Andrew Sweatt, M.D., Stanford University, and Nadine Al-Naamani, M.D., M.S., University of Pennsylvania, are the research awardees of the 2017 PHA/ATS Research Fellowship in Pulmonary Arterial Hypertension and Aldrighetti Research Award for Young Investigators, respectively. In the first of a two-part series, Dr. Sweatt discusses his research journey, grant awarded study and involvement with the PHA Research Room.
While I initially embarked on a career in pulmonary and critical care medicine with other clinical and research interests in mind, including critical care and acute respiratory distress syndrome, my love for PH was born and grew during fellowship training at Stanford University. PH strikes a chord with me given the condition’s association with a range of systemic diseases and risk factors, the fascinating physiology involving complex and delicate heart-lung interaction, and the opportunity to establish long-lasting and meaningful relationships with patients during their journey. The adult PH care team at Stanford, an accredited PH Care Center, is also largely responsible for my interest in the subspecialty. Immediately, I wanted to become part of this multidisciplinary group because I was impressed by the true sense of team. I had never encountered this degree of camaraderie during my medical training.
My initial clinical affinity for PH led me to seek out related research opportunities during the end of my fellowship training. I already knew that I wanted to embark on a career as a physician-scientist, though before being exposed to the PH environment at Stanford I had not yet found an area of focus, the right mentor, or the infrastructure needed to begin this quest. As I gained clinical experience and saw more patients with PAH, I quickly became intrigued by the marked clinical diversity across patients. While it is well understood that a wide range of predisposing conditions (genetic, various disease states, many drug/toxin exposures) underlie the development of PAH, there are several more layers that add to complexity. Even patients with the same cause of PAH demonstrate different responses to therapy and clinical outcomes, though the sources of this variability remain largely unknown. For this reason, I feel that there is immense research opportunity in PH.
At last year’s American Thoracic Society (ATS) Conference, I met and received career guidance from well-established PH physician-scientists that have had longstanding relationships with the PHA. During this networking, I discovered PHA Research Program and learned about the opportunity to apply for the PHA/ATS Research Fellowship in Pulmonary Arterial Hypertension Grant. The aim of my proposed research is to identify hidden subgroups of patients that are distinct from one another on the molecular level in blood measurements. I will apply unsupervised machine learning to analyze blood measurements in a large number of PAH patients, an approach where sophisticated computer algorithms are used to find hidden structure and patterns in complex data. My goal is to sort patients into subgroups based on different inflammation/immune system profiles in blood, rather than using clinical traits for grouping as the field does currently. Discovery of these immune subtypes may address deficiencies in our current clinical and therapeutic characterization of PAH. In preliminary analyses I have found that PAH can be separated into 4 groups (“clusters”), each with their own distinct protein immune profiles. These clusters do not overlap with traditional PAH subtypes, but do identify cohorts with different clinical disease severity and survival.
My proposal aims to expand this cutting-edge approach to (1) determine if our discovered protein-based PAH immune clusters remain stable over time, (2) understand the impact of applied therapies and disease progression on these protein profiles, and (3) identify differences in gene expression patterns between clusters. By defining clusters more comprehensively, we may begin to understand which novel immune-targeting therapies are most appropriate in each patient subgroup. While precision medicine remains elusive today, my proposal is intended to provide progress towards personalization of care in a rare disease.
I feel fortunate be part of the PHA Research Room committee for the first time, and very much look forward to the opportunity to experience the Room firsthand in late June. It is a very unique opportunity for PH researchers that I think is probably underutilized by our scientific community. The Research Room provides the chance to collect survey data and/or biological samples from the largest and most diverse set of PH patients assembled anywhere at the same time. In addition, it provides several patients their only viable opportunity to participate in research.
The research support that the PHA is providing is crucial to my career development at this early stage. I hope to make the most of this support and remain involved with PHA for years to come.
The PHA Research Room helps researchers further their studies by allowing for the collection of data, including phenotypic information and biological specimens, from PH patients and their families. To join Dr. Sweatt and other researchers, submit your pioneering study today.