Jelic Lab
Location and Contact Information
Principal Investigator
The Jelic Lab 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.
Overview of Active Projects
The Effects of Sleep Restriction on Endothelial Activation in pre- and post-menopausal women
- American Heart Association 16SFRN29050000 (P.I.: Jelic)
- AHA Strategically Focused Research Network
- The major goal of this project is to investigate molecular mechanisms of endothelial dysfunction in sleep restriction, an emerging cardiovascular risk factor.
Vascular Endothelial Activation in Sleep Apnea
- R01 HL106041-06A1 (PI: Jelic)
- NIH/NHLBI
- The goal of this project is to determine whether reduced endothelial complement inhibition is mediated by cholesterol accumulation in endothelial cells in OSA and whether CPAP and/or statins reverse these changes.
Obstructive Sleep Apnea and Subclinical Lung Injury in Health and Disease
- R01 137234-01A1 (Contact PI: Jelic, MPI: Jelic/Gottlieb)
- NIH/NHLBI
- The goal of this study is to determine whether obstructive sleep apnea contributes to subclinical lung injury.
Insufficient Sleep in Women and Endothelial Cell Oxidative Stress
- American Academy of Sleep Medicine (AASM) Young Investigator Award 216-FP-1 (Role: Mentor)
- Mentee: Riddhi Shah, PhD
- The goal of this study is determine whether sleep restriction reduces expression of cofactors that mediate antioxidant response in endothelial cells in healthy women.
Race and sleep health during pregnancy in the nuMom2b cohort
- American Academy of Sleep Medicine (AASM) Young Investigator Award 216-FP-1 (Role: Mentor)
- Mentee: Maristella Lucchini, PhD
- The goal of this study is to investigate the relationship between race and sleep disordered breathing (SDB) in the NuMoM2b cohort through the National Sleep Research Resource.
Treatment of Obstructive Sleep Apnea and Complement Activation.
- American Thoracic Society ASPIRE Fellowship Award (Role: Mentor)
- Mentee: Neha Patel, MD
- The goal of this study is to determine whether treatment of OSA with CPAP and/or statins improves endothelial protection against complement activity.
Endothelial Cell Cholesterol Metabolism Dysregulation in Obstructive Sleep Apnea
- American Heart Association Career Development Award (Role: Mentor)
- Mentee: Su Gao, PhD
- The goal of this study is to investigate molecular mechanisms mediating altered cholesterol metabolism in endothelial cells in patients with OSA.
Select 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
Tall AR, Jelic S. How Broken Sleep Promotes Cardiovascular Disease. Nature. 2019;566(7744):329-330.a.
Thompson AE, Ranard BL, Wei Y, Jelic S. Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure. JAMA Intern Med 2020 Jun 17;180:1537-9.