The nonprofit Three Lakes Foundation is partnering with Yale University and the University of Pittsburgh to form the Three Lakes Consortium for Pulmonary Fibrosis (TLC4PF)—a “multiyear, multimillion-dollar initiative” to accelerate new treatments and ultimately cure the disease.

The TLC4PF aims to change how idiopathic pulmonary fibrosis is diagnosed and treated, Dana Ball, executive director of the Chicago, Illinois-based foundation, said in a press release.

“The consortium provides a framework for cooperation and coordination among leading pulmonary researchers at medical institutions dedicated to improving care and health outcomes through the development and delivery of new medicines,” said Ball, whose foundation aims to serve as a catalyst for uniting research, industry, and philanthropy to speed up diagnosis of IPF and accelerate new therapies.

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Added Cheryl Nickerson-Nutter, PhD, the foundation’s executive vice president of research and development: “Three Lakes Foundation is bringing together many of the top investigators in pulmonary research supported by well-known medical research institutions to collaborate on making a cure for PF a reality. Together, we can bring new hope to patients and their families.”

Specifically, TLC4PF says it will use artificial intelligence and the latest single-cell profiling techniques “to develop novel precision therapies by creating a dynamic, public atlas of cell and compound fibrosis-specific signatures.”

Demystifying IPF

Naftali Kaminski, MD, heads the Three Lakes Consortium for Pulmonary Fibrosis (TLC4PF). Credit: TLC4PF

Heading up that effort is Naftali Kaminski, MD, professor of medicine and pharmacology at Yale’s School of Medicine in New Haven, Connecticut. The Israeli scientist, who’s credited with multiple discoveries—including peripheral blood protein and gene biomarkers as well as novel drug targets—is also chief of the school’s Pulmonology, Critical Care and Sleep Medicine division.

“I’m very passionate about genomics and our patient population, and really excited about the new technologies that allow us to actually demystify pulmonary fibrosis,” said Dr. Kaminski, speaking to Rare Disease Advisor from New Haven. 

“In the last 10 years, there’s been a dramatic increase in our understanding of idiopathic pulmonary fibrosis,” he said. “On the other hand, we have only 2 FDA-approved drugs, and 11 other drugs that have failed. And there are a lot of clinical trials. Now, I always like to focus on the positive, and when I started my career, people said you couldn’t do a clinical trial in IPF. Now there are many. But when I look at them, some of these molecular targets were discovered when I was still a fellow 20 years ago. That’s way too long.”

Dr. Kaminski received his medical degree from Hebrew University-Hadassah Medical School in Jerusalem and completed a residency in internal medicine at Hadassah Mount Scopus University Hospital, also in Jerusalem, as well as a fellowship in pulmonary medicine with Israel’s Sheba Medical Center at Tel HaShomer, just outside Tel Aviv.

He came to Yale after 11 years at the University of Pittsburgh Medical Center in Pennsylvania, where he established the Simmons Center for Interstitial Lung Disease (ILD)—the nation’s first comprehensive clinic dedicated to ILD research and treatment.

“I belong to a group of physicians that don’t like the name ‘idiopathic,’” he said. “Idiopathic means we don’t know the cause, but the truth is that for 50% of diseases, common diseases, we don’t really know exactly the cause, right? For example, if somebody has COVID-induced pneumonia, we know that the virus caused that. But if somebody has COPD, it’s [either due to] smoking or air pollution. And if you have coronary heart disease, it’s because of cholesterol, or maybe not.”

In much the same way, Dr. Kaminski said, IPF “is a disease that’s not caused by any of the known causes, but we know it’s strongly associated with genetics and that it runs in families. So although it’s called ‘idiopathic,’ we actually have a better feeling of the risk factors for pulmonary fibrosis than with many other diseases.”

Strategies for Expediting Drug Discovery

He and others have recently completed the largest single-cell analysis to date. The TLC4PF Connectome group, which does computational and single-cell analysis, is led by Dr. Kaminski and consists of experts in computational biology, machine learning, single-cell transcriptomic, and proteomics. Members include:

  • Xiting Yan, PhD, assistant professor, Center for Precision Pulmonary Medicine, Yale School of Medicine 
  • Ziv Bar-Joseph, PhD, professor of computational biology, Carnegie Mellon University, Pittsburgh
  • Jun Ding, PhD, assistant professor, Meakins-Christie Laboratory, McGill University, Quebec, Canada
  • Geremy Clair, PhD, scientist, Pacific Northwest National Laboratory, Richland, Washington
  • Oliver Eickelberg, MD, visiting professor of medicine and vice chair, Department of Medicine, University of Pittsburgh.

Meanwhile, the PF Translation workgroup will create a unique pipeline of human translational pulmonary fibrosis models to help researchers expedite drug discovery and validation for PF. This workgroup will be led by Melanie Königshoff, MD, PhD, visiting professor of medicine at the University of Pittsburgh School of Medicine. Her team members include: 

  • Kambez Benam, PhD, visiting associate professor, Swanson School of Engineering, University of Pittsburgh 
  • Brigitte Gomperts, MD, professor of pediatrics and pulmonary medicine, University of California-Los Angeles
  • Ivan Rosas, MD, professor and section chief, Baylor College of Medicine, Houston, Texas.

“Instead of trying to reinvent the wheel and coming up with new compounds, why don’t we see whether any of these known compounds can, at least computationally or analytically, be predicted to reverse or make a fibrotic cell normal,” Dr. Kaminski said. “And then we prioritize them, pick a few, and go to clinical trials much faster.”

This approach, also known as repurposing drugs, is cheaper “because you don’t have to make the drug, and it’s safer because many of these drugs have been tested in humans, so there are no surprises or side effects.”

Pulmonary fibrosis occurs when lung tissue becomes damaged and scarred. Over time, scarring destroys the lungs, making it harder for oxygen to enter the bloodstream and causing breathing to become difficult. Between 40,000 and 50,000 Americans are diagnosed each year with PF, and another 40,000 die annually.

Uncovering the Early Roots of PF

In a separate development, Three Lakes Foundation will also fund a study by researchers at Vanderbilt University Medical Center in Nashville, Tennessee, to identify early drivers of PF. The team will use a highly sophisticated platform to sequence single-cell tissue collected from people with a family history of the disease. This tissue contains biospecimens from presymptomatic individuals and offers a chance to probe the beginning of early ILD.

Jonathan Kropski, MD, and Nicholas Banovich, PhD, will collaborate on a Three Lakes Foundation project to research early predictors of pulmonary fibrosis. Credit: Three Lakes Foundation

“To develop transformative therapies, it is essential to understand what initiates the disease and what drives progression of the disease,” said Jonathan Kropski, MD, assistant professor at Vanderbilt’s Department of Medicine. “To do this, research must focus on the very earliest aspect of the disease—before people develop symptoms and before it can be detected on X-rays or CT scans of the lung.”

Dr. Kropski will oversee study operations, analysis, and coordination among the sites along with Nicholas Banovich, PhD, an associate professor at the Translational Genomics Research Institute, a City of Hope affiliate. Dr. Banovich, an expert on human genetics, genomics, and single-cell biology, will supervise the analysis of lung tissue samples.