Rahul Kumar, Ph.D., received the 2019 PHA/ATS Research Fellowship, one of three individual Pulmonary Hypertension Association research grants awarded last year, to study inflammation and how it contributes to pulmonary hypertension (PH). This award is in collaboration with the American Thoracic Society Foundation. His funded proposal is titled “Crosstalk Between Bone Marrow Compartment and Inflamed Lungs in Hypoxic Pulmonary Hypertension.” Dr. Kumar is associate professional researcher in the department of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Center at the University of California, San Francisco (UCSF).
Dr. Kumar recently explained how his research may lead to improved patient outcomes:
“Altering inflammation has the potential to be an exciting new approach to treating patients with pulmonary hypertension, but blocking inflammation broadly has not been successful to date. We think that better understanding exactly how inflammation contributes to pulmonary hypertension will help us identify better, more effective drugs to treat this disease.”
Dr. Kumar said his research group uses a well-established model of pulmonary hypertension to understand how pulmonary vascular disease results from inflammation. Mice are exposed to low oxygen levels, the same driver of hypoxic pulmonary hypertension. Worldwide, hypoxia-induced pulmonary hypertension is one of the most common causes of pulmonary hypertension.
“We believe that this form of the disease also has important similarities to other cardiovascular diseases and cancer, where hypoxia is a critical element,” Dr. Kumar says. “We have seen that hypoxia exposure leads to inflammation of the lungs, with the recruitment of bone-marrow derived cells into the lungs. Upon recruitment these cells convert into macrophages and releases a harmful protein called thrombospondin-1.
“Studies by our group and others have shown that the thrombospondin-1 contributes to multiple forms of cardiovascular disease, including pulmonary hypertension; and its protein level associates directly with the median survival of patients with pulmonary hypertension. We have also reported that thrombospondin-1 contributes to the pulmonary hypertension in patients with scleroderma.
“Our goal is to understand the cellular and molecular mechanisms that cause recruitment of thrombospondin-1 producing pathologic cells into the lungs. Overall our work will help us in identify new targets for intervention and find new ways to manage and treat patients with pulmonary hypertension.”