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With Research Programs on Both Sides of the Atlantic, Melanie Königshoff Hopes to Make Lung Repair a Reality

Even among physician-scientists, whose energy levels seem set a standard deviation above the mean, Melanie Königshoff, MD, PhD, stands out.

Dr. Königshoff directs two lung regeneration programs—one she helped build at the Helmholtz Zentrum in Munich; the other she recently started at the University of Colorado. She mentors students and young investigators in both programs. She is on the editorial board of five international journals, including the ATS Blue and Red Journals. She is working on becoming credentialed in Colorado so she can see patients. And she is the incoming chair of the Respiratory Cell and Molecular Biology (RCMB) Assembly.

Dr. Königshoff plays down any notion that her ambitious professional life or ability to multitask is preternatural.  “I enjoy what I do, and if I had to give up part of it, I would feel that something is missing,” she says.

Dr. Königshoff traces her desire to combine many things rather than focus on a single activity to her early curiosity about science and her belief that a holistic approach to discovery is necessary to advance medicine.

“I considered the traditional PhD/basic science career, but through internships involving patients, I realized that I liked the patient involvement too,” she says. “Being a physician-scientist has allowed me to do both.”

Is WNT a Key to IPF and COPD?

Much of Dr. Königshoff’s research has focused on the WNT signaling pathway, which is found in all multicellular eukaryotic organisms. Without WNT’s complex orchestration of proteins passing signals through cell receptors, the human lung would never develop.

“Certain WNT pathways seem to go quiet with age, but they can also become very concretely dysregulated, which makes WNT an attractive pathway to study,” she says.
“Melanie has done some seminal work in pulmonary fibrosis and now COPD that conceptualizes the disease mechanisms and puts human and animal models together to provide a detailed mechanistic look at the WNT pathway,” said one of her mentors, Naftali Kaminski, MD, chief of pulmonary, critical care, and sleep medicine at Yale. “And she has begun exploring potential therapies.”

In a 2016 Annals ATS article describing the pathway and its importance, Dr. Königshoff and her coauthors wrote that dysregulation might not represent the cause of pulmonary fibrosis and COPD, but rather their consequence. 

If that proved to be the case, would she consider her research a dead end?

“I don’t think so because cause or consequence is an oversimplification of how disease develops,” she explains. “Even if WNT dysregulation turns out to be a consequential factor, we may be able to modify it and halt the progression of the disease--something we are unable to do for any chronic lung disease today.”

Creating a Human Model for Lung Disease

Another major contribution Dr. Königshoff has made to respiratory research is the development of 3D lung tissue cultures from patients. With these tissues, she and a multidisciplinary team in Germany created human models for lung disease that push understanding beyond animal models.

In one experiment, the researchers took tissue from the lung of a smoker with COPD and studied the tissue ex vivo.  “We activated pathways that we thought might be regenerative and actually saw some changes in the tissue occur,” Dr. Königshoff says.

Carlo Mümmler, MD, who worked as a medical student in Dr. Königshoff’s lab during this time, says that her optimism is motivating and “her passion for science” creates a “big team spirit.” Even when his experiments failed, Dr. Mümmler says, after talking to his mentor, he was “full of new ideas and a different perspective.”

In building a new lung repair and regeneration pathway, Dr. Königshoff is excited by the opportunity that the University of Colorado’s two bioengineering departments and its Gates Center for Regenerative Medicine present to create a multidisciplinary team focused on answering some of the most difficult questions about lung disease.

RCMB: “Changed My Life and Career”

As the incoming chair of RCMB, Dr. Königshoff sees another opportunity to bring people together. The assembly, she says, is the perfect place to connect basic scientists and translational and clinical researchers. 
“A huge number of postdocs come to the International Conference from all over the world,” she says. “We need to create opportunities for them to interact with clinical fellows, because it’s the best time in their career to identify people asking similar questions but from a different perspective.”

Dr. Königshoff still recalls her first RCMB meeting as a postdoc/fellow from Germany. “It felt like home very quickly,” she says. “And for the first time in my career, I had women as role models. It changed my life and career.”

Wherever her career takes her, Dr. Königshoff appears to enjoy the journey, a theme that extends into her personal life. In her spare time, she likes to explore the natural beauty and wildlife of Colorado and the American West. On one such visit to Yellowstone National Park, she saw a pack of 15 wolves. A sight, she says, that produced “instant goose bumps.”