Wolosker Herman - Professor
Main Research Area
We have been studying the roles of unconventional transmitters, like the d-amino acids in the central nervous system. We are particularly interested in the regulation of NMDARs by d-serine, a d-enantiomer previously thought to be restricted to bacteria or lower invertebrates. Work in our laboratory helped to establish d-serine as a major physiologic ligand for NMDARs that mediates NMDAR synaptic responses and neurotoxicity both in vitro and in vivo. In addition to neurotransmission, NMDARs also play a major role in neurodegeneration, and their excessive activation contributes to neuronal death in several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. In the past few years, we elucidated the mechanisms of d-serine synthesis by the enzyme serine racemase and discovered novel pathways regulating d-serine production and release from neural cells. We also discovered that d-serine is the dominant NMDAR co-agonist mediating neurotoxicity, raising the possibility that drugs that curb d-serine synthesis or release might be useful in neurodegenerative diseases where NMDARs are over-stimulated.
Our laboratory investigates several aspects of D-serine neurobiology utilizing molecular biology, biochemical, cell biology, mouse genetic models, and more recently electrophysiological techniques.
Candidates of all backgrounds and levels are welcome. They do not need previous experience in biochemistry or neuroscience but should be curious and fearless in challenging some cherished dogmas in the field.
Items 1 – 12
1: Ehmsen JT, Ma TM, Sason H, Rosenberg D, Ogo T, Furuya S, Snyder SH, Wolosker H.
D-serine in glia and neurons derives from 3-phosphoglycerate dehydrogenase.
J. Neurosci. 24/07/2013; 30: 12464 – 12469
2: Rosenberg D, Artoul S, Segal AC, Kolodney G, Radzishevsky I, Dikopoltsev E, Foltyn VN, Inoue R, Mori H, Billard JM, Wolosker H.
Neuronal D-serine and glycine release via the Asc-1 transporter regulates NMDA receptor-dependent synaptic activity
J Neurosci. 01/01/2013; 8: 3533 – 3544
3: Rosenberg D, Kartvelishvily E, Shleper M, Klinker CM, Bowser MT, Wolosker H.
Neuronal release of D-serine: a physiological pathway controlling extracellular D-serine concentration.
FASEB J. 01/01/2010; 8: 2951 – 2961
4: Balan L, Foltyn VN, Zehl M, Dumin E, Dikopoltsev E, Knoh D, Ohno Y, Kihara A, Jensen ON, Radzishevsky IS, Wolosker H.
Feedback inactivation of D-serine synthesis by NMDA receptor-elicited translocation of serine racemase to the membrane
Proc Natl Acad Sci U S A. 01/01/2009; 18: 7589 – 7594
5: Wolosker H, Dumin E, Balan L, Foltyn VN
D-amino acids in the brain: D-serine in neurotransmission and neurodegeneration.
FEBS J. 01/01/2008; 14: 3514 – 3526
6: Dumin, E., Bendikov, I., Foltyn, V.N., Misumi, Y., Ikehara, Y., Kartvelishvily, E., and Wolosker, H.
Modulation of D-serine levels via ubiquitin-dependent proteasomal degradation of serine racemase
J. Biol. Chem. 11/10/2006; 281: 20291 – 20302
7: Kartvelishvily, E., Schleper, M., Balan, L., Dumin, E., and Wolosker, H.
Neuron-derived D-Serine Release Provides a Novel Means to Activate N-Methyl-D-aspartate Receptors
J. Biol. Chem. 10/10/2006; 281: 14151 – 14162
8: Wolosker H
D-Serine regulation of NMDA receptor activity,
Science STKE 01/01/2006;
9: Shleper, M., Kartvelishvily, E, and Wolosker, H.
D-Serine is the Dominant Endogenous Coagonist for NMDA Receptor Neurotoxicity in Organotypic Hippocampal Slices
J. Neurosci. 12/10/2005; 41: 9413 – 9417
10: Foltyn, V.N., Bendikov, I., De Miranda, J., Panizzutti, R., Dumin, E., Schleper, M., Li, P., Toney, M.D., Kartvelishvily, E., and Wolosker, H.
Serine racemase modulates intracellular D-serine levels through an alpha/beta-elimination activity.
J. Biol. Chem. 01/01/2005; 280: 1754 – 1763
11: De Miranda, J., Panizzutti, R., Foltyn, V. N., and Wolosker, H.
Cofactors of Serine Racemase that Physiologically Stimulate the Synthesis of the N-methyl-D-aspartate (NMDA) Receptor Coagonist D-Serine.
Proc. Natl. Acad. Sci. U S A 01/01/2002; 99: 14542 – 14547
12: Panizzutti, R., De Miranda, J., Ribeiro, C.S., Engelender, S., and Wolosker, H.
A New Strategy to Decrease NMDA Receptor Co-activation: Inhibition of D-serine Synthesis by Converting Serine Racemase into an Eliminase.
Proc. Natl. Acad. Sci. U S A 01/01/2001; 98: 5294 – 5299