LINK-J & UCサンディエゴ　ジョイントウェビナーシリーズ　第13回 with 神戸大学「細胞内シグナル伝達と脂質研究」 セッション3－癌などの疾病の情報伝達系に関する最新の研究

Presentation Abstracts

Dr. Zhang's talk
"Illuminating the Biochemical Activity Architecture of the Cell"

The complexity and specificity of cellular processes require spatial microcompartmentation and dynamic modulation of the underlying biochemical activities, such as dynamic phosphorylation and dephosphorylation catalyzed by specific protein kinases and phosphatases, respectively. We hypothesize that cellular biochemical activities are spatially organized into an “activity architecture” and reorganization and restructuring of this activity architecture lead to disease. In this talk, I will introduce a series of genetically encoded fluorescent biosensors that we have developed to monitor biochemical events in living cells, and then present a couple of studies where we combine quantitative fluorescence imaging with targeted perturbations as well as biochemical and functional assays to probe the subcellular regulation of cAMP/PKA and ERK signaling pathways.

Dr. Maehama's talk
"Hippo-YAP Signaling Pathway in Squamous Cell Carcinoma Onset and Progression"

The Hippo-YAP signaling pathway regulates organ size, tissue homeostasis, and tumorigenesis in mammals. The Hippo core complex which consists of MST and LATS kinases and their adaptor proteins, SAV1 and MOB1, blocks the translocation of YAP1/TAZ proteins to the nucleus, curtailing cell growth. Activation of YAP1/TAZ occurs in many human malignancies and promotes their initiation, progression and metastasis. To clarify the molecular mechanism of YAP-driven cancer development in vivo, we generated mice that were deficient for critical Hippo component MOB1 to increase intrinsic YAP activity.
The deletion of MOB1 in the tongue and cervix in mice resulted in the rapid and highly reproducible development of squamous cell carcinoma (SCC) in these tissues. Consistently, immunohistochemical analysis showed strong YAP activation in human cervical and tongue cancers from the pre-cancerous stage. Genetic alterations, such as TP53, PTEN, FAT1, frequently observed in tongue cancers all increased YAP activity in tongue cancer-derived cell lines, and the effect was additive. Risk factors for cervical cancer, such as cigarette smoke condensates and estrogen, also increased YAP activity in cervical epithelial cells. These observations suggest that genetic and environmental risk factors induce incremental activation of YAP. These cancer onsets may initiate when YAP activity eventually exceeds an oncogenic threshold, indicating Hippo-YAP signal as a major driver for for the onset of these SCCs.
This talk will focus on the molecular mechanism for SCCs with showing our recent progress in SCC mouse model studies. In addition, our recently developed potent YAP inhibitors will be discussed.

Biographies

Dr. Yasuhito Shirai, Professor, Graduate School of Agricultural Science, Kobe University
Yasuhito Shirai is a Professor and Vice Dean of the Graduate School of Agricultural Science at Kobe University. He also serves as the Director of Americas Division in the Institute for Promoting International Partnership.
Shirai earned his PhD in 1994 in the Graduate School of Agricultural Science, Kobe University. He became an Assistant Professor in the Graduate School of Science and Technology and then in the Biosignal Research Center (BSRC). While he was assistant professor at BSRC, he worked as a visiting scholar at the University California San Diego in 2000-2001. He was promoted to an Associate Professor in the BSRC and obtained a second PhD degree from the School of Medicine of Kobe University in 2005. Finally, he was promoted to a Professor in the Laboratory of Chemistry and Utilization of Animal Production Resources in the Department of Agrobioscience, Graduate School of Agricultural Science. He conducts signal transduction research focusing PKC and DGK to develop functional food, medical food, and medicine.

Dr. Itay Budin, Assistant Professor of Chemistry and Biochemistry, UC San Diego
Dr. Itay Budin is an Assistant Professor in the Departments of Chemistry & Biochemistry and Bioengineering at UC San Diego. Trained as a biophysicist, his lab investigates the interplay between lipid chemistry and cell membrane function. Dr. Budin received his PhD from Harvard University and carried out postdoctoral studies as a Miller Fellow at UC Berkeley. He is the recipient of the Walter Shaw Young Investigator Award in lipid biology from the American Society for Biochemistry and Molecular Biology and early career awards from the National Science Foundation and US Department of Energy.

Dr. Jin Zhang, Professor and vice Chair, Department of Pharmacology & Professor, Departments of Chemistry & Biochemistry and Bioengineering

Dr. Jin Zhang received her PhD in Chemistry from University of Chicago in 2000. After completing her postdoctoral work in the laboratory of Roger Tsien at UC San Diego, she joined the faculty of Johns Hopkins University School of Medicine in 2003. She was promoted to Professor of Pharmacology in 2013. In 2015 she moved back to UC San Diego and is currently Professor and Vice Chair in Department of Pharmacology. Research in her lab focuses on developing enabling technologies to probe the active molecules in their native environment and characterizing how these active molecules change in diseases including cancer. Dr. Zhang is a recipient of the Biophysical Society Margaret Oakley Dayhoff Award (2009), NIH Director’s Pioneer Award (2009), John J. Abel Award in Pharmacology (2012), Pfizer Award in Enzyme Chemistry (2012), NCI Outstanding Investigator Award (2015 and 2022), Robert R. Ruffolo Career Achievement Award in Pharmacology (2022), Protein Society Christian B. Anfinsen Award (2022) and Biophysical Society Carolyn Cohen Innovation Award from (2023). She was elected as a Fellow of the American Association for the Advancement of Science in 2014, a Fellow of the American Institute for Medical and Biological Engineering in 2019 and a Fellow of American Society for Pharmacology and Experimental Therapeutics in 2021. Dr. Zhang also received UC San Diego Chancellor's Award for Excellence in Postdoctoral Scholar Mentoring in 2019 and UC San Diego Jacobs School of Engineering Outstanding Graduate Student Mentoring Award in 2022.

Dr. Tomohiko Maehama, Associate Professor, Kobe University Graduate School of Medicine
Tomohiko Maehama is Associate Professor at the Graduate School of Medicine, Kobe University, Japan. He graduated from Tokyo Institute of Technology, Japan in 1990 and obtained his PhD degree in 1995 at the Graduate School of Bioscience there in the lab of Professor Toshiaki Katada. After a JSPS Research Fellow there and a Research Fellow at University of Michigan Medical School in the lab of Professor Jack E. Dixon, he became a Research Investigator at Tokyo Metropolitan Institute for Medical Science in 2000 and was promoted as a Laboratory Chief at National Institute of Infectious Diseases in 2006. Then he has been in the current position in Kobe University since 2016. His research interests are to elucidate molecular mechanisms of cancer development, particularly focusing on functions of tumor suppressors.