"Biology is King" - Blake Cady
Our lab investigates fundamental questions in surgical oncology, with a particular focus on pancreatic cancer, including tumor initiation, progression, metastasis, and therapy resistance. Our mission is to bridge the gap between basic science and precision oncology to stratify patients for therapies and develop more effective treatment strategies.
The unfolded protein response (UPR) is a crucial intracellular signaling network that mitigates endoplasmic reticulum (ER) stress caused by misfolded proteins. Within the hostile tumor microenvironment (TME) and under oncogene activation, tumor cells frequently encounter ER stress but leverage the UPR to adapt and sustain malignant growth. A key UPR sensor, inositol-requiring enzyme 1 (IRE1), resides in the ER membrane and activates the transcription factor XBP1s through its cytoplasmic kinase-endoribonuclease module. This activation enhances ER-mediated protein folding, promoting cellular adaptation to ER stress and facilitating tumor progression.
Over the past 10 years, we have extensively studied the biological significance of the UPR, particularly IRE1, in various cancers. Our preclinical research has provided compelling evidence supporting IRE1 as a potential therapeutic target in multiple myeloma and triple-negative breast cancer. Building on this foundation, we are now investigating the role of the UPR in pancreatic cancer.
To achieve this, we employ a comprehensive set of molecular biology and biochemical techniques, including transcriptomic and proteomic analyses, alongside advanced bioinformatics approaches. Our research integrates multiple models, from cancer cell lines and patient-derived organoids to primary patient samples and in-silico models. As a team, we are committed to translating fundamental mechanistic insights into innovative therapeutic strategies to combat pancreatic cancer. Additionally, we are exploring the potential of the UPR as a prognostic and predictive biomarker, aiming to refine patient stratification and treatment approaches.
Our work is driven by the conviction that understanding cancer biology at its core is the key to advancing precision medicine and surgery and improving patient outcomes.