Houston Methodist. Leading Medicine.
Houston Methodist. Leading Medicine

Research

Research

 

The mission of the Chao Center is to identify new strategies and develop new methods for the diagnosis and treatment of Alzheimer’s and other neurodegenerative diseases, using high throughput biotechnologies, systems biologic modeling, drug screening and repositioning, and quantitative multi-scale imaging. The Center works closely with the Alzheimer’s and Dementia Clinical Center and the Neurodegenerative Disease Clinic of the Houston Methodist Neurological Institute at Houston Methodist Hospital in translating the research results to patient bedside. It also seeks extramural grants from the NIH and other funding agencies, as well as other philanthropy support in combating neurodegeneration and associated neurological disorders.

 

Research Projects:

 

Drug Discovery and Repositioning for Alzheimer’s disease

 

Drug-target discovery and drug repositioning in Alzheimer’s disease using bioinformatics and systems biology methods

Better understanding the pathophysiology of Alzheimer's disease (AD) at the early stages will help to make breakthroughs for developing effective therapeutics. In this project, we will apply bioinformatics and systems biology methods to examine the mechanism and signaling pathway underlying synapse abnormality in both cellular and mouse models of AD in order to discover potential drug-targets and repurpose known drugs for the new targets.
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High content screening for neural stem cell differentiation

We are developing novel high-content screening assays and associated bioinformatics analysis and modeling software that can be used for neural stem cell research and drug discovery. Using the assays, we carry out screenings for reagents that can regulate the self-renewal and differentiation of neural stem cells.
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High content drug screening and quantitation of neurite outgrowth

Large scale compound screening has been impeded by the lack of automatic tools to assess the changes to neurites. Through an NIH funded project, we recently developed a software package, NeuriteIQ, for the automated labeling and quantification of neuronal processes and dendritic spine morphology analysis. Armed with this powerful tool, we are carrying out a screen of all known clinical compounds. We currently have collected a library of >3,000 compounds.
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High content screening and analysis of dendrite spine morphology

Acquisition and quantitative analysis of high resolution images of dendritic spines are challenging tasks but are necessary for the study of animal models of neurological and psychiatric diseases. Currently available methods for automated dendritic spine detection are, for the most part, customized for 2D image slices, not volumetric 3D images. By using the NeuronIQ (Neuron Image Quantitator) project, we intend to develop a fully automated method for the detection and segmentation of dendritic spines from 3D confocal microscopy images; neuron types include normal neurons, neurodegenerative neurons, and medium-sized spiny neurons (MSNs). Automated detection is critical for the development of new 3D neuronal assays which can be used for the screening of drugs and studies of their therapeutic effects.
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High content analysis of neuronal synaptic activities

We are developing novel image-based assays to measure neuronal synapse activity. Traditional assays using electrophysiology are demanding and have very low throughput. We are developing novel image processing programs for automated image based synapse assays such as the FM dye assay. Through the use of automation, the assay can be carried out in a high-throughput manner so that studies like genome-wide screening or drug screening can be carried out.
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Stem Cell Medicine for Alzheimer’s Disease

 

Genetically engineered neural stem cells for neuroregeneration

We are developing genetically engineered neural stem cells for the treatment of neurodegenerative diseases. Genetic modification is not only used to enhance the capability of neural stem cells, but also to enable us to control the activity of the cells after transplantation (Figure 1), thus make neural stem cells safer and more efficient transplantation medicine.
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High content screening for neural stem cell differentiation

We are developing novel high-content screening assays and associated bioinformatics analysis and modeling software that can be used for neural stem cell research and drug discovery. Using the assays, we carry out screenings for reagents that can regulate the self-renewal and differentiation of neural stem cells.
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Optogenetics for Alzheimer’s studies

 

Optogenetic manipulation of cholinergic/astrocyte coupling for defective neurovascular coupling and network dysfunction

Based on the observations that neurovascular coupling is disrupted in Alzheimer’s patients, cholinergic neurons massively die, and astrocytes greatly proliferate. Normally, cholinergic signaling activates astrocytes, increases blood flow, and disrupts network synchrony. Network synchrony can lead to seizures and neurodegeneration. This project investigates the activation of cholinergic neurons reverse these phenotypes and how early must intervention begin, using the optogenetic technology and bioinformatics methods.
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Diagnostic Neuroimaging

 

Photoacoustic imaging on nenatal hypoxia-ischemia encephalopathy

Brain damage resulting from hypoxic-ischemia in newborns remains a major cause of long-term disability among survivors. Hypoxic-ischemia triggers sequential cascades of neurotoxic events that are initiated withinhours, last for days and weeks after injury, and results in prominent neuronal loss. An imaging method which can detect the damaged areas early after hypoxic-ischemia would be very valuable to identify the high-risk newborns for neuroprotective treatment.
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Multimodal neuroimaging and gene expression studies of ASD

Autism spectrum disorders (ASD) are characterized by impairments in social interactions and cognitive abilities that are typically identified before the age of 3. Previous studies have suggested that the deficit of physical connectivity among different regions of the brain, rather than a localized region, might be the culprit of ASD. A newly developed neuroimaging technique, Diffusion Tensor Imaging (DTI), can be used to track white matter fiber pathways and reconstruct brain connectivity circuitry.
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