Major Research Interests:
To understand the molecular basis for disease development and progression of diabetic retinopathy (DR); Targeted genomics, epigenomics and proteomics-based identification of early biomarkers of diabetes and its neuronal and vascular complications of the eyes � O-GlcNAc and S-nitrosylated proteins; RNAi technology and therapeutics to prevent/slow down the progression of DR.
Chronic hyperglycemia in diabetes leads to increased cellular oxidative stress, ER stress, mitochondrial dysfunction, inflammation and pre-mature cell death. We have recently shown that thioredoxin interacting protein (TXNIP), which binds to and inhibits the anti-oxidant and thiol reducing function of thioredoxin (Trx), is a mediator of cellular oxidative and ER stress, inflammation and apoptosis of retinal cells in vitro under diabetic conditions and that TXNIP expression is highly induced in diabetic retinas. TXNIP knock down in vivo by intravitreal injection of siRNA ameliorates several retinal abnormalities in diabetic rats, which include aberrant extracellular matrix gene expression, inflammation, neuronal injury and glia activation. Our current research further investigates the critical role of TXNIP in cellular oxidative/nitrosative stress, mitochondrial stress, autophagy/mitophagy dysregulation and neurovascular injury in DR. We use several cellular and STZ-induced diabetic animal models to answer some of these important questions. Our research has been funded by Foundation and NIH/NEI grants. In addition, I am an instructor of Medical Histology Course for the first year medical students. My laboratory is also open for students who are interested in diabetes research and eager to learn molecular and biochemical methodologies.
Research Educator, Full time, PhD, Histology and Cell Biology
Education and Appointment:
- Ph.D., Biochemistry, Indian Institute of Science, Bangalore, India
- Assistant Professor, Departments of Anatomy/Cell Biology and Ophthalmology, Wayne State University School of Medicine, Detroit, MI
Professional and Faculty Appointments:
- Instructor, 1997- 2001, Department of Medicine, The University of Mississippi Medical Center, Jackson, MS
- Assistant Professor (Research), 2001-2005, Departments of Internal Medicine and Physiology, Wayne State University School of Medicine, Detroit, MI
- Assistant Professor, 2005-present, Departments of Anatomy/Cell Biology and Ophthalmology, Wayne State University School of Medicine, Detroit, MI
Research Area: Diabetic Retinopathy – Neurovascular Protection, RNAi therapeutics
1. Perrone L, Matrone C, Singh L.P. (2014) Epigenetic modifications and potential new treatment targets in diabetic retinopathy. J Ophthalmol. 2014:789120. PMID: 25165577
2. Singh L.P. (2014) The NLRP3 Inflammasome and Diabetic Cardiomyopathy: Editorial to: "Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model" by Beibei Luo et al. Cardiovasc Drugs Ther. 28(1):5-6.
3. Singh L.P. (2013) Thioredoxin Interacting Protein (TXNIP) and Progression of Diabetic Retinopathy. J Clin Exp Ophthalmol, 4: 287.
4. Devi TS, Hosoya KI, Terasaki T, Singh L.P. (2013) Critical role of TXNIP in oxidative stress, DNA damage, and apoptosis of pericytes in high glucose: Implications for diabetic retinopathy. Exp. Cell Res. 319:1001�1012. PMID: 23353834
5. Singh, L.P., Devi, TS, Nantwi, KD. (2012) Theophylline Regulates Inflammatory and Neurotrophic factor Signals in Functional Recovery after C2-Hemisection in Adult Rats. Exp. Neurol., 238:79-88. PMID: 22981449
6. Devi TS, Lee I, H�ttemann M, Kumar A, Nantwi KC, Singh L.P. (2012) Txnip links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: Implications for diabetic retinopathy. Exp. Diab Res., 2012;2012:438238.
7. Devi TS, Hosoya K, Terasaki T, and Singh LP. (2011) GSK-3-CREB axis mediates IGF-1-induced ECM/adhesion molecule expression, cell cycle progression and monolayer permeability in retinal capillary endothelial cells: Implication for Diabetic Retinopathy. Biochim Biophys Acta-Molecular basis of disease 1812(9):1080-1088. PMID: 21549192
8. Sbai O, Devi TS, Melone MA, Feron F, Khrestchatisky M, Singh L.P., and Perrone L. (2010). RAGE-TXNIP axis is required for S100B-promoted Schwann cell migration, fibronectin expression and cytokine secretion. J Cell Science 123(Pt 24):4332-4332
9. Perrone L, Devi TS, Hosoya K, Terasaki T, and Singh LP. (2010). Inhibition of TXNIP Expression In Vivo Blocks Early Pathologies of Diabetic Retinopathy. Cell Death and Disease 1, e65; doi:10.1038/cddis.2010.42. PMID: 21364670
10. Perrone L, Devi TS, Hosoya K, Terasaki T, and Singh LP. (2009). Thioredoxin-Interacting Protein (TXNIP) induces inflammation through chromatin modification in retinal capillary endothelial cells under diabetic conditions. J Cell Physiol. 221(1):262-272.