Faculty Spotlight: Tian Yi Zhang, MD, PhD

Tian Yi Zhang, MD, PhD
Assistant Professor of Medicine (Hematology) Member, Stanford Cancer Institute

When Tian Yi Zhang became a physician, she had no idea she would develop an interest in drug discovery. With a PhD in cellular and molecular immunology in hand, she considered herself purely a physician/scientist—someone with an innate interest in understanding and treating diseases and in helping patients, but not in conducting clinical trials for drug manufacturers.

That changed after the birth of her second child, a son named Isaac. Diagnosed at 4 months with a rare genetic disease called spinal muscular atrophy, Isaac, now 3, has received three first-in-human drugs—ones that undoubtedly saved his life.

"Had Isaac been born when my daughter [who is now 6] was, the disease likely would have been fatal for him, as there was no treatment or cure," explains Dr. Zhang, a board-certified hematologist and assistant professor of hematology at Stanford University School of Medicine. "The first drug he received was FDA-approved only about a year before he was born."

Dr. Z, as her patients like to call her, is fully aware that the people behind the development of the drugs her son continues to take are the reason he's thriving. "I have firsthand experience with how drug invention can benefit people who have no cure or options," she says. "I feel so strongly about doing drug discovery now because I was a direct beneficiary. I've benefited from people like me, and I want to pay it forward."

AML and Drug Discovery

With a clinical and research interest in acute myeloid leukemia (AML), Dr. Zhang's experience with drug discovery began when she and her fellow researchers discovered an off-target effect from the drug Idhifa (enasidenib). While that drug was being used to help a specific subset of AML patients—those with an IDH2 mutation—Dr. Zhang and her colleagues found a surprising yet beneficial side effect.

"AML patients are almost always transfusion dependent because the disease affects blood cell development," Dr. Zhang explains. "While reviewing published clinical trial data, we noticed that almost half of the AML patients who had received Idhifa actually became transfusion independent because their red blood cell and platelet production improved so much."

Suspecting that Idhifa could affect not just cancer cells, but also the stem cells that make red blood cells and platelets, Dr. Zhang has undertaken an investigator-initiated trial to test her theory. She hopes to confirm that the drug is indeed capable of boosting blood cell production in patients with AML and other myeloid cancers such as myelodysplastic syndrome and chronic myelomonocytic leukemia.

CHIP Clinic

Scientists have long known that certain gene mutations, such as the TP-53 mutation, increase the risk of developing various types of cancer. The problem is, new mutations are constantly being discovered, and it's often unclear which are the most high risk. Many of these mutations are referred to as clonal hematopoiesis of indeterminate potential, or CHIP.

Toward that end, the Division of Hematology will be opening a clinic to research which mutations are potentially the most problematic—and to counsel patients with a mutation that could put them at risk. Led by Dr. Zhang, the Stanford Clonal Hematopoiesis Clinic will be the only one of its kind in the Bay Area, and just one of five in the United States, to offer specialized, individualized care for people with a CHIP mutation.

Biobanking Registry

As part of her quest to conduct the research necessary to help diagnose and treat AML, and to identify the mutations that are likely to lead to this and other cancers, Dr. Zhang is in the process of establishing a biobanking registry. With the aim to modernize the existing tissue banking system, she and her team will not only expand on the information that is currently collected, but the registry will be entirely digital, automated, and efficient.

Expanding data collection to include patient diagnosis, treatment, clinical characteristics, clinical outcome, and other data, Dr. Zhang and her team will be able to conduct patient tracking over time and generate overall survival data and response to therapy. It will also help them conduct research with minimal manual curation—a process that up to now has been time-consuming and laborious.

Cancer Immunotherapy Research

Many experts in immunology believe that the immune system not only conducts surveillance of infectious agents in the body, but that it also looks for abnormal cancer cells—and that in many cases, these cells are killed before they become a tumor. "It's a common, established theory that this process, called immunosurveillance of tumor generation, happens all the time," Dr. Zhang says. "The question is, why does it sometimes work, while at other times it doesn't?"

That's just one element of the immunotherapy research Dr. Zhang is interested in. "We also hope to determine whether we can use immunotherapy in cases where we suspect the immune system plays a role in immune evasion of cancer cells," she says.

All of this takes time, effort, and lots of hard work—with huge potential payoffs.

Just look at Isaac.

BIOGRAPHY

Dr. Zhang earned her PhD in cellular and molecular immunology, as well as her MD at the University of Utah School of Medicine. She completed her internal medicine residency at the University of Utah and her hematology/oncology fellowship at Stanford University School of Medicine. Board-certified in internal medicine and hematology, Dr. Zhang is the recipient of several awards, including from the American Society of Hematology. Results of her research have been published in the Journal of Cancer Research, the Journal of Clinical Investigation, The Journal of Immunology, Leukemia & Lymphoma, and Science Translational Medicine. Visit The Zhang Lab, https://www.thezhanglabstanford.com/, for more information.