Strengthening Connections Between Fibrosis Researchers

Consortium aims to address unmet need for anti-fibrotic therapies

Mark Couch

(May 2017) The Consortium for Fibrosis Research & Translation aims to unify campus researchers and clinicians who, due to their concentrated focus on a particular organ, may not have recognized similarities of their work.

“This is a group that is focused on fibrosis, which is essentially excessive scarring,” said Tim McKinsey, PhD, professor of medicine and director of the Consortium for Fibrosis Research & Translation (CFReT).

“Fibrosis is a wound-healing process that can be beneficial, but it can also be very deleterious,” he said. “If your internal organs become scarred, they become dysfunctional. It’s estimated that about 45 percent of the deaths in the Western world are due to some form of fibrosis.” The goal of the CFReT is to investigate and understand the common elements about fibrosis in different organ systems, and ultimately develop therapies that could address those deleterious effects.

“Unfortunately there really are no treatment options for people with fibrosis,” McKinsey said. “There are a couple of drugs used to treat a lung fibrosis disorder called idiopathic pulmonary fibrosis or IPF, which is a deadly condition. There are two FDA approved drugs for IPF, but neither are very effective. So there’s really a huge unmet medical need for the development of novel anti-fibrotic therapies.”

What do the molecular pathways in cardiac fibrosis, for example, tell researchers that might be useful in understanding progressive scarring in lung, liver, or kidney?

“One of the goals of our center to define novel biochemical pathways that commonly regulate fibrosis in diverse organ systems because we feel that those will be crucial drug targets,” he said.

“The CFReT is unique in that it brings together experts in the basic science and the clinical treatment of people with fibrotic diseases,” McKinsey said. “There are centers of excellence in fibrosis that are related to a particular organ scattered around the country, but this is the first consortium of its kind where experts in fibrosis across organ systems are under one roof.”

Mary Weiser-Evans, PhD, professor of medicine and co-director of CFReT, said the approach to research that might consider fibrosis has traditionally been focused on specific organ systems.

“While the CFReT is a unique multidisciplinary approach, there is an underlying complication because many of the other organ-specific centers across the country are NIH-funded and at the NIH there are individual institutes that would fund a liver fibrosis center or a pulmonary fibrosis center. So our goal is to bring together multiple institutes to get this funded, which will be complicated.”

Such an approach creates a natural tendency for specialists to flock together. For CFReT investigators, the goal is to find the common ground between the hepatologists, cardiologists, pulmonologists and others. While initially focused on heart, lung, liver, and kidney fibrosis, an unexpected, but welcomed result of the CFReT has been increased interest from investigators from other disciplines, including neuroscientists, scleroderma specialists, and researchers focused on eye fibrosis.

“In putting this application together, we had an opportunity to talk to a diverse group of investigators, including liver experts and lung experts. It turns out we have a lot in common, but we tend to talk to just the heart or vessel experts,” said McKinsey, who runs a laboratory focused on molecular mechanisms of heart failure.

One of the key duties of the leaders of the Transformational Research Funding initiatives will be to establish centers of excellence on the Anschutz Medical Campus that can continue after the initial funding awards wind down.

“A main focus of ours is sustainability,” McKinsey said. “After five years of funding, we want to make sure we can continue to maintain and grow this very special consortium.”

To that end, the CFReT has established the Fibrosis Innovation Group (FIG) and hired Keith Koch, PhD, who has held research and leadership roles in the private sector, to lead the effort. The FIG is modeled after structures used by successful biotechnology companies and nonprofit research institutes with units that provide useful services to other researchers and that can help advance the ongoing work of the members of CFReT.

At this start-up stage, the CFReT has been investing directly in work of campus researchers, whether they are well-established faculty members or promising graduate students.

“We have an internal granting system where we provide pilot funds to investigators, and we have now funded six distinct investigators with these pilot funds,” said McKinsey. “The goal is to generate preliminary data that will lead to new grant applications and industry collaborations.” For example, Michel Chonchol, MD, professor of medicine and direc-tor of the polycystic kidney disease program in the Division of Renal Diseases and Hypertension, received a CFReT grant that will support imaging work with patients.

“We have funded a clinician, Michel Chonchol, to perform a study in humans with something called polycystic kidney disease, which is a genetic disorder that has a severe fibrotic component, and he’s using an imaging method called MRE (magnetic resonance elastography) to quantify fibrosis in these patients. Such a study would not have been possible without funding from the CFReT.”

So far, two graduate students in existing programs on campus – one in Pharmacology and another in Integrated Physiology – have been funded through CFReT, Weiser-Evans said. “One is working on iPS (induced pluripotent stem) cells in heart regeneration and fibrosis.” Such research is crucial because fibrosis can interfere with normal organ structure and function.

“Organ regeneration is inhibited by fibrosis,” McKinsey said. “So this student is looking at the interplay between fibrosis and cardiac regeneration.”

In addition, the funding is supporting a lecture series and additional faculty recruitment efforts. A seminar series started last November with guest speakers already scheduled throughout 2017. Furthermore, Maggie Lam, PhD, from UCLA will be joining the CFReT as an Assistant Professor starting May 1.

In addition to building a community of researchers on campus, the leaders of CFReT also want to raise awareness of the impact of fibrosis on day-to-day life.

“I think when talking to lay public, it’s important to convey some common examples of how fibrosis can affect your life,” McKinsey said. “I have friend who has a form of eye fibrosis. He is essentially blind because he had surgery and as the wound healing response occurred, it never resolved. That means his eye became progressively fibrotic and scarred over. So that’s an example of how fibrosis is not going to kill you but it can significantly affect your quality of life.” He cited another example.

“A colleague of mine has a friend who’s a singer and unfortunately she has this rare disorder where her vocal chords become fibrotic and she can’t sing any more. She’s not going to die from that, but she can’t do what she loves. So it’s not just that fibrosis is deadly. It certainly is deadly, but it can also can significantly affect your quality of life.”