Developmental Neuroimmune Lab

About

Dedicated to advancing understanding of gene-environment interactions that influence the development, disease, and regeneration of the central nervous system (CNS). The research focuses on two major areas:

Myelination and white matter biology – We investigate the molecular mechanisms underlying oligodendrocyte development, myelin formation and plasticity, demyelination, and remyelination. These studies provide insights into white matter impairments observed in conditions such as Neonatal Opioid Withdrawal Syndrome (NOWS) and Multiple Sclerosis (MS).
Neuroinflammation and cell communication – We study the mechanisms of cell-to-cell communication within immune and inflammatory responses in neurodevelopmental, neuroinflammatory, neurotraumatic disorders, and gliomas.

Our lab employs diverse technical platforms, including genetic manipulation, embryonic or tissue electroporation, stereotactic focal injections of drugs, viruses, or cells, and neurobehavioral assays. We also develop and utilize multiple rodent models, such as drug-induced demyelination/remyelination, spinal cord and brain injury, chronic or intermittent hypoxia exposure, and orthotopic xenograft models of diffuse intrinsic pontine glioma (DIPG), glioblastoma (GBM), neuroblastoma (NB), and osteosarcoma (OS).

Key Research Areas

Oligodendrocyte development, myelination, and white matter development
Myelin plasticity, demyelination, and remyelination
Cell-to-cell communication and neurocircuitry in neurodevelopmental, neurodegenerative (e.g. MS), and neurotraumatic disorders
Tumor immune microenvironment (TIME) in pediatric high-grade glioma and immunotherapy
Development of CAR-T cellular therapies in malignant pediatric solid tumors.

Current Projects

Project 1 – Developmental neurotoxicity of cadmium: connecting early-life environmental exposure to risk of neurodevelopmental disorders.
Project 2 – Epigenomic reprogramming by early-life environmental cadmium exposure and its impact on pediatric high-grade glioma and CAR T-cell immunotherapy.
Project 3 – Targeting the CXCL12-CXCR4 signaling axis to restore glial homeostasis in demyelinating diseases.
Project 4- Neuroinflammatory pathways and immune targets for therapeutic intervention in rotational acceleration-deceleration neonatal brain injury.

Team

Wenxin (Wendy) Zeng, Researcher, wenxin.zeng@louisville.edu, 852-2217

Bin Yang, Research Assistant II, bin.yang@louisville.edu, 852-2217

Recent Publications

Oberoi, R., Chu, T., Mellen, N., Jagadapillai, R., Ouyang, H., Devlin, L.A.^#, and Cai, J.^# (2019) Diverse changes in myelin protein expression in rat brain after perinatal methadone exposure. Acta Neurobiologiae Experimentalis 79: 354-360. doi: 10.21307/ane‑2019‑033.
Xu, H., Wang, J., Cai, J., Feng, W., Wang, Y., Liu, Q, Cai, L. (2019) Protective effect of lactobacillus rhamnosus GG and its supernatant against myocardial dysfunction in obese mice exposed to intermittent hypoxia is associated with activation of Nrf2 pathway. International Journal of Biological Sciences 15(11): 2471-2483.
Chu, T., Zhang, Y-P., Tian, Z., Ye, C., Zhu, M., Shields, B.E., Kong, M., Barnes, G.N., Shields, C.B.^#, and Cai, J.^# (2019) Dynamic response of microglia/macrophage polarization following demyelination in mice. Journal of Neuroinflammation 16: 188.
Wang, J., Zhang, J., Chen, L., Cai, J., Li, Z., Zhang, Z, Wang, Y. Zhou, S., Liu, Q., and Cai, L. (2019) Combination of broccoli sprout extract and zinc provides better protection against intermittent hypoxia-induced cardiomyopathy than monotherapy in mice. Oxidative Medicine and Cellular Longevity 2019: Article ID 2985901. doi: 10.1155/2019/2985901.
Lin, X., Jagadapillai, R., Cai, J., Cai, L., Shao, G, Gozal, E. (2020) Metallothionein induction attenuates the progression of lung injury in mice exposed to long-term intermittent hypoxia. Inflammation Research 69: 15–26. doi: 10.1007/s00011-019-01287-z.
Liu, Qi, Liu, Y., Li, F., Barve, S., Chen, Y., Pan, C., Gu, Z., Shao, T., He, L., Zhang, L., Zhou, G., Zhang, X., Cai, J., McClain, C., and Feng, W. (2020) Probiotic culture supernatant improves metabolic function through FGF21-adiponectin pathway and intestinal bile acid metabolism in mice. The Journal of Nutritional Biochemistry 75: 108256. doi: 10.1016/j.jnutbio.2019.108256
Kang, Y., Zhang, G., Huang, E.C., Huang, J., Cai, J., Cai, L., and Keller, B.B. (2020) Sulforaphane prevents right ventricular injury and reduces pulmonary vascular remodeling in pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol. 318(4):H853-H866. doi: 10.1152/ajpheart.00321.20 19.
Zhang, Y., Cao, H., Qiu, X., Xu, D., Chen, Y., Barnes, G.N., Tu, J., Gyabaah, A.T., Gharbal, A.H.A.A., Peng, C., Cai, J.^#, and Cai, X.H.^# (2020) Neuroprotective effects of adenosine A1 receptor signaling on cognitive impairment induced by chronic intermittent hypoxia in mice. Frontiers in Cellular Neuroscience 14: Article 202.
Tian, Z., Chu, T., Shields, B.E., Zhu, Q., Zhang Y-P., Barnes, G.N., Wang, Y., Shileds, C.B., and Cai, J. (2020) Platelet-activating factor deteriorates lysophosphatidylcholine-induced demyelination via its receptor-dependent and -independent mechanisms. Molecular Neurobiology 57: 4069-4081. doi: https://doi.org/10.1007/s12035-020-02003-3.
Tian, Z., Ning, C., Fu, C., Xu, F., Zou, C., Zhu, Q., Cai, J.^#, and Wang, Y.^# (2020) CALCOCO2 silencing represents a potential molecular therapeutic target for glioma. Archives of Medical Science (published online) doi: https://doi.org/10.5114/aoms.2020.95880.
Chu, T., Shields, B.E., Zeng, W., Zhang, Y-P., Wang, Y., Barnes, G.N., Shields, C.B.^#, and Cai, J.^# (2021) Dynamic glial response and crosstalk in demyelination-remyelination and neurodegeneration processes. Neural Regeneration Research 16 (7): 1359-1368.
Gozal, E., Jagadapilllai, R., Cai, J., and Barnes, G.N. (2021) Potential crosstalk between sonic hedgehog-WNT signaling and neurovascular molecules: Implications for blood brain barrier integrity in ASD. Journal of Neurochemistry 159 (1): 15-28.
Wise, J.P., Young, J.L., Cai, J., and Cai, L. (2022) Current Understanding of Hexavalent Chromium [Cr (VI)] Neurotoxicity and New Perspectives. Environment International 158: 106877.
Zhang, G., Kang, Y., Cathey, D., LeBlanc, A.J., Cai, J., Cai, L., Wang, S., Huang, J., and Bradley, B.K. (2022) Sulforaphane does not protect right ventricular systolic and diastolic functions in Nrf2 knockout pulmonary artery hypertension mice. Cardiovascular Drugs and Therapy 36(3):425-436. doi: 10.1007/s10557-022-07323-1.
Gibson, J.M., Chu, T., Zeng, W., Wethall, A.C., Mellen, N., Devlin Phinney, L.A.^#, Cai, J.^# (2022) Perinatal Methadone Exposure Attenuates Myelination and Induces Oligodendrocyte Apoptosis in Neonatal Rat Brain. Experimental Biology and Medicine 247(12): 1067-1079 (feature article, press release with Globe Newswire and AP News).
Gourévitch, B., Pitts, T., Iceman, K., Reed, M., Cai, J., Chu, T., Zeng, W., Morgado-Valle, C., Mellen, N. (2023) Synchronization of inspiratory burst onset along the ventral respiratory column in the neonate mouse is mediated by electrotonic coupling. BMC Biology 21: Article 83.
Shrader, S.H., Mellen, N., Cai, J., Barnes, G.N., Song, Z-H. (2024) Cannabidiol is a behavioral modulator in BTBR mouse model of idiopathic autism. Frontiers in Neuroscience 18: 1359810.
Vielee, S., Isibor, J., Buchanan, W.J., Roof, S.H., Patel, M., Meaza, I. Williams, A., Toyoda, J.H., Lu, H., Wise, S.S., Kouokam, J. C., Wise, J. L., Aboueissa, A-M, Cai, J., Cai, L., Wise, J.P. Jr. (2024) Employing a toxic aging coin to assess hexavalent chromium (Cr[VI]) neurotoxic effects on behavior: heads for age differences. Toxicology and Applied Pharmacology 489: 117007.
Vielee, S., Isibor, J., Buchanan, W.J., Roof, S.H., Patel, M., Meaza, I. Williams, A., Toyoda, J.H., Lu, H., Wise, S., Kouokam, J. C., Wise, J. L., Aboueissa, A-M, Cai, J., Cai, L., Wise, J.P. Jr. (2024) Female Rat Behavior Effects from Low Levels of Hexavalent Chromium (Cr[VI]) in drinking water evaluated with a toxic aging coin approach. Applied Sciences 14(14): 6206.
Vielee, S., Buchanan, L., Roof, S.H., Kahloon, R., Evans, E., Isibor, J., Patel, M., Meaza, I.I., Lu, H., Williams, A., Kouokam, J. C., Wise, S.S., Guo, L., Wise, R.M., Wise, J. Y., Cai, L., Cai, J., Wise, J.P. Jr. (2024) Chromium Selectively Accumulates in the Rat Hippocampus After 90-Days Drinking Water Exposure and Induces Age- and Sex-Dependent Metal Dyshomeostasis. Toxics 12(10): 722.
Shields, L.B.E., Iyer, V.G., Kluthe, T., Jawad, K., Cai, J., Zhang, Y-P., Shields, C.B. (2025) Clinical and Electrodiagnostic Correlations of Ultrasound-Detected Markedly Enlarged Median Nerve at the Wrist. Neurology International 17: 124.