The Doctor of Philosophy Seminar and Examination of Jing Ju

Biography

Jing Ju, originally from Nanjing, China, is a committed researcher specializing in the interplay between neuroinflammation and vascular biology in ischemic stroke. During his PhD, Jing uncovered the role of EphA4 in immune-mediated arteriogenesis following ischemic stroke. His research has provided valuable insights into the molecular mechanisms that drive neuroinflammation and vascular remodeling, contributing to the development of novel therapeutic approaches for stroke treatment.

Jing holds a Master’s degree in Cancer Biology from Drexel University and a Master’s degree in Biochemistry and Molecular Biology from Nanjing Medical University. He is passionate about advancing the field of neurovascular biology and plans to continue his research in neuroscience post-PhD.

Funded by

NIH NINDS (R01 NS112541) 
MCB 
IGEP in Regenerative Medicine 
VMCVM Office of Research and Graduate Studies 

Awards and Academic Achievements

2023-2024 Graduate School Doctoral Assistantship

2022-2023 Regenerative Medicine IGEP Assistantship. 

Spring 2023 1st Place poster presentation at 32nd Annual Research Symposium

Spring 2022 MCB Travel Award to the 2022 Annual Symposium of the National Neurotrauma Society.

Lay Language Abstract 

Stroke, a life-threatening condition, occurs when blood flow to part of the brain is disrupted due to the vascular occlusion of a major brain artery, such as the middle cerebral artery (MCA). Within protective layers of our brain, there are pre-existing pial collateral vessels that act as backup connections. These vessels play an important role in increasing cerebral reperfusion and preventing tissue damage after ischemic stroke. One fascinating aspect of stroke recovery involves peripheral-derived immune cells (PICs). These immune cells migrate into the blood hypo-perfused region of the brain and regulate the growth of collateral vessels. However, the specific functions of PICs, particularly a receptor called EphA4, has remained unclear. Our research delved into the immune response following ischemic stroke using genetically modified mice. We examined immune cell populations, infarct volume (the damaged brain tissue), functional recovery, and collateral vessel diameters. Notably, we discovered that deletion of PIC-specific EphA4 enhanced collateral vessel remodeling. This led to decreased infarct volume, better blood flow, and improved functional recovery within 24 hours after ischemic stroke. Furthermore, we explored a signaling pathway involving Tie2 and PI3K in peripheral-derived monocytes/macrophages. This crosstalk between EphA4 and Tie2, mediated through PI3K regulation, played a critical role in suppressing collateral vessel remodeling. In summary, understanding how immune cells contribute to stroke recovery may pave the way for novel therapeutic approaches to enhance outcomes for stroke patients.

Publications

1. Soliman, E., Gudenschwager Basso, Ju, J., Willison, A., Theus, M.H. Skull bone-derived immune cells infiltrate the damaged cortex and exhibit anti-inflammatory properties. Brain Behavior and Immunity (in revision).

2. Ji, X., E, Zhang, X., Zhang, T., Xue, Y., He, M., Li, C., Huang, Y., Ju, J., et al. PNPLA7 mediates Parkin-mitochondrial recruitment in adipose tissue for mitophagy and inhibits browning. Nature Communications (in revision).

3. Fritsch L E, Kelly C, Leonard J, Ju, J., et al. STING-dependent signaling in microglia or peripheral immune cells orchestrates the early inflammatory response and influences brain injury outcome[J]. Journal of Neuroscience, 2024, 44(12).

4. Gudenschwager Basso E K, Ju J, Soliman E, et al. Immunoregulatory and neutrophil-like monocyte subsets with distinct single-cell transcriptomic signatures emerge following brain injury[J]. Journal of Neuroinflammation, 2024, 21(1): 41.

5. Soliman E, Leonard J, Basso E K G, Ju, J., et al. Efferocytosis is restricted by axon guidance molecule EphA4 via ERK/Stat6/MERTK signaling following brain injury[J]. Journal of Neuroinflammation, 2023, 20(1): 256.

6. Cash, A., Brickler, T., Jager, C.D, Johnson, Z., Mills, J., Ju, J., Sotiropoulos, Y., Chen, M., Wang, X., Xie, H, Theus, M.H. Endothelial deletion of EPH receptor A4 alters single-cell profile and Tie2/Akap12 signaling to preserve blood–brain barrier integrity[J]. Proceedings of the National Academy of Sciences, 2023, 120(41): e2204700120.

7. Kowalski, E.A., Soliman, E., Kelly, C., Basso, E.K.G., Leonard, J., Pridham, K., Hazy, A., Ju, J., Cash, A., Jager, C.D, Kaloss, A.M., Ding, H., Hernandez, R.D., Coleman, G., Wang, X., Olsen, M.L., Pickrell, A.M., Theus, M.H. Monocyte proinflammatory phenotypic control by ephrin type A receptor 4 mediates neural tissue damage. JCI insight, 2022, 7(15).

8. Fritsch, L., Ju, J., Basso, E.K.G., Soliman, E., Paul, S., Chen, J., Kowalski, E.A., Tuhy, T., Somaiya, R., Wang, X., Allen, I., Theus, M. H., Pickrell, A.M. Type I Interferon Response is Mediated by NLRX1-cGAS-STING Signaling in Brain Injury. Frontiers in Molecular Neuroscience (2022): 53.

9. Ciraku, L., Bacigalupa, Z.A., Ju, J., Moeller, R.A., Minh, G.L., Lee, R.H., Smith, M.D., Ferrer, C.M., Trefely, S., Izzo, L.T., Doan, M.T., Gocal1, W.A., Agostino, L.D., Shi, W., Jackson, J.G., Katsetos, C.D., Wellen, K.E., Snyder, N.W., Reginato, M.J. O-GlcNAc Transferase Regulates Glioblastoma Acetate Metabolism via Regulation of CDK5-dependent ACSS2 phosphorylation. Oncogene 41, no. 14 (2022): 2122-2136.

10. Ahmed, S., Travis, S.D., Díaz-Bahamonde, F.V., Porter, D.D., Henry, S.N., Mykins, J., Ravipati, A., Booker, A., Ju, J., Ding, H., Ramesh, A.K., 2021. Early influences of microbiota on white matter development in germ-free piglets. Frontiers in Cellular Neuroscience, 2021, 15: 520.

11. Soliman, E., Mills, J., Ju, J., Kaloss, A.M., Basso, E.K.G., Groot, N., Kelly, C., Kowalski, E.A., Elhassanny, M., Chen, M., Wang, X., Theus, M. H. Conditional deletion of EphA4 on Cx3cr1-expressing microglia fails to influence histopathological outcome and blood brain barrier disruption following TBI. Frontiers in Molecular Neuroscience, 2021, 196.

12. Li, Q., Yu Q, Ju, J., You, T., Yan, Z., Nan, X., Zhong, J., Zhou, JE. Therapeutic effect of IFN-α long-circulating liposome targeting at platelet-derived growth factor receptor-β on hepatic fibrosis. Current Pharmaceutical Design, 2017, 23(20): 3034-3046.

Presentations

Ju, J. Theus, M. H. Immune regulation of pial collateral vessels in ischemic stroke. 41st Annual Neurotrauma Symposium 2024, San Fransico, CA, June 2024.

Ju, J. Theus, M. H. The emerging role of peripheral-derived immune cells in the remodeling of pre-existing pial collateral vessels following ischemic stroke. 40th Annual Neurotrauma Symposium 2023, Austin, TX, June 2023.

Ju, J. Theus, M. H. Novel regulation of peripheral-derived immune cells contributes to the pial collateral remodeling following ischemic stroke” Research in Progress Seminar. October 2022.

Ju, J. Theus, M. H. Peripheral-derived immune cells contribute to the remodeling of pial collateral vessels following ischemic stroke. 39th Annual Neurotrauma Symposium 2022,Atlanta, GA, June 2022.

Ju, J. Theus, M. H. Novel regulation of peripheral-derived immune cells in the remodeling of pial collateral vessels following ischemic stroke. International Stroke Conference 2022, New Orleans, LA, February 2022.

Ju, J. Novel regulation of immune-mediated arteriogenesis following ischemic stroke” Research in Progress Seminar. July 2021.

Ju, J. Kowalski, E.A., Kaloss A, Basso, E.K.G., Wang, X., Theus, M. H. Peripheral immune cell-mediated remodeling of pre-existing pial collateral vessels in a murine model of ischemic stroke. American Society for Neural Therapy and Repair, Clearwater, FL, August 2021.

Examination Graduate Committee

Major Advisor/Chair:

Michelle H. Theus, PhD
Professor
Department of Biomedical Sciences and Pathobiology

Graduate Advising Committee Members:

Liwu Li, PhD 
Professor
Department of Biological Sciences

Jia-Qiang He, PhD
Associate Professor
Department of Biomedical Sciences and Pathobiology

William R. Huckle, MS, PhD
Associate Professor
Department of Biomedical Sciences and Pathobiology