Thu Pham

I study the intricate gene regulatory mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN), a common side effect that affects up to 50% of patients treated with certain chemotherapy drugs. Using stem cell technologies, CRISPR gene editing approaches, and cutting-edge epigenetic tools, I aim to identify novel potential therapeutic targets for CIPN treatment and prevention.

Despite the approval of a significant number of targeted cancer therapies in recent years, cytotoxic chemotherapy remains a mainstay in the treatment of multiple cancers. Cytotoxic therapy, particularly with microtubule-targeting agents (MTAs), is often dose-limited by the development of peripheral sensory neurotoxicity. This chemotherapy-induced peripheral neuropathy (CIPN) can persist after dose reductions and discontinuation of therapy, significantly impacting patients’ quality of life. With the critical role that MTAs play in cancer treatments, it is important to understand the molecular mechanisms underlying CIPN so that novel therapeutic strategies can be developed for its prevention and treatment. Until recently, mechanistic investigations of CIPN relied on rodent models; however, these findings did not translate into human studies, indicating an urgent need for the development of a better human-relevant study system. Furthermore, like many complex diseases, the genetic risk of CIPN is primarily attributed to variants in non-coding regions of the genome, which have been substantially understudied. To address these knowledge gaps, my project employs multi-omics approaches and CRISPR-based methods to explore the transcriptional changes and epigenetic landscape in human sensory neurons derived from induced pluripotent stem cells upon MTA exposure. My work aims to link genes and pathways to MTA-induced neurotoxicity and define the functional consequences of non-coding genetic risk variants associated with CIPN.