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Xin Lin, Ph.D.
Professor and Chairman, Department of Basic Medical Sciences, Tsinghua University School of Medicine

Facing challenges head-on

Xin Lin has dealt with cancer for many years, not only as a scientist but also as a cancer survivor. His personal experience gave him a deeper understanding of patients’ expectations, which solidified his determination to explore better cancer treatments. Working as a professor at Tsinghua University, Lin developed a T cell therapy with fewer side effects that may better treat blood cancer and tumors in the future, realizing bench-to-bedside translation to fulfill patients’ hope.

In 2011, Xin Lin was diagnosed with cancer again. This time, it was lung cancer, the king of cancers.

“At that moment, I thought ‘It’s over. This is the second time I’ve got cancer,’” says Lin. Lost, helpless, and anxious, emotion surrounded him. As a professor of molecular and cellular oncology, Lin has “dealt” with cancer for many years. It wasn’t until the reality of the disease struck him, twice, that he finally saw the other side of it.

Before, Lin just considered his cancer research as a job, an intellectual puzzle to solve. Now, as a cancer patient himself, he has a deeper understanding of patients’ expectations.

“As a cancer patient, you feel very helpless. You hope to be cured, but you also have to face the fact that your life is dimming,” says Lin. Before, Lin just considered his cancer research as a job, an intellectual puzzle to solve. Now, as a cancer patient himself, he has a deeper understanding of patients’ expectations. The urgency and importance of cancer research become evident.

Fortunately, Lin caught the lung cancer early and recovered after surgically removing the tumor. However, after the two incidents, Lin felt a strong and clear sense of duty, which drove his devotion to cancer research.

In 2012, Lin, who was cancer-free, once again challenged the disease. This time, as a scientist, continuing his work and facing challenges in scientific research head on.

Embracing challenges, returning to China mid-career

Lin was the first batch of students enrolled in Shanghai University of Science & Technology after the reinstatement of China’s college entrance exams in 1978. He studied chemistry for his bachelor’s degree and later pursued biochemistry as a graduate student after attending his father’s lecture by chance, which kindled his interest in immunology. Lin took 13 years to switch gears from chemistry to immunology. It was not until 1995 that he finally set foot on the right path when he joined the University of California, San Francisco, as a postdoctoral fellow in immunology.

After realizing their dreams, people tend to settle down. But not Lin. He enjoys the scramble. “I think it has something to do with my personality. I like the challenge,” he says.

“Life is a scramble,” is Lin’s motto. Between work, research, and life, everything is continuously changing and scrambling.

After 2000, Lin taught at the School of Medicine, the University of New York at Buffalo, and then the University of Texas MD Anderson Cancer Center. As his position changed, he switched from studying immune mechanisms to tumor research. Lin’s determination to explore clinical treatment in cancer solidified following his cancer diagnoses in 2009 and 2011.

In 2013, Lin started to consider returning to China. The MD Anderson Cancer Center, where he worked, is a world-class cancer research, diagnosis, and treatment facility. The US News & World Report’s “Best Hospitals” survey ranked MD Anderson Cancer Center as the top hospital for cancer care in the US for years. Many of Lin’s family and friends told him not to give up his faculty position in the US and suggested that if he stayed, he’d be able to climb the academic ladder and reach achievements and fame one day.

However, Lin chose to return to China for a second career. “First, I was driven by a strong sense of belonging. I’ve always hoped to succeed in my field and give back to my country. Second, I have become a professor and program director at the University of Texas MD Anderson Cancer Center. My life settled and was predictable. There weren’t any challenges,” he says.

In 2014, Lin officially joined Tsinghua University as a medical school professor and the chairman of the Department of Basic Medical Sciences, opening a new round of challenges in his life.

Exploring and developing innovative cellular immunity interventions

Having accomplishments in the field of cancer research is not an easy task. When every road seems like a dead-end, how do you create your own path?

Since 2014, Lin’s lab has been focusing on T cell immunotherapy application. T cell is a type of immune cell that plays a vital role in the body’s immune defense. T cells kill tumor cells but can also be easily “exhausted” by tumor cells, which may prevail and win the battle.

To help the T cells make a comeback, scientists “installed” a guidance switch called CAR through genetic engineering and sent the cells back into the body to fight the cancer. Clinical studies have confirmed the CAR-T cell therapy’s efficacy in blood cancers.

In clinical research, Lin’s lab targeted tumor cells directly with STAR-T cell therapy, which effectively increased T cells’ survival time in the body.

Lin wasn’t satisfied by merely following in the footsteps of scientists before him. He redesigned CAR and invented a brand new structure called STAR, which he applied to patent. In clinical research, Lin’s lab targeted tumor cells directly with STAR-T cell therapy, which effectively increased T cells’ survival time in the body. Moreover, the technology reduced T cell exhaustion, which prevented tumor escaping and tumor recurrence. “Compared to conventional CAR-T cell treatment in blood cancers, STAR-T cell therapy performs better, has fewer side effects, and is easier to work with for designing multi-target variants. The new therapy also has a better effect on solid tumors,” says Lin, sharing his latest results with excitement. “This project is our most important breakthrough in recent years. It will be published in Science Translational Medicine soon.”

Lin’s lab has established two independent intellectual property platforms, STAR-T and TCR-T. Besides praising his team’s concerted effort, Lin also attributes his achievements to China’s close integration of basic research and clinical application. “There are many clinical samples and questions in China, which increases research and clinical integration opportunities. It also opens up and boosts translational research. This is the country’s unique advantage,” he says.

Diligently focusing on tumor research and treatment innovation

To Lin, cancer research has become a career that he strives for with his life. He is happy that he chose to return to China and believes that doing research at Tsinghua University is on par with the MD Anderson Cancer Center in the US, if not better.

“The students at Tsinghua University are excellent. The ones who joined my lab not only have a wealth of knowledge, but they also have a passion for research,” says Lin. “My experience has exceeded my expectations!” So far, his lab has published more than 100 research papers, including one in Nature Medicine in 2017 that illustrated the molecular mechanism of JNK1 negatively regulating antifungal immune responses. In 2018, his paper in Immunity revealed a novel mechanism of how intestinal fungi play a role in colon tumors’ pathogenesis by regulating myeloid suppressor cells. In Nature Communications, his 2019 paper demonstrated that the K63 ubiquitination modification of RIPK1 could regulate cell death during inflammation by regulating the RIPK1 kinase activity. Now, his latest study on STAR-T cell therapy for treating tumors will be published in Science Translational Medicine.

Returning to China, Lin witnessed the rapid development of life sciences and basic medical sciences. Being a part of the science community, he is incredibly grateful for the country’s strategy in providing strong support for precision medicine and the increase in research funding, investment and talent recruitment in the Beijing area. “Beijing has a large number of universities and research institutes. The active recruitment of talents in recent years, brought many scientists who were abroad back here. These scientists not only brought back the latest technologies and shepherded future research directions, but also drove the international collaborations through their connections worldwide,” he says.

“Thanks to the support of the funding and platforms, many high-tech applications have been applied to cancer research, such as single-cell sequencing, genomics, and big data research. It’s all possible now. I believe, with the support, cancer research will become translational soon.”

Looking at the next 10 years, Lin hopes to see breakthroughs in China’s biopharmaceutical industry. “With stable investment and the active recruitment of talents, I believe that China will develop tumor immunotherapy drugs or targeted cancer therapy on its own within 10 years,” he says.

The exploration of science will always be about taking the initiative and action to move towards your goal. Lin will continue to embrace challenges, investigate cancer for innovative treatments, and promote bed-to-bedside translation to bring hope to patients.