PHA/ATS/Pfizer Research Fellowship in Pulmonary Arterial Hypertension Grant Winner 2012

Eric AustinEric D. Austin, MD, MSCI

Department of Pediatrics
Vanderbilt University School of Medicine
Title: "Integrative Genomic Approach to Pulmonary Arterial Hypertension"
Term: January 15, 2013 through January 14, 2015

Summary of Research Project:

Pulmonary arterial hypertension (PAH) is a complex disease impacted by the interaction of many genes and other factors, and may occur in families with multiple individuals developing PAH over time. Bone morphogenetic protein receptor type 2 (BMPR2) mutations associate with PAH in most families with multiple affected individuals, but only ~25% of mutation carriers ever develop PAH. As a result, most BMPR2 mutation carriers never develop PAH; however, we lack a mechanism to predict those BMPR2 mutation carriers most likely to develop PAH. We also lack PAH therapies to specifically address BMPR2-related defects. We hypothesize that an integrative systems-based approach to genes and gene expression, made possible by advanced genetic and bioinformatic analyses, can be used to study other genetic factors in BMPR2 mutation carriers which associate with PAH. To test this hypothesis, we will apply next generation sequencing techniques to a previously genotyped cohort of BMPR2 mutation carriers with and without PAH, and develop and refine algorithms that integrate the data to provide comprehensive systems-level models of gene expression and signaling dynamics.

Familial pulmonary arterial hypertension is a complex disease impacted by the interaction of many genes and factors, and to some extent provides a ‘human model’ of PAH. Genetic variants, such as BMPR2 mutations, confer disease risk by acting on multiple molecular networks or biologic pathways, and thus require integrative analytic approaches at the network and pathway levels. Presumably, novel analytic approaches will both improve the power of genetic association studies and shed light on the biologic processes in which the variants act. We expect to uncover complex networks of gene variants and gene expression that distinguish those subjects with PAH from those without PAH. We anticipate that this will contribute to the development of predictive models of PAH and novel therapeutic approaches for BMPR2 mutation carriers as well as the larger community of PAH patients.

Curriculum Vitae 

NAME: Eric Austin, MD, MSCI
POSITION TITLE: Assistant Professor of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn.


Institution and Location Degree Year(s) Field of Study
University of Pennsylvania, Philadelphia, Penn. BA 1996 History; Chemistry
Emory University School of Medicine, Atlanta, Ga. MD 2001 Medicine (cum laude)
Vanderbilt University School of Medicine, Nashville, Tenn. MSCI 2008 Translational Science



I am a pulmonologist and NIH-funded physician-scientist with a combined laboratory-based and patient-oriented translational research program that focuses on pulmonary hypertension and other cardiopulmonary morbidities in children and adults with and without preexisting known genetic risks, including BMPR2 gene mutations. I have specialty training in translational research techniques, and been mentored for over 5 years by Dr. James E. Loyd, Dr. John A. Phillips III and colleagues at Vanderbilt University in the design and maintenance of translational research using longitudinal cohorts of patients and family members with cardiopulmonary disease or genetic risk. In particular, my expertise focuses on evaluating the manner in which genetic, biochemical, environmental and other abnormalities promote phenotypic expression of pulmonary hypertension and other cardiopulmonary diseases in children and adults. I direct a prospective longitudinal cohort study of patients with pulmonary hypertension, with deep phenotyping in concert with biologic sample acquisition for genetic and biochemical studies at regular intervals; and, treat subjects with lung diseases including pulmonary hypertension. We recently used whole exome sequencing to identify a novel variant involved in PAH, and I have the motivation, training, and enthusiasm to complete this proposal successfully.


Positions and Employment

  • 2001-2004, Resident in Pediatric Medicine, University of Colorado Health Sciences Center, Denver, CO
  • 2001-2005, Resident, followed by Chief Resident and Instructor in Pediatric Medicine, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO
  • 2005-2008, Postdoctoral Fellow, Department of Pediatrics, Division of Pediatric Pulmonary Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 2008-present, Assistant Professor of Pediatrics, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee

Select Other Experience and Professional Memberships, Recent

  • 1998-present, Sigma Xi, The Scientific Research Society
  • 2001-present, American Academy of Pediatrics
  • 2005-present, Pulmonary Hypertension Association
  • 2006-present, American Thoracic Society, Pulmonary Circulation Assembly and Pediatric Assembly of ATS
  • 2010-present, American Lung Association Regional Leadership Council
  • 2010, 2010 Pediatric Academic Societies' Annual Meeting, Scientific Session Moderator
  • 2011, 2011 American Thoracic Society International Meeting, Scientific Session Moderator

Honors, Recent

  • 2000, Alpha Omega Alpha (AOA) Honor Society, Emory University School of Medicine
  • 2008, 4th World Health Organization Symposium on Pulmonary Hypertension Award
  • 2009, Vanderbilt University, Department of Pediatrics, Turner-Hazinski Research Scholar Award
  • 2010, Society for Pediatric Research


  1. Phillips JA 3rd, Poling BS, Phillips CA, Stanton KS, Austin ED, Cogan JD, Wheeler LW, Chang Y, Newman JH, Dietz HC, Loyd JE. Synergistic heterozygosity for TGFß1 SNPs and BMPR2 mutations modulates the age at diagnosis and penetrance of Familial Pulmonary Arterial Hypertension (FPAH). Genet Med. 10:359-365, 2008. PMID: 18496036
  2. Hamid R, Cogan JD, Austin E, Hedges LK, Phillips JA 3rd, Newman JH, Loyd JE. Penetrance of pulmonary arterial hypertension is modulated by the expression of normal BMPR2 allele. Hum Mutat. 30(4):649-654, 2009. PMID: 19206171
  3. Austin ED, Cogan JD, West JD, Hedges LK, Hamid R, Dawson EP, Wheeler LA, Parl FF, Loyd JE, Phillips JA 3rd. Alterations in oestrogen metabolism: Implications for higher penetrance of FPAH in females. Eur Respir J. 34(5):1093-1099, 2009.  PMID: 19357154
  4. Austin ED, Phillips JA 3rd, Cogan JD, Hamid R, Wheeler LA, Robbins IM, Newman JH, Loyd JE. Truncating and missense BMPR2 mutations differentially affect the severity of heritable pulmonary arterial hypertension. Respir Res. 10(1):87, 2009. PMID: 19785764
  5. Hamid R, Phillips JA 3rd, Holladay C, Cogan JD, Austin ED, Backeljauw PF, Travers SH, Patton JG. A molecular basis for variation in clinical severity of isolated growth hormone deficiency type II. J Clin Endocrinol Metab. 94(12):4728-4734, 2009. PMID: 19837935
  6. Austin ED, Rock MT, Vnencak-Jones CT, Mosse CA, Yoder SM, Robbins IM, Loyd JE, Meyrick BO. T lymphocyte subset abnormalities in the peripheral lung and blood in pulmonary arterial hypertension. Respir Med. 104(3):454-462, 2010. PMID: 19880300
  7. Hamid R, Hedges LK, Austin ED, Phillips JA 3rd, Loyd JE, Cogan JD. Transcripts from a novel BMPR2 termination mutation escape nonsense mediated decay by downstream translation re-initiation: implications for treating pulmonary hypertension. Clin Genet. 77(3):280-286, 2010. PMID: 20095988
  8. Austin ED, Ahmad F, Hamid R. Somatic mutations in pulmonary arterial hypertension: primary or secondary? Am J Respir Crit Care Med. 182(9):1094-1096, 2010. PMID: 21041561
  9. Lane K, Talati M, Austin ED, Hemnes A, Johnson JA, Fessel JP, Blackwell T, Mernaugh RL, Robinson LJ, Fike C, Newman J, Roberts LJ, West J. Oxidative injury is a common consequence of BMPR2 mutations. Pulm Circ. 1(1):72-83, 2011. PMID: 21904662
  10. Hemnes AR, Pugh ME, Newman AL, Robbins IM, Tolle J, Austin ED, Newman JH.  End tidal carbon dioxide tension: pulmonary arterial hypertension versus pulmonary venous hypertension and response to treatment. CHEST. Nov 2011; 140(5): 1267-73.  Epub May 26, 2011. PMID: 21622547
  11. Ikonomou L, Hemnes AR, Bilousova G, Hamid R, Loyd JE, Hatzopoulos AK, Kotton DN, Majka SM, and Austin ED.  Programmatic change: lung disease research in the era of induced pluripotency.  Am J Physiol Lung Cell Mol Physiol. Dec 2011; 301(6):L830-5.  Epub 2011 Oct 7. PMID: 21984571
  12. Austin ED, Menon S, Hemnes AR, Robinson LR, Talati M, Fox KL, Cogan JD, Hamid R, Hedges LK, Robbins I, Lane K, Newman JH, Loyd JE, West J. Idiopathic and heritable PAH perturb common molecular pathways, correlated with increased MSX1 expression. Pulm Circ. 2011 Jul;1(3):389-98. PMID: 22140629
  13. Flynn R, Zheng S, Fessel J, Cogan JD, Austin ED, Loyd JE, West J, Zhao Z, Hamid R. Connectivity Map analysis of NMD+ BMPR2 related HPAH provides insights into disease penetrance. Am J Respir Cell Mol Biol. 2012 Feb 3. [Epub ahead of print]
  14. Austin ED, Hamid R, Hemnes AR, Loyd JE, Blackwell T, Yu C, Phillips JA III, Gaddipati, R, Gladson S, Gu E, West J, Lane KB. BMPR2 expression is suppressed by signaling through the estrogen receptor. Biology of Sex Differences. 2012 Feb 20;3(1):6. [Epub ahead of print]
  15. Austin ED, Ma L, LeDuc C, Rosenzweig EB, Borczuk A, Phillips JA III, Palomero T, Sumazin P, Kim R, Talati MH, West J, Loyd JE, Chung WK. Whole exome sequencing to identify a novel gene (Caveolin-1) associated with human pulmonary arterial hypertension. Circulation: Cardiovascular Genetics. 2012, accepted for publication.



5K23HL098743-02 (Austin), 08/01/2010-05/30/2015
"Variations in Estrogen Exposures may Modify Pulmonary Arterial Hypertension"
Investigates the hypothesis that abnormal sex hormone metabolism (resulting in altered sex hormone ratios) is a risk factor for PAH, incorporating biomarker and genotyping studies of patients and at-risk subjects, as well as gene expression data.

NIH Loan Repayment Program (Austin), 07/01/2007-06/30/2013
Mentor: James E. Loyd, M.D. (Pulmonary Arterial Hypertension NIH grants P01HL072058 and GCRCRR000095)
"The Use of Clinical, Laboratory, and Radiographic Methods to Facilitate the Diagnosis and Management of Familial and Idiopathic Pulmonary Arterial Hypertension in Children and Adults"

1R01HL111259-01 (Loyd), 01/01/2012–12/31/2016
"Caveolar Defects Underlie the Genetic Origins of PAH"
The goal of this project is to align experienced basic and physician scientists with the goal to understand the
functions of pathways which we have shown are integral in the pathogenesis of Pulmonary Arterial Hypertension (PAH). Using our large cohort of patients, as well as unique cell and animal models, we will test our hypothesis that defects in caveolae represent a common mechanism underlying the molecular basis of PAH.  Dr. Austin directs the longitudinal human cohort component of this study, to evaluate for systemic evidence of endothelial dysfunction among PAH patients and those at risk.
Role: Co-Investigator

Entelligence Research Scholar Award (Austin), 08/01/2011-07/31/2012
Actelion Foundation
"Sex Hormone Abnormalities in Pulmonary Arterial Hypertension"
Investigates the hypothesis that abnormal sex hormone metabolism (resulting in altered sex hormone ratios) is a risk factor for PAH, using GC/MS to study patients and unaffected but at-risk kin.


P01 HL Application (Loyd) Submitted, Review Pending
“Hormonal, Metabolic and Signaling Interactions in PAH”
We intend to use a unique cohort of families with PAH and patients with IPAH to study metabolic variations in PAH. 


Turner-Hazinski Research Scholar Award (Austin), 07/01/2009 – 06/30/2011                   
Vanderbilt University Department of Pediatrics
"Estrogens, BMPR2 Expression, and the Modification of Pulmonary Arterial Hypertension"
Examines the role of estrogens and other sex hormones in the
modification of pulmonary arterial hypertension associated with mutations in the BMPR2 gene, using GC/MS as well as gene expression analyses.

5K12RR017697 (Brown), 07/01/2006–08/2031/09
Vanderbilt University Clinical Research Scholars Program
Role: Scholar and Clinical Scientist
Mentor: James E. Loyd, M.D. (Pulmonary Arterial Hypertension NIH grants P01HL072058 and GCRCRR000095) Project: Abnormal T cell Milieu in Idiopathic Pulmonary Arterial Hypertension

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