PHA/ATS Research Fellowship in Pulmonary Arterial Hypertension Grant Winner 2017

Andrew John Sweatt, MD

Instructor of Medicine
Stanford University
Title: “Deep immunophenotyping of pulmonary arterial hypertension by unsupervised machine learning”
Term: December 1, 2017-November 30, 2019

Summary of Research Project:

Pulmonary arterial hypertension (PAH) is a chronic condition defined by elevated blood pressure in the lungs. It often leads to progressive heart failure and death despite treatment. PAH arises due to a range of underlying diseases, genetic mutations, or exposures, and clinical outcomes vary widely across patients. Despite this complexity, there is a one-size-fits-all approach to treatment as all approved therapies relax lung arteries to lower blood pressure. Molecular mechanisms of PAH progression remain poorly understood. Evidence does suggest that inflammation plays a significant role, thus novel PAH therapies that target immunity are under investigation. However, it is not known if various degrees and types of inflammation exist in PAH. In preliminary work, we measured a large set of proteins related to inflammation in the blood of PAH patients. We used computer learning to uncover protein signatures, which identified distinct patient subgroups that appeared to have different patterns of inflammation. If protein levels had not been measured, patient subgroups would have remained ‘hidden’ since they were not distinguished by visible traits (age, sex, race, PAH cause, etc.). Survival rates and disease severity differed between protein-based subgroups, which suggests that the protein signatures may have a role in PAH progression. Our proposed study aims to (i) explore protein signatures over time as PAH is treated, and (ii) better understand the ‘hidden’ subgroups by evaluating genetic profiles in blood. Complex computational algorithms will be used to analyze protein and gene data. Our approach may provide insight about mechanisms of inflammation in PAH, and could help determine if certain patients are more likely to benefit from immune targeting therapies.

Curriculum Vitae

Education/Training

2001 Research assistant, University of Nevada, Allie M. Lee Cancer Research Lab (Reno, NV)

2003 Research assistant, The Jackson Laboratory, Mouse Genome Informatics (Bar Harbor, ME)

2004-2005 Teaching assistant, University of Connecticut, Biomedical Engineering (Storrs, CT)

2004-2005 Research assistant, University of Connecticut, Molecular and Cell Biology (Storrs, CT)

2009-2012 Internship and residency- Internal Medicine, University of Colorado Health Sciences Center (Aurora, CO)

2012-2013 Staff physician, Kindred Long Term Acute Care Hospitals (Aurora and Denver, CO)

2012-2013 Hospitalist, Presbyterian St. Luke’s Medical Center-Health One (Denver, CO)

2012-2013 Instructor of Medicine, University of Colorado Health Sciences Center, Internal Medicine (Aurora, CO)

2013-2016 Clinical Fellowship, Stanford University, Pulmonary/Critical Care Medicine (Stanford, CA)

2015-2016 Postdoctoral Research Fellow, Stanford University (Stanford, CA)

2016- Instructor of Medicine, Stanford University, Pulmonary/Critical Care Medicine (Stanford, CA)

Vera Moulton Wall Center for Pulmonary Vascular Disease (Stanford, CA)

East Bay Pulmonary Hypertension Clinic Director, Stanford University (Emeryville, CA)

Mentored Research Support

Deep immunophenotyping in pulmonary arterial hypertension
NIH/NHLBI K12 Career Development Program in ‘Omics’ of Lung Diseases
Role: Trainee 07/2016 – Present HL120001-03
Program Leaders: Marlene Rabinovitch, MD and Mark Nicolls MD
Co-Mentors: Roham Zamanian MD, Purvesh Khatri PhD

Using a proteomic signature as a tool for early detection of pulmonary arterial hypertension Blue Lips Foundation Grant
Role: Co-investigator 01/2017 – Present
PIs: Roham Zamanian, MD and Lorinda Chung, MD

Selected Publications

Shaller B, Kholdani C, Sweatt A, Hedlin H, Hsi A, Spikerkoetter E, Zamanian R. Using Near-Infrared Spectroscopy to Characterize the Effects of Inhaled Nitric Oxide on Skeletal Muscle Oxygen Saturation in Adults with Pulmonary Arterial Hypertension. Am J Resp Crit Care Med, 2016; 193;A3961.

Sweatt A, Regalia K. Kaposiform Lymphangiomatosis: An Unforeseen Cause of Spontaneous Hemothorax and Episodic Hemoptysis. Am J Resp Crit Care Med, 2016; 193: A3346.

Amsallem M, Sweatt A, Aymami M, Kuznetsova T, Lu H, Mercier O, Fadel E, Schnittger I, McConnel M, Rabinovitch M, Zamanian R, Haddad F. Right Heart End-Systolic Remodeling Index Strongly Predicts Outcomes in Pulmonary Arterial Hypertension: Comparison with validated models. Circulation Cardiovascular Imaging, 2017 Jun; 10(6). PMID: 28592589.

Sweatt A, Spiekerkotter E, Hsi A, Sung Y, De Jesus Perez V, Kudelko K, Zamanian R. Evaluation of Changes in Static and Pulsatile Hemodynamic Indices Across Longitudinal Vasoreactivity Tests in PAH. Am J Resp Crit Care Med, 2016; 193: A7319