Dr. Andrew Hsieh elected member of American Society for Clinical Investigation

Physician-scientist demonstrated central role protein synthesis plays in cancer
Dr. Andrew Hsieh
Dr. Andrew Hsieh balances patient care with cutting-edge studies examining how changes in protein synthesis can drive cancer. Photo courtesy of Seattle Cancer Care Alliance

Fred Hutchinson Cancer Research Center molecular biologist and oncologist Dr. Andrew Hsieh was elected in the 2022 class of members of the American Society for Clinical Investigation. As a national medical honor society, ASCI supports the scientific efforts, educational needs and clinical aspirations of physician-scientists. ASCI election recognizes outstanding records of early scholarly achievement, as members must be 50 years or younger when elected.

“I’m very honored to be recognized by one of the U.S.’s oldest society for physician-scientists,” Hsieh said. He attributed his successes to his mentors, dedicated trainees and staff, and supportive family.

Hsieh has been at the forefront of efforts to look beyond DNA to reveal other cellular processes that can drive cancer development and progression. He has uncovered how important changes in the way cells make proteins can drive prostate and bladder tumors. When stymied by lack of technology, he and his lab members have developed their own research techniques.

“Andrew is an extraordinary physician-scientist who is eminently deserving of recognition by the ASCI,” said Fred Hutch President and Director Emeritus Dr. Gary Gilliland, who helped support Hsieh’s nomination. “He was nominated by internationally recognized leaders in his field, outside of the Hutch, for consistently generating novel insights into the biology and therapy of prostate cancer that has important implications in other disease entities. I have no doubt that he will continue to do so!”

Hsieh and the 2022 class will be formally inducted on April 8 at the joint meeting for ASCI, the Association of American Physicians and the American Physician-Scientists Association.

Looking beyond genes

Working with patients, Hsieh has been able to see that as powerful as the links between DNA and cancer may be, the picture is not complete. In order to develop more treatments, scientists need a more complete understanding of other cancer-driving cellular processes. He focuses on how cells make proteins, the key molecules that shape our cells’ structure, function and behavior.

To make proteins, cells first copy the information in our genes into molecules called messenger RNA, or mRNA. Protein-building molecular factories then read, or “translate,” the instructions in mRNA to create proteins. If this process gets rewired, changing which mRNAs get translated into protein and how much protein is made, cellular processes can get thrown off. Toggling certain proteins up or down could promote cancer development, growth and progression.

Hsieh and his team have uncovered important changes in mRNA translation that drive prostate and bladder tumors. They revealed that the androgen receptor, which responds to male hormones like testosterone and fuels prostate cancer growth, suppresses protein synthesis — and when prostate tumors ramp down the androgen receptor, they turn up translation of mRNAs encoding proteins that promote cell growth. While this gives prostate tumors a new avenue for growth, it could also represent a new treatment target.

Protein production is also key for efficient bladder tumor growth, and lab studies by Hsieh and postdoctoral fellow Dr. Sujata Jana showed that suppressing it could be a way to slow disease progression.

When the technology to answer a question doesn’t exist, Hsieh doesn’t back down. He and then-postdoc Dr. Yiting Lim (now a senior scientist at Seattle-area biotech company Evotec Biologics), recently described a new technique they dubbed PLUMAGE, which allows them to reveal potential drug targets hiding in previously difficult-to-study regions of DNA. PLUMAGE provides researchers a high-throughput strategy to determine whether mutations in regions of DNA outside genes can have cancer-promoting effects.

And Hsieh’s curiosity extends beyond cancer. With Hutch colleague Dr. Patrick Paddison, Hsieh showed that developing red blood cells use a specific molecular modification to ensure that red blood cell-specific mRNAs get turned into protein. The finding could help explain what’s behind certain anemias and blood cancers.

“Andrew’s work is exactly what the American Society for Clinical Investigation was designed to recognize and highlight — namely cutting-edge innovation that has direct links to and from clinical medicine," said Hutch prostate cancer researcher Dr. Pete Nelson, who heads the Pacific Northwest Prostate Cancer SPORE and holds the Endowed Chair for Prostate Cancer Research.

"This is often very challenging, yet Andrew has repeatedly shown the ability to make novel laboratory discoveries in the important area of gene regulation involving how messenger RNA is translated into proteins, and to demonstrate how it relates to the biology and treatment of cancers in patients," Nelson said.

Balancing research with patient care

Constant questioning is part of being a scientist, Hsieh said.

“I see the [election to ASCI] as an endorsement of the work we’ve done so far, pushing the envelope and diving deep into mechanistic science that’s patient-relevant,” he said.

Hsieh has been balancing research with patient care since medical school. While heading a lab, he also sees patients with prostate and bladder tumors as a medical oncologist at Seattle Cancer Care Alliance, the Hutch’s clinical care partner.

Even as a medical student at the Albert Einstein College of Medicine in New York City, Hsieh wanted to do more than give patients currently available treatments. Cancer geneticist Dr. William Sellers, then at the Dana-Farber Cancer Institute, gave Hsieh a research opportunity in his lab. Seeing Sellers heading a research lab as an M.D. helped Hsieh realize that the medical degree he was working toward didn’t preclude an academic career in science.

“I saw the possibilities and decided to test that [road] out for myself,” Hsieh said.

Eleven years and several fellowships later, Hsieh was able to start his own research laboratory at Fred Hutch. But fewer clinicians or researchers are seeking to walk the same tightrope.

“Having societies like ASCI around to buttress that and say, important science can come from folks who are medically oriented, is important to growing this vital stream of biomedical innovators,” Hsieh said.

He continues to draw inspiration from his patients and prioritize ensuring that his laboratory and clinical work inform each other.

“I’m very grateful to all patients I’ve seen over the past 15 years as a cancer doctor,” Hsieh said. “Those who’ve given me the privilege of walking with them through their journey with cancer, and whose stories have inspired the trajectory of my lab.”

Hsieh is the eleventh Hutch faculty member elected to ASCI. The most recent inductees include Drs. Marie Bleakley, McGarry Houghton, Stephanie Lee and Amanda Paulovich. Bleakley holds the Gerdin Family Endowed Chair for Leukemia Research, Lee holds the David and Patricia Giuliani/Oliver Press Endowed Chair in Cancer Research, and Paulovich holds the Aven Foundation Endowed Chair. 

Sabrina Richards, a staff writer at Fred Hutchinson Cancer Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a PhD in immunology from the University of Washington, an MA in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at srichar2@fredhutch.org.

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