Dr. Jack Elias has cared for patients who simply had no good options, but he’s also seen — and generated — significant advances in clinical capability. As he began his work as Brown’s seventh dean of medicine and biological sciences, he articulated a vision that is clear, ambitious, and convinced that while progress may not be easy, it is attainable and badly needed.
“If every doctor went out and changed how we treat one disease for the better, think about the progress that we’d have at the end of a generation,” he said.
Elias, a physician-scientist specializing in pulmonary medicine, has confronted ailments such as asthma, which can be managed but remains incurable and fundamentally unexplained, and pulmonary fibrosis, which carries a dire prognosis. Throughout his early career at the University of Pennsylvania, where he earned his M.D. in 1976, and Yale University where he rose to become chair of medicine, he has worked in the lab to bring greater hope to patients of those two conditions and other difficult diseases of the lung. He has brought his research group and lab to Brown so that he can continue to lead that work.
His latest paper appeared in the journal Cell Reports (Cell Press) on August 22, just days before he officially started at Brown. The study delves deeply into the molecular workings of disease but has an unambiguous clinical relevance. He and his co-authors showed that a particular protein associated with myriad consequences for health – both good and bad – depends on a partner protein, to which it must bind.
Until this study, what scientists knew was that the protein known as chitinase 3-like-1 (abbreviated as “Chi311”) and also called “YKL-40” in humans, comes from a gene family found in a wide variety of organisms, even plants. When it is working properly, it protects against pathogens and inflammation, but when it is too abundant, or “overexpressed,” it’s associated with asthma, inflammation and cancer.
“It is very clear that if it is not being regulated properly the good things it does turn into bad things because it is being produced when it shouldn’t or it’s at a level where it shouldn’t be,” Elias said. “The question was how do these molecules do what they do.”
The answer came in the study’s definitive proof that Chi311 and YKL-40 bind to a receptor protein called interleukin 13 receptor alpha 2 (IL-13Rα2). Elias and his team not only caught the proteins in act of binding, but also showed in a comprehensive series of experiments in mice and with human cells, that the activity of Chi311/YKL-40 depends on the receptor’s presence. For example, in mouse models in the lab, Elias’s team found that treatment with YKL-40 helped normal mice and mice that lacked Chi311 overcome conditions such as bacterial infection, or exposure to high levels of oxygen, but not if they lacked IL-13Ra2.
Seeds of a new treatment strategy may lie within that newly described relationship between these two proteins. If you can manipulate proteins with a beneficial effect, Elias said, then you have a “therapeutic target.”
Elias’s earlier research helped lay the groundwork for these kinds of studies. Years ago at Yale, he collaborated with colleagues to create a mouse model that allowed for genetic manipulations related to lung disease. “My lab has developed the techniques that allow any scientist in the world to take any gene that they want and express it in the mouse lung,” he said. “You can ask the question if this gene is expressed in the lung, how does it make the lung abnormal and does this abnormality look like a human disease.”
The so-called “transgenic” mouse model allows him and other researchers to follow a virtuous cycle of research in which troublesome human genes can be evaluated in mice, which leads to new hypotheses that can be tested in patient populations.“From mouse to man and back again,” Elias said. “That’s the title of a grand rounds talk I have given many times.”
During more than two decades of teaching, Elias has mentored scores of graduate and medical students. He is also a co-editor of the two-volume text Fishman's Pulmonary Diseases and Disorders, the leading reference for the field. The next edition is in production now. Elias has also contributed to the profession, serving in leadership roles such as the presidency of the Association of American Physicians and on the Advisory Council of the National Heart Lung and Blood Institute and the Council of Councils of the National Institutes of Health.
He said his interest in serving in such leadership and administrative roles, becoming chair of medicine at Yale in 2006 and now dean at Brown, has come from wanting to help others advance medicine and the life sciences.
There is progress to be made, and Elias wants Brown’s biology and medical students to be the next generation of people who make it. “[I want to] to influence large numbers of people and trainees so that they go out and get excited and ask and answer questions in a way that makes a difference,” he said.