDP-Glucose Dehydrogenase by Photoactivated Amino Acid Cross-Linking , Biochemistry (2016)
- Loss of exogenous androgen dependence by prostate tumor cells is associated with elevated glucuronidation potential , Hormones and Cancer (2016)
- Hyaluronidase Hyal1 Increases Tumor Cell Proliferation and Motility through Accelerated Vesicle Trafficking , Journal of Biological Chemistry (2015)
- Methylation-independent repression of Dnmt3b contributes to oncogenic activity of Dnmt3a in mouse MYC-induced T-cell lymphomagenesis , Oncogene (2015)
- Characterization of IRDye 800CW chlorotoxin as a targeting agent for brain tumors , Analytical Biochemistry (2013)