The research laboratory of Neurosurgery engages in a wide range of basic and translational projects on diseases of the central nervous system. Our research programmes cover areas ranging from neuro-oncology to neuro-vascular and neuro-trauma studies. We aim to provide the scientific rationale and preclinical evidence to guide and inform future studies and practices in clinical neuroscience. Our research team consists of neurosurgeons, basic scientists, postgraduate research students as well as medical students who collaborate for the rapid translation of pioneering researches. We have established a number of innovative in vitro and in vivo platforms for studying different clinical conditions that have enabled us to form close collaborative ties with other multidisciplinary teams as well as pharmaceutical companies.

Research Interests

Glioblastoma

Targeting cancer vulnerabilities

By looking into the cancer pathophysiology, our team has been finding the faulty genes that drive cancer progression. To do this, we have established single-cell RNA sequencing platform using patient tumor samples to allow a better understanding of the molecular weakness in cancer cells. We have also developed different animal-based platforms to further investigate the molecular basis that sets them apart from non-tumor cells, such as cancer metabolism, and to explore the translational potential by targeting these vulnerabilities while leaving healthy cells unharmed.

Finding new ways to tackle chemoresistance

Temozolomide is the current standard chemotherapy and often represents the control-arm in clinical trials. However, drug resistance and tumor relapse is almost inevitable. Over the last decade, we have identified promising targets and signalling pathways that drive chemoresistance in glioblastoma. Our research focuses on translating these findings into clinical application, including preclinical evaluation of new combination therapies and the use of nanoparticles for better drug delivery.

Understanding tumor immune microenvironment

The ability of cancer cells to evade the immune system represents a major contributing factor to cancer progression. Despite substantial efforts in understanding the immune evasion mechanism, there is still no FDA-approved immunotherapy for glioblastoma. Our research findings suggested the crosstalk between cancer metabolism and immune response. We aim to better understand the mechanisms by which the metabolic signalling pathways may involve in shaping the immunosuppressive phenotypes. Furthermore, we also study the role of tumor associated macrophage in regulating cancer immune evasion..

Intracerebral haemorrhage (ICH)

Understanding the pathophysiology of ICH

The pathophysiological process of ICH within the primary site of injury (the gray matter) has been well-studied, however, patients with ICH are still associated with high morbidity and mortality rates with no effective treatments available. It is not until recent years that white matter injury in the brain was found after subcortical ICH. Our research has demonstrated for the first time the prolonged demyelination of the contralesional dorsal corticospinal tract in the spinal cord after ICH. We aim to further investigate the underlying pathophysiological mechanisms that undermined the structure integrity after prolonged damage in cervical spinal cord of ICH patients.

Developing new strategies for neuroprotection

Our finding that corticospinal tract integrity within the spinal cord may correlate with functional recovery post-ICH has opened up new therapeutic directions on how ICH patients should be treated and rehabilitated. Our research focuses to develop or repurpose drugs to improve neurological outcomes in patients after ICH, possibly through enhancing hematoma clearance or preserving neuronal survival, with an ultimate goal taking new drugs from the lab to the clinic.

Spinal cord injury

The quest for neuroprotective drugs

Spinal cord injury is a catastrophic condition that affect patients’ physical, mental and social well-being. Current therapeutic strategies include early operations for mechanism decompression, symptomatic relief, supportive care and rehabilitation. Our neuro-trauma team focuses on exploring the neuroprotective agents that can enhance neuronal survival as well as to promote motor recovery after spinal cord injury.

Contact

Postgraduate study positions are available. Please send us your CV with research interest for consideration.

Professor Gilberto Ka-Kit LEUNG Tsang Wing-Hing Professor in Clinical Neuroscience Email: gilberto@hku.hk Tel: +852 2255 3368

Related Publications

1. Zhu Z, Kiang KM, Li N, Liu J, Zhang P, Jin L, He X, Zhang S, Leung GK. Folate enzyme MTHFD2 links one-carbon metabolism to unfolded protein response in glioblastoma. Cancer Letters. 2022.
2. Liu J, Li N, Zhu Z, Kiang KM, Ng ACK, Dong CM, Leung GK. Vitamin D enhances hematoma clearance and neurologic recovery in intracerebral hemorrhage. Stroke. 2022.
3. Choudhury A, Magil ST, Eaton CD, Prage BC, Chen WC, Cady MA, Seo K, Lucas CG, Casey-Clyde TJ, Vasudevan HN, Liu SJ, Villanueva-Meyer JE, Lam T, Pu JK, Li L, Leung GK, Swaney DL, Zhang MY, ChanJW, Qiu Z, Martin MV, Susko MS, Braunstein SE, Bush EAO, Schulte J, Butowski N, Sneed PK, Berger MS, Krogan NJ, Perry A, Phillips JJ, Solomon DA, Costello JF, McDermott MC, Rich JN, Raleigh DR. Meningioma DNA methylation grouping reveals biologic drivers and therapeutic vulnerabilities. Nature Genetics. 2022.
4. Li N, Yao M, Liu J, Zhu Z, Lam T, Zhang P, Kiang KM, Leung GK. Vitamin D promotes remyelination by suppressing c-Myc and inducing oligodendrocyte precursor cell differentiation after traumatic spinal cord injury. International Journal of Biological Sciences. 2022.
5. Lai JHC, Liu J, Yang T, Huang J, Liu Y, Chen Z, Lee Y, Leung GK, Chan KWY. CEST MRI for longitudinal assessment of intracerebral hemorrhage and deferoxamine treatment at 3T in a mouse model. Stroke. 2022.
6. Yao M, Fang J, Li J, Ng ACK, Liu J, Leung GK, Song F, Zhang J, Chang C. Modulation of the proteoglycan receptor PTP promotes white matter integrity and functional recovery after intracranial hemorrhage stroke in mice. Journal of neuroinflammation. 2022.
7. Lee S, Pang L, Cheng Y, Liu J, Ng ACK, Leung GK. A previous hemorrhagic stroke protects against a subsequent stroke via microglia alternative polarization. Communications biology. 2022.
8. Liu J, Zhu Z, Leung GK. Erythrophagocytosis by microglia/Macrophage in intracerebral hemorrhage: From mechanisms to translation. Frontiers in cellular neuroscience. 2022.
9. Sun S, Kiang KM, Leung GK. Chaperone protein P4HB predicts temozolomide response and prognosis in malignant glioma. Oncology Letters. 2022.
10. Liu Y, Leong ATL, Zhao Y, Xiao L, Mak HKF, Tsang ACO, Lau GKK, Leung GK, Wu EX. A low-cost and shielding-free ultra-low-field brain MRI scanner. Nature Communications. 2021.
11. Kiang KM, Sun S, Leung GK. ADD3 deletion in glioblastoma predicts disease status and survival. Frontiers in Oncology. 2021.
12. Kiang KM, Chan AA, Leung GK. Secondary gliosarcoma: the clinicopathological features and the development of a patient-derived xenograft model of gliosarcoma. BMC Cancer. 2021.
13. Jin L, Kiang KM, Cheng Y, Leung GK. Pharmacological inhibition of serine synthesis pathway enhances temozolomide chemo-efficacy by decreasing MGMT expression and ROS-mediated DNA damage in glioblastoma. Laboratory Investigation. 2021.
14. Lo CS, Kiang KM, Leung GK. Anti-tumour effects of vitamin D in glioblastoma: Mechanism and therapeutic implications. Laboratory Investigation. 2021.
15. Li N, Chau CYC, Liu J, Yao M, Kiang KM, Zhu Z, Zhang P, Cheng H, Leung GK. Postcooling but not precooling benefits motor recovery by suppressing cell death after surgical spinal cord injury in rats. World Neurosurgery 2021.
16. Kiang KM, Zhang P, Li N, Zhu Z, Jin L, Leung GK. Loss of cytoskeleton protein ADD3 promotes tumor growth and angiogenesis in glioblastoma multiforme. Cancer Letters. 2020.
17. Zhu Z, Leung GK. More Than a Metabolic Enzyme: MTHFD2 as a Novel Target for Anticancer Therapy? Frontiers in Oncology. 2020.
18. Ng ACK, Yao M, Cheng SY, Li J, Huang JD, Wu W, Leung GK, Sun H. Protracted Morphological Changes in the Corticospinal Tract Within the Cervical Spinal Cord After Intracerebral Hemorrhage in the Right Striatum of Mice. Frontiers in Neuroscience. 2020.
19. You J, Tsang Aco, Yu PLH, Tsui ELH, Woo PPS, Lui CSM, Leung GK. Automated hierarchy evaluation system of large vessel occlusion in acute ischemia stroke. Frontiers Neuroinformatics. 2020.