The research interest of my laboratory is to study the roles of microRNAs (miRNAs) in the eye and ocular diseases. miRNAs are small, non-coding, regulatory RNAs and constitute a newly recognized level of gene expression regulation. Our long term goal is to uncover the roles miRNAs in normal development and function of the eye, as well as in ocular diseases so as to identify novel miRNA-based therapeutic targets for the treatment of various ocular diseases.
One of the major projects is to study the roles of miR-183/96/182 cluster in retina and other sensory organs. Previously, we reported one of the first miRNA transcriptomes of mouse retina, and identified a conserved miRNA cluster, the miR-183/96/182 cluster, which is highly expressed in the retina and all major sensory organs (Xu et al. 2007. JBC). Recently we created a knockout mouse model and showed that inactivation of miR-183/96/182 in mice resulted in congenital retinal dysfunction, progressive retinal degeneration, and abnormalities in multiple sensory organs (Lumayag et al. PNAS. 2013). Currently, we are working on molecular mechanisms underlying retinal and other sensory diseases caused by inactivation of miR-183/96/182 and identification of disease-causing mutations in miR-183/96/182 cluster in human.
Recently, we and others have shown that miR-183/96/182 cluster is also expressed and play important roles in immune system and neuro-immune cross-talks. We have expanded our research to study the roles of miR-183/96/182 in neuro-immune/inflammatory responses in bacterial keratitis model.
The second major project in my laboratory is on miRNAs in diabetic retinopathy (DR). Previously, we reported one of the first systemic studies on miRNAs in DR and identified key miRNA signatures reflecting pathological changes of early DR (Kovacs et al. IOVS. 2011). Currently, we focus on miR-146 and several other miRNAs to dissect their involvement in DR and test their potential as therapeutic targets for treatment of DR. We also are developing miRNA biomarkers in the vitreous, aqueous and plasma as diagnostic biomarkers for DR and other retinal diseases.
For teaching, I teach Gross Anatomy for Year I medical students and participate in the Biology of the Eye course for graduate/undergraduate.
Research Educator, Full time, PhD, Gross Anatomy
Education and Training
- 2002 � 2004 Postdoc. Dept of Medical Genetics & Microbiology. University of Toronto
- 2000 � 2002 Postdoc. Howard Hughes Med Inst/Johns Hopkins University, School of Medicine.
- 1995-2000 Ph.D. Predoctoral Training Program in Human Genetics, The Johns Hopkins University School of Medicine
- 1986-1991 M.D. Peking Union Medical College (PUMC)
- 1983-1986 pre-med Peking University
- 7/2013-present Associate Professor, Department of Ophthalmology/Kresge Eye Institute, and Department of Anatomy & Cell Biology, Wayne
State University, School of Medicine, Detroit, MI
- 2009 � 6/2013 Director, Core lab for miRNA and Gene Expression, Rush Translation Science Consortium (RTSC), Rush University Medical Center, Chicago
- 2004 � 6/2013 Assistant Professor. Depts of Pharmacology, Ophthalmology, Neurological Sciences, Rush University Medical Center, Chicago
- Sept, 2011 Young Investigator award. 7th Congress of the Federations of Asian and Oceanian Physiological Societies (FAOPS). microRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats.
- June 2007. Our paper entitled �The proliferation and expansion of retinal stem cells require functional Pax6� (Xu S, et al. Dev Biol. 2007 304:713-21), was selected for Faculty of 1000 Biology because of its high scientific merit and impact.
- 1992 Young Investigator Award, first prize, by the Chinese Association of Genetics, Beijing for the excellent research work on �a new procedure for DMD/BMD diagnosis-Amp-FLP linkage analysis�,
- Cowan C, Muraleedharan CK, O�Donnell JJ, III, Singh PK, Lum H, Kumar A, and Xu S. microRNA-146 Inhibits Thrombin-induced NF-B Activation and Subsequent Inflammatory Responses in Human Retinal Endothelial Cells. Invest Ophthalmol Vis Sci. 2014 Jul 1;55(8):4944-51. PMID: 24985472.
- Lumayag S, Haldin CE, Corbett NJ, Wahlin KJ, Cowan C, Turturro S, Larsen P, Kovacs B, Witmer PD, Valle D, Zack DJ, Nicholson DA, and Xu S. Inactivation of the microRNA-183/96/182 cluster results in syndromic retinal degeneration. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):E507-16. PMID: 23341629.
- Kovacs B, Lumayag S, Cowan C, Xu S. microRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats. Invest. Ophthalmol. Vis. Sci. 2011 Jun 21; 52(7): 4402-9. Print 2011 Jun. PMID: 21498619
- Xu S. microRNA expression in the eyes and their significance in relation to functions. Prog Retin Eye Res. 2009 Mar;28(2):87-116. Epub 2008 Nov 28. (invited review). PMID: 19071227.
- Xu S*, Witmer D, Kovacs B, Lumayag S and Valle D*. (2007). MicroRNA Transcriptome Of Mouse Retina And Functional Study of a Sensory Organ Specific miRNA cluster. J Biol Chem. 282(34):25053-25066. PMID: 15456885. (*: corresponding authors).
- Perez SE, Lumayag S, Kovacs B, Mufson EJ and Xu S. (2008) -Amyloid Deposition and Functional Impairment in the Retina of the APPswe/PS1∆E9 Transgenic Mouse Model of Alzheimer�s Disease. Invest Ophthalmol Vis Sci. 2009 Feb;50(2):793-800. PMID: 18791173.
- Kovacs B, MacCumber MW, Xu S. (2007). Adult Retinal Stem Cell Spheres Hold Potential for Diabetic Retinopathy (DR) Treatment. Retina Today. Nov/Dec 2007: 41-42.
- Liu H, Xu S, Wang Y, Mazerolle C, Thurig S, Coles BLK, Ren J, Taketo MM, van der Kooy D, Wallace VA. (2007). Ciliary margin transdifferentiation from neural retina is controlled by canonical Wnt signaling, Developmental Biology 308(1):54-67. PMID: 17574231.
- Xu S, Sunderland ME, et al. (2007). The proliferation and expansion of retinal stem cells require functional Pax6. Dev Biol. 304(2):713-21. PMID: 17316600.
- Xu S, Wang Y, Zhao H, Zhang L, Xiong W, Yau KW, Hiel H, Glowatzki E, Ryugo DK, Valle D. (2004). PHR1, a PH Domain-Containing Protein Expressed in Primary Sensory Neurons. Mol Cell Biol. 24:9137-51. PMID: 10585447.
- Xu S, Ladak R, Swanson DA, Soltyk A, Sun H, Ploder L, Vidgen D, Duncan AM, Garami E, Valle D, McInnes RR. (1999). PHR1 encodes an abundant, pleckstrin homology domain-containing integral membrane protein in the photoreceptor outer segments. J Biol Chem 10;274(50):35676-85. PMID: 10585447.