Ashiwel S. Undieh, PhD
Philadelphia, PA 19107
(215) 503-9052 fax
Most Recent Peer-reviewed Publications
- Intracellular endothelin type B receptor-driven Ca2+ signal elicits nitric oxide production in endothelial cells
- Agonist-selective effects of opioid receptor ligands on cytosolic calcium concentration in rat striatal neurons
- Differential subcellular distribution of rat brain dopamine receptors and subtype-specific redistribution induced by cocaine
- Pharmacology of signaling induced by dopamine D1-like receptor activation
- Brain-derived neurotrophic factor signaling modulates cocaine induction of reward-associated ultrasonic vocalization in rats
Research and Clinical Interests
Signal transduction; Epigenomics; neuroproteomics Addictive disorder; Depressive disorder; animal models
Research in the Laboratory of Integrative Neuropharmacology is aimed at clarifying how multiple epigenomic and signaling mechanisms integrate to coordinate function among brain dopamine systems. Dopamine is important in the regulation of mood, cognition, motivation, motor activity, and neuroendocrine function. Abnormal dopamine function is implicated in diverse neuropsychiatric diseases including addiction, schizophrenia, depression, Parkinson disease, Huntington disease, and Tourette disorder. To accelerate the development of innovative treatments that could cure or prevent these disorders, it is important to understand the molecular mechanisms by which brain function is regulated or disrupted by dopamine or by drugs like cocaine and amphetamine that act by modulating synaptic dopamine levels. In attempting to address this enormous task, we employ integrative experimental approaches that probe genomic/epigenomic and neurochemical mechanisms in correlation with physiological and behavioral models. This approach enables us to continually validate the functional significance of the molecular observations, thus increasing the prospective translational efficiency of our findings. Focusing on the overarching question of how dopamine may recruit epigenomic and multiple signaling mechanisms to mediate addictive disorders or to mitigate depressive illness, our ongoing projects include: signaling mechanisms in dopamine receptor synergism; neurolipid signaling in depression and antidepressant mechanisms; cellular structural proteins and their regulation by dopamine; and epigenomics of psychostimulant addiction and neurotoxicity.
The techniques used in our research include animal models (of addiction, depression, Parkinson disease, etc); Behavioral analysis, Stereotaxic microinjection; Laser capture microdissection; Cell/tissue culture; Cell proliferation and cell death; Neurogenesis and neuronal differentiation; Receptor binding; Autoradiography; Cell signaling; Protein phosphorylation; DNA methylation analysis; PCR/RT-PCR/qPCR; RNAi, Gene and protein transfection, Gene expression analysis; Neurochemical and signaling assays; Immunochemical techniques; Electrophoresis; Microarrays; Chromatography; Flow cytometry; Fluorescence and confocal microscopy; Mass spectrometry; Bioinformatics; and Pharmacometrics.
We expect findings from this research to increase our understanding of multiple fundamental brain functions such as mood and motivation, and to facilitate the development of novel treatments for various dopamine-associated brain disorders.