Cardiopulmonary Research Program

The Cardiopulmonary Research Program (CRP) at the Krannert Cardiovascular Research Center studies the basic molecular underpinnings of heart and lung disorders using state-of-the-art precision medicine tools and techniques. Led by Ankit A. Desai, MD, CRP is dedicated to understanding the mechanisms and genetics of pulmonary arterial hypertension and sickle cell cardiomyopathy, complemented by Dr. Desai’s active clinical practice serving patients with pulmonary arterial hypertension and sickle cell disease for more than 15 years. The program employs genome-wide association study strategies to prioritize functional and preclinical studies of candidate genes that lead to the development of pulmonary arterial hypertension and heart failure.

Illustration of pulmonary hypertension with normal blood vessel comparison, with both heart and lungs displayed.

Pulmonary arterial hypertension is a type of high blood pressure that impacts the arteries in the lungs and the right side of the heart when blood vessels in the lungs become narrowed, blocked or damaged. This condition over time can lead to right heart failure.

Sickle cell disease is a genetic condition and type of anemia characterized by an abnormal shape of red blood cells that become blocked in blood vessels or break down, and cause harm to multiple organs including the heart.

CPR focuses on three major cardiovascular domains:

Genetic mechanisms of pulmonary arterial hypertension (PAH) and right heart failure, which impacts the heart’s right ventricle, with a particular focus on endothelial cell signaling
Genetic mechanisms of inflammation-mediated ventricular tachycardia and cardiomyopathy in patients with sickle cell disease
Novel molecular mechanisms of beta-blockers in myocardial infarction via beta-adrenergic independent signaling.

These areas reflect CPRs multi-disciplinary expertise across molecular biology, cellular signaling and animal physiology. Each domain is fundamentally grounded in omics-based platforms and studies of diverse populations and health disparities.

Current Treatment Challenges

There is a growing need to improve patient outcomes and quality of life, as more people are impacted by pulmonary arterial hypertension that could lead to increased morbidity and mortality. Pulmonary arterial hypertension largely affects women (~4:1 female to male ratio) with survival rates estimated to be around 50% at 7 years despite the addition of multiple therapies. Dr. Desai’s group is focused on addressing this dismal prognosis by better understanding the complexity of its pathogenesis. Studies are aimed at new molecular pathways that are discovered from genetic studies in patients and translating them as targets for novel therapies.

Stock Photo illustration of Sickle Cell Heart Circulation

Sudden death is an increasingly reported cause of early death in patients with sickle cell disease and is considered a top five cause of death. Recent published data suggest a high prevalence of heart arrhythmias (nearly 25%) in patients with sickle cell disease, but little is known about possible links between heart arrhythmias and sudden death, highlighting a poorly characterized and potentially underrecognized health risk for these patients. Dr. Desai’s lab was one of the first labs to demonstrate increased vulnerability for the development of heart arrhythmias in “humanized” sickle mouse models. Their lab showed that targeting inflammation and a novel protein called interleukin 18 may alleviate the development of sickle cell cardiomyopathy and associated heart arrythmias. Their lab is now focused on translating these findings to patients, and exploring new therapies that may treat patients who suffer from this condition.

Highlighted Publications

Genetic determinants of risk in pulmonary arterial hypertension: International genome-wide association studies and meta-analysis

Rhodes CJ, Batai K, Bleda M, Haimel M, Southgate L, Germain M, Pauciulo MW, Hadinnapola C, Aman J, Girerd B, Arora A, Knight J, Hanscombe KB, Karnes JH, Kaakinen M, Gall H, Ulrich A, Harbaum L, Cebola I, Ferrer J, Lutz K, Swietlik EM, Ahmad F, Amouyel P, Archer SL, Argula R, Austin ED, Badesch D, Bakshi S, Barnett C, Benza R, Bhatt N, Bogaard HJ, Burger CD, Chakinala M, Church C, Coghlan JG, Condliffe R, Corris PA, Danesino C, Debette S, Elliott CG, Elwing J, Eyries M, Fortin T, Franke A, Frantz RP, Frost A, Garcia JGN, Ghio S, Ghofrani HA, Gibbs JSR, Harley J, He H, Hill NS, Hirsch R, Houweling AC, Howard LS, Ivy D, Kiely DG, Klinger J, Kovacs G, Lahm T, Laudes M, Machado RD, MacKenzie Ross RV, Marsolo K, Martin LJ, Moledina S, Montani D, Nathan SD, Newnham M, Olschewski A, Olschewski H, Oudiz RJ, Ouwehand WH, Peacock AJ, Pepke-Zaba J, Rehman Z, Robbins I, Roden DM, Rosenzweig EB, Saydain G, Scelsi L, Schilz R, Seeger W, Shaffer CM, Simms RW, Simon M, Sitbon O, Suntharalingam J, Tang H, Tchourbanov AY, Thenappan T, Torres F, Toshner MR, Treacy CM, Vonk Noordegraaf A, Waisfisz Q, Walsworth AK, Walter RE, Wharton J, White RJ, Wilt J, Wort SJ, Yung D, Lawrie A, Humbert M, Soubrier F, Trégouët DA, Prokopenko I, Kittles R, Gräf S, Nichols WC, Trembath RC, Desai AA, Morrell NW, Wilkins MR. Lancet Respiratory Medicine. 2018 Dec 5. pii: S2213-2600(18)30409-0. doi: 10.1016/S2213-2600(18)30409-0. ^Co-first authors; *Co-senior authors; #Co-corresponding authors. PMID: 30527956. PMCID: PMC6391516. ^Editorial available.

IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias.

Gupta A, Fei YD, Kim TY, Xie A, Batai K, Greener I, Tang H, Ciftci-Yilmaz S, Juneman E, Indik JH, Shi G, Christensen J, Gupta G, Hillery C, Kansal MM, Parikh DS, Zhou T, Yuan JX, Kanthi Y, Bronk P, Koren G, Kittles R, Duarte JD, Garcia JGN, Machado RF, Dudley SC, Choi BR, Desai AA. Blood. 2020 Nov 12. PMID:33181835.

This schema shows mechanism of prolonged repolarization and acute response and Myocardial Fibrosis in Chronic Response. We report a novel role for interleukin-18 (IL-18) in the development of ventricular tachycardia and sickle cell cardiomyopathy.

Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension.

Karnes JH; Wiener HW; Schwantes-An TH; Natarajan B; Sweatt AJ; Chaturvedi A; Arora A; Batai K; Nair V; Steiner HE; Giles JB; Yu J; Hosseini M; Pauciulo MW; Lutz KA; Coleman AW; Feldman J; Vanderpool R; Tang H; Garcia JGN; Yuan JX; Kittles R; de Jesus Perez V; Zamanian RT; Rischard F; Tiwari HK; Nichols WC; Benza RL; Desai AA; American Journal of Respiratory and Critical Care Medicine. 2020 Jan 7

SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics

Sangam S, Sun X, Shwantes-An T, Yegambaram M, Lu Q, Shi Y, Cook T, Fisher A, Frump AL, Coleman A, Sun Y, Liang S, Crawford H, Lutz KA, Maun AD, Paucilio MW, Karnes JH, Chaudhary KR, Stewart DJ, Langlais P, Jain M, Alotaibi M, Lahm T, Jin Y, Gu H, Tang H, Nichols WC, Black SM^, Desai AA^. ^-Co-senior authors. In Press. American Journal of Respiratory and Critical Care Medicine. 3/2023.

This figure illustrates the mediated repression of SOX17. To understand the protective effects of SOX17 in vivo, we connect SOX17-mediated inhitibition of HIF2a with enhanced oxidative phosphorylation and mitochondrial function in endothelial cells.

Principal Investigator

Ankit A. Desai, MD

Associate Professor of Medicine
Adjunct Associate Professor of Medical & Molecular Genetics
Associate Program Director for Research - Cardiovascular Disease Fellowship

Read Bio

Cardiopulmonary Core Research Member

Samisubbu R. Naidu, PhD

Assistant Research Professor of Medicine

Cardiopulmonary Fellow

Yinan Shi, PhD

IU School of Medicine Collaborators

Micheala A. Aldred, PhD

Catherine and Lowe Berger and Pauline L. Ford Professor of Pulmonary Medicine

Andrea L. Frump, PhD

Assistant Professor of Medicine

Nicholas E. Harrison, MD

Assistant Professor of Emergency Medicine

Seethal A. Jacob, MD

Associate Professor of Pediatrics

Il-Man Kim, PhD

Associate Professor of Anatomy, Cell Biology & Physiology

Yen-Chun (Charly) Lai, PhD

Assistant Professor of Medicine

Roberto F. Machado, MD

Dr. Calvin H. English Professor

Tae-Hwi L. Schwantes-An, PhD

Assistant Professor of Medical & Molecular Genetics

External Collaborators

Raymond Benza, MD - Professor of Medicine, Ohio State University

Stephen Black, PhD - Professor of Medicine, Florida International University

Stephen Chan, MD, PhD - Professor of Medicine, University of Pittsburgh

Julio Duarte, PharmD, PhD - Assistant Professor of Pharmacotherapy and Translational Research, University of Florida- Gainesville

Joe GN Garcia, MD - Professor of Medicine, University of Arizona

Mohit Jain, MD, PhD - Associate Professor of Medicine & Pharmacology, University of California, San Diego

Jason H Karnes, PharmD, PhD - Associate Professor of Pharmacy Practice and Science, University of Arizona

William C Nichols, PhD - Professor of Pediatrics, Cincinnati Children’s Hospital Medical Center

Franz Rischard, DO - Associate Professor of Medicine, University of Arizona

Chris Rhodes, MRC, PhD - Senior Lecturer, Imperial College, London

Haiyang Tang, PhD - Research Associate Professor, Florida International University

Jair Tenorio, PhD - Research Associate, Molecular Genetics, Hospital Universitario La Paz, Madrid

Martin R. Wilkins, DSc - Professor of Pharmacology, Imperial College, London

Jason Yuan, MD, PhD - Professor of Medicine, University of California, San Diego