Welcome to the Hsieh Lab

Protein synthesis control in normal and disease physiology

The process by which mRNAs are translated into proteins is a highly energetic and meticulous process that is essential for life. Work from our laboratory and others have demonstrated a central role for protein synthesis control in the maintenance of normal cell physiology as well as dynamic transitions in cell fate choice (Guzzi et al. Cell 2018, Kuppers et al. bioRxiv 2018). Moreover, our work has uncovered a remarkable level of translation specificity which can be usurped by diseases such as cancer to drive cellular transformation, uncontrolled proliferation, evasion of apoptosis, and metastasis (Hsieh et al. Cancer Cell 2010, Hsieh et al. Nature 2012, Hsieh et al. Science Signaling 2015). Our research seeks to understand why specific aspects of the translation machinery are essential for normal and disease physiology at a molecular, cellular, and organismal level.

 

How we study mRNA translation

In order to study protein synthesis control we utilize a confluence of cutting-edge technologies including new animal models, whole transcriptome tissue-based ribosome profiling, quantitative imaging strategies, and primary cell-based assays. These tools enable our group and our collaborators to interrogate the functional proteome in normal tissues and cancer 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 (Sheridan et al. Oncotarget 2015, Graham et al. IND 2018). Ultimately, we aim to merge our fundamental discoveries in translational control biology with the clinical needs of 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.