Dr Zeyad Nassar

Over the past 10 years of my postgraduate degrees and postdoctoral training, I have developed diverse experiences in cancer research including developing novel angiogenesis modulators for colon and breast cancer, deciphering the role of lipid raft proteins in prostate cancer progression, investigating the potential interplay between opioid analgesia and breast tumor metastasis, inspecting the role of lipid raft proteins in glioblastoma in responding to interstitial fluid pressure and tumor invasiveness, and finally lipid biology and metabolism in prostate cancer.

Since 2016, I have developed a deep interest in elucidating lipid metabolism and membrane lipid roles in the regulation of processes linked to aggressive and treatment resistant prostate cancer behaviors and investigating their potential for therapeutic targeting. My ultimate goal is to perform research that impacts patients’ lives. I have been funded by scholarships and fellowships throughout all stages of my research career. During my MSc and PhD degrees, I built extensive basic science expertise and employed multiple preclinical models focused on drug discovery and development for cancer. My MSc degree demonstrated the antiangiogenic activities of natural/synthetic products in colon and breast cancers. This work led to 1 patent for the natural product koetjapic acid, and 2 clinical trials for the natural product Nuvastatic™ (NCT04552600, NCT04546607). My PhD at The University of Queensland (UQ) studied 2 transmembrane proteins that form a special type of lipid rafts called caveolae. This work resulted in 5 first-author articles in high quality journals (Nature Reviews Urology and International Review of Cell and Molecular Biology, Oncotarget).

To achieve my goal of running a more translational research program, I relocated in 2016 to the University of Adelaide to work in a highly translational research group experienced in patient-derived models, biobanking, “bench to bedside” research and clinical trials. In prostate cancer (PCa), fatty acid oxidation (FAO) plays a crucial role in fueling disease initiation and progression. My research activities have provided strong evidence that PCa cells exhibit increased FAO compared to non-malignant cells and showed that clinical PCa is amenable to FAO targeting. I provided the first clinically relevant evidence, using patient-derived prostate tumor explants, that targeting FAO in prostate cancer is efficacious. In addition, I showed that activated FAO pathways mediate drug resistance and demonstrated that targeting FAO sensitizes PCa to novel drug treatments. I identified DECR1, which catalyzes the rate-limiting step in an auxiliary pathway for poly unsaturated fatty acid β-oxidation, as a previously unrecognized androgen-repressed and anti-ferroptosis enzyme in PCa cells and found its expression to be correlated with disease progression. This work provided a novel opportunity to target a selective class of fatty acids (with likely less toxicity), rather than shutting down FAO of all classes. My current projects: 

1) Develop selective inhibitors against DECR1, this will be the first-in-field specific inhibitor for PUFA oxidation. 

2) Investigate the epigenetic role of FAO in modulating gene expression to support PCa progression and treatment resistance. 

3) Repurpose clinically-approved FAO inhibitors for PCa treatment.

4) Decipher the role of mitochondria dynamic proteins in PCa progression, and investigate the potential of targeting.