By Scot Macdonald
Dr. Kuo stands before banks of Zebrafish tanks, which he uses to seek improved treatments for Ewing sarcoma. (Photo by Dr. Julia Ma)
In November 2011, Christopher Kuo lost his brother, Stanley, to osteosarcoma and vowed to dedicate his life to improving treatments for bone cancers. The A.P. Giannini Foundation is helping Dr. Kuo fulfill that commitment, selecting him as one of this year’s A.P. Giannini Foundation Postdoctoral Research Fellowship & Career Development Award winners.
“We are proud to support Dr. Kuo’s research, which holds great promise to advance our understanding, and treatment, of bone cancers,” Mark C. Perry, Chairman of the Foundation, said. “We are committed to supporting innovative research by postdoctoral biomedical researchers across California, who are laying the foundation for the development of innovative treatments to improve the quality of life of individuals around the world diagnosed with cancer.”
“I lost my brother to osteosarcoma and I promised him I would make an impact in the treatment of sarcomas,” Dr. Kuo said. “I am extremely grateful, and appreciate the opportunity to take advantage of the A.P. Giannini Fellowship. It is a hard and grueling path to become a physician scientist, so you really need the protected time that the Fellowship makes possible to focus on research. The Foundation provides a unique opportunity to conduct research while offering courses on how to be a scientist, an engaging speaker, and a leader in the field. I have found the courses extremely helpful.”
A Crooked Path to Cancer Research
Dr. Kuo’s path to medicine was far from straight. Born in Los Angeles, he was raised in Taiwan before returning to California to attend the University of California, San Diego (UCSD). He was a breakdancer and studied dance at UCSD. Then his brother Stanley was diagnosed at the age of 25 with a rare bone cancer, osteosarcoma, which affects about 250 American children and adolescents each year. Christopher vowed to find a cure for osteosarcoma and switched to studying biochemistry and cell biology, before attending Rush Medical College in Chicago.
Stanley’s oncologist was Judith Sato, MD. She received her hematology/oncology training at Children’s Hospital Los Angeles (CHLA). Christopher sought to follow her path. Fulfilling his goal, he matched for his residency with CHLA as a George Donnell Pediatric Scientist scholar and stayed on to complete a pediatric hematology/oncology fellowship in June 2023. He is now a clinical instructor of pediatrics at the Keck School of Medicine of USC and conducts research at CHLA.
Sarah Hamm-Alvarez, PhD, vice chair, basic research, at the Keck School of Medicine of USC, said, “We are incredibly proud of Dr. Kuo’s work, and thankful to the A.P. Giannini Foundation for their support. This fellowship provides up to three years of funding for projects that aim to prevent and cure human diseases, and have a tremendous impact.”
Dr. Kuo’s research focuses on Ewing sarcoma; a rare cancer of the bone and tissues around the bone. It is challenging to treat and therapies have not significantly improved for decades. Patients with localized disease have greater than 80 percent survival rate after five years, but if the cancer has spread, most do not survive five years. Even patients that survive suffer from significant toxicities of the therapies they have received, such a secondary malignancies.
“We really need to change that,” Dr. Kuo said. “We need better, more targeted and less toxic therapies.”
Dr. Kuo’s research focuses on the complex tumor microenvironment of Ewing sarcoma, including tumor and non-tumor cells, cell-to-cell communication, and the immune system’s role in cancer growth. Dr. Kuo is studying macrophages—a type of immune cell. He uses biopsy samples and a novel zebrafish genetic model of Ewing sarcoma to better understand the spatial mapping and gene expression of tumors. The novel zebrafish genetic model of Ewing sarcoma, created at USC and CHLA by Drs. Elena Vasileva and James F. Amatruda, uses zebrafish to study the immune system and its interaction with Ewing sarcoma. Under fluorescent light, the Ewing sarcoma cells will light up green. This is the first and currently the only immunocompetent animal model of Ewing sarcoma.
Bone sarcoma and sarcomas in general have what is called a cold tumor microenvironment, which means that few immune cells can reach the tumor, making immunotherapy more challenging. Dr. Kuo is seeking a way to make the tumor environment “hotter,” which will allow more immune system cells to reach the tumor and, possibly, kill the cancer cells. If he can figure out the signaling mechanism to change the microenvironment, his discovery also holds the promise of improving treatments for other types of sarcoma.
About the Giannini Fellowship
Giannini postdoctoral fellows are among the most highly respected medical and scientific investigators in their respective fields, and have served as mentors to succeeding generations of young scientists. The Foundation awards six to eight fellowships annually, and funds fellowships up to three years. Recent awards support research in embryonic development, Parkinson’s and Alzheimer’s diseases, autism, immunity and aging; and novel therapies to address fertility issues, cystic fibrosis, melanoma, Hepatitis B, diabetes, and prostate cancer.
Amadeo Peter Giannini was born in 1870 in San Jose, California. Known affectionately as “A.P.,” Giannini was not only an innovator in banking, but also a man with remarkable integrity and extraordinary faith in human character. The son of Italian immigrants, A.P. left school at age 13 to work in a wholesale produce business in San Francisco. He retired at 31, married and financially secure. In 1904, A.P. founded the Bank of Italy. From the beginning, he was a unique banker, making loans to immigrants, farmers, small businesses, women, and minorities. The bank’s loans and deposits quintupled within a year.
In 1909 Giannini began purchasing banks throughout California, converting them into branches of the Bank of Italy. By 1918 the Bank of Italy had become the first statewide bank in the United States. In 1930 the Bank of Italy was renamed the Bank of America, and soon became the largest banking institution in the world.
A.P. was committed to promoting the discovery and treatment of human disease. On his 75th birthday, May 6, 1945, he created and endowed the A. P. Giannini Foundation with a personal gift of nearly $500,000 to support innovative research in the basic sciences and applied fields. Since its inception, the Foundation has provided funding to more than 900 postdoctoral biomedical researchers at California’s accredited medical schools—most recently to Dr. Kuo.