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Creating a Road Map to Cure Pulmonary Fibrosis

June 07, 2022
by Jane E. Dee

Bill Vick of Dallas, Texas was lost in a reflective silence as he drove back to his home after receiving life-altering news: his doctor had just told him that he had an incurable disease and little could be done.

The diagnosis was Idiopathic Pulmonary Fibrosis (IPF), also called pulmonary fibrosis (PF), a disease in which the lung develops fibrosis – scarring – for an unknown reason. IPF is a progressive disease with a median survival of three to five years, although some patients live longer.

Wanting to know more about his diagnosis, Vick researched IPF. A name kept coming up: Naftali Kaminski, MD, a leader in the field of pulmonary fibrosis. Vick, the founder of PF Warriors, an international support group for people with IPF, decided he wanted to meet Kaminski, so he traveled to the American Thoracic Society (ATS) International Conference where Kaminski was speaking, and invited Kaminski to breakfast. Kaminski accepted.

Vick was already seated in the hotel dining room when Kaminski arrived. As Kaminski walked toward Vick, he attracted the attention of other people in the room. “Everybody knew who he was,” Vick said. “I just couldn't believe it. Here he was with all of these people who were leaders in that disease segment, and he was having breakfast with me.”

Creating a Road Map

Kaminski, the Boehringer Ingelheim Pharmaceuticals, Inc. Professor of Medicine (pulmonary) at Yale School of Medicine (YSM) and chief of Pulmonary, Critical Care & Sleep Medicine (Yale-PCCSM) in the Department of Internal Medicine, is an internationally known physician-scientist in the field of lung diseases. Kaminski is recognized as being at the forefront of using new technology in medical research, culminating in his recent development of single-cell atlases. Kaminski also is a champion of gender and ethnic diversity in medicine.

As chief of Yale-PCCSM, Kaminski oversees all the pulmonary, critical care and sleep medicine clinical activities at Yale New Haven Hospital, as well as the hospital's Winchester Center for Lung Disease, and the Yale Centers for Sleep Medicine.

“Dr. Kaminski is an extraordinarily talented physician-scientist who brings enormous passion and commitment to his scientific work,” said Gary Désir, MD, vice provost for faculty development and diversity at Yale University, and chair of the Department of Internal Medicine at YSM. “This passion and dedication carry over into his steadfast commitment to diversify, equity, inclusion and belonging.”

Kaminski, who earned his MD from Hebrew University in Israel, came to the U.S. for a fellowship at the University of California, San Francisco, where he studied microarray technology, a powerful tool for examining the expression of thousands of genes simultaneously.

“This technology was ready to explode, and many advancements would come of it,” said Augustine M.K. Choi, MD, the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine who recruited Kaminski in 2002 for his first faculty position at the University of Pittsburgh. “I knew that he was positioned to be a leader in the field.”

Twenty years after Choi recruited him, Kaminski returned to the ATS International Conference in May 2022 – the same conference where he had met Vick - as the J. Burns Amberson Lecturer, an award that recognizes a career of major lifetime contributions and is considered one of the highest honors a respiratory diseases researcher can receive.

Kaminski’s lecture, “Charting a Road Map to Curing Human Pulmonary Fibrosis,” focused on his embrace of technology to understand human lung disease and explained how he navigated the path from early insights into molecular and gene networks in pulmonary fibrosis to today’s cutting-edge analysis of what happens at a cellular level.

“I do hope that through my story about creating a road map to curing pulmonary fibrosis, I will be able to convey at least some of the magic of biomedical respiratory research, as well as the importance and value of our community,” Kaminski said. “In receiving this recognition, I am a representative of all the people who have supported me over the years: mentors, collaborators, lab members, researchers, clinicians -- and always patients and their families.”

A Forward-Thinking Physician-Scientist

Kaminski’s biggest contribution to Yale-PCCSM has been his ability to expand simultaneously its research, clinical and educational programs. “Since he became section chief, Yale-PCCSM has helped launch the careers of a record number of young physician-scientists,” said Lynn Tanoue, MD, MBA, professor of medicine (pulmonary), and vice chair for clinical affairs, internal medicine. “The section’s grant funding is at a record high. Publications from both research and clinically focused faculty and fellows have increased tremendously. I think that the section now truly represents the three major pillars of academic medicine – clinical, research, education – with enormous depth and success.”

Kaminski was recruited to Yale from the University of Pittsburgh in 2012 by Jack A. Elias, MD, chief of internal medicine at the time. At Pittsburgh, Kaminski had been the Dorothy P. and Richard P. Simmons Endowed Chair for Pulmonary Research. Elias said Kaminski’s knowledge of lung disease science stood out to him. “He was ready to make big discoveries, and he was ready to take new system-wide approaches to lung disease,” said Elias, senior health advisor at Brown University and the former dean of the university’s Warren Alpert Medical School.

Kaminski is known for his creative and patient-centric approach to medical research, said Erica L. Herzog, MD, PhD, professor of medicine (pulmonary) and associate dean for medical student research at YSM. “Dr. Kaminski takes a really different approach, which is incredibly unique, and I think it's one of the reasons why he was selected to receive the Amberson award, and why he has obtained international stature,” said Herzog.

In his research, Kaminski starts with the patient and works backwards, Herzog explained. “He is the first person to apply large-scale sequencing to lung tissue from patients with IPF. He is among the first to apply large-scale single-cell-omics to patients with IPF. And, what is really remarkable about his efforts is that he's extremely collaborative and makes this data available before it's even published, freely sharing his discoveries to accelerate advancements. An example of that is the IPF Cell Atlas, which I think is probably to date his crowning achievement,” Herzog said.

Researchers can design interventions for IPF using the IPF Cell Atlas, which gives them “a much better, deeper understanding of what happens to every single cell in the human IPF lung, and hopefully other fibrotic lung diseases,” Kaminski said. “Maybe we can actually fix it, not just slow down the disease,” he added. “First you create the atlas, and then you can start planning routes to reverse the disease.”


A Paradigm Shift

When Kaminski published a paper on a remodeling enzyme in 2002, it created a stir by providing a new way of looking at fibrosis. The research article showed that there were active mechanisms of ongoing change in the lung, and that perhaps these could be targeted. The paper also showed that the enzyme MMP-7 was found to be elevated in the lungs and blood of patients with IPF – a finding that identified a potential target for therapeutic intervention.

“That was a huge paradigm shift, because it was really the first time that there had been evidence using samples from humans, which was a very distinctive aspect of Naftali's work, and that this process of active remodeling could be targeted, and there was potentially hope to alter the natural history of the disease,” Herzog said.

Kaminski’s next salient finding came from looking at markers in the peripheral blood, “at the immunologic milieu of what the blood of patients with IPF looked like,” Herzog said. “That was a very new, and at the time, controversial approach because in the early 2000s, IPF was viewed as a disease that only affected the lung, with no detectable change in any other tissue compartment,” she said. “Naftali broke down that dogma.”

To Herzog, the director of the Yale Interstitial Lung Disease Center of Excellence, Kaminski is an innovative thinker who is not afraid to take intellectual risks. “While he and I have very, very different approaches to science, I always learn from his ideas and the way in which he takes seemingly disparate entities and is able to frame them in a new way to cross boundaries and further discovery.”

Melanie Königshoff, MD, PhD, professor of medicine, and associate chief of research, Division of Pulmonary, Allergy, and Critical Care Medicine at the University of Pittsburgh, said Kaminski is a trailblazer and inspiring role model for many lung disease researchers. “His ability to connect data as well as people has moved the field forward,” Königshoff said.

For Vick, Kaminski’s research gives him hope for a cure. “I think that most patients in this disease segment think that if Dr. Kaminski says something about IPF, it has to be true,” said Vick. “He's got that kind of a reputation. But in real life, if you will, he's a nice person. He's a good man. And I found him to be very open and receptive.”

For Kaminski, the guidepost for his research is its impact on the lives of people with IPF. “When patients are diagnosed with IPF, they hear that they have this lethal condition that nobody heard of, and that little is known about it,” said Kaminski. “But the truth is we have drugs that slow down the disease, and in recent years we have learned a lot about what happens in the lung with IPF, so better drugs are on the horizon,” he said. “I take every opportunity to communicate with patients, and patients advocates. I enjoy telling them about our work, and hearing from them – we are after all, on the same team.”

A Champion for Diversity

As chief at Yale-PCCSM, Kaminski has led the section to unprecedented growth and success with a noticeable focus on equity, wellness, diversity, and engagement. “Naftali is a very creative scientist, and a brilliant guy,” said Elias. “He is also a nice person who cares very much about the people in his program.”

Kaminski, a first-generation physician, mentioned his parents in his lecture. Both were child refugees and holocaust survivors. “They taught me to always support the sick, the poor, the disadvantaged, and to see value in all humans,” he said. “This guides me in everything I do.”

Kaminski is an outspoken advocate for diversify, equity and social responsibility in the medical and scientific communities. “When he became division chief at Yale, he knew that his responsibility was to more than just his own lab and research, but to foster the career development of others in his program and beyond,” said Choi. “And from what I've seen, he has exceeded that. He has mobilized the unity, the spirit, the diversity of the people in his program.”

Said Herzog, “If you look at how our section has grown and diversified since his arrival, I think you could say that it was him coming here.

“Looking at the diversity, looking at the large increase in success of the scientific and clinical faculty, looking at the discoveries that are being made here on a daily basis, and looking at the pipeline of young people who are going on to build their careers, I think you can say that his unwavering commitment to make sure that everybody has an equal opportunity to have their contributions valued -- and to value non-traditional contributions equal to what we commonly say is important -- I think has really improved the climate in the section and our ability to succeed as a group as well as individually,” she said.

To watch a video of Naftali Kaminski, MD’s Amberson Lecture, go here.

The Section of Pulmonary, Critical Care and Sleep Medicine is one of the eleven sections within YSM's Department of Internal Medicine. To learn more about Yale-PCCSM, visit PCCSM's website, or follow them on Facebook and Twitter.

Submitted by Jane E. Dee on June 06, 2022