Awards and Honors
Degrees:
M.D., University of Kansas School of Medicine (Kansas) (1988)
B.S., University of Kansas (Kansas) (1983)
Research Interests
Molecular Mechanisms of Salt Balance, Hypertension, and Kidney Disease
Research Interests
The Sun Lab explores the fascinating frontiers of RNA metabolism dysfunction and RNA-targeting therapeutics in neurodegenerative diseases. The nervous system has extremely complex RNA processing regulation and dysfunction of RNA metabolism has emerged to play crucial roles in multiple neurological diseases. Mutations and pathologies of several RNA-binding proteins are found to be associated with neurodegeneration in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). An alternative RNA-mediated toxicity arises from microsatellite repeat instability in the human genome. The expanded repeat-containing RNAs could potentially induce neuron toxicity by disrupting protein and RNA homeostasis through various mechanisms. We are interested in deciphering the RNA processing pathways altered by the ALS-causative mutants to uncover the mechanisms of toxicity and molecular basis of cell type-selective vulnerability. We also apply various high-throughput screening platforms to identify small molecule and genetic inhibitors of neuronal toxic factors. We aim to bridge basic mechanistic studies and translational disease modeling to decipher molecular mechanism of pathogenesis, identify novel biomarkers and promising drug targets for therapy development by combining innovative techniques and interdisciplinary approaches.
Publications
View her publications by clicking here.
Research Interests
Biochemistry and chemistry of lipids and lipid metabolizing enzymes involved in signaling cascades
A major effort in our laboratory is focused on understanding the biochemistry and chemistry underlying the molecular aspects involved in regulating lipid metabolizing signaling enzymes and the physiological roles of this regulation. Control of lipid metabolizing enzymes involves the modulation of two key parameters; their sub-cellular distribution and their intrinsic enzymatic activity. Our studies have concentrated on three families of lipid-metabolizing signaling enzymes: diacylglycerol kinases, phospholipases D, and phospholipases C.
Specific Areas of Interest
Interfacial Enzymology of Lipid Metabolizing Signaling Enzymes: We are particularly interested in identifying the critical modulating proteins, lipids, and post-translational modifications that alter the localization and/or activity of lipid metabolizing enzymes. In these studies we consider the fact that these enzymes act as interfacial enzymes and their regulation includes a number of interfacial-dependent parameters. Our recent studies have identified some of the diacylglycerol metabolizing enzyme DGK-θ (diacylglycerol kinase-theta) interfacial parameters that are altered upon neuronal depolarization. Further, our studies demonstrated that activation of DGK-θ requires a protein that contains a polybasic region. We have recently obtained evidence that identifies at least one, if not only, activator binding domain on DGK-θ.
Enzyme Structure/Function Studies: We are also interested in the structural components of these enzymes that are critical for their distribution/re-distribution to specific sub-cellular compartments. Additionally, and to compliment the enzymology studies, we are interested in elucidating the catalytic mechanism(s) of these enzymes. These studies will be conducted partly in collaboration with Dr. Mario Amzel. Our long-term goal is to understand the biochemistry and chemistry of these enzymes and determine how changes in their sub-cellular localization and/or enzymatic activity affect their signaling functions.
Physiological Functions of DGKs in Neurons: There is growing evidence that DGKs play physiological roles in mammalian neurons. This evidence includes cellular localization of specific isoforms, and the observations that likely modulate (a) susceptibility to epileptic seizures (DGK-ε), (b) neuronal spine density (DGK-ζ and DGK-β), and (c) pre-synaptic glutamate release during DHPG (3,5-dihydroxyphenylglycine)-induced long-term potentiation (DGK-ι). We are currently examining the role of DGK-θ in glutamatergic neurons. These studies have initially focused on identifying the physiologic regulator of DGK-θ, and test the hypothesis that this enzyme modulates induced glutamate release in these mammalian neurons. We discovered that DGK-θ modulates glutamate release from cortical and hippocampal neurons in part by modulating synaptic vesicle cycling. These studies are conducted in collaboration with Dr. Rick Huganier’s laboratory.