Section: Research

Postdoctoral Position Available

Jianhua Zhou, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Medicine

Other Affiliation(s):
   Interdisciplinary Graduate Program
   Program in Neuroscience

Molecular Pathogenesis of Neurodegenerative Diseases

The goal of this laboratory is to investigate molecular mechanisms of neurodegenerative diseases, including spinal muscular atrophy (SMA), Parkinson's disease (PD) and Alzheimer's disease (AD).

1. Identification of compounds/drugs that reverse aberrent splicing of disease causing genes. We have developed cell-based assays and identified small molecules that regulate alternative splicing of exon 7 in the SMN gene and of exon 10 in the tau gene using high throughput screening (HTS). The goal of this project is to continue to identify and characterize potential therapeutic targets for SMA and tauopathies by correcting abnormal splicing. We also plan to expand our projects to establish cell based assays and to carry out HTS for BACE1 and Bcl-X genes
   
2. Functional studies of SMN proteins. Using the yeast two-hybrid screening, we have identified Rpp20 that interacts with the SMN protein. Immuno-fluorescence analysis co-localizes SMN with TIA-1/R and G3BP, two characteristic assemblers of stress granules, cellular structures that are formed under stressed condtions to protect cells. Since local protein synthesis is crucial for neurons, we hypothesize that motor neurons are possibly more vulnerable to stress insults, resulting in their death in SMA patients due to a lower level of SMN protein that fails to protect RNA species in long-stretched axons. Our project is to study functions of SMN in stress granules and in response to stressors in cultured cells and in primary neurons of SMN mice models.
   
3. Investigation of molecular basis of Parkinson's disease in cells and in Drosophila models . One of the genes identified to cause Parkinson’s disease is parkin, an ubiquitin E3 ligase. Using the yeast two-hybrid screen, we isolated a RING finger protein in a Drosophila library that interacts with the Drosophila parkin. The human orthologue of the protein was identified as Nrdp1, an ubiquitin E3 ligase that promotes ubiquitination and degradation of EGFR/ErbB kinase receptors. Co-transfection of Nrdp1 and parkin into cells demonstrates that Nrdp1 destabilizes the parkin protein, indicating that Nrdp1 functions as a parkin modulator. Based on these observations, we hypothesize that over-expression of Nrdp1 or suppression of Nrdp1 would affect levels of parkin protein, thereby Parkinson's disease (PD)-related phenotypes induced by parkin and parkin-related proteins. Our goals are to a)to examine the effects of Nrdp1/parkin on ubiquitination and degradation of substrates and on cell growth, apoptosis and differentiation; b) to examine expression of Nrdp1/parkin in PD and control brains; and c) to generate Nrdp1 models in Drosophila.

Office: LRB-325
Phone: 508-856-1323
E-mail: Jianhua.Zhou@umassmed.edu
Keywords: RNA Splicing, Cell Biology, Parkinson's Disease, Neurodegeneration, Motor Neuron Disease

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Zhou for additional details.