Current Projects supervised under Prof. Des Richardson — Centre for Cancer Cell Biology and Drug Discovery (CBDD)

Current projects

Current projects (9)

A Novel Paradigm to NO Biology and Regulation

This project aims to assess if GST P1 and other GST family members (GST A and M) form an integrated system of NO storage and transport together with MRP1 in macrophages, endothelial cells, and hepatoma cells. These aims collectively serve to test the hypothesis that NO is not freely diffusible in cells but is rather stringently regulated by interacting with proteins to enable transport and storage. (Read more…)

Tiffany Russell (Honours Candidate) — **Tiffany Russell (PhD Candidate)**

**Prof. Des Richardson (Primary Supervisor)**

Development of Innovative Chemotherapeutics for Cancer Treatment that Overcome Drug-Resistance and Polyamine Metabolism

For patients, it’s devastating news when the drug that has been working in treating their cancer is no longer effective and multi-drug resistance (MDR) develops. Poor response to chemotherapy is linked to the resistance protein, P-glycoprotein (Pgp). We discovered special anti-cancer drugs (thiosemicarbazones known as DpC and Dp44mT) that cleverly “hijack” and use Pgp in lysosomes to kill tumours. (Read more…)

**Dr. Mahendiran Dharmasivam (Post-doctoral Felllow)**

Developing Novel Calcium Channel Antagonists Using Artificial Intelligence To Better Treat Parkinson’s Disease

Parkinson’s disease (PD) therapeutics are dismal as Levodopa and dopamine-agonists, poorly treat patient symptomologies. Manifesting -synuclein and iron pathologies ultimately cause complete neuronal death within the Substantia Nigra of PD patients. Synaptic physiology mandates the opening of voltage-gated calcium channels in response to action potentials. (Read more…)

**Dr. Linlin Ma (Secondary Supervisor)**

Dissection of the Mechanisms of Iron Metabolism of Human Neuroblastoma and the Use of Innovative Iron-Binding Drugs as Novel Anti-Cancer Therapeutics

Neuroblastoma (NB) is an aggressive and the most common extracranial solid tumor of childhood with a 17-month median age of diagnosis. Interestingly, the serum ferritin level of patients was found to be related to the prognosis of NB patients, with high levels suggesting a poor prognosis and low levels a good prognosis. Research has demonstrated that the intracellular iron concentration of NB cells is extremely higher than other types of cancer cells and this extremely high level of iron concentration indicates the unusual up-taken and metabolism of iron in cells. (Read more…)

Pharmacological Ascorbate Levels Inhibit Expression of WNT Signaling Proteins, Polyamine Pathway Enzymes and Cell Cycle Progression Proteins to Inhibit Tumor Cell Growth

The history of the anti-cancer activity of ascorbate (Asc) has been a controversial one. This originally arose as the mechanism behind the anti-cancer activity of Asc could not be explained due to the lack of understanding of the pharmacokinetics of Asc. However, upon distinguishing the effect of oral and intervenous routes of administration on Asc levels in patients, a clear difference between physiological (induced via oral administrations) and pharmacological concentrations of Asc (induced via the intravenous route) was highlighted… (See more).

Mahan Gholam Azad (Research Assistant) — **Mahan Gholam Azad (PhD Candidate & Research Assistant)**

Novel NAD Enhancing Therapeutics for Alzheimer’s Disease.

Alzheimer’s disease (AD) is a multi-factorial disease that remains an intractable problem in the elderly and no cure exists. Notably, AD affects 35 million people worldwide and is the most common cause of dementia. Thus, accelerating innovation in AD therapeutics is an urgent priority, particularly as current therapies target only 1 aspect of the complex pathology in AD. (Read more…)

Overcoming the “Triad of Death” in Cancer by Developing Frontier, Anti-Cancer Drugs for the Treatment of Deadly Childhood Neuroblastoma

Neuroblastoma is a deadly childhood tumour which causes around 15% of the cancer deaths of children. Its resistance to standard chemotherapies has made it a challenging condition to treat. Therefore, the evaluation of new innovative therapies for neuroblastoma remains critical. Our laboratory over the past 30 years has developed a series of frontier therapeutics for cancer, such as Dp44mT and DpC, which inhibit tumour growth by a unique mechanism. (Read more…)

Tharushi Wijesinghe (Honours Candidate) — **Tharushi Wijesinghe (PhD Candidate)**

**Dr. Mahendiran Dharmasivam (Secondary Supervisor)**

The development of new generation chemotherapeutical drugs for cancer treatments

Dr. Dai’s project is focused on the development of new generation chemotherapeutical drugs for cancer treatments. His work is based on previous CBDD anticancer drug studies, and aiming to develop the drug candidates with rapid anti-cancer activity and the ability for the treatment of resistant cancers. His research includes the chemical synthesis of novel anti-cancer chelators, the structure-activity relationship study and the evaluation of the biological activity in vivo. (Read more…)

NDRG1 upregulation by metal chelators and its effect on c-CBL phosphorylation in pancreatic cancer

This project attempts to elucidate for the first time a novel mechanism by which NDRG1 inhibits cancer involving the protein c-Cbl in pancreatic cancer cells. The c-Cbl protein is an E3 ubiquitin ligase that initiates the degradation of proteins via proteasomal degradation. c-Cbl can inhibit oncogenic pathways in cancer by inducing the degradation of receptor tyrosine kinases such as epidermal growth factor receptor (EGFR). However, phosphorylation on Tyr731 and Tyr774 enables c-Cbl to recruit proteins such as the p85 phosphoinositide 3-kinase (PI3K) regulatory subunit and CT10 regulator of kinase (Crk) which subsequently promotes… (Read more…)