Page 10 - Rappaport Institute Magazine 2024

BIOCHEMISTRY
Herman Wolosker, MD, PhD Professor of Biochemistry
MD, 1992 – Fed Univ of Rio de Janeiro, Brazil PhD, 1996 – Fed Univ of Rio de Janeiro, Brazil
Brain Metabolism in Health and Disease
Our research focuses on understanding the roles of unconventional neurotransmitters in the brain and new metabolic pathways that regulate neurodevelopment. We are particularly interested in the regulation of NMDARs by D-serine, a D-amino acid previously thought to be restricted to bacteria. D-Serine is now considered the major physiological ligand of NMDARs and mediates synaptic plasticity and neurodegeneration. In recent years, we discovered novel pathways regulating D-serine production and release that play a role in synaptic plasticity and brain development. We are studying a new metabolic pathway between astrocytes and neurons, which we have termed the serine shuttle, in which astrocytes export L-serine for the neuronal production of D-serine. The serine shuttle is essential for synaptic plasticity and neurodevelopment in vivo. Recently, we identified additional metabolic pathways dependent on blood-brain barrier (BBB) amino acid transporters and established new mouse models to study their role in health and disease.
Selected Publications
ˆ Neame, S., Safory, H., Radzishevsky, I., Touitou, A., Marchesani, F., Marchetti, M., Kellner, S., Berlin, S., Foltyn, V.N., Engelender, S., Billard, J.M., Wolosker H. (2019) The NMDA receptor activation by D-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle. Proc. Natl. Acad. Sci. U S A 116 (41) 20736-20742. ˆ Bodner, O., Radzishevsky, I., Foltyn, V.N., Touitou, A., Valenta, A., Rangel, I.F., Panizzutti, R., Kennedy, R.T., Billard, J.M., and Wolosker, H. (2020) D-Serine signaling and NMDAR-mediated synaptic plasticity are regulated by system A-type of glutamine/D-serine dual transporters. J. Neurosci 40(34):6489–6502.
ˆ Liu, Y., Wu, Zilong, Armstrong, D.*, Wolosker, H.* and Zheng, Y.* (2022) Detection and analysis of anomalistic chiral molecules as disease biomarkers. Nat Rev Chem 7, 355–373.
ˆ Radzishevsky, I., Odeh, M., Bodner, O., Zubedat, S., Shaulov, L., Litvak, M., Esaki, K., Yoshikawa, T., Agranovich, B., Li, W.|H., Radzishevsky, A., Gottlieb, E., Avital, A. and Wolosker, H. (2023) Impairment of serine transport across the blood-brain barrier by deletion of Slc38a5 causes developmental delay and motor dysfunction. Proc. Natl. Acad. Sci. USA 120 (42) e2302780120.
Grants and Awards
Israel Science Foundation
Ministry of Health
NIH 2R01NS098740
2010 – OneMind Rising Star, USA 2012 – Teva Award on Rare Diseases 2022 – Andre Cohen Deloro Prize
hwoloske@technion.ac.il
Herman Wolosker Lab
Localization of the BBB transporter Slc38a5 (magenta) in veins and capillaries of the BBB (green). This transporter mediates an essential influx of serine required for neurodevelopment. From Radzishevsky et al., 2023.