细胞感知和适应氧气变化机制研究的发展

来源：中国科学杂志社

2019年诺贝尔生理学或医学奖近日授予了美国科学家威廉·凯林、格雷格·塞门扎以及英国科学家彼得·拉特克利夫，以表彰他们在“发现细胞如何感知和适应氧气供应”方面所做出的贡献。

该研究曾于2016年获得拉斯克基础医学研究奖，Science Bulletin 2016年第21期News & Views栏目发表文章“The history of oxygen sensing: 2016 Lasker Award for Basic Medical Research”，回顾和评述了细胞感知和适应氧气变化机制研究的发展。

以下是该文作者对这项研究获得诺贝尔奖的影响、研究的现状和未来发展方向以及华人科学家做出重要贡献的看法：

Qing Zhang

Ph.D. | Associate Professor

Department of Pathology

UT Southwestern Medical Center

This is a well-deserved prize since this prize solves the puzzles on how animal species adapt to the oxygen concentration. More importantly, these findings carry significance implications in diseases and their treatments, including cancer, anemia, inflammatory bowl disease, heart disease and many more. Given an example, in kidney cancer setting, von Hippel Lindau (VHL) tumor suppressor is lost in 70-80% which leads to HIF2a upregulation. Right now, HIF2a inhibitors developed from UT Southwestern originated scientists have been actively used in clinical trials and showed promising response in kidney cancer patients.

There are still many things to be studied in this field. First, how to therapeutically target these signaling molecules in the oxygen sensing pathways. VEGF is a critical downstream effector of oxygen sensing pathway and VEGF inhibitors have been widely used in various cancer settings. Prolyl hydroxylase inhibitors have been proved in China to treat anemia. HIF2a inhibitors are undergoing clinical trials in US to be potentially used in cancer patients, starting with kidney cancer. In addition, there are also HIF independent signaling pathways that may be targeted in these diseases as well.

It takes a village to discover these important findings. For example, a few Chinese scientists (Guang-Liang Wang and Bing-Hua Jiang from Semenza Group, Haifeng Yang from Kaelin group) have played pivotal roles on identifying these critical oxygen sensing pathways. Their contributions cannot be stressed enough. They are the pride of our Chinese scientific community.

biographical sketch of the author

Dr. Zhang obtained his Bachelor’s degree from Wuhan University in China in 2001 followed by a Ph.D study working with Dr. Jennifer Grandis at Department of Pharmacology, University of Pittsburgh School of Medicine until Late 2005. From early 2006 to 2011, He worked as a postdoc fellow under the supervision of the Nobel Laureate Dr. William Kaelin at Dana Farber Cancer Institute on prolyl hydroxylase and oxygen sensing pathway in cancer. He worked as an instructor from 2011-2012 at Harvard Medical School before becoming an assistant professor at Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill in Feb of 2013. He was promoted to associate professor with tenure in Feb of 2019 at UNC Chapel Hill and now he is an associate professor with tenure in the Department of Pathology at UT Southwestern Medical Center in Dallas. He is currently holding the title of Cancer Prevention & Research Institute of Texas (CPRIT) Scholar in Cancer Research.

His research has been continuously funded by the National Institute of Health. Currently his research is supported by the National Cancer Institute, Department of Defense (DOD), American Cancer Society (ACS), CPRIT as well as Kidney Cancer Research Alliance (KCCure).

He is a member of both the American Society for Investigative Pathology (ASIP) and American Association for Cancer Research (AACR). He obtained various awards, including CPRIT Rising Star Award, ASIP Ramzi Cotran Early Career Investigator Award, DOD KCRP Idea Development Award, ACS Research Scholar Award, Kimmel Scholar Award, V Scholar Award, Susan. G. Komen Career Catalyst Award and Mary Kay Foundation Award. He also served as the Associate Scientific Advisor at Science Translational Medicine.