Reggie H. Lee, PhD (P.I.)
Assistant Professor of Neurology
Post-Doctoral Fellow: Neurology, 2016-19 LSU Health Shreveport
Post-Doctoral Fellow: Neurology, 2013-16, University of Miami, Miller School of Medicine
PhD: Pharmacology, 2005-11, Tzu Chi University, Taiwan
News
The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism 2023 (in press).
The goal of this study is to investigate the mechanisms underlying serum/glucocorticoid-regulated kinase 1-mediated brain injury following ischemia.
Our abstract entitled: "The role of serum/glucocorticoid-regulated kinase 1 in ischemic brain injury following cardiac arrest" was selected for oral presentation at Neuroscience 2022 (San Diego, CA)
Dr. Reggie Lee received R01 Award from the National Institutes of Health - April 1, 2022
The goal of this study is to investigate the role of novel kinases in cerebral ischemia.
Dr. Celeste Wu received Career Development Award from the American Heart Association - July 1, 2021
The goal of this study is to investigate the role of fatty acids in cerebral blood flow modulation, neuroinflammation, and mitochondrial dysfunction in Alzheimer's disease.
Publication - May, 2021
Activation of Neuropeptide Y2 Receptor Can Inhibit Global Cerebral Ischemia-Induced Brain Injury. NeuroMolecular Medicine. 2021 May 21. doi: 10.1007/s12017-021-08665-z. PubMed PMID: 34019239.
Dr. Reggie Lee received Grant-in-Aid Award from Center for Brain Health at LSU Health Shreveport - January 1, 2021
The goal of this study is to investigate the mechanisms underlying protein arginine methyltransferases 1-mediated ischemic brain injury after cardiac arrest.
Publication - September, 2020
Upregulation of serum and glucocorticoid-regulated kinase 1 exacerbates brain injury and neurological deficits after cardiac arrest. Am J Physiol Heart Circ Physiol 2020 Nov 1;319(5):H1044-H1050. doi: 10.1152/ajpheart.00399.2020. Epub 2020 Sep 18. PMID: 32946263.
Dr. Reggie Lee received Career Development Award from the American Heart Association - July 1, 2019
The goal of this study is to investigate the role of serum/glucocorticoid-regulated kinase 1 in cardiac arrest-induced brain injury.
Dr. Reggie Lee received Grant-in-Aid Award from the Research Council at LSU Health Shreveport - July 1, 2019
The goal of this study is to study the role of protein arginine methyltransferases 1 in serum/glucocorticoid regulated kinase 1-mediated ischemic brain injury after cardiac arrest.
Research
Cardiopulmonary arrest and stroke are the major cause of death/disability in the U.S. with poor prognosis and survival rates. The current therapeutic challenges are physiologically complex because they involved hypoperfusion [decreased cerebral blood flow], neuroinflammation, and mitochondrial dysfunction. Our long-term goal is to identify these complex regulatory elements that ultimately control neuronal viability in order to lay the foundation for a common therapy greatly improving outcome. Our laboratory is currently investigating 1) the therapeutic potential of novel kinase inhibitors (e.g., Serum/Glucocorticoid Regulated Kinase) against cardiac arrest and stroke and 2) regulatory mechanisms of cerebrovascular dynamics by sympathetic nervous system in cerebral ischemia. To study cardiac arrest and stroke, we use clinically relevant models of cardiac arrest and stroke (asphyxia- and KCl-induced rodent cardiac arrest and photothrombotic stroke model) coupled with cutting-edge techniques, including in vivo two-photon laser scanning microscopy for real-time analyses of cortical cerebral blood flow; Microspectrofluorometry for mitochondrial ion homeostasis; Mitochondria respiration measurements in a hippocampal slice preparation via Seahorse respirometry.
Cerebral Ischemia
Novel Kinases in Ischemic Brain Injury
Cardiopulmonary arrest (CA) is a major cause of death/disability in the US affecting up to 325,000 people/year with only a 10% survival rate. The brain is the most sensitive organ to ischemia because it depends on major ionic fluctuations utilizing large amounts of energy. Identifying complex regulatory elements that contribute to neuronal viability is of high therapeutic potential. As such, kinases are one of the most important regulatory enzymes in eukaryotic cells, which modulate biological activity of proteins. Abnormality of kinases are linked to ischemic brain damage.
We discovered that novel serum/glucocorticoid-regulated kinases (SGKs, members of serine/threonine-protein kinase family) are highly expressed in brain NEURONS that are susceptible to ischemia (e.g., hippocampus and cortex). The primary goal of this project is to elucidate how SGKs modulate neuronal survival after cerebral ischemia. We hypothesize that SGKs expression is enhanced after cerebral ischemia, which leads to hypoperfusion, neuroinflammation, mitochondrial dysfunctional, and neurological deficits.
Neurovascular Coupling
Autonomic Nervous System in Cerebral Ischemia
The cerebral arteries densely innervated by perivascular nerves from the sympathetic and parasympathetic outflows of the autonomic nervous system. These nerves play a central role in vascular tone regulation. Perivascular sympathetic nerves mediating global ischemia-induced hypoperfusion are not well-defined. Therefore, the purpose of this project is to delineate the pathophysiological mechanism(s) of the perivascular sympathetic nerves on ischemia-induced cerebral blood flow derangements as related to brain injury/neurocognitive deficits. We hypothesize that perivascular sympathetic nerves on cerebral arteries mediate cerebral blood flow derangements and neuronal cell death in the hippocampus and cortex after ischemia. We are currently investigating 1) if sympathetic nervous system contributes to cerebral blood flow derangements, neuronal cell death, and neurological deficits following ischemia 2) if attenuation of the sympathetic nervous system provides beneficial effects to combat against ischemia-related neuronal deficits. 3) potential neurotransmitters (e.g., norepinephrine, neuropeptide Y, and nitric oxide) involved in cerebrovascular disease processes.
Lipids in Alzheimer's Disease
Fatty acids and Alzheimer's Disease
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases in the United States. Risk factors for AD are associated with age and gender. Women are more likely to develop a rapid progression of dementia than men with a greater risk of developing vascular dementia as compared to males. We previously discovered that mRNA and protein expression of fatty acid synthase in brain regions were significantly decreased with the aged AD mice. The goal of this project is to explore the pathophysiological role of fatty acid synthase in the aged brain of AD. We hypothesize that fatty acid synthase is critical for age-related brain function to maintain cerebral blood flow and the mitochondria, and prevent neuroinflammation and learn/memory degradation. The present study can lead to novel therapies/targets against AD.
Publications
Selected Publications
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Wu CY, Zhang Y, Xu L, Huang Z, Zou P, Clemons GA, Li C, Citadin CT, Zhang Q, Lee RH. The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism 2023 (in press).
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Acosta CH, Clemons GA, Citadin CT, Carr WC, Sayuri Berto Udo M, Tesic V, Sanicola HW, Freelin AH, Toms JB, Jordan JD, Guthikonda B, Rodgers KM, Wu CY, Lee RH, Lin HW. A role for protein arginine methyltransferase 7 in repetitive and mild traumatic brain injury. Neurochemistry International 2023 Jun;166:105524. PMID: 37030326.
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Acosta CH, Clemons GA, Citadin CT, Carr WC, Sayuri Berto Udo M, Tesic V, Sanicola HW, Freelin AH, Toms JB, Jordan JD, Guthikonda B, Rodgers KM, Wu CY, Lee RH, Lin HW. PRMT7 can prevent neurovascular uncoupling, blood-brain barrier permeability, and mitochondrial dysfunction in repetitive and mild traumatic brain injury. Experimental Neurology 2023 Aug;366:114445. PMID: 37196697.
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Clemons GA, Couto E Silva A, Acosta CH, Udo MSB, Tesic V, Rodgers KM, Wu CY, Citadin CT, Lee RH, Neumann JT, Allani S, Prentice H, Zhang Q, Lin HW. Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease. J Cell Physiol. 2022 Aug 29;. doi: 10.1002/jcp.30858. PubMed PMID: 36036549.
- Yang L, Wu, C, Li, Y, Dong, Y, Wu, CY, Lee, RH, Brann DW, Lin HW, Zhang QG. Long-term exercise pr-training attenuates Alzheimer's disease-related pathology in a transgenic rat model of Alzheimer's disease. GeroScience 2022 Jun; 44(3): 1457–1477. PMID: 35229257
- Lee RH, Wu CY, Citadin CT, Couto E Silva A, Possoit HE, Clemons GA, Acosta HC, de la Llama VA, Neumann JT, Lin HW. Activation of Neuropeptide Y2 Receptor Can Inhibit Global Cerebral Ischemia-Induced Brain Injury. NeuroMolecular Medicine. 2021 May 21. doi: 10.1007/s12017-021-08665-z. PubMed PMID: 34019239.
- Wu CY, Couto E Silva A, Citadin CT, Clemons GA, Acosta CH, Knox BA, Grames MS, Rodgers KM, Lee RH, Lin HW. Palmitic acid methyl ester inhibits cardiac arrest-induced neuroinflammation and mitochondrial dysfunction. Prostaglandins Leukot Essent Fatty Acids (PLEFA). 2021 Feb;165:102227. doi: 10.1016/j.plefa.2020.102227. Epub 2020 Dec 17. PMID: 33445063.
- Lee RH (Corresponding author), Grames MS, Wu CY, Lien CF, Couto E Silva A, Possoit HE, Clemons GA, Citadin CT, Neumann JT, Pastore D, Lauro D, Della-Morte D, Lin HW. (2020) Upregulation of serum and glucocorticoid-regulated kinase 1 exacerbates brain injury and neurological deficits after cardiac arrest. Am J Physiol Heart Circ Physiol 2020 Nov 1;319(5):H1044-H1050. doi: 10.1152/ajpheart.00399.2020. Epub 2020 Sep 18. PMID: 32946263.
- Chen P, Wu CY, Clemons GA, Citadin CT, Couto E Silva A, Possoit HE, Azizbayeva R, Forren NE, Liu C, Rao KN, Krzywanski DM, Lee RH, Neumann JT, Lin HW. (2020) Stearic acid methyl ester affords neuroprotection and improves functional outcomes after cardiac arrest. Prostaglandins, leukotrienes, and essential fatty acids (PLEFA).
- Wu CY, Clemons GA, Lopz-Toledano MA, Citadin CT, Lee RH, Lin HW. (2020) SC411 enhances cerebral blood flow after ischemia in the Townes mouse model of sickle cell disease. Prostaglandins, leukotrienes, and essential fatty acids (PLEFA).
- Couto E Silva A, Wu CY, Citadin CT, Clemons GA, Possoit HE, Grames MS, Lien CF, Minagar A, Lee RH, Frankel A, Lin HW. Protein Arginine Methyltransferases in Cardiovascular and Neuronal Function. Molecular Neurobiology. 2019 Dec 10. doi: 10.1007/s12035-019-01850-z. PMID:31823198.
- Wu CY, Lee RH, Lee MH, Do Couto E Silva A, Hsieh TH, Possoit HE, Brackett AL, and Lin HW. (2018). Role of neuroinflammation in pathophysiology of traumatic brain injury. Neuroinflammation. Amsterdam, Netherlands, Elsevier.
- Lee RH, Couto E Silva A, Possoit HE, Lerner FM, Azizbayeva R, Citadin CT, Wu CY, Neumann JT, Lin HW. (2018) Palmitic acid methyl ester is a novel neuroprotective agent against cardiac arrest. Prostaglandins, leukotrienes, and essential fatty acids (PLEFA). Nov 23. pii: S0952-3278(18)30212-6. doi: 10.1016/j.plefa.2018.11.011. PMID: 30514597.
- Lee RH, Lee MH, Wu CY, Couto E Silva A, Possoit HE, Hsieh TH, Minagar A, Lin HW. Cerebral ischemia and neuroregeneration. Neural Regen Res. 2018 Mar; 13(3): 373–385. PMID: 29623912.
Wu CY, Lerner FM, Couto E Silva A, Possoit HE, Hsieh TH, Neumann JT, Minagar A, Lin HW, and Lee RH. (2018). Utilizing the modified T-maze to assess functional memory outcomes after cardiac arrest. J. Vis. Exp. (131), e56694, doi:10.3791/56694. PMID: 29364254. (Corresponding author). - Lee RH, Couto E Silva A, Lerner FM, Wilkins CS, Valido SE, Klein DD, Wu CY, Neumann JT, Della-Morte D, Koslow SH, Minagar A, and Lin HW. (2017) Interruption of Perivascular Sympathetic Nerves of Cerebral Arteries Offers Neuroprotection Against Ischemia. Am J Physiol Heart Circ Physiol 312(1): H182-188. PMID: 27864234.
- Lee RH, Vasquez JJ, Do Couto E Silva A, Klein DD, Valido SE, Chen JA, Lerner FM, Wu CY, and Lin HW (2015). Fatty acid methyl esters as a potential therapy against cerebral ischemia. Oilseeds and fats, Crops and Lipids, DOI: 10.1051/ocl/2015040.
- Wu CY, Lee RH, Chen PY, Tsai AP, Chen MF, Kuo JS, and Lee TJ. (2014). L-type calcium channels in sympathetic α3β2-nAChR-mediated cerebral nitrergic neurogenic vasodilation. Acta Physiol 211(4): 544-558. PMID: 24825168.
- Lee RH, Wilkins CS, Do Couto E Silva A, Valido SE, Wu CY, and Lin HW. (2014). Fatty Acids in Vascular Health. Palmitic Acid: Occurrence, Biochemistry and Health Effects. Hauppauge NY. NOVA.
Lee RH, Tseng TY, Wu CY, Chen PY, Chen MF, Kuo JS, and Lee TJ. (2012). Memantine inhibits α3β2-nAChRs-mediated nitrergic neurogenic vasodilation in porcine basilar arteries. PLoS One 7(7): e40326. PMID: 22792283. - Chen MF, Huang YC, Long C, Yang HI, Lee RH, Chen PY, Hoffer BJ, and Lee TJ. (2012). Bimodal effects of fluoxetine on cerebral nitrergic neurogenic vasodilation in porcine large cerebral arteries. Neuropharmacology 62(4): 1651-1658. PMID: 22155207.
- Lee TJ, Chang HH, Lee RH, Chen PY, Lee YC, Kuo JS, and Chen MF. (2011). Axo-axonal interaction in autonomic regulation of the cerebral circulation. Acta physiologica 203(1): 25-35. PMID: 21159131.
- Lee RH, Liu YQ, Chen PY, Liu CH, Chen MF, Lin HW, Kuo JS, Premkumar LS, and Lee TJ. (2011). Sympathetic α3β2--nAChRs mediate cerebral neurogenic nitrergic vasodilation in the swine. Am J Physiol Heart Circ Physiol 301(2): H344-354. PMID: 21536845.
- Lee RH, LEE CC, Lee RP, and Chen HI. (2005). Blood chemistry of nonstroke cerebral small vessel disease. Chinese Journal of Radiology 30(3): 159-166.
Team
Reggie Lee, PhD (P.I.)
Assistant Professor
The overall research goal in Dr. Lee's laboratory is to study potential therapeutics against cerebral ischemia. The major research focus is to investigate the pathophysiological role of serum-/glucocorticoid-inducible kinase 1 (SGK1) in the context of cardiac arrest. He has found that upregulation of SGK1 following cardiac arrest is responsible for cerebral blood flow derangements, neuronal cell death, neurological deficits. His lab is currently investigating 1) the therapeutic potential of SGK1 inhibitor against cardiac arrest and 2) mechanisms underlying SGK1-mediated brain injury and neurological deficits after cardiac arrest. Dr. Lee's research interests include: protein kinases, cerebral ischemia, neuroprotection, autonomic nervous system, and cerebral blood flow autoregulation.
Peibin Zou
Research Associate
LSU Health Shreveport
(Neurology, Research Associate, 2023-current)
Email: peibin.zou@lsuhs.edu
Yulan Zhang, M.S.
Research Associate
LSU Health Shreveport
(Neurology, Research Associate, 2022-current)
Email: yulan.zhang@lsuhs.edu
Fang Huang, M.S.
Research Associate
LSU Health Shreveport
(Neurology, Research Associate, 2023-current)
Email: fang.huang@lsuhs.edu
Positions
Post-doctoral Fellows and Graduate Students
We welcome applicants from different universities/colleges to join our lab. We expect applicants to be highly motivated and interested in the science. There is space available for outstanding applicants to participate in various exciting research both in vivo and in vitro projects. To apply, please email your CV to huichao.lee@lsuhs.edu.
Extramural Funding
R01 from the National Institutes of Health
1R01NS126273-01 NIH/NINDS
Title: Kinase regulation in cerebral ischemia
Role: Principal Investigator (PI) Approximate Amount: $1.83 million Duration: 4/1/2022-3/31/2027
Transformational Project Award from the American Heart Association
23TPA1069224 AHA
Title: Mechanisms of serum/glucocorticoid regulated kinase 1-mediated ischemic brain injury
Role: Principal Investigator (PI)
Approximate Amount: $300,000
Duration: 7/1/2023-6/30/2026
Career Development Award from the American Heart Association
21CDA856826 AHA
Title: Long-chain Acyl-CoA Synthetase 3 (ACSL3) in Vascular Dementia
PI: Celeste Wu Approximate Amount: $231,000
Duration: 7/1/2021- 6/30/2024
Contact
Contact Us
LSU Health Shreveport
Department of Neurology
1501 Kings Hwy
Shreveport, LA 71103
Email: Huichao.Lee@lsuhs.edu
Office: (318) 675-8021