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Putting their heads together: when engineers and clinicians talk medicine

New initiative brings clinical pathologists and Wyss scientists together to solve healthcare’s biggest problems

By Lindsay Brownell

(BOSTON) —  When David Walt, Ph.D. joined the Wyss Institute and Brigham and Women’s Hospital (BWH) in mid-2017, he described how his experience founding and serving on the Boards of Illumina, Inc. and Quanterix Corp. taught him that using science to change the world requires shifting priorities from the number of academic papers published to the amount of impact a given project can have on improving human health across the globe.

David Walt (right) organized lab tours and presentations from Peng Yin (left) and Wesley Wong (not pictured) to showcase some of the Wyss Institute’s molecular robotics technologies and generate discussion with pathology clinicians. Credit: Wyss Institute at Harvard University

As part of the effort to help his colleagues at the Wyss Institute and BWH start thinking about how to translate scientific research into real-world solutions, Walt coordinated the first of what will be multiple “field trips” between the two institutions by bringing nine BWH Pathology Fellows to the Wyss Institute’s Longwood campus last month to learn about projects in the labs of faculty members Peng Yin, Ph.D. and Wesley Wong, Ph.D.

“The Wyss Institute is full of really smart people who are working on futuristic technologies that aren’t quite ready to be used in the clinic. But if we can match the capabilities of those technologies to the right clinical applications, then maybe we can push a technology’s development forward so that it solves a real problem with the potential to have a tremendous impact on improving human health and happiness,” said Walt, who is a Core Faculty member of the Wyss Institute, Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard Medical School (HMS), and Professor of Pathology at BWH.

Wyss Postdoctoral Fellow Feng Xuan (left) explains his research to BWH pathologists. Credit: Wyss Institute at Harvard University

The visit began with a presentation by Yin about his lab’s primer exchange reaction (PER) technology and its potential application to dramatically reduce the time and improve the quality of diagnostic tests, as it has higher sensitivity and lower levels of background noise than existing technologies.

Next, the fellows learned about the Wong lab’s DNA nanoswitches while Darren Yang, Ph.D. – a Research Scientist at the Wyss Institute and Research Fellow at Boston Children’s Hospital – performed a demonstration that used DNA nanoswitch technology to detect the presence of PSA (a biomarker for prostate cancer) in a sample in about 20 minutes.

“I’m a physics person, so what often attracts me to problems is an interesting question that will reveal something new about physics. We originally developed these DNA nanoswitch assays to study how force can affects how molecules bind and interact, but we soon realized that they could be used for many translational applications as well, such as detection and compound screening. There’s something motivating about knowing that by developing this approach, we could help solve real-world clinical problems, in addition to satisfying our curiosity about nature,” said Wong, who is an Associate Faculty member at the Wyss Institute, an Assistant Professor at HMS, and an Investigator at Boston Children’s Hospital.

The BWH fellows provided feedback about the existing iterations of the Wyss technologies, and shared some of their struggles with existing molecular diagnostic techniques.

Wyss Research Scientist Darren Yang demonstrates how the Wong lab’s DNA nanoswitch technology can be used to detect proteins in samples within 20 minutes. Credit: Wyss Institute at Harvard University

“A lot of the reactions that we perform in clinical assays actually happen quite quickly, but human hands need to be manipulating them throughout the procedure, so we often end up only doing an assay once or twice a week,” said Clinical Pathology Fellow Alissa Keegan, M.D., Ph.D. “Making the overall workflow surrounding a reaction as simple as possible and automating as many of the steps as possible would help us diagnose and treat patients much faster.”

“One of the biggest problems I see with my patients in the intensive care unit, is that we don’t know if they’re responding to antibiotic treatment or not. Having a series of rapid measurements for known sepsis biomarkers in their blood that could be performed every few minutes would be a perfect use case for the technologies that we’ve seen here today,” said Sanjat Kanjilal, M.D., also a Clinical Pathology Fellow at BWH.

Wesley Wong presents his lab’s work on DNA nanoswitches for protein detection and characterization. Credit: Wyss Institute at Harvard University

The pathology fellows and residents plan to draw up a comprehensive list of problems that they experience in their clinical practice to help further guide the Wyss’ project development, and invited Wyss researchers to visit their labs to get an even better sense of their work environment and its challenges. The Wyss also plans to host another group of fellows in the near future for a session focused on medical devices.

“Getting this kind of immediate feedback on our research allows us to investigate alternative uses and new directions that we might not have otherwise thought to pursue, and we are excited to see where these conversations lead,” said Yin, who is a Core Faculty member at the Wyss Institute and a Professor at HMS.

“The Wyss Institute sits at the physical and intellectual nexus of healthcare technology, a stone’s throw away from some of the world’s top hospitals. Increasing our collaborations with clinicians will greatly help our efforts to solve the biggest problems in healthcare through disruptive technology innovation and development,” said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS).

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