A Second Chance at Life

One of the country’s top transplant researchers is Dr. Barbara Murphy, the Dublin-born chair of medicine at Mount Sinai Health System in New York. Her expertise in the field of renal transplants gives patients a second chance to live healthy, normal lives. 

 

Dr. Barbara Murphy, Murray M. Rosenberg Professor of Medicine and chair of the Department of Medicine for Mount Sinai Health System in New York, clearly recalls the patient she met while in medical school who made her want to specialize in nephrology (the diagnosis and treatment of kidney disease) and transplant immunology (the study and care of how the human body receives transplanted organs).

During her final years at the Royal College of Surgeons in Dublin, Dr. Murphy met a young patient – only a few years younger than she was at the time – who had juvenile rheumatoid arthritis and consequently developed amyloidosis (the build-up of amyloid proteins in organs and tissues), and then kidney failure.

“I saw her on dialysis when I was a medical student,” Dr. Murphy recalls. “Then I saw her later on when she came and got her kidney transplant, and then I took care of her as a renal registrar – I saw her all the way through.

“By then, she had gone to college and become a teacher. Just to see the impact that the transplant had on her and her life – it had a significant impact on me, I was totally fascinated by it.”

That encounter would set Dr. Murphy, born and raised in the South Dublin suburbs, on a remarkable course: a fellowship in clinical nephrology at Beaumont Hospital in Dublin in 1989, followed by postdoctoral training with a fellowship in nephrology at Harvard Medical School’s Brigham and Women’s Hospital – the very hospital where the first-ever successful organ transplant (a kidney) was performed in 1954, by Dr. Joseph Murray, a pioneering Irish American surgeon who would go on to win the Nobel Prize.

Harvard was both a milestone and a return for Murphy. Like so many young Irish, she had spent time in the U.S., in Boston, on a J-1 summer visa during college. One day, she got on the wrong bus back to her home for the summer and wound up taking a long detour down Longwood Avenue, driving through the Harvard Medical School campus. She thought, at the time, “Imagine going here, wouldn’t it be absolutely incredible?” Later on that summer, she returned to the campus and bought her first stethoscope in the medical supply shop there.

After working at Beaumont, Dr. Murphy knew her future lay in the U.S. “I always knew I would probably have to leave Ireland, but I never thought I would end up where I did,” she says. “At that point there were very few pure specialist transplant nephrologists, but many of them had trained at Brigham. So I quickly realized that was the place where I wanted to be, and I identified two incredible mentors, Dr. Charles Carpenter and Dr. Mohamed Sayegh, who really helped guide my career.”

Starting there in 1993, Dr. Murphy trained in transplant immunology at the Laboratory of Immunogenetics and Transplantation. She was recruited to Mount Sinai Medical Center in New York as Director of Transplant Nephrology in 1997 and was named chief of the Division of Nephrology in 2003, becoming one of the youngest division chiefs in the U.S. and one of only a few women to hold that title at the time. In 2011, she was appointed dean for Clinical and Population Based Research and Director of Conduits at The Institute for Translational Science.

Dr. Murphy was named chair of the Samuel Bronfman Department of Medicine at the Icahn School of Medicine at Mount Sinai in 2012, becoming the first female chair of medicine of an academic medical center in New York City and only the second female chair at a top 20 medical school in the U.S. Since the formation of Mount Sinai Health System in 2013, as a result of the merger of Continuum Health Partners with the Mount Sinai Medical Center, Dr. Murphy has served as chair of medicine for the Mount Sinai Health System and dean for Clinical Integration and Population Health.

A renowned researcher, Dr. Murphy was awarded the Young Investigator Award in Basic Science by the American Society of Transplantation in 2003 and served a term as president of the society just six years later, in 2009. She has also served as chair of the World Transplant Congress and was named Nephrologist of the Year by the American Kidney Fund in 2011.

Her key areas of research have focused on genetics and genomics in transplantation, and she was one of a small group of investigators to challenge the paradigm that HIV positive patients could not receive a transplant, co-authoring a landmark paper that has lead to renal transplantation in HIV positive individuals being standard of care.

A New Yorker for 19 years now, Dr. Murphy lives in Westchester with her Irish American husband, Peter Fogarty, who works as an engineer, and their six-year-old son, Gavin. They return to Ireland many times a year to visit her parents.

The late July week that we met in her office at Mount Sinai’s complex on Manhattan’s Upper East Side, the results of a groundbreaking study led by Dr. Murphy had just been published in the medical journal The Lancet to great acclaim.

The Genomics of Chronic Allograft Rejection (GoCAR) study began in 2007 and involved patients and researchers from five U.S. hospitals and one in Sydney, Australia, with Dr. Murphy as the principal investigator.

The GoCAR study weighed the use of genetics and genomics in predicting the outcome of organ transplant implantation, with the aim of identifying a gene set capable of predicting kidney transplants at risk of progressive injury or loss due to fibrosis long before the current indicators doctors use to determine whether a transplant will fail.

This is vital work. According to the National Kidney Foundation, kidney disease is the ninth leading cause of death in the U.S., claiming more lives each year than breast cancer or prostate cancer. There are currently over 100,000 individuals waiting for kidney transplants in the U.S. In 2014, 17,107 kidney transplants took place – 11,570 from deceased donors and 5,537 from living donors. According to the Organ Procurement and Transplantation Network, transplanted kidneys from deceased donors fail in four percent of cases one year after transplant and 21 percent of cases five years after transplant; when the kidney comes from a living donor, these figures improve to a three percent failure rate at one year and 14 percent five years after transplant.

In an official release, Dr. Murphy called the study “the first of its kind.”

“By helping us better understand the causes of damage to transplanted kidneys, this study has the potential to change how we monitor and manage all renal transplant patients,” she said.

The ability to identify renal transplant recipients at risk for a loss of the new organ before any irreversible damage occurs, she added, would mean “doctors might eventually have the opportunity to change the therapeutic approach in order to prevent fibrosis from progressing at all.”

The following are excerpts from our discussion about the study and its future implications, Dr. Murphy’s exceptionally empowering upbringing (she and her two siblings are all doctors; the first in their family), and her vision as chair of the Department of Medicine at what is now one of the largest not-for-profit health systems in the country.

 

 

What sparked your passion for transplant nephrology?

First of all, I’ve always been fascinated by the kidneys and how they work. Then, starting in medical school, I loved looking after kidney transplant patients because you transform their lives. Dialysis is wonderful; it’s great that we have it. But it just about maintains patients with kidney failure; it’s not a life. There are plenty of people who manage to balance dialysis with going to work, but for most people it’s very disabling. And the mortality rate is really quite drastic.

That’s why it’s incredibly important for people to be offered the option of a kidney transplant early, for them to explore the possibility of a living donor and to get off dialysis so that they can live longer, do better and have a good life. I love seeing how well patients do afterwards. For all the years that I’ve been in this profession, the interaction between a living donor and the recipient in the recovery room still makes me proud to be a physician and to play a part in such a life-affirming moment.

I don’t do clinical work anymore – I miss it incredibly, but you have to be available at all times to your patients, and because of the significant administrative roles that I have, that wouldn’t be possible; you have to be able to give your all to your patients. I do maintain my research, however.

Congratulations on the publication of the GoCAR study, can you tell me more about it?

We’re looking at the use of genetics and genomics in predicting the outcome of transplant implantation. The idea is that, we know that if we do a kidney biopsy on a patient at three months and we see fibrosis, then that patient is unlikely to do as well as other patients. Fibrosis will progress and they will likely go on to lose their kidney.

So the hypothesis was: why can’t you see molecular changes earlier? Can we pick up molecular signatures before the actual injury has occurred and use them to predict who will do badly?

We followed transplant patients for two years, doing serial biopsies, drawing blood, and tracking their progress. Ultimately we were able to identify a gene set that predicted which individuals would go on to develop fibrosis at one year and two years after the transplant, have a decline in their kidney function, and lose their allograft.

We’re also looking at identifying signatures in the blood that will pick up who has underlying inflammation that wouldn’t be picked up in our routine labs, so that we can pick out patients with what we call sub-clinical rejection. We can then risk stratify them immunologically and manage their immunosuppression in a more appropriate and personalized way rather than doing a standard approach for everybody.

Lastly, we’re also starting to look at the signatures in other organs to see if this approach will work for other transplants as well.

What was your upbringing like?

I’m from Dublin – Knocklyon, on the south side of Dublin. I’m the youngest of three children, all of us doctors. My parents were, depending on how you look at it, either fortunate or unfortunate enough to have three kids in medical school at the same time, all doing exams at the same time.

Was there a history of medical workers in your family?

No, though I do now have cousins in the medical profession. My dad, John, had his own airfreight company, and my mother, Ann, worked with him and also designed bridal wear.

I’m not sure how it happened, but from an early age, Kieran, Celine, and I all said we wanted to be physicians. Our parents were, and are, incredibly devoted to us. They instilled in us this incredible work ethic: that we needed to be driven and determined but at the same time strike a balance and enjoy life. They gave us the sense that if we put our minds to it, we could do anything. The values they taught us formed the foundation for where all three of us are now and how we manage our lives. The only thing is that we all left Ireland: Kieran lives and works in Canada, and Celine in Australia.

What was it like to enter the medical profession in Ireland as a woman?

It’s funny – this wasn’t even that long ago, but when I was starting out, almost all of the attending physicians in Ireland were male. When I started in nephrology, only eight percent of nephrologists were female. When I was in final med, my professor of medicine at the time kept saying to me, “You know, you think you can have it all, but you can’t. You’re not going to be able to have a family and a career; you’re going to have to make a choice.” And now look at me.

There were actually lots of instances like that. Going back further, when I was in school in Ireland the career guidance counselor asked me what I wanted to do, and I said that I wanted to be a doctor. She told me, “But you’ll be taking the place of a boy.” That just made me even more determined.

My mother promptly changed my school. Her attitude was, and she would often say, “It’s as important for my daughters to have a career as it is for my son to be able to cook.”

So while I didn’t have any female role models in medical school, I did have a role model in my mother, a really strong one.

Now you’re the role model.

Actually, when I became the department chair here, we had a huge upswing in female residents. We weren’t preferentially choosing female candidates, but the number of outstanding applicants who were female and chose to apply here certainly increased, possibly because they knew it was one of the few medical departments with a female chief. We swung suddenly to 75 percent female that year, and now we’re around 65 percent female in our residency program, which is still high.

I should add, though, that I have had wonderful male mentors, especially once I arrived in Boston at Brigham and Women’s. At that point there were relatively few pure specialist transplant nephr-ologists, but many of them had trained at Brigham, where the first transplant ever took place. I identified two incredible mentors there, Charles Carpenter and Mohamed Sayegh, and they really helped guide my career.

I repeatedly say to female residents and medical students, you don’t necessarily need a female model and mentor, you just need somebody who’s going to guide you and advocate for you. If that person happens to be female, then that’s great.

What’s your greatest priority as department chair? How did it alter following the merger between Mount Sinai and Continuum [which was finalized in January 2014]?

Since Mount Sinai went through the merger with Continuum we have seven hospitals around the city. I oversee the Department of Medicine, the largest academic department throughout those seven hospitals, the clinical practice as well as the research and the education. We have just over 700 residents and fellows in three residency programs.

From the perspective of the department, what we’re doing is focusing on developing clinical institutes – and we’ve already initiated several – where we bring multiple specialties together to coordinate the care around individuals with specific chronic diseases. So a patient should be able to come in and receive the majority of the care that they need in that one environment, with the physicians and care providers working together. One example is the diabetes institute where we’ve brought together the adult and pediatric diabetologists, so a patient can transition from being a young individual with diabetes to moving forward to your adult care provider. Then, in the same area we have nutrition, bariatrics, nephrology, hepatology; all the specialties that an individual might need to participate in their care, along with their clinical diabetes educator and nursing.

That sounds like a very patient-focused approach.

It can be very difficult as a patient to navigate through the medical system; with a chronic disease you may have multiple physicians involved in your care. But if you bring all these people together, there’s an improvement in the communication, and there’s a coordinated approach to that patient’s care. The additional effect of this is that it creates an environment that facilitates clinical and translational research.

I mentioned diabetes as an example, but we’re taking this approach in a variety of specialties. Our goal is to develop an outstanding environment for patients that provides the very best coordinated care, which is augmented and enhanced by groundbreaking and innovative clinical and translational research which further improves our patients’ lives.

Thank you, Dr. Murphy. ♦