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Xu
Shunbin
MD,PhD
Assistant Professor
Facilitator, Micro CT/Histology
Neurological Sciences, Ophthalmology
Graduate College
1735 W. Harrison St.
Cohn Research Building
Suite 318
Chicago,IL 60612
1735 W. Harrison St.
Cohn Research Building
Suite 363
Chicago,IL 60612
(312) 563-3554
(312) 563-3571
shunbin_xu@rush.edu
PhD, Predoctoral Training Program in Human Genetics
The John Hopkins University School of Medicine, 2000

MD, Peking Union Medical College, 1991

Animal Diseases, Biological Sciences, Eye Diseases, Genetic Structures, Nervous System Diseases
Animal surgery/Modeling, Bioinformatics, Circadian Phase Assessments, Flow Cytometry, Gene Transfection, Imaging Techonology, Immunohisto-/immunocytochemistry, In Situ Hybridization, PCR, Real-time PCR, si RNA, Spectrophotometry, Tissue Culture (Primary, Cell Line), Transgenic Animal Technology/Microinjection, Western Northern Southern Blotting

Dr. Shunbin Xu obtained his MD from Peking Union Medical College, and his PhD in Human Genetics and Molecular Biology in the Johns Hopkins University.

The ultimate goals for his research are deeper understanding of molecular mechanisms of retinal diseases, and developing new therapies for the treatment of various retinal degenerative diseases. These goals are approached by the following major research programs:

1. microRNAs in retina, retinal development and diseases:

Background on miRNAs in retina and retinal diseases: microRNAs are newly discovered, small, non-coding, regulatory RNAs. They are about 20-24 nucleotides in size, and have been identified in all metazoans. miRNAs do not encode proteins, but regulate the expression of protein-coding genes by annealing to their target sites in the 3'untranslated region (3'UTR) of protein-coding genes by sequence complementarity to induce either breakdown of the mRNAs, or inhibition of translation of the targeted protein-coding genes. It is estimated that more than 1000 miRNAs may exist in the human genome. Each miRNA regulates mRNA transcripts of up to hundreds of downstream target genes. One miRNA can be targeted by multiple miRNAs. Approximately, 1/3-1/2 of all protein-coding genes are estimated to be subjected to miRNA regulation. Therefore, miRNAs have become a newly recognized, major level of regulation of gene expression at post-transcriptional levels, playing important roles in the fine-tuning of gene expression. miRNAs have been shown to be involved in all aspects of biological functions and pathways, including cellular proliferation, differentiation and cell fate determination, apoptosis, etc. Mutations in miRNAs and/or their target sites of downstream target genes may result in diseases or increase the susceptibility to diseases. Understanding the roles of miRNAs in retina, retinal development and retinal diseases will be of great importance in basic understanding of retinal biology and the molecular mechanisms of retinal diseases, and therefore, in identification of novel therapeutic targets and development of novel therapeutic reagents for the treatment of retinal diseases.


Major projects:

1) The roles of miRNAs in diabetic retinopathy and their potential as novel therapeutic targets for the treatment of diabetic retinopathy;

2) The roles of miRNAs in age-related macular degeneration and their potential as novel therapeutic targets;


3) miRNA in glaucoma and their potential as novel therapeutic targets;


4) miRNAs in inherited retinal degenerations;


5) miRNAs in retinoblastoma and treatment;


6) Identification and functional characterization of miRNAs involved in retinal development.


2. stem cells and application of stem cells in transplantation treatment of retinal degeneration.

Background on stem cells and applications to the treatment of retinal degenerative diseases: More Americans than ever are facing the threat of blindness. About one million Americans older than 40 years old are blind. The number of blind persons in the US is projected to increase by 70% to 1.6 million by 2020. The leading causes of vision impairment and blindness in the US are diabetic retinopathy (DR), age-related macular degeneration (AMD), cataract and glaucoma. More than 8 million Americans have AMD, with more than 1.6 million Americans over age 60 have advance AMD. DR affects more than 5.3 million Americans age 18 and older. About 2.2 million Americans are diagnosed with glaucoma. Additionally, retinitis pigmentosa (RP), an inherited retinal degenerative disease, affects about 1/3500 individuals. In spite of different etiology, most of these blind-causing diseases, including AMD, DR, glaucoma and RP, result in different forms of retinal degeneration. There is still no efficient treatment for most of retinal degenerative diseases. Although progress has been made on gene therapy for the treatment of certain forms of inherited retinal diseases, e.g. RP and Lebers congenital amarosis, gene therapy may only apply to the treatment of the single-gene diseases with known mutations. However, many retinal diseases, e.g. AMD, are multifactor diseases, correction of mutations in a single gene may not result in efficient treatment of the disease. Moreover, gene therapy is unlikely to be effective once the affected cells have degenerated. Replacement of the lost photoreceptors and other retinal neurons by cell transplantation therapy may restore the function of damaged neural circuit in degenerated retinas and holds unique promise to the treatment of retinal degenerative diseases.

Major Projects:

1) subretinal transplantation of retinal progenitor cells in retinal degenerative mouse eye to test the feasibility of retinal transplantation therapy:

Recently, we performed subretinal transplantation using retinal progenitor cells (RPCs) derived from newborn mouse retina in both wild type and retinal degenerative mouse eyes, and showed that RPCs can integrate into the photoreceptor layer of the host retina and differentiate into rod photoreceptors. Additionally, we showed that transplanted RPCs also may integrate into the inner retinal layers and differentiate into other types of retinal neurons, e.g. bipolar cells, in rd1 mouse eyes (6). These results substantiated the feasibility of cell transplantation therapy for the treatment of retinal degenerative diseases.

2) Guided differentiation of iPS cells into retinal cell types and transplantation of iPS cell-derived retinal cells for the treatment of retinal degenerative diseases:

Recently, in vitro reprogramming of terminally differentiated somatic cells into pluripotent ESC-like cells [termed "induced pluripotent stem cells", or iPS cells] has been achieved by introducing four transcription factors [Oct4,Sox2,c-myc,Klf4, or OCT4,SOX2,NANOG,LIN28] into the somatic cells. Like ESCs, iPS cells can be robust expanded in vitro to provide unlimited cell source; under appropriate environment, iPS cells can be differentiated into mature cells of all three germ layers. Generation of iPS cells from somatic cells of an individual patient not only circumvents ethical problems of using ESCs, but also enables large-scale production of patient-specific cells of the cell types affected by the patient's disease for autologous transplantation therapy. When the disease is caused by known mutations in certain genes, the genetic defects in the iPS cells derived from patient's somatic cells can be corrected by gene-specific targeting to produce patient-specific cells with corrected genotype. Application of iPS cells to transplantation treatment has recently been explored in hematopoietic system for the treatment of sickle cell anemia in mouse and in neural system for the treatment of neurodegenerative diseases, e.g. Parkinson's disease and amyotrophic lateral sclerosis (ALS) in mouse and human, respectively. These reports provided proof of principle, supporting that iPS cells hold great promise to the future autologous transplantation therapy.

To overcome the challenges facing transplantation therapy for the treatment of retinal degenerative diseases, including limited cell source and immune rejections, etc, we are studying derivation of retinal pigmented epithelial cells (RPE), photoreceptor cells and other retinal cells from iPS cells, and test the potential of iPS cell-derived retinal cells in transplantation treatment of retinal degeneration. We are working in two steps towards patient-specific therapy:

(1) derivation of retinal pigmented epithelial cells (RPE), photoreceptor cells and other retinal cells from existing mouse and human iPS cell lines, and test the potential of iPS cell-derived retinal cells in transplantation treatment of retinal degeneration.

(2) derivation of patient-specific iPS cells from epithelial cells of patients' plucked hair, and produce RPE and other retinal cell types from patients' own iPS cells for transplantation therapy for the treatment of age-related macular degeneration and other types of retinal degenerative diseases.

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