The Umar Laboratory’s research is focused on investigating the molecular mechanisms and pathophysiology of primary and secondary forms of pulmonary hypertension and associated right ventricular dysfunction. Our long-term goal is to devise novel regenerative therapies for these cardiopulmonary disorders. We are also interested in investigating novel strategies for perioperative cardiopulmonary protection.
Pulmonary hypertension is a chronic pulmonary vascular disease without a definitive cure. We are using state-of-the-art in vivo mouse and rat models, in vitro cell culture systems, and human blood and tissue samples to investigate the molecular mechanisms of the development of primary and secondary pulmonary hypertension. We are also investigating adverse structural and electrical remodeling of the right ventricle secondary to pressure overload that often leads to arrhythmias and sudden death.
Our laboratory is interested in investigating perioperative cardiopulmonary dysfunction and strategies that lead to perioperative organ protection.
Local anesthetic-induced cardiotoxicity is a deadly complication of the use of local anesthetics in clinical practice. Our laboratory is investigating the molecular mechanisms of development and rescue of cardiotoxicity and cardiac arrest secondary to overdose of local anesthetics, such as bupivacaine, using a rat model. We are particularly interested in high-risk states such as pregnancy.
Patients with pulmonary fibrosis and other restrictive lung processes undergo routine surgical procedures, as well as major cardiothoracic surgeries. These patients are at higher risk for developing ventilator-induced lung injury (VILI), making ventilator management of these patients extremely challenging. We believe that compared to the determination of tidal volumes based on predicted body weight, more pulmonary-focused metrics to set lung-protective tidal volumes are more predictive of low pulmonary compliance and can be used to achieve less injurious mechanical ventilation. We aim to investigate this important clinical question using rodent models and aim to apply our results to benefit patients.
Echocardiographic studies suggest that 40% to 50% of patients with prolonged septic shock develop myocardial depression, as defined by a reduced ejection fraction. We are interested in developing animal models of sepsis-induced cardiac dysfunction and investigating the role of novel therapies.
Soban Umar, MD, PhD is an Associate Professor in Residence at the Department of Anesthesiology and Perioperative Medicine, Division of Molecular Medicine in the David Geffen School of Medicine at UCLA. Dr. Umar received his medical degree from Nishtar Medical University in Pakistan and his Ph.D. in Cardiovascular Physiology and Molecular Cardiology from Leiden University in Leiden, The Netherlands. Dr. Umar completed his postdoctoral training in Cardiovascular Medicine and his Residency in Anesthesiology at UCLA. Dr. Umar is a physician-scientist who works as a clinical Anesthesiologist and is the principal investigator of a Basic Cardiovascular Medicine research laboratory. Dr. Umar also serves as the Residency Research Coordinator for the Anesthesiology Residency Program at UCLA/David Geffen School of Medicine. He has received funding from American Thoracic Society (ATS), Foundation for Anesthesia Education and Research (FAER) and UCLA Cardiovascular Theme.
Umar S, Li J, Hannabass K, Vaillancourt M, Cunningham C, Moazeni S, Mahajan A, Eghbali M. Free Fatty Acid Receptor G-protein-coupled Receptor 40 Mediates Lipid Emulsion-induced Cardioprotection. Anesthesiology. 2018 April. doi: doi:10.1097/ALN.0000000000002195 Epub 2018 April 3 PMID: 29620570 https://www.ncbi.nlm.nih.gov/pubmed/29620570
This paper highlights the mechanisms of direct cardioprotective effects of lipid emulsion. More importantly, we have identified the key cell membrane receptor responsible of the effects of lipid emulsion in the heart.
Umar S, Cunningham CM, Itoh Y, Moazeni S, Vaillancourt M, Sarji S, Centala A, Arnold AP, Eghbali M (2017). The Y Chromosome Plays a Protective Role in Experimental Hypoxic Pulmonary Hypertension. Am J Respir Crit Care Med. 2017 Sep 21. doi: 10.1164/rccm.201707-1345LE. [Epub ahead of print] No abstract available. PMID: 28934553https://www.ncbi.nlm.nih.gov/pubmed/28934553
The role of sex chromosomes in the development of pulmonary hypertension has not been studied in the past. We conducted the first investigation of the role of sex chromosomes, in the absence of gonadal hormones, in the development of hypoxia-induced PH using the unique Four Core Genotypes (FCG) and XY* mouse models. We found that the Y chromosome is protective against development of hypoxia-induced pulmonary hypertension in gonadectomized mice. UCLA newsroom: http://newsroom.ucla.edu/releases/genes-on-y-chromosome-protect-against-pulmonary-hypertension-study-suggests
Vaillancourt M, Chia P, Sarji S, Nguyen J, Hoftman N, Ruffenach G, Eghbali M, Mahajan A, Umar S (2017). Autonomic nervous system involvement in pulmonary arterial hypertension. Respir Res. 2017 Dec 4;18(1):201. doi: 10.1186/s12931-017-0679-6. Review. PMID: 29202826 https://www.ncbi.nlm.nih.gov/pubmed/29202826
In this review, we summarize the multiple aspects of autonomic nervous system involvement in pulmonary arterial hypertension and provide an overview of the different pharmacological and invasive strategies used to target autonomic nervous system for the treatment of PAH.
Umar S, Partow-Navid R, Ruffenach G, Iorga A, Moazeni S, Eghbali M (2017). Severe pulmonary hypertension in aging female apolipoprotein E-deficient mice is rescued by estrogen replacement therapy. Biol Sex Differ. 2017 Mar 20;8:9. doi: 10.1186/s13293-017-0129-7. eCollection 2017. PMID: 28344760. https://www.ncbi.nlm.nih.gov/pubmed/28344760
The combined role of female sex, oxidized lipids and aging in pulmonary hypertension has not been investigated before. Hence, we investigated the development of pulmonary hypertension in young and middle-aged female apolipoprotein e-deficient mice and explored the role of estrogen replacement therapy for aging females. Our results suggested that only aging female apolipoprotein e-deficient but not wild type mice developed severe pulmonary hypertension compared to younger females. Exogenous estrogen therapy rescued pulmonary hypertension and right ventricular hypertrophy possibly through restoration of lung estrogen receptor beta expression.
Li J, Ruffenach G, Kararigas G, Cunningham CM, Motayagheni N, Barakai N, Umar S, Regitz-Zagrosek V, Eghbali M (2017). Intralipid protects the heart in late pregnancy against ischemia/reperfusion injury via Caveolin2/STAT3/GSK-3β pathway. J Mol Cell Cardiol. 2017 Jan;102:108-116. doi: 10.1016/j.yjmcc.2016.11.006. Epub 2016 Nov 12. PMID: 27847332 https://www.ncbi.nlm.nih.gov/pubmed/27847332
The heart of a rodent in late pregnancy is more prone to ischemia/reperfusion injury compared to that of a non-pregnant rodent. Intralipid protects the heart in late pregnancy against ischemia/reperfusion injury by inhibiting the mPTP opening through the Cav2/STAT3/GSK-3β pathway.
Sharma S, Ruffenach G, Umar S, Motayagheni N, Reddy ST, Eghbali M (2016). Role of oxidized lipids in pulmonary arterial hypertension. Pulm Circ. 2016 Sep;6(3):261-73. doi: 10.1086/687293. Review. PMID: 27683603. https://www.ncbi.nlm.nih.gov/pubmed/27683603
We focused on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of pulmonary hypertension. This review also discussed the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in pulmonary hypertension.
Anwar A, Ruffenach G, Mahajan A, Eghbali M, Umar S (2016). Novel biomarkers for pulmonary arterial hypertension. Respir Res. 2016 Jul 20;17(1):88. doi: 10.1186/s12931-016-0396-6. Review. PMID: 27439993. https://www.ncbi.nlm.nih.gov/pubmed/27439993
A simple non-invasive test to frequently monitor patients with pulmonary hypertension is much needed. The search for a novel biomarker for pulmonary hypertension that can be detected by a simple test is ongoing, and many different options are being studied. Here we reviewed some of the new and unique pre-clinical options for potential pulmonary hypertension biomarkers. A biomarker that can be detected in blood, urine or breath condensate and correlates with disease severity, progression and response to therapy may result in significant cost reduction and improved patient outcomes.
Iorga A, Li J, Sharma S, Umar S, Bopassa JC, Nadadur RD, Centala A, Ren S, Saito T, Toro L, Wang Y, Stefani E, Eghbali M (2016). Rescue of Pressure Overload-Induced Heart Failure by Estrogen Therapy. J Am Heart Assoc. 2016 Jan 22;5(1). pii: e002482. doi: 10.1161/JAHA.115.002482. PMID: 26802104. https://www.ncbi.nlm.nih.gov/pubmed/26802104
Estrogen pre-treatment has been shown to attenuate the development of heart hypertrophy, but it was not known whether estrogen could also rescue heart failure. We discovered that estrogen rescues pre-existing heart failure in mice by restoring cardiac estrogen and aromatase levels, stimulating cardiac angiogenesis, and by suppressing myocardial fibrosis.