New endowed professorship established in experimental pathology

In the 1980s, Joseph A. Madri, M.D., Ph.D., professor of pathology; and Leonard Bell, M.D. ’84, then a postdoctoral fellow; enjoyed lingering in Madri’s lab after work and cooking up plans to launch a biotech company one day. “We had a folder on the Mac called ‘Fantasy,’” Madri recalls. Fantasy would become reality when Madri, Bell, and four colleagues met in 1991 at the Omni Hotel in New Haven, and set a course that would bring a startup called Alexion to life the following year.

Today Alexion is a global biopharmaceutical company that employs 3,000 people. It is a world leader in developing life-extending therapies for people with rare, devastating, and potentially fatal diseases of the blood and bone.

The success of the company he helped to found has inspired Madri and his wife Lucille to endow a new professorship at the School of Medicine—the Joseph A. and Lucille K. Madri Professor of Experimental Pathology.

Madri says he owes many professional achievements to the faculty, postdocs, and students in his lab and the medical school’s Department of Pathology, who have informed and inspired his work.

“We felt strongly that we should give back now that we have the ability,” Madri says. “I am a strong proponent of doing that through research that benefits the department’s research enterprise, so we came up with a professorship for an experimental pathologist.”

The professorship’s first occupant is Gerald S. Shadel, Ph.D., who also is professor of pathology and of genetics, and director of the Yale Center for Research on Aging (Y-Age). “Gerry Shadel is an ideal person to be the inaugural Madri professor, an outstanding scientist who is committed to understanding the cellular and molecular mechanisms of aging,” says Robert J. Alpern, M.D., dean and Ensign Professor of Medicine.

Shadel, who became a member of the faculty in 2004, researches the role of mitochondria—energy generators within cells—in disease, aging, and the immune system. Shadel’s laboratory has contributed crucial knowledge to the understanding of mitochondrial gene regulation and metabolic stress signaling pathways. The lab’s groundbreaking aging studies have shown that mitochondrial respiration and reactive oxygen species signaling are key components of conserved longevity pathways.

Madri notes that in making his gift, he had a particular desire to support a mid-career researcher, and he is confident Shadel is the right choice. “He is an outstanding investigator,” says Madri. “He has a true and abiding interest in developing the department, its research, and its educational mission.”

Madri also continues to pursue his own abiding goal—to help people worldwide whose health needs are often forgotten. The company he launched has worked hard to achieve that vision.

Alexion Pharmaceuticals extends the lives of people who are afflicted with two rare blood diseases: atypical hemolytic-uremic syndrome and paroxysmal nocturnal hemoglobinuria.

“We treat people who have paroxysmal nocturnal hemoglobinuria in 50 countries, and now they have a life expectancy that parallels the average person in their particular country, and they are productive members of society,” says Madri.

The company makes therapies that also treat the bone-softening disease hypophosphatasia, as well as lysosomal acid lipase deficiency, a condition in which uncontrolled accumulation of cholesterol and triglycerides leads to organ damage and early death.

“If I do nothing else in science, having helped thousands of people live a long, productive life is more than enough reward for me,” he says.

The Madris have spent their entire professional lives at Yale. Joseph Madri arrived as a postdoc in 1975. Lucille Madri held administrative roles at the university for 25 years.

It is rare for a faculty member to endow a professorship, but Madri says Yale and the Department of Pathology deserve such a special gift. “Yale is a unique place and the postdocs and students who’ve cycled through the lab have been outstanding,” he says.