M. Iqbal Bhuiyan, PhD (P.I.)
Assistant Professor of Neurology
Post-Doctoral Fellow: Neurology, 2014-17, University of Pittsburgh
Post-Doctoral Fellow: Pharmacology, 2010-14, Catholic University of Korea
PhD: Biomolecular Science, 2004-10, Korea University of Science and Technology (UST)
MSc: Food Engineering and Bioprocess Technology, 2002-03, Asian Institute of Technology (AIT), Thailand
BSc: Biotechnology, 1995-2000, Khulna University, Bangladesh
News
Research
Disorders of the cerebral circulation rank among the leading causes of cognitive impairment and dementia, yet currently, there are no treatments for vascular contributions to cognitive impairment and dementia (VCID) and post-stroke cognitive impairment and dementia (PSCID). Understanding the mechanisms behind vascular contributions is essential for developing effective therapies for VCID and PSCID, given the wide range of factors that contribute to cognitive decline in the elderly and the resultant social and economic burden.
Dr. Iqbal’s research focuses on ionic dysregulation and inflammation associated with ischemic stroke, obesity, and VCID. The goal of his research is to identify therapeutic targets and the pathogenic mechanisms by which ion transporter proteins and their related signaling cascade contribute to brain cell death in response to hypoperfusion and inflammation that give rise to neurological and cognitive impairments. Utilizing translational and drug development approaches, his lab works on the development of innovative therapeutics for ischemic stroke and vascular dementia. The Iqbal lab combines mouse models of vascular dementia, ischemic stroke, obesity and hypertension, as well as in vitro brain cell models to address research questions. A variety of biochemical assays, confocal microscopy, laser speckle imaging for CBF measurement, and neurocognitive behavioral tests are routinely used in his research.
Current research focus in his lab includes the following:
- Ion transporter cascade, astrogliosis, and white matter lesions
- Inflammatory cytokines in VCID pathogenesis
- Pathophysiology of ischemic stroke and VCID with obesity/hypertension comorbidity
Ion transporter cascade, astrogliosis, and white matter lesions
VCID is currently considered as one of the leading causes of dementing illness. The key feature of VCID is diffuse white matter lesions (WML), detected as white matter hyperintensities (WMHs) on MRI scans. However, the underlying mechanisms for pathophysiological changes of white matter lesions and VCID are unknown and there is no treatment for symptomatic VCID. Hypertension and atherosclerosis are the most significant risk factors for dementia epidemics. Using a mouse model of VCID with chronic bilateral carotid artery stenosis (BCAS), we discovered that ion transporter cascade WNK-SPAK-NKCC1 is activated in white matter tracks, which is associated with reactive astrogliosis, WML and cognitive deficits. Further investigation of these molecular and cellular mechanisms of VCID will reveal new knowledge which will be helpful for the development of therapeutic intervention for VCID.
Figure: Schematic summary of ion transporter signaling involved in reactive astrogliosis, oligodendrocytes death, and cognitive impairment.
Inflammatory cytokines in VCID pathogenesis
Reactive astrogliosis and inflammation are the main features in white matter and hippocampus damage in vascular dementia. However, how hypoperfusion stimulates NF-кB-mediated inflammation leading to myelin loss and hippocampal lesions remain unknown. The increased expression of pro-inflammatory cytokines in VCID patients’ plasma, cerebral spinal fluid, and brain tissues suggests that cytokine signaling plays a critical role in the initiation and progression of VCID pathogenesis.
Pathophysiology of ischemic stroke and VCID with obesity/hypertension comorbidity
Stroke remains the 5th leading cause of death and long-term adult disability in the USA because only ~15% patients benefiting from current standard therapies (tissue plasminogen activator and endovascular recanalization) due to their short therapeutic windows and strict inclusion criteria. Hypertension is the most significant risk factor for stroke epidemics. Angiotensin II (Ang II)-induced neurogenic hypertension is associated with worsened ischemic brain damage. However, the clinical trials have shown that blood pressure (BP) lowering treatments in the acute stage of ischemic stroke offer no benefits in improving patient outcomes, possibly due to the negative impact on cerebral perfusion. These findings underscore the need for novel therapeutic strategies that block Ang II-mediated detrimental effects in the ischemic brains without lowering BP and impairing cerebral perfusion. Furthermore, since obesity and its associated metabolic comorbidities, including dyslipidemia, are critical contributors to cognitive impairment, one of our research focuses is to understand how metabolic diseases contribute to ischemic stroke and PSCID.
Publications
Selected Publications
Complete list of our published work at
► https://www.ncbi.nlm.nih.gov/myncbi/mohammad%20iqbal.bhuiyan.1/bibliography/public/
► https://scholar.google.co.kr/citations?user=460C-n4AAAAJ&hl=en
- Bhuiyan M.I.H., Habib K, Sultan M, Fenghua Chen, Jahan I, Weng Z, Rahman M, Islam R, Foley M, Hitchens T, Deng X, Sun D, Cao G. SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia. CNS Neuroscience and Therapeutics, 2024: 30. https://doi.org/10.1111/cns.14654. PMID: 38433018 (corresponding author)
- Chen Zhiping M; Nadya P, Marie R, Jie M, Dennis Z, Nikitha H, Bhuiyan, M.I.H., Steven G. Abolishing UCHL1’s hydrolase activity exacerbates ischemia-induced axonal injury and functional deficits in mice. Journal of Cerebral Blood Flow and Metabolism. 2024: https://doi.org/10.1177/0271678X241258809 (corresponding author)
- Weng Z, Cao C, Stepicheva A, Chen F, Foley L, Cao S, Bhuiyan M.I.H., Wang Y, Wang Q, Hitchens KT, Sun D, Cao G. A novel needle mouse model of vascular cognitive impairment and dementia. Journal of Neuroscience, 2023: 43, 7351-7360. https://doi.org/10.1523/JNEUROSCI.0282-23.2023. PMID: 25740520
- Bhuiyan M.I.H., Fischer S, Patel SM, Oft H, Zhang T, Foley LM, Zhang J, Hitchens TK, Molyneaux BJ, Deng X, Sun D. Efficacy of novel SPAK inhibitor ZT-1a derivatives (1c, 1d, 1g & 1h) on improving post-stroke neurological outcome and brain lesion in mice. Neurochemistry International, 2023: 162, https://doi.org/10.1016/j.neuint.2022.105441. PMID: 36375633
- Bhuiyan M.I.H., Young CB, Jahan I, Hasan MN, Fischer S, Azlan NF, Liu M, Chattopadhyay A, Huang H, Kahle K, Zhang J, Poloyac SM, Molyneaux BJ, Straub AC, Deng X, Gomez D, Sun D. NF-kB signaling-mediated activation of WNK-SPAK-NKCC1 cascade in worsened stroke outcomes of Ang II-hypertensive mice. STROKE, 2022: 53, 1720-1734. DOI: 10.1161/STROKEAHA.121.038351. Pubmed PMID: 35272484. (co-corresponding author).
- Liu Q, Bhuiyan, M.I.H., Liu R; Song S, Begum G, Young CB, Foley LM, Chen F, Hitchens TK, Cao G, Chattopadhyay A, He L, Sun D. Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function. Journal of Neuroinflammation, 2021: 18, 187. doi.org/10.1186/s12974-021-02234-8. PMID: 34454529.
- Zhang J*, Bhuiyan M.I.H.* (shared first-authorship), Zhang T*, Karimy JK, Wu Z, Pigott VM, Zhang J, Huang H, Hassan MN, Skrzypiec AE, Mucha M, Duran D, Huang W, Pawlak R, Foley LM, Hitchens TK, Minnigh MB, Poloyac SM, Alper SL, Molyneaux BJ, Trevelyan AJ, Kahle KT, Sun D, and Deng X. Modulation of brain cation-Cl- cotransport via the SPAK kinase inhibitor ZT-1a. Nature Communications, 2020; 11, 78. doi:10.1038/s41467-019-13851-6. PMID: 31911626.
- Huang H, Bhuiyan M.I.H., Jiang T, Shanshan S, Shankar S, Taraneh T, Eric L, Schreppel P, Hintersteininger M, Yang SS, Lin SH, Molyneaux BJ, Zhang Z, Erker T, Sun D. A novel NKCC1 inhibitor STS66* reduces brain damage in mice after ischemic stroke. Stroke, 2019, 50, 1021-1025. PMID: 30862257
- Bhuiyan M.I.H., Song S, Yuan H, Begum G, Kofler J, Kahle KT, Yang SS, Lin SH, Alper SL, Subramanya AR, Sun D. WNK-Cab39-NKCC1 signaling increases the susceptibility to ischemic brain damage in hypertensive rats. J Cereb Blood Flow Metab. 2017, Vol. 37(8) 2780–2794. DOI: 10.1177/0271678X16675368. PMID: 27798271.
- Bhuiyan M.I.H., Kim J.C., Hwang S.N., Lee M.Y, and Kim S.Y. Ischemic tolerance is associated with VEGF-C and VEGFR-3 signaling in the mouse hippocampus, Neuroscience, 2015; 290: 90-102. DOI: 1016/j.neuroscience.2015.01.025. PMID: 25637798
- Bhuiyan M.I.H., Lee J.W., Kim S.Y. and K.O. Cho, Exogenous expression of Lin28 contributes to survival and proliferation of mouse primary cortical neurons in vitro, Neuroscience, 2013; 248: 448-458. DOI: 10.1016./j.neuroscience.2013.06.023. PMID: 23806711.
- Bhuiyan M.I.H., Islam M.N, Jung S.Y, Yoo H.H, Lee Y.S, and Jin C. Involvement of ceramide in ischemic tolerance induced by preconditioning with sublethal oxygen-glucose deprivation in primary cultured cortical neurons of rats, Biological & Pharmaceutical Bulletin, 2010; 33(1): 11-17. PMID: 20045928.
Team
Positions
Post-doctoral Fellows and Graduate Students
We welcome applicants (postdoc, undergraduate and graduate students) from different universities/colleges to join our lab. We expect applicants to be highly motivated and interested in our current research directions. 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 Dr. Iqbal at mohammad.iqbal@lsuhs.edu.
Contact
Contact Us
LSU Health Shreveport
Department of Neurology
Biomedical Research Institute Rm F8-36
1501 Kings Hwy
Shreveport, LA 71103
Email: mohammad.iqbal@lsuhs.edu
Office: (318) 675-4932
