Nobel Prize winner's story: He nearly gave up his research and discovered the key to cancer-suppressing genes

Professor William GKaelin (left), Professor Peter JRatcliffe (centre), and Professor Gregg LSemenza (right) (pictured)don't know how William felt when he heard about the awardYou know, a few decades ago, he was on the verge of giving up researchstory to begin with his college careerDespite earning a degree in mathematics and chemistry from Duke University, William didn't have much interest in his lab work"The lab gave me a bad feeling, " William said" After a brief internship at Johns Hopkins Hospital, William went to the Dana Faber Cancer Institute to begin training in clinical oncologyHowever, in order to meet the graduation requirements, William had to do two years of basic researchIn this way, he went back to the laboratory in the wrong wayIf you think William is in love with scientific research, you're wrongIn fact, the lab trip was a "disaster"Less than four months after William began working, the lab closed"I was full of signs in my life that I was told that my research life in the lab wasn't right for me, " William recalls afterwards Professor David Livingston played a decisive role in William's scientific path (Photo: Dana Faber Cancer Institute) In confusion and distress, Professor David Livingston reached out to William and put him in the laboratory Professor Livingston was one of the pioneers in the study of retinoblastoma, and was very successful in clarifying the mechanism of this cancer In Professor Livingston's lab, William isolated the E2F protein and found it to bind to DNA to promote cell proliferation In normal cases, E2F is inhibited by the anti-cancer protein RB, which prevents excessive cell division However, when the RB protein mutates, the cells divide uncontrolledly, leading to the birth of retinoblastoma this unexpected experience completely changed William's career plans With access to both cancer patients and first-line cancer research, William realized that "for these patients, the ultimate hope comes from a precise understanding of the molecular mechanisms of cancer and the effective therapies that translate from this knowledge." In 1992, William opened his own laboratory Looking for potential research projects, he learned of a genetic disease called von Hippel-Lindau disease Patients with the disease produce tumors in the kidneys, adrenal glands, pancreas, and central nervous system William notes that these tumors grow in blood vessel-rich areas, and that they secrete red blood cell production, which stimulates the production of red blood cells These characteristics suggest that oxygen may play a key role in their growth The VHL protein structure (photo source: Emw (CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)) subsequent results also confirm this At that time, the gene VHL associated with Hipper-Lindor syndrome had been found William's team found that when oxygen was plentiful, the VHL protein labeled an oxygen-deficient inducing factor called HIF to degrade, and when oxygen was low, VHL lost the ability to label HIF, so HIF remained in the cell and promoted the production of blood vessels and red blood cells How, how do these cells know if there is oxygen around them? after years of exploration, William and his team have the answer: it turns out that with plenty of oxygen, the efficiency of intracellular hydroxylase increases, allowing hIF proteins to get a hydroxyl VHL is able to identify this hydroxyl and initiate subsequent adjustment functions The breakthrough finding, first realized by humans that hydroxylation is vital to cellular signaling pathways, was published in the 2001 issue of Science more important, William's discovery is universal In a variety of diseases, his team found that oxygen plays a role in tumor formation For example, the VHL gene in patients with kidney cancer often mutates, causing excessive VEGF (vascular endothelial growth factor) in the body, which in turn promotes the production of blood vessels and red blood cells Based on this principle, new drug developers are working on VEGF as a target point Currently, the FDA has approved a variety of VEGF inhibitors for the treatment of kidney cancer based on this achievement, William shared this year's Nobel Prize in Physiology or Medicine with two other scientists who independently discovered the mechanism of the same signaling pathway For William, however, the award came a little lonely - in the past, whenever William received honours, his wife Caroline would be there to share the joy with him Four years ago, however, Caroline, a breast cancer doctor, left the world with breast cancer William, who has studied cancer all his life, was powerless to do anything about it ", she saw her daughter graduate from Yale, saw her son accepted from Yale, and celebrated our 25th wedding anniversary, William said 's death made William feel the pain of the family of cancer patients, and made him more aware of the importance of basic research In addition to his work, William is also actively involved in promoting cancer research - Caroline has participated in the Pan-Mass Challenge several times in her lifetime to help raise money for the Dana Faber Cancer Institute William completed the challenge on her wife's behalf after her death Now William will feel happy if he can make new discoveries that benefit others As for honor, it's something out of the world "As long as you're serious about research and you've been asking good questions, you don't have to worry too much about winning, " says William References: s1 s Nobel Prize Ingenor Physiolog 2019, Retrieved October 7, 2019, from https:// s Retrieved October 7, 2019, from http://