We study the mechanisms of ischemic white matter injury (WM), which is a portion of the brain that contains primarily myelinated axons and glial cells such as astrocytes, oligodendrocytes, and microglia. We discovered that Class 1 histone deacetylases (HDACs) are universal therapeutic targets to protect young and aging WM against ischemia. Our studies demonstrate that epigenetic changes are not limited to neuronal nuclei, but also occur in glial cells in response to WM injury. Indeed, glial cell acetylation can directly regulate axon function to promote recovery following injury. The beneficial effects of HDAC inhibitors in WM involve recruitment of nitric oxide synthase (NOS) isoforms and specific microRNAs (miRNAs) to conserve mitochondrial dynamics and ATP production.
Utilizing electrophysiology and various advanced imaging techniques, together with proteomics and molecular assays, our lab is in a unique position to serve as an interface between different scientific fields such as glial biology, aging, stroke, multiple sclerosis, traumatic brain injury, axonal degeneration, and neurodegenerative diseases. Because our laboratory focuses on age-related physiological changes in WM, neurovascular units, and glia-axon interactions, we aim to distinguish normal aging-related changes from neurodegenerative conditions. In addition, our expertise in working with optic nerve allows us to naturally expand our research into the visual pathway, encompassing diseases such as glaucoma and age-related retinal degenerative diseases.
Our collaborative efforts with our clinical collaborators allow for the discovery of translational approaches to advance therapeutic options for patients who suffer from stroke as well as other WM-related diseases.
Hung Vu Thien Nguyen, Ph.D.
Hung Nguyen received his Ph.D. in Biomedical Sciences under the mentorship of Dr. Cesario V. Borlongan at the Morsani College of Medicine, University of South Florida. His Ph.D. work focused on mitochondrial dysfunction in retinal ischemia and utilizing mesenchymal stem cells as a potential therapeutic option. Hung is joining Dr. Selva Baltan's lab as a postdoctoral fellow, where he will study mitochondrial dysfunction in white matter injury in neurological diseases and aging. Outside of the lab, Hung enjoys hiking and photography.
Sarah Zerimech, Ph.D.
Sarah left her birth city, Lille, to achieve a Master’s degree at University of Nice Sophia Antipolis. In 2019, she completed her PhD at Institut de Pharmacologie Moleculaire et Cellulaire (IPMC) in Sophia Antipolis, where she studied the mechanisms of cortical spreading depression the electrophysiology correlate of migraine aura, using electrophysiology imaging and optogenetics.
Sarah loves swimming, and until high school was a competitive swimmer. She also reads a lot (Classical, Sci-Fi, Fantasy, Thriller) and loves writing novels and short stories; there are a lot of universes in her mind, waiting to be born. Sarah is a single child, and her parents live and work in France; she also has two aunts living in San Francisco. She cannot wait to have her beautiful cat with her, when this Covid19 thing calms down.
Lijuan (Helen) Liu, D.V.M.; Research Associate
Lijuan (Helen) Liu, D.V.M., is a research associate. She joined APOM in January of 2013. Dr. Liu received her DVM degree in China. Most recently, Dr. Liu worked in Dr. Donna Van Winkle’s lab, studying the mechanisms of cardio protection induced by opioid peptides and
epoxyeicosatrienoic acids. Specifically, she used cardiomyocytes isolated from adult or neonatal mouse to study signal transduction (PI3K-AKT pathway) transactivated by G protein-coupled receptors (opioid receptors and EGFR receptors). In addition, she also
provided service for other laboratory personnel from OHSU in providing basic training for cardiomyocyte isolations and culture. Currently, she is working as the lead technician for the APOM Research Histology Core, providing technical expertise and support for a variety of research projects. Outside of the lab, Helen enjoys dancing and taking care her parents at home.
Isabela Harmon, B.S.; Research Associate
Isabela Harmon was born and raised in Anchorage, Alaska. She earned her bachelor’s degree in Behavioral Neuroscience from Scripps College in 2022. During her undergraduate education, Isabela spent 4 years as a lead researcher and data analyst for Professor Tessa Solomon-Lane’s neuroscience lab. In this lab, she investigated the long-term impacts of juvenile Astatotilapia burtoni social behaviors on individual development and group social dynamics through neuroendocrinological, neurophysiological, and behavioral measures. She received CNA in the state of Illinois in 2023. During her free time, Isabela volunteers at animal shelters, learns new baking recipes, hikes, paints, and reads fantasy novels. She loves receiving book recommendations! You’ll commonly find her frequenting antique stores and museums.
1. Murphy SP, Lee RJ, McClean ME, Pemberton HE, Uo T, Morrison RS, Bastian C, Baltan S.
MS-275, a class I histone deacetylase inhibitor protects the p53 deficient mouse against ischemic injury. J of Neurochem 129:509-515, 2014.
2. Baltan S. Excitotoxicity and mitochondrial dysfunction underlie age-dependent ischemic white matter injury. Adv Neurobiol. 11:151-170, 2014.
3. Baltan S. Excitotoxicity and mitochondrial dysfunction underlie age-dependent ischemic white matter injury. Glutamate and ATP at interface of metabolism and signaling in the brain. Editors: Parpura V., Schousboe A., Verkhrastsky A. Springer, New York, NY, USA. 2014.
4. Baltan S. Can lactate serve as an emergency energy substrate for axons in good times and in bad, in sickness and in health? Metab. Brain Dis. 1:25-30, 2015. PMID:25034458
5. Ransom BR, Goldberg MP, Baltan S. Molecular pathophysiology of white matter anoxic-ischemic injury. Editors Lo E, Grotta JC, Wolf PA Churchill Livingstone, Elsevier, Philadelphia, USA, 2015.
6. Baltan S. Age-specific expression and location of NMDA receptors on oligodendrocytes determine vulnerability of white matter to ischemia. Neuropharmacology, 2016, 110:626-632. PMID:26407763
7. Provencio, JJ, Seerapu, H, Brunet, S, Baltan,S, Swank, V, Khapre, R, Ransohoff, RM. delayed deterioration associated with vasospasm after subarachnoid hemorrhage is mediated by NMDA receptors. Brain Beh and Imm. 2016, 54:233-242. PMID:26872422
8. Saab AS, Tzevetavona ID, Trevisiol A, Baltan S, Dibaj P, Kusch K, Mobius W, Goetze B, Jahn HM, Hunag W, Steffens H, Schomburg ED, Perez-Smartin A, Perez-Cerda F, Bakhtiari D, Matute C, Lowel S, Griesinger C, Hirrlinger J, Kirchhoff F, Nave KA. Oligodendrocglial NMDA Receptors regulate glucose import and axonal energy metabolism. Neuron 2016: 91: 119-132. PMID:27292539.
9. Stahon K, Bastian C, Griffith S, Grahame K, Brunet S, Baltan S. Age-related changes in axonal and mitochondrial ultrastructure and function render white matter more susceptible to ischemia J of Neurosci. 2016. 28: (39): 9990-10001. PMID:27683897
10. Yin, X., Kidd, GJ. Ohno, N., Perkins GA., Ellisman M., Bastian, C., Brunet, S., Baltan, S., and Trapp, BD (2016). Proteolipid protein deficient myelin promotes axonal mitochondrial dysfunction via altered metabolic coupling. J of Cell Biol. 2016, 215: 531-542. PMID:27872255.
11. Brunet S, Bastian C, Baltan S. Ischemic White Matter Injury: An age-dependent process.
Editors; Chen, J. and Zhang J. Springer, New York, NY, USA. 2016.
12. Parpura V, Fisher ES, Lechleiter JD, Schousboe A, Waagepetersen HS, Brunet S, Baltan S, Verkhratsky A. (2017) Glutamate and ATP at the interface signaling and metabolism in astroglia: examples from pathology. Neurochem Res. 2017 42(1) 19-34. PMID:26915104
13. Hu X, Hou H, He W, Ge Y, Yin X, Chinthasar B, Kidd GJ, Sylvain B, Trapp BD, Baltan S and Riqiang Yan. BACE1 regulates the proliferation and cellular functions of Schwann cells. Glia. 65: 712-726, 2017. PMID:28191691
14. Baltan S, Bastian C, Quinn J, Brunet S. CK2 inhibition preserves white matter from ischemic injury. Neurosci. Lett. 2018 ePub ahead of print. PMID: 30125643.
15. Bastian C, Politano S, Day J, McCray A, Brunet S, and Baltan S. Mitochondrial dynamics and preconditioning in white matter. Conditioning Medicine 1(2): 64-72 2018.
16. Bastian C, Zaleski J, Stahon KE, Parr B, Brunet S, and Baltan S. NOS3 inhibition confers post-ischemic protection to young and aging white matter integrity by conserving mitochondrial dynamics and Miro-2 levels. J of Neuroscience. 38 (28) 6247-6266, 2018. PMID 29891729
17. Baltan S, Bastian C, Quinn J, Aquila D, McCray A, and Brunet S. CK2 inhibition protects white matter from ischemic injury. Neurosci Lett. EPub ahead of publication, 2018 PMID30125643.
18. Bastian C, Politano S, Day J, McCray A, Brunet S and Baltan S. Mitochondrial dynamics and preconditioning in white matter. Cond. Med. 1(2):64-72, 2018. PMID 30135960.
19. Bastian C, Quinn J, Tripathi A, Aquilla D, Dutta R, Baltan S, Brunet S. CK2 inhibition Confers White Matter Functional Protection against Ischemia by differentially regulating CDK5 and AKT signaling pathways. Neurobiol. Dis. 126: 47-61, 2019. PMID 29944965
20. Baltan S, Shi Y, Keep RF, Chen J. The effect of aging on brain injury and recovery after stroke. Neurobiol. Dis. 126: 1-2, 2019.
21. Baltan S. Stroke in CNS White Matter: Models and Mechanisms 2019. Neuroscience Letters, 2019, In Press.PMID:31377245.
22. Bastian C, Quinn, J, Doherty C, Franke C, Faris A, brunet S, Baltan S. Role of brain glycogen during ischemia, aging and cell-to-cell interactions. Adv. Neurobiol. 23:347-361, 2019. PMID: 31667815
23. Bastian C, Quinn J, Doherty C, Franke C, Faris A, Burnet S., Baltan S, The impact of aging on astrocyte-axon lactate shuttle and glia-glia interaction. Brain glycogen metabolism, Editors: Di Nuzzo, M and Schousboe A. Adv. Neurobiol, 23:347-361, 2019. PMID: 31667815.
24. Bastian C, Brunet S, Baltan S. Ex-vivo studies of optic nerve axon electrophysiology. Axon degeneration; Methods and protocols. Editor: Elisabetta Babetto. Springer New York, 2019 (In Press).
25. Reversible loss of neuronal function in a mouse model of demyelination/remyelination. Das A, , Bastian C, Trestan L, Dey, T, Trapp B, Baltan S, Dana H. (under revision, preprint Dec 2019).
Refer below links for further information