Dr. Ugra S. Singh
Ph.D., Kanpur University
(Central Drug Research Institute, Lucknow), India
Office: (803) 253-5851
Fax: (803) 216-3428
Understanding the retinoic acid (RA) signaling in health and disease is our long term objective. How a defective retinoic acid signaling leads to fetal alcohol syndrome in children of alcoholic mothers, and causes neuronal malformations in maternal diabetes is the focus of our present research work.
Mechanism of Alcohol Induced Neurotoxicity: Excessive intake of alcohol not only affects normal functioning of the adult brain, but also affects embryonic development in pregnant women. It increases ethanol level in the blood producing irreversible neurotoxic effects in the unborn babies that lead to fetal alcohol syndrome (FAS). Children born with FAS have abnormal facial features with mild to severe mental retardation. Findings from in vivo studies in experimental animals have shown that the cerebellum is one of the most sensitive areas in the brain that is affected by ethanol neurotoxicity. Cerebellar granular neurons (CGNs) exposed to ethanol lose their potential to undergo proper neuronal differentiation and eventually undergo apoptosis. RA is locally synthesized in brain and required for brain patterning during embryonic development. Studies have shown that ethanol increases RA level in cerebellum. To study the mechanism of ethanol induced toxicity, and whether RA is involved, is the focus of our studies.
Neuronal Development in Diabetic Embryopathy: Diabetes mellitus is a common metabolic disorder that affects the peripheral as well as the central nervous system (CNS). It increases the risk of dementia by approximately 60% in elderly population which is associated with cognitive deficits and neurophysiological and structural changes in the brain. These changes are due to impairments in differentiation and/or survival of neurons. In case of maternal diabetes situation becomes more complicated. Children born to diabetic mothers have high risk of brain developmental disorders. It has been reported that RA is required for differentiation of neurons in the developing brain, and maintenance of plasticity and regeneration in the adult neurons. Our studies have shown that under diabetic condition (hyperglycemia), RA-induced differentiation of embryonic cortical neurons is impaired. Using rodent animal model of diabetic embryopathy we are interested in dissecting the RA signaling components that might be specifically targeted and involved in mediating harmful effects of diabetes on differentiation of cortical neurons.
Search PubMed for publications by Dr Ugra Singh
- Joshi S, Guleria R, Pan J, DiPette D and Singh US. Heterogeneity in retinoic acid signaling in neuroblastomas; role of matrix metalloproteinases in retinoic acid-induced differentiation. BBA 2007. 1772:1093-1102.
- Joshi S, Guleria R, Pan J, Bayless KJ, Davis GE, DiPette D, and Singh US. Ethanol Impairs Rho GTPase Signaling and Differentiation of Cerebellar Granule Neurons in a Rodent Model of Fetal Alcohol Syndrome. Cellular and Molecular Life Sciences 2006. 63:2859-2870.
- Guleria R, Pan J, DiPette D, and Singh US. Hyperglycemia inhibits retinoic acid-induced activation of Rac1, prevents differentiation of cortical neurons, and causes oxidative stress in a rat model of diabetic pregnancy. Diabetes 2006. 55(12): 3326-34.
- Joshi S, Guleria R, Pan J, DiPette D and Singh US. Retinoic acid receptors and tissue-transglutaminase mediate short term effect of retinoic acid on migration and invasion of neuroblastoma SH-SY5Y cells. Oncogene 2006. 25:240-47.
- Weylie B, Zhu J, Singh US, Sandy A, Forough R. Phosphatidylinositide-3-Kinase (PI3K) is important in late stage fibroblast growth factor-1 (FGF-1) mediated angiogenesis in vivo. J Vasc Res 2006. 43:61-69.
- Forough R, Weylie B, Patel C, Ambrus S, Singh US, Zhu J. Role of AKT/PKB signaling in fibroblast growth factor-1 (FGF-1)-induced angiogenesis in the chicken chorioallantoic membrane (CAM). J Cell Biochem 2005. 94(1):109-16.
- Pan J, Yu-Lin K, Jeethendran S, Joshi S, DiPette, D and Singh US. Phosphatidylinositol 3-kinase and Rac1 mediate retinoic acid effects on neuronal differentiation in SH-SY5Y cells. J Neurochem. 2005;93(3):571-83.
- Forough R, Weylie B, Patel C, Ambrus S, Singh US, Zhu J Role of AKT/PKB signaling in fibroblast growth factor-1 (FGF-1)-induced angiogenesis in the chicken chorioallantoic membrane (CAM). J Cell Biochem. 2005 Jan 1;94(1):109-16.
- Pan J, Singh US, Takahashi T, Oka Y, Palm-Leis A, Herbelin BS, and Baker KM. PKC Mediates Cyclic Stretch-Induced Cardiac Hypertrophy Through Rho Family GTPases and Mitogen-Activated Protein Kinases in Cardiomyocytes. Journal of Cell Physiol 2005, 202:536-552.
- Palm-Leis A, Singh US, Herbelin BS, Olsovsky GG, Baker KM, Pan J. Mitogen-activated protein kinases and mitogen-activated protein kinase phosphatases mediate the inhibitory effects of all-trans retinoic acid on the hypertrophic growth of cardiomyocytes. J. Biol. Chem. 2004, 279:54905-54917.
- Singh US, Jing P, Yu-Lin Kao, Joshi S, Kerry Y and Baker KM. Tissue-transglutaminase mediates activation of RhoA and MAP kinase pathways during retinoic acid-induced neuronal differentiation of SH-SY5Y cells. J. Biol. Chem. 2003. 278:391-399.
- Boehm JE, Singh US, Coombs C, Antonyak MA, and Cerione RA. Tissue transglutaminase protects against apoptosis by modifying the tumor suppressor protein p110 RB. J. Biol. Chem. 2002. 277:20127-20130.
- Antonyak MA, Singh US, David AL, Jason EB, Carolyn C, Marsha MZ, Page RL and Cerione RA. Effects of tissue transglutaminase on retinoic acid induced cellular differentiation and protection against apoptosis. J. Biol. Chem. 276:33582-33587, 2001.
- Singh US, Kunar MT, Yu-Lin K and Baker KM. Role of tissue transglutaminase II in retinoic acid-induced activation of RhoA associated kinase-2. EMBO J. 20:2413-2423, 2001.