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Aaron B. Waxman, MD, PhD
Associate Physician, Brigham and Women's Hospital
Associate Professor of Medicine, Harvard Medical School

Brigham and Women's Hospital
Department of Medicine
Pulmonary
75 Francis Street
Boston, MA 02115

Research Location: Peter Bent Brigham

Phone: 617-525-9733 or 732-7420
Fax: 617-264-6873 or 732-7421
Email: abwaxman@partners.org

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Research Narrative:

The unifying theme for my research activities is pulmonary vascular disease. My research focuses on the pulmonary vascular remodeling that reflects a common pathway leading to right heart failure. My own basic research has focused on the inflammatory mechanisms of vascular remodeling.  Using a transgenic animal that overproduces IL-6 in the lung, I have shown that IL-6 type cytokines alter pathways that regulate cell death/proliferation; IL-6 signaling can regulate the balance of cell death proteins, which in turn alter mitochondrial structure/permeability/function; the IL-6 mouse model replicates most of the features of human pulmonary arterial hypertension. These findings provided insight into the pathologic changes now recognized as key features of PVD. As a direct extension of our animal work, we have characterized abnormalities of inflammatory mediators and oxygen extraction in patients with PAH and have ongoing studies suggesting that a component of dyspnea in these patients is related to mitochondrial dysfunction. Using invasive CPET we have begun to examine the response of the diseased pulmonary vascular bed to exercise and alterations in the transpulmonary flux of inflammatory mediators and metabolites to better understand the pathways responsible for the physiologic findings, with particular attention paid to interactions between the skeletal muscle mitochondria and the pulmonary vasculature. We have shown that patients with PAH have impaired system O2 extraction during exercise and delayed phosphocreatine recovery following exercise, both consistent with a mitochondrial defect underlying exercise intolerance PAH.


Education:
Yale University School of Medicine, 1992, MD
Albany Medical College, 1987, PhD

Publications (Pulled from Harvard Catalyst Profiles):

1. Singh I, Rahaghi FN, Naeije R, Oliveira RKF, Vanderpool RR, Waxman AB, Systrom DM. Dynamic right ventricular-pulmonary arterial uncoupling during maximum incremental exercise in exercise pulmonary hypertension and pulmonary arterial hypertension. Pulm Circ. 2019 Jul-Sep; 9(3):2045894019862435.

2. Kohli P, Kelly VJ, Kehl EG, Rodriguez-Lopez J, Hibbert KA, Kone M, Systrom DM, Waxman AB, Venegas JG, Channick R, Winkler T, Harris RS. Perfusion Imaging Distinguishes Exercise Pulmonary Arterial Hypertension at Rest. Am J Respir Crit Care Med. 2019 Jun 01; 199(11):1438-1441.

3. Singh I, Oliveira RKF, Naeije R, Rahaghi FN, Oldham WM, Systrom DM, Waxman AB. Pulmonary Vascular Distensibility and Early Pulmonary Vascular Remodeling in Pulmonary Hypertension. Chest. 2019 May 20.

4. Singh I, Rahaghi FN, Naeije R, Oliveira RKF, Systrom DM, Waxman AB. Right Ventricular-Arterial Uncoupling During Exercise in Heart Failure With Preserved Ejection Fraction: Role of Pulmonary Vascular Dysfunction. Chest. 2019 May 16.

5. Yu Q, Tai YY, Tang Y, Zhao J, Negi V, Culley MK, Pilli J, Sun W, Brugger K, Mayr J, Saggar R, Saggar R, Wallace WD, Ross DJ, Waxman AB, Wendell SG, Mullett SJ, Sembrat J, Rojas M, Khan OF, Dahlman JE, Sugahara M, Kagiyama N, Satoh T, Zhang M, Feng N, Gorcsan J, Vargas SO, Haley KJ, Kumar R, Graham BB, Langer R, Anderson DG, Wang B, Shiva S, Bertero T, Chan SY. BOLA (BolA Family Member 3) Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension. Circulation. 2019 May 07; 139(19):2238-2255.

6. Hahn RT, Waxman AB, Denti P, Delhaas T. Anatomic Relationship of the Complex Tricuspid Valve, Right Ventricle, and Pulmonary Vasculature: A Review. JAMA Cardiol. 2019 May 01; 4(5):478-487.

7. Hahn RT, Delhaas T, Denti P, Waxman AB. The Tricuspid Valve Relationship With the Right Ventricle and Pulmonary Vasculature. JACC Cardiovasc Imaging. 2019 Mar; 12(3):564-565.

8. Platz E, Merz A, Silverman M, Lewis E, Groarke JD, Waxman A, Systrom D. Association between lung ultrasound findings and invasive exercise haemodynamics in patients with undifferentiated dyspnoea. ESC Heart Fail. 2019 02; 6(1):202-207.

9. Schissler AJ, Gylnn RJ, Sobieszczyk PS, Waxman AB. Ultrasound-assisted catheter-directed thrombolysis compared with anticoagulation alone for treatment of intermediate-risk pulmonary embolism. Pulm Circ. 2018 Oct-Dec; 8(4):2045894018800265.

10. Samokhin AO, Stephens T, Wertheim BM, Wang RS, Vargas SO, Yung LM, Cao M, Brown M, Arons E, Dieffenbach PB, Fewell JG, Matar M, Bowman FP, Haley KJ, Alba GA, Marino SM, Kumar R, Rosas IO, Waxman AB, Oldham WM, Khanna D, Graham BB, Seo S, Gladyshev VN, Yu PB, Fredenburgh LE, Loscalzo J, Leopold JA, Maron BA. NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary arterial hypertension. Sci Transl Med. 2018 Jun 13; 10(445).