Dr Zeyad Nassar

Current research projects: 

Precision medicine aims to customise treatments based on the unique characteristics of each patient's disease. Unlike the traditional "one-size-fits-all" approach, precision medicine improves our ability to predict which treatments will be safe and effective for individual patients based on their genetic makeup. Adopting precision medicine could reduce both financial and time costs, improve patients' quality of life, and potentially extend their lifespan. Despite advances in other cancer types, precision medicine for prostate cancer remains underdeveloped. My program aims to advance precision medicine in prostate cancer through the innovative use of synthetic lethality to identify and validate new therapeutic targets

1. Identifying Vulnerabilities in Prostate Cancer Using Synthetic Lethality Approaches for Precision Medicine

Prostate cancer (PCa) presents a significant clinical challenge due to its heterogeneity and the presence of mutations that drive tumor progression and therapy resistance. One promising strategy for targeting these cancers is synthetic lethality, a concept where two genetic alterations together lead to cell death, but individually, they do not. This project aims to utilize synthetic lethality approaches to uncover novel vulnerabilities in prostate cancer cells harboring specific mutations, with the goal of advancing precision medicine. We will focus on mutations commonly found in prostate cancer, such as those in the PTEN, BRCA2, and AR genes. By integrating clinical data with large-scale CRISPR-Cas9 genetic screens, we will systematically identify genes whose loss, in combination with specific mutations, leads to cancer cell death. This approach will allow us to pinpoint potential therapeutic targets that are uniquely vulnerable in mutant prostate cancer cells, offering insights into new drug development opportunities. The project will employ CRISPR-based libraries to perturb genes in prostate cancer cell lines derived from patient samples, enabling us to analyze gene interactions in a clinically relevant context. By correlating synthetic lethality interactions with patient-specific genetic profiles, we aim to develop a framework for personalized therapeutic strategies that can more effectively target the underlying mutations in prostate cancer, improving patient outcomes and enabling more precise, mutation-driven treatments.

2. Investigating a Diet Intervention to Target Prostate Cancer Cells with Different Mutations

1. Prostate cancer (PCa) is a leading cause of cancer-related deaths, and its progression is influenced by genetic mutations and variations in tumor biology. Recent studies suggest that diet may play a pivotal role in modulating cancer cell behavior and influencing therapeutic outcomes. This project aims to investigate the impact of a specialized diet intervention on prostate cancer cells harboring different genetic mutations, focusing on their growth, survival, and response to treatment.

   The study will examine how specific dietary components interact with prostate cancer cells that carry various mutations commonly associated with PCa, including mutations in the PTEN, BRCA2, and AR genes. By employing both in vitro (cell culture) and in vivo (mouse model) approaches, we will evaluate how these dietary factors influence tumor proliferation, metastasis, and gene expression in mutated versus wild-type cancer cells.

   The goal of this project is to identify dietary strategies that could enhance the effectiveness of existing cancer therapies, potentially offering a non-invasive complement to traditional treatments. By tailoring diet-based interventions to the specific genetic profiles of prostate cancer, this research could lead to personalized, mutation-targeted nutrition strategies that improve patient outcomes and quality of life. 

3. Exploiting Prostate Cancer Metabolic Dependencies to Develop New Therapeutics Coupled with Circulating Prognostic and Predictive Biomarkers

My published research has contributed substantially to a body of work indicating that PCa cells activate a process called fatty acid oxidation to generate the energy to support cancer cell proliferation and drug resistance. In addition to energy production, fatty acid oxidation products modulate cancer cell gene expression, which might enable cancer cells to progress to a more aggressive form. In this project, we will study the impact of fatty acid oxidation on PCa biology to understand how this process supports cancer progression. In addition, this proposal aims to discover new, clinically safe fatty acid oxidation targets and evaluate the efficacy of inhibition of these targets to suppress tumor growth and progression. We will employ in vitro studies that include cell lines representative of all PCa stages, in vivo patient-derived xenograft models and human prostate tumors that mimic the disease biology and better predict drug efficacy in the in the human body