Translational Scientist II, Hale Family Center For Pancreatic Cancer Research
Bio Research Interests Key Publications
Bio
Dr. Neetu Saxena received her master’s in Biotechnology from Indian Institutes of Technology-Roorkee, India followed by Ph.D. from Jawaharlal Nehru University, India in Molecular Biology and Biochemistry. During her Ph.D., she engineered D-Hydantoinase, an industrial enzyme, to increase its activity towards non-natural substrates. She then completed her postdoctoral training at National Institutes of Health, USA where she performed first metabolic characterization of Succinate dehydrogenase subunit B (SDHB)-mutated kidney cancer. She applied her expertise in cancer metabolism field in her next role as a research associate at Vancouver prostate Centre and identified a novel crosstalk between succinate dehydrogenase and androgen receptor, the major driver of prostate cancer and introduced a combination therapy to overcome treatment resistance in prostate cancer. She later established a new translational research laboratory at Vancouver Prostate Centre as Project Manager and managed multiple immune-oncology projects for biomarker development. She joined as a Translational Scientist in Hale Family of Pancreatic Cancer at Dana Farber Cancer Institute in 2023.
Research Interests
Primary focus of Dr. Saxena’s research career has been drug discovery contributing to understand treatment resistance mechanisms, identify new drug targets, screen small molecule inhibitors, and develop new biomarkers for urological cancers. Her research work led to the discovery of Hsc20, a dedicated chaperone, for transferring iron-sulfur clusters to SDHB and then how common mutations found in this subunit in patients impaired iron-sulfur cluster delivery to this protein making it dysfunctional. This study was featured as an editor’s choice in JNCI (2014). She has described the tumorigenic effect of succinate, an intermediary metabolite generated as a result of dysfunctional succinate dehydrogenase activity, in SDHB-mutated kidney cancer and treatment-resistance prostate cancer. Her study describing a novel crosstalk between succinate dehydrogenase and androgen receptor, the major driver of prostate cancer, was featured by Science in Vancouver newsletter from Stemcell Technologies. Additionally, she has explored stress granules, chaperone-mediated autophagy, and dynamic phase-separation as other adaptive survival mechanisms in prostate cancer against acute treatment stress.
In her current role as Translational Scientist at Hale family of Pancreatic Cancer Research, she is leading correlative studies for multiple pancreatic cancer clinical trials focused on finding new drugs, treatment combinations, and biomarkers in collaboration with industries and academic institutions around the globe. In this regard, she is managing tumor, plasma, serum, PBMCs, and organoid biobanks at Hale family and designing their downstream processing to answer scientifically relevant questions. In parallel, she is further refining pancreatic organoid models to mimic patient tumors more effectively and efficiently.
Key Publications
Androgen receptor (AR) antagonism triggers acute succinate-mediated adaptive responses to reactivate AR signaling. EMBO Mol Med., (2021).
SDHB-Deficient Cancers: The role of mutations that impair iron sulfur cluster delivery. J Natl Cancer Inst. (2016).
Regulation of AR mRNA translation in response to acute AR pathway inhibition. Nucleic Acid Res. (2022).
G3BP1-linked mRNA partitioning supports selective protein synthesis in response to oxidative stress. Nucleic Acid Res. (2020).
Ivermectin inhibits HSP27 and potentiates the efficacy of oncogene targeting in tumor models. JCI, (2020).
Cochaperone binding to LYR motifs confers specificity of iron sulfur cluster delivery. Cell Metabolism, (2014).
Chaperone-mediated autophagy promotes PCa survival during ARPI through selective proteome remodeling. Oncogene, (2023).
