Research Projects
Molecular vulnerabilities and therapeutic resistance in malignant glioma

Objective and Significance:

Current research focuses on 
1. Investigating the molecular mechanisms to therapeutic resistance in glioblastoma
2. Understanding cancer metabolism and mitochondrial dynamics in glioblastoma

Glioblastoma is the most aggressive primary brain tumor in adults. Despite the use of standard chemotherapy temozolomide having shown promising results in improving patient survival, drug resistance and tumor relapse is almost inevitable. Over the last decade, we have made substantial progress in identifying molecular targets and signalling pathways that drives chemoresistance in glioblastoma, including the endoplasmic reticulum stress signalling pathway and autophagy. To allow a better understanding on how tumor heterogeneity in glioblastoma contribute to chemoresistance, we apply single cell-RNA sequencing and other novel tools including CRISPR screen to uncover novel mechanistic insights. We aim to answer fundamental questions such as how do treatment-resistant cells evolve and the oncogenic pathways that drive tumor recurrence during therapeutic treatments.

Mitochondria are indispensable for cellular metabolism in both transformed and non-transformed cells. In order to sustain rapid cell proliferation and support biosynthesis of anabolic precursors, cancer cells are particularly susceptible to perturbations of mitochondrial function. Apart from cell metabolism, mitochondria have also been implicated in many other cellular functions, including autophagy and apoptotic cell death. Despite the Warburg theory that proposed aerobic glycolysis as the main source of energy for cancer cells, recent studies revealed the metabolic or mitochondrial heterogeneity in glioblastoma, suggesting that oxidative phosphorylation remained as an alternative energy source. Such metabolic heterogeneity may arise from the genetic or molecular factors that are cell-intrinsic, or it may arise from the cellular interaction with the tumor microenvironment. We aim to investigate whether and how the tumor microenvironment may play a role in regulating tumor growth via modulating cancer metabolism and mitochondrial dynamics. In translational perspective, we aim to provide the scientific basis for the development of therapeutic interventions. 

Dr KMY Kiang, Department of Surgery

Dr. MY Kiang is currently a Research Assistant Professor at the Department of Surgery. She obtained her Ph.D. in neuro-oncology from the University of Hong Kong, and received her postdoctoral training with a research focus on therapeutic resistance in glioblastoma. During which she has also been trained in the Brain tumor centre of the Cincinnati Children’s Hospital in USA. Her research interest include the identification of molecular alterations that drive cancer relapse, finding new ways to tackle drug resistance and translating these findings into clinical application using novel therapeutic strategies and combination treatment regimens.

Biography
HKU Scholars Hub
mykiang@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.