Shioko Kimura, Ph.D., in her CCR lab in 2014.
Shioko Kimura, Ph.D., is a biochemist who specializes in endocrinology. She studies how certain genes and proteins work in the thyroid gland and the lungs, both when they are healthy and diseased. After almost 40 years at NCI, she has announced her retirement.
Kimura received her Ph.D. in chemistry at Hokkaido University in Sapporo, Japan, in 1979. After completing a postdoctoral fellowship at Queen’s University in Kingston, Canada, she joined the NIH as a visiting fellow at the National Institute of Child Health and Human Development. In 1986, she moved to the NCI as a visiting associate scientist in the Laboratory of Molecular Carcinogenesis. Kimura became a Senior Investigator in 1998 in the Laboratory of Metabolism, which eventually became the Cancer Innovation Laboratory in 2022.
Kimura’s research particularly focuses on the NKX2-1 gene, which acts as a master switch that controls many other important genes in the thyroid and the lungs. Her team was the first to identify and clone the gene, and they demonstrated how the encoded homeobox transcription factor protein NKX2-1 is crucial for development, homeostasis, function, physiology, and disease pathogenesis including cancer of the brain, thyroid, and/or lung. Other related molecules that Kimura and her team studied include the enzyme thyroid peroxidase and the secreted protein SCGB3A2.
Over the course of her career, Kimura has provided extensive service to the scientific community by sitting on several editorial boards, editing and reviewing for a variety of journals and grants, and participating on numerous NIH and NCI committees. Her dedication to some of these activities spans for over a decade. At the NIH, Kimura has been particularly involved with committees to advance women and Asian American and Pacific Islander researchers in science and workplace civility practices. In 2021, she received the NIH Director’s Award as part of the CCR Women Scientist Advisors.
In the Q&A below, Kimura describes her scientific achievements, advice for other scientists, and her retirement activities.
Which scientific achievement(s) or accomplishments are you most proud of?
The accomplishment I am most proud of is our discovery of NKX2-1, a homeodomain transcription factor, and our finding that it is critical for the genesis of the thyroid, lung, ventral forebrain and pituitary, as revealed by establishing and characterizing the Nkx2-1 knockout and later the Nkx2-1 conditional knockout mouse models. These models have been distributed throughout the world and have contributed to an enormous advancement of our understanding of the critical roles that NKX2-1 plays in these various organs. Our studies have led the use of NKX2-1 as a routine diagnostic marker for lung adenocarcinoma in humans. NKX2-1 is also widely used as a lineage marker in the thyroid and lung development and pluripotent stem cell/induced pluripotent stem cell fields.
Further, we identified Cldn18 (Claudin-18, a tight junction molecule) and Scgb3a2 (Secretoglobin 3A2, a cytokine-like secretory protein), as NKX2-1 downstream target genes in the lung. Claudin 18.2, an alternatively produced isoform predominantly expressed in nonmalignant gastric epithelium, has been studied by many scientists and has become a target for cancer therapy. An anti-claudin 18.2 antibody is now in phase 3 clinical trials to treat advanced-stage gastric cancers, and a possible use of claudin 18.2 as a target for pancreatic cancer treatment is also emerging.
Our most recent quest is to unravel the biological functions of SCGB3A2. My lab, including a former postdoc of mine, has demonstrated that SCGB3A2 exhibits growth factor, anti-inflammatory, anti-fibrotic, anti-apoptotic, anti-emphysematous, and anti-cancer activities in the lung. We discovered that syndecan-1 (SDC1) is a cell surface receptor for SCGB3A2 and further found that SCGB3A2 is a lipopolysaccharide (LPS)-binding protein. Binding of a SCGB3A2-LPS complex to SDC1 is the mechanism by which LPS is transported into cells, providing an answer to a question that has long perplexed investigators: the entrance of LPS into cells. Cytosolic LPS activates the non-canonical inflammasome pathway, leading to pyroptosis, the programmed inflammatory cell death pathway. Notably, we found that this pyroptosis pathway leads to decreased proliferation of some cancer cells when they are treated with both SCGB3A2 and LPS. Thus, SCGB3A2 has the potential to be developed as a therapeutic to treat various lung diseases. My former postdoc, who is now a professor in Japan, is continuing this work. I will continue to help as an NCI special volunteer, and I will also work with a biotech company to develop drugs based on SCGB3A2’s activities.
How did the intramural environment at CCR impact your career or facilitate your research?
The NIH intramural environment is equipped with free thinking and cooperation among investigators. Because there are so many scientists working in diverse fields in CCR and NIH with broad expertise in many areas, you can find colleagues readily willing to collaborate. Also, CCR and NIH provide many excellent core facilities that we can use to advance our studies. We fully took advantage of these opportunities, and because of this, our research was able to move forward.
Do you have any advice for the next generation of cancer researchers?
Nowadays, the advances in knowledge and technology are extremely fast, and it can be easy to fall behind. You must always keep eyes and ears open towards various advances and constantly ask yourself what the best option is to answer your most important questions. You can spend hours of your precious time on questions that would not solve fundamental questions, but you need to focus and spend time on critical questions that eventually helps make our lives better.
Another major piece of advice I have is for PIs, related to training and working with students and postdoctoral fellows. These are the ones working in the lab, that actually “carry the mail.” Proper management and treatment of your lab members is critical: work closely with those young investigators that are not well-trained and are highly motivated when they enter your lab, and encourage them to explore new ideas that could expand the breadth of your research program. Your one push can make them a lot better as a researcher when they get lost or unfocused.
Is there anything you are looking forward to most in your retirement?
Since some of my postdocs and postbacs who recently left the NIH do not have all their research results published, I will continue working as a special volunteer on their data and preparation of their manuscripts for submission, which is critical for their future careers. Also, I hope that my work with a local biotech company will bring SCGB3A2 closer to development as a therapeutic in treating lung diseases. However, at first, I would like to relax a little after decades of intense research in the NCI and NIH and spend some time in my hometown in northern Japan.
Dr. Shioko Kimura will retire on June 30, 2025.