HSIEH LAB

Welcome to the Hsieh Lab

Protein synthesis control in human disease

The process by which mRNA is translated into a protein is a highly energetic and meticulous process that is essential for life. However, protein synthesis can also be usurped by cancer to drive cellular transformation, uncontrolled proliferation, evasion of apoptosis, metastasis, and drug resistance (Hsieh et al. Cancer Cell 2010, Hsieh et al. Nature 2012, and Hsieh et al. Science Signaling 2015). The primary focus of the Hsieh lab is to unravel the post-transcriptional mechanisms that govern the genesis and progression of epithelial malignancies. Our research seeks to understand how rogue cells co-opt the critical interface between RNA and the protein synthesis machinery to drive specific cancer behavior at a molecular, cellular, and organismal level.

Our tools

In order to study protein synthesis control in cancer we utilize a confluence of cutting edge technologies including new animal models, whole transcriptome ribosome profiling, novel imaging strategies, and primary cell based assays. These tools enable our group and our collaborators to interrogate the functional cancer proteome at an unprecedented level and depth.

The application of protein synthesis research

Our laboratory seeks to apply our bench side findings to clinically relevant themes such as castration resistant prostate cancer, and advanced bladder cancer both of which are incurable. To this end, we utilize primary patient samples, patient derived xenografts, and close collaborations with our medical colleagues at the University of Washington and elsewhere around the world. We are intrigued by the potential of therapeutically targeting the translation apparatus in cancer as well as utilizing the translational signature of cancer to predict disease behavior (Hsieh et al. BJC 2011, Hsieh et al. Nature 2012, Edlind and Hsieh AJA 2014, Sheridan et al. Oncotarget 2015).
 
Ultimately, we aim to utilize our fundamental discoveries in translational control biology to tackle critical issues faced by cancer patients today.
 

The translation apparatus illustrated here is an extraordinarily complex, dynamic, and elegant machine necessary for all walks of life (Ze animation). We seek to uncover the fundamental mechanisms by which alterations to the process of mRNA translation determine cancer phenotypes.