Bio

Jim J.-C. Sheu, molecular biologist, received his Ph.D. degree from National Tsing-Hua University, Taiwan and post-doc training at the Johns Hopkins Medical Institutes, USA. Before he went to Hopkins, Dr. Sheu served as Director of Protein Drugs at Development Center for Biotechnology (DCB), Taiwan to develop human neutralizing antibodies against infectious diseases. Dr. Sheu’s study focuses on the discovery of novel cancer-driving genes using genomewide technologies and their functional roles in cancer development. The research topics include genome instability triggered by aberrations of chromatin remodeling factors, gentotoxic shock induced by unbalanced ribosome biogenesis, and cancer stemness manipulated by cytoskeleton-mediated cell adhesion. Of note, Dr. Sheu recently discovered novel keratin fusion events during the development of oral squamous cell carcinoma (OSCC). Since keratin filament is critical for mechano-sensing, nuclear integrity and gene regulation, his study thus reveals a novel mechanism in OSCC carcinogenesis. Achievements in cancer biology research made Dr. Sheu won “Marquis Who’s Who in the World” in 2013, and MOST (the Ministry of Science and Technology/Taiwan) Academic Research Award “Wu-Da-You Memorial Award” in 2014. He was also recognized as a Top 5% Biomedical Researcher in the World by Sparrho study in 2016.

Research Specialty
Cancer genomics/genetics, Cell adhesion, Keratin filament, Mechanotransduction, Chromatin remodeling, Functional genomics in TCM (traditional Chinese medicine)

Research Projects
1. Chromatin remodeling factor Rsf-1 triggers genome instability during cancer development
2. Biological functions of novel keratin fusions in cancer stem cell development
3. Using ribosome biogenesis as a therapeutic target for treating endometriosis and the associated complications

Recent Highlight Projects

Keratin fusions induce cancer stemness by nuclear remodeling
Keratin intermediate filament (IF) is a component of cytoskeleton which provides necessary mechanical support for cells to conquer mechanical stresses. Recent studies in tissue engineering showed undeniable evidence that cell stiffness in response to the softness of extracellular matrix can direct stem cell reprogramming for differentiation via mechanotransduction. Our recent study identified several novel keratin chimeras in OSCC, and their existence correlated with cancer progression and poor clinical outcome. When expressed in OSCC cells, the keratin fusions competed with the wild type and disturbed the keratin network, resulting in reduced perinuclear array and nuclear deformation. Expression of carcinogen-responsive fusion variants in OSCC cells upregulated TGF- and G-CSF signaling, leading to cell stemness, drug tolerance, and cancer aggressiveness. Notably, cells expressing keratin fusions can easily adapt to a soft 3-D culture condition in vitro and formed larger, less differentiated tumors in vivo. Our study therefore revealed a novel mechanism in OSCC carcinogenesis via the formation of keratin chimeras.

Awards and Honors

Professional Memberships and Services

Institute