Dr. Lechleiter's laboratory is interested in the molecular and cellular mechanisms of protection during drug addition, ischemic stress, stroke, traumatic brain injury (TBI) and age-associated neurodegenerative diseases. Most strategies to reduce, slow and repair the severity of brain injuries and diseases have focused almost exclusively on neurons.
We have focused our research on the potential of astrocytes as a novel theurapeutic avenue for brain treatment.
Astrocytes are known to play a crucial role in supporting and protecting neuronal function and in modulating brain energy metabolism. A therapeutic strategy that increases energy production is inherently robust, since the number of potential neuroprotective processes that benefit are significantly higher than a single molecular target.
Zheng W, LT Watts, D Holstein, Prajapati, S.I., Keller, C., Grass, E., Walter, C. and Lechleiter, J.D. (2010) Purinergic Receptor Stimulation Reduces Cytotoxic Edema and Brain Infarcts in Mouse Induced by Photothrombosis by Energizing Glial Mitochondria. PLoS One 5 (12): e14401. PMCID: PMC3008710
Bollo, M., Paredes, R.M., Holstein, D., Zheleznova, N., Camacho, P., and Lechleiter, J.D. (2010). Calcineurin Interacts with PERK and Dephosphorylates Calnexin to Relieve ER Stress in Mammals and Frogs. PLoS One 5 (8): e11925. PMCID: PMC2916823
Zheng W, LT Watts, D Holstein, Wewer, J. and Lechleiter, J.D. (2013) P2Y1R-initiated, IP3R-dependent Stimulation of Astrocyte Mitochondrial Metabolism Reduces and Partially Reverses Ischemic Neuronal Damage in Mouse. J. Cerebral Blood Flow & Metabolism 33, 600-611. PMCID: PMC3618399
Chocron*, E.S., Sayre*, N.L., Holstein, D., Saelim, N., Ibdah, J.A., Dong, L.Q., Zhu, X., Cheng, S.Y. and Lechleiter, J.D. (2012) The Trifunctional Protein Mediates Thyroid Hormone Receptor Dependent Stimulation of Mitochondria Metabolism.Mol. Endocrinology 26, 1117-1126. *co-first authorsPMCID: PMC3385793
Chen, Y., Holstein, D.M., Aime, S., Bollo, M. and Lechleiter, J.D. (2016) Calcineurin beta protects brain after injury by activating the unfolded protein response. Neurobiol Dis94, 139-156. PMID: 27334877
Sayre*, N.L., Sifuentes, M., Holstein, D., Cheng, S.Y., Zhu, X. and Lechleiter, J.D. (2017) Stimulation of astrocyte fatty acid oxidation by thyroid hormone is protective against ischemic stroke-induced damage. J. Cerebral Blood Flow & Metabolism 37, 514-527, PMID: 26873887