The Wolfgang laboratory studies the role and regulation of cellular and organismal metabolism. The research in the Wolfgang laboratory utilizes biochemistry and molecular genetics to understand the molecular mechanisms used to sense and respond to nutritional/metabolic cues. We are particularly interested in deciphering the roles of unexplored metabolic enzymes/pathways and determining novel roles of cannonical metabolic pathways in under-explored cells and tissues.
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.
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We are currently focused on using streaming data systems in connection with high performance and cloud based computer systems to enable feedback and control for addressing physiologically important research questions. Our most recent work is in developing the Metabolic Compass App (see http://www.metaboliccompass.com). This is an iPhone based ResearchKit/HealthKit App that supports the electronic consent and data collection and analysis of health related temporal information. Our research goal is to enable participants to see their health data in the context of circadian timing and to test ideas behind intermittent fasting and time-restricted feeding in a large population. This is very similar, though at a different scale to our work with molecular dynamics systems: the analysis and understanding of temporally defined information.
We also continue to work towards understanding and control of large-scale conformational molecular changes that drive function. This includes ongoing projects that are focused on database controls for molecular dynamics systems. We have developed new algorithms (Dynamic Importance Sampling) and our information-based order parameter. The current projects includes collaborations with Mario Amzel, Phil Cole and Peter Devreotes on PIP2/PIP3 signaling through PI3K, AKT, and PTEN; work with Svetlana Lutsenko’s group on copper transporting membrane pumps, and our continued development of MDDB (Molecular Dynamics Database) and Molecular Marshal: database feedback and control platforms for use on local and distributed computers. We are in the process of generalizing these platforms to other scientific problems and are active contributors to IDIES (Institute for Data Intensive Engineering and Sciences) and MARCC (Maryland Advanced Research Computer Center) at JHU.
