PSC Investigator Profile: Tom Hemming Karlsen, M.D., Ph.D.

Feb 11, 2019 | Konstantinos N. Lazaridis, M.D. | @klazaridis | Comments (2)

2019-02-08 Dr. Karlsen

A decade ago, Tom Hemming Karlsen, M.D., Ph.D., who leads the Norwegian PSC Research Center (NoPSC), joined forces with Konstantinos Lazaridis, M.D., of Mayo Clinic to uncover the culprits driving PSC. At the time, neither could have foreseen the transformative power of their collaborative genetic study on the global PSC research landscape. The transformation was possible, Dr. Karlsen says, thanks to a unique spirit of community.

“We realized that to have robust and significantly valuable findings, we had to come together,” says Dr. Karlsen. In so doing, they ushered in a new era of research between the largest PSC referral centers in the U.S. and Norway that did away with the old customs of secrecy and competing laboratories not sharing research findings.

To address the numerous unanswered questions about PSC, in 2009 Drs. Lazaridis and Karlsen collaborated to build the PSC Resource Of Genetic Risk, Environment and Synergy Studies, termed PROGRESS, a comprehensive collection of clinical data and research biospecimens from over 1,300 PSC US patients. And in 2010, Dr. Karlsen co-founded the International PSC study group.

“By establishing the international group in this relatively narrow research area for a rare disease, there is only a minimum of competition and as much complementarity and collaboration as possible,” says Dr. Karlsen. “We don’t have people working on redundant topics and competing, which is often the case in academia. Instead, we helped bring people together in a constructive way.”

More recently, in his role as Professor of Internal Medicine at University of Oslo and the Head of Research of the Division of Surgery, Inflammatory Diseases and Transplantation, Dr. Karlsen has worked to expand what used to be mostly clinical research into a comprehensive translational research unit aiming to cover all areas of PSC research. His goal: Understanding what causes the disease by exploring disease mechanisms through basic research focused on immunology and metabolism and then translating those more mechanistic studies for clinical utility, such as the development of biomarkers.

The NoPSC Research Center has grown from a small, Oslo-based team of three to a team of 25-30 supported by more than $2.5 million annually of competitive grants funding. As the European leader in PSC research, NoPSC maintains a substantial biorepository and data resource from over 700 Norwegian PSC patients. Moreover, researchers from NoPSC have pioneered studies of genetics and microbiome in PSC.

“If you really want to dramatically change the way we’re dealing with disease, you have to understand it,” says Dr. Karlsen. “I think there is some big secret hidden somewhere within PSC. I think that there is something very fundamental hidden currently in disease pathophysiology, which to me is exemplified by the many paradoxes in the disease – it’s like a puzzle that doesn’t come together. I tend to say that the day we fully understand PSC; biology will have changed a little bit.”

To uncover that secret, Dr. Karlsen is collaborating with Dr. Lazaridis and researchers from Emory University and the University of Illinois as part of a recently funded National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) RC2 grant. For this project, Dr. Karlsen is enthusiastic about the application of artificial intelligence and its potential to generate answers to the fundamental questions about disease development. In addition, the use of unbiased technologies may shed new light on how to improve diagnosis and prognostication for PSC patients.

“A twenty percent lifetime risk of cancer for PSC patients is a lot when you’re living with a chronic disease,” says Dr. Karlsen. “If by these multi-omics technologies, we can come up with new tools to provide an early diagnosis of cancer in the patient, which can then be removed by liver transplantation, I think it would be wonderful.”

As part of the RC2 collaboration, Dr. Karlsen and Dr. Johannes Hov in his team will lead studies to investigate the role of gut microbiota, specifically how the diversity of bacteria in the gut influences development of PSC. Such studies come on the heels of reports that 25-30% of PSC patients who undergo a liver transplant experience disease recurrence. Dr. Hov’s group will collect information about gene content in gut microbiota and also use associated technologies to assess the metabolic influences from that gene content by measuring a wide variety of physiologic compounds. Of note, therapies to manipulate the contents of the gut are currently being tested.

“The main thing that is important to be aware of as a patient is that if you go five years back we were using one drug, which we don’t really know if it works, and there was not much innovation going on. Today, five years later there are many, many drugs being tested for PSC and some of them show very promising results,” says Dr. Karlsen. “I think PSC will change from a disease which you basically are told we cannot do anything about it to a disease we can treat in some way or the other, and I think that transformation will happen in the next 5-10 years.”

Such confidence stems from what he says makes Mayo Clinic such a great partner. “I appreciate Mayo’s very stable and robust commitment to PSC, which goes decades back, like ours in Oslo,” says Dr. Karlsen. “The fact we have now worked together for so many years, actually has allowed us to get to know each other very well and I value many of the Mayo colleagues as friends as much as academic collaborators.”

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