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Yale Medicine Magazine, 2021 Issue 166

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Transplant surgeon David Mulligan leads efforts to improve patient care; make more organs transplantable; and test 3D printing that could ease the field’s dire shortages in the future.

Halfway through his urology residency David Mulligan, MD, professor of surgery and division chair of transplantation and immunology, assisted surgeons during a liver transplant operation. He was fascinated by the rigorous detective work the field requires, drawing from many areas of medicine, including hepatology, nephrology, immunology, endocrinology, and pathology. The constant severe shortage of available organs to transplant in the United States energized him even more. Mulligan wanted to address this overarching challenge by contributing directly to the field. He told his department chair and mentor at the time that he would specialize in multiorgan transplants instead. “He thought I was crazy, but he said, ‘If that’s what you want to do, I will help you,’ ” Mulligan recalled. He finished his urology residency and another residency in general surgery before starting a fellowship in multiorgan transplants at Baylor University Medical Center in Dallas.

For Mulligan’s first job, he chose a leadership position at the Mayo Clinic in Arizona to build a multiorgan transplant center from scratch. He saw this location as an opportunity to increase local and national patient access to organ transplant surgery. During his 15-year tenure there, he helped grow the center’s average number of surgical transplant procedures from 33 per year to more than 500.

Yale recruited Mulligan in 2013 to direct the Yale New Haven Transplantation Center. One of the first issues he wanted to resolve was lessening the burden of in-person visits for transplant patients—who receive follow-up care for life at the New Haven clinic—after surgery. Those efforts led to a first-of-its-kind telemedicine app that was enthusiastically received by transplant patients. Also, within the center, Mulligan established the Yale Transplant Research Unit so that basic and clinical scientists as well as physicians and surgeons could test and improve new technology like reperfusion machines and 3D organ bioprinting within transplant medicine. Through all of this, he’s worked to raise awareness that healthy people can directly save lives by donating a kidney or part of their liver. Research has shown that patients who receive organs from living donors have much better outcomes.

Earlier this year, Mulligan became president of the United Network for Organ Sharing (UNOS), which manages the nation’s transplant waiting list and tracks every single transplant in the United States—among its many other roles advocating for and supporting the transplant community. In 2019, a record-breaking number of 39,719 transplants took place in the country, but at the latest count, more than 109,000 people are waiting for life-saving organs according to UNOS.

As Yale Medicine Magazine began a video interview with Mulligan, he was answering a flurry of texts from colleagues concerned about new legislation that could affect how organs are distributed across the country.

In 2016, you launched a telemedicine program to improve patient care. Did that serve as a precursor to the MyChart telehealth app the Yale health care system uses now? Yes. We designed the app to address problems our patients faced after surgery. They have about three follow-up visits each week for a month after the procedure. During these visits, we go over their lab results, see how they’re feeling, and adjust their medications. Our patients were driving hours to get to the clinic, missing work, and having to make childcare arrangements. It wasn’t very patient-centered care. So we worked with a team of Yale engineering students in collaboration with the Center for Biomedical Innovation and Technology (CBIT) to create this platform called VIP Transplant.

The team wrote the code in a universal software language that could interface with any electronic medical record platform. This code had the capacity to split the screen for video; send patients reminders about their next visit; set timers for when they needed to take their medicine; and have a simple way to reach their patient care coordinator. We shared this code with our Epic information technology team so they could build in these capabilities into the MyChart app that we use across our health system today.

A major need in the field has been to expand the parameters of usable organs so that more can be transplanted. How does a device like the OrganOX machine you are using do that? We are investigating how to improve the quality of livers and kidneys that may come from deceased donors who are older—and we are increasingly getting more organs from this population—or who had liver or kidney injuries. We put these organs in a reperfusion machine called OrganOX and use it to pump blood through the organ so we can study it and find out what might be impairing its function. We want to find out if we can resuscitate it. The machine cleans and assesses the organ and delivers medicine and nutrients to improve its quality. In the future with FDA approval, we may be able to use it regularly for more successful transplants. This might be one of the single biggest advances that will contribute to organ transplantation in the United States in the next five years.

You and your team use 3D bioprinters to print the liver. Where are you in that process now? With living surgery, we can remove part of a liver in both a living organ donor and the recipient. The organ will grow to its full size again and take on normal physiologic function in six to eight weeks. Right now, we can use a 3D bioprinter to print liver cells. They grow and mature from stem cells to hepatocytes—liver cells that make up the liver. These then coalesce into these clusters of cells and form their own bile ducts. If we deliver a nutrient-rich blood supply to these cells, they will manufacture bile and proteins and synthetically function as liver cells do. We want to reproduce this on a larger scale by printing structures of the blood vessels and bile ducts. We're still a good decade away from being able to literally take a sample of someone's cells who has liver disease and print a new liver and give it to them to replace their diseased one. But many of these projects end up having exponential growth and we could see this happen sooner.