Sanja Jelic, MD
Associate Professor of Medicine
Division of Pulmonary, Allergy, and Critical Care Medicine
Curriculum VitaeHome Page Address:
Jelic Laboratory
P&S 8 Rm 512
630 W. 168th Street
New York, NY 10032
Tel: (212) 342-0256
E-mail:sj366@cumc.columbia.edu
The laboratory is conducting research on the molecular mechanisms that mediate vascular endothelial activation and increased cardiovascular risk in patients with obstructive sleep apnea (OSA). The cyclic nature of the hypoxic insult clearly distinguishes OSA from other conditions that activate endothelium such as hypertension, diabetes or elevated LDL cholesterol. To gain insight into novel pathways that mediate vascular risk in OSA, we employed an unbiased approach using a phage display library and mass spectrometry to identify differentially expressed plasma membrane proteins on endothelial cells harvested from OSA patients. This led to the discovery that patients with OSA have decreased protection against complement attack, suggesting a novel mechanism of vascular injury in OSA. Currently, we are investigating the mechanisms regulating the function of the lipid-raft anchored complement inhibitor CD59 in endothelial cells, with a focus on cholesterol homeostasis in intermittent hypoxia. In another project, we are exploring the mechanisms underlying the excessive susceptibility of the vascular tissue to the toxins in secondhand smoke (SHS) and the vascular effects of inhaled nicotine in electronic cigarettes. As a part of AHA Strategically Focused Go Red for Women Research Network, the laboratory is also investigating the mechanisms linking sleep deprivation to increased cardiovascular risk.
Pubmed Link
Selected Publications:
Jelic S, Padeletti M, Canfield S, Higgins C, Kawut SM, Onat D, Colombo P, Basner RC, Factor P, Le Jemtel T. Inflammation, Oxidative Stress and Repair Capacity of the Vascular Endothelium in Obstructive Sleep Apnea. Circulation 2008;117:2270-8.
Jelic S, Lederer D, Adams T, Padeletti M, Colombo P, Factor P, Le Jemtel T. Vascular Inflammation in Obesity and Sleep Apnea. Circulation 2010;121:1014-21. PMCID:PMC2864627
Marin JM, Alvar A, Villar I, Forner M, Nieto D, Carrizo SJ, Barbe F, Vicente E, Wei Y, Nieto FJ, Jelic S. Association between Treated and Untreated Obstructive Sleep Apnea and Risk of Hypertension. JAMA. 2012;307:2169-76.
Emin M, Wang G, Castagna F, Rodriguez-Lopez J, Wahab R, Wang J, Adams T, Wei Y, Jelic S. Increased Internalization of Complement Inhibitor CD59 May Contribute to Endothelial Inflammation in Obstructive Sleep Apnea. Sci Transl Med. 2016;8:320ra1. doi: 10.1126/scitranslmed.aad0634. PMID:26738794
Aggarwal B, Makarem N, Shah R, Emin M, Wei Y, St-Onge MP, Jelic S. Effects of Inadequate Sleep on Blood Pressure and Endothelial Inflammation in Women: Findings from the American Heart Association Go Red for Women Strategically Focused Research Network. J Am Heart Assoc. 2018;7(12).
Funding:
American Heart Association 16SFRN29050000 (PI: Jelic) 2016 - 2020
AHA Strategically Focused Research Network
Title: The Effects of Sleep Restriction on Endothelial Activation in pre- and post-menopausal women
The major goal of this project is to investigate molecular mechanisms of endothelial dysfunction in sleep
restriction, an emerging cardiovascular risk factor.
R56HL106041 (PI: Jelic) 2016 - 2017
NIH/NHLBI
Title: Vascular Endothelial Activation in Sleep Apnea
This project will determine whether intermittent hypoxia-induced cholesterol accumulation in endothelial cells alters complement inhibition leading to endothelial dysfunction and increased vascular risk in obstructive sleep apnea.
2 R01 HL106041-06A1 (PI: Jelic) 2017 - 2021
NIH/NHLBI
Title: Vascular Endothelial Activation in Sleep Apnea
The goals of this project are:
1) To determine whether reduced complement inhibition promotes endothelial dysfunction in OSA and whether CPAP reverses these changes
2) To determine whether reduced complement inhibition is mediated by cholesterol accumulation in ECs in OSA and whether CPAP reverses these changes, and
3) To determine whether statins prevent endothelial dysfunction in OSA by preserving complement inhibition using randomized design. Using an innovative approach to characterize human vascular endothelium, the proposed studies may advance our understanding of vascular dysfunction in OSA and provide the basis for clinical trials of novel therapeutic strategies, such as addition of statins to the standard CPAP therapy, for preventing and/or reversing vascular risk in OSA.