A family tragedy, an unexpected discovery, and some daunting questions led to the founding of a new precision medicine center

 

“My mother wanted me to be a doctor and I was sure of it until high school when my uncle-in-law suddenly fell ill,” recalls Xiling Shen, the Hawkins Family Associate Professor of Biomedical Engineering at Duke University and Director of the Sherry and John Woo for Big Data and Precision Health Center.

“He kept coughing and was losing weight. He was treated for pneumonia for four months before he was officially diagnosed with colon-cancer lung metastasis. I remember asking myself back then, ‘How can medicine be so imprecise? How could doctors not know?’”

Having witnessed his uncle-in-law’s pain and suffering, Dr. Shen told his mother that he could never be a doctor witnessing such trauma on a daily basis. So he went on to become an electrical engineer, preferring to deal with machines that came with no emotional toll. He completed his PhD at Stanford University in 2005, at a time when his advisor had kidney cancer.

“Unlike my uncle-in-law, he was diagnosed early enough to be cured,” Dr. Shen said. “We embarked on long discussions on how complex biological circuits can go wrong and whether electrical circuits can shed some light.” Dr. Shen began using engineering tools to model biological circuits and found that many seemingly “trivial” or “redundant” features were essential for robustness or to avoid the circuit from malfunctioning. “I moved to become an electrical engineering professor at Cornell University in 2009,” Dr. Shen continues. “I was approached by a clinical geneticist who specialized in colorectal cancer after I gave a talk on how circuits can regulate the cell cycle.”

Dr. Shen thought the gentleman asked a rather daunting question, “It’s fascinating to know how the regulatory circuits can break down in a million ways and give rise to cancer but how can we fix them?” That got him wondering if he could modulate each patient’s cancer “circuitry” in a way that could be fixed.

However, the actual turning point didn’t arrive until later that year when Dr. Shen read a paper by the Hans Clevers’ lab describing 3D organoids, a new technology allowing the modelling and manipulation of primary patient tissues and growing them to resemble actual organs. “I realized I could leverage the technology for functional testing,” Dr. Shen says. “Together with genomics sequencing and new gene-editing technologies to measure aberrations in the biological circuit and to safeguard breakdown at the DNA level in each patient, in order to develop personalized therapy.”

In 2016, Dr. Shen met Oncologist Dr. David Hsu while visiting Duke University. Being aware of Dr. Shen’s work, Dr. Hsu asked, “Why haven’t you designed new organoid-based clinical trials to make a real impact?”

“That shook me and brought me to think about my uncle-in-law and how I could do something to help cancer patients,” Dr. Shen says. “So I moved my lab to Duke and began working with Dr. Hsu on precision cancer therapy clinical trials.

However, the duo faced a huge challenge. No pharmaceutical company would sponsor clinical trials that did not involve drugs. Fortunately, the effort impressed philanthropist and biotech industry executive John Woo, who agreed to fund more than $3 million over three years, to establish the Sherry and John Woo for Big Data and Precision Health Center at the Duke University Pratt School of Engineering in October 2018.

The Center aims to support global research in the advancement of personalized medicine by being a catalyst for generating new partnerships between medicine and tech industries and developing innovative methodologies to turn diverse and well-curated healthcare data into actionable clinical insights. The Center’s first clinical trial was approved in September 2019 with patient recruitment starting in January 2020.

A project is already underway in China, where a team is setting up a national network of health data parks to improve local rural care delivery. The Center’s first annual symposium was held in October 2019. The full-day conference had 25 speakers showcasing significant findings in personalized medicine, genomic engineer, genomic regeneration, AI and health data. Duke faculty are also eligible for pilot grants of up to $150,000 to explore new ideas for collaborative projects.

Presently, there are four divisions within the Center: AI imaging, health data, precision medicine and iGEM (International Genetically Engineered Machine Team).

The precision medicine division focuses on establishing an organoid biobank for multiple cancer types; developing a rapid organoid therapeutic assay to pair the right therapy with the right patient at the right time and facilitating the identification of novel drugs and the development of new therapeutics.

One of the projects entails rapid organoid therapeutic assay (ROTA) or the rapid generation of organoids and drug testing of patient tumor cells to guide oxaliplatin-based treatment for patients with colorectal cancer liver metastasis. The Center hopes to improve targeted treatment while minimizing toxicity in patients.

“Precision medicine requires big data, which is inherently noisy and full of unpredictability,” Dr. Shen explains. “Likewise, my journey into the field of big data and precision medicine has already been filled with unexpected turns. Seemingly irrelevant experiences and skills picked up along the journey end up making us unique. Every turning point can be that missing piece that, together, helps us solve a giant puzzle.”