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Shuying Sun

Shuying Sun

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

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Thomas-Woolf

Thomas B. Woolf

Research Interests

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.

Publications

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G-William-Wong

G. William Wong

Research Interests

Metabolic Physiology of Secreted Hormones
Our lab seeks to understand mechanisms employed by cells and tissues to maintain metabolic homeostasis. We are broadly interested in how secreted hormones control various aspects of sugar and fat metabolism. Our current efforts centered on addressing how fat and muscle-derived secretory proteins (adipokines and myokines), identified in our lab, regulate tissue crosstalk and signaling pathways to control energy metabolism. We use genetic approaches (gain and loss-of-function mouse models), and cell model systems, to address the function of CTRP family of hormones in physiological and pathophysiological context.

Publications

Publications

Rajini-Rao

Rajini Rao

Research Interests

Discovery and molecular mechanisms of novel ion transporters.
The Rao laboratory studies the role of novel ion transporters in human health and disease. One project focuses on the calcium signaling in breast cancer. We showed that an isoform of the secretory pathway Ca2+-ATPase, SPCA2, interacts with ion channels to drive tumor proliferation. We are currently investigating how downregulation of SPCA2 promotes epithelial to mesenchymal transition. A second project relates to the endosomal Na+/H+ exchangers NHE6 and NHE9 that are linked to autism, Christianson syndrome, ADHD and a growing list of neurodevelopmental and neurodegenerative disorders. We use a powerful PheWAS approach combined with model structure-driven evolutionary conservation analysis and functional screening of human variants to identify, evaluate and predict causality of autism-associated mutations. Loss of eNHE function results in hyperacidic endosomes, which increases amyloidogenic processing, and turnover of cell surface receptors and neurotransmitter transporters to impact neurotransmitter uptake and synaptic development.  On the other hand, overexpression of NHE9 in glioblastoma confers chemoradiation resistance due to “inside out” control of oncogenic signaling. Our lab also discovered NHA2, an unusual Na+/H+ exchanger that is implicated in essential hypertension and plays a role in salt handling in the kidney. We make extensive use of 3D/organoid cultures, confocal microscopy, live cell calcium and pH imaging, and phenotype complementation in yeast to investigate mammalian transport proteins.

Publications

Bibliography

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