Lars Bellner, Ph.D.
Instructor of Pharmacology
Lipidomics & Mass Spectrometry Core (LCMS) Manager
Department of Pharmacology
Basic Science Building, Rm. 531
15 Dana Road
Valhalla, NY 10595
Heme oxygenase 1 (HO-1) in obesity, metabolic syndrome and diabetes type II: HO-1 expression provides protection of stem cell function and regulation of adiposity. HO-1, together with Cytochrome P450-derived eicosatrienoic acids (EETs), also serve as mediators of cross-talk between adipose tissue and the vasculature. Our studies focus on the impact of HO-1 and EETs on adipocyte stem cell dysfunction, adipocyte expansion and hypertrophy and their role in vascular endothelial integrity. The heme oxygenase-EET axis provides protection in cardiac tissue and preserves heart function thereby attenuating myocardial infarction (MI) and heart failure. Both in vitro and in vivo models of diabetes and obesity are utilized to examine the use of stem cell intervention and gene therapy to amplify HO-1 levels.
Ocular surface inflammation and neovascularization: We have shown that injury to the ocular surface provokes an inflammatory and angiogenic response that is exaggerated in the absence of or deficiency in heme oxygenase expression. The heme oxygenases are enzymes that metabolize heme into iron, carbon monoxide (CO, a potent endogenous vasorelaxant and anti-inflammatory molecule) and biliverdin/bilirubin (antioxidants) and they are critical for the resolution of inflammation and to maintenance of cellular and tissue homeostasis. Studies in the lab are directed towards the elucidation of the cellular and molecular mechanisms underlying the anti-inflammatory and cytoprotective actions of the heme oxygenases, particularly heme oxygenase 2, in the cornea. These studies address the pathophysiological processes involved in corneal inflammation and neovascularization, a major problem in clinical ophthalmology.
- EET enhances renal function in obese mice resulting in restoration of HO-1-Mfn1/2 signaling, and decrease in hypertension through inhibition of sodium chloride co-transporter. Schragenheim J, Bellner L, Cao J, Singh SP, Bamshad D, McClung JA, Maayan O, Meissner A, Grant I, Stier CT Jr, Abraham NG. Prostaglandins Other Lipid Mediat. 2018 Jul;137:30-39.
- Singh SP, McClung JA, Bellner L, Cao J, Waldman M, Schragenheim J, Arad M, Hochhauser E, Falck JR, Weingarten JA, Peterson SJ, Abraham NG. CYP-450 Epoxygenase Derived Epoxyeicosatrienoic Acid Contribute To Reversal of Heart Failure in Obesity-Induced Diabetic Cardiomyopathy via PGC-1 α Activation. Cardiovasc Pharm Open Access. 2018;7(1).
- Singh SP, Bellner L, Vanella L, Cao J, Falck JR, Kappas A, Abraham NG. Downregulation of PGC-1α Prevents the Beneficial Effect of EET-Heme Oxygenase-1 on Mitochondrial Integrity and Associated Metabolic Function in Obese Mice. J Nutr Metab. 2016;2016:9039754.
- Singh SP, Schragenheim J, Cao J, Falck JR, Abraham NG, Bellner L. PGC-1 alpha regulates HO-1 expression, mitochondrial dynamics and biogenesis: Role of epoxyeicosatrienoic acid. Prostaglandins Other Lipid Mediat. 2016 Sep;125:8-18.
- Waldman M, Bellner L, Vanella L, Schragenheim J, Sodhi K, Singh SP, Lin D, Lakhkar A, Li J, Hochhauser E, Arad M, Darzynkiewicz Z, Kappas A, Abraham NG. Epoxyeicosatrienoic acids regulate adipocyte differentiation of mouse 3T3 cells, via PGC-1α activation, which is required for HO-1 expression and increased mitochondrial function. Stem Cells Dev. 2016 Jul 15;25(14):1084-94.
- Bellner L, Marrazzo G, van Rooijen N, Dunn MW, Abraham NG, Schwartzman ML. Heme oxygenase-2 deletion impairs macrophage function: implication in wound healing. FASEB J. 2015 Jan;29(1):105-15.
- Lin D, Halilovic A, Yue P, Bellner L, Wang K, Wang L, Zhang C. Inhibition of miR-205 impairs the wound-healing process in human corneal epithelial cells by targeting KIR4.1 (KCNJ10). Invest Ophthalmol Vis Sci. 2013 Sep 11;54(9):6167-78.
- Fox T, Gotlinger KH, Dunn MW, Lee OL, Milman T, Zaidman G, Schwartzman ML, Bellner L. Dysregulated heme oxygenase-ferritin system in pterygium pathogenesis. Cornea. 2013 Sep;32(9):1276-82.
- Vanella L, Sodhi K, Kim DH, Puri N, Maheshwari M, Hinds TD, Bellner L, Goldstein D, Peterson SJ, Shapiro JI, Abraham NG. Increased heme-oxygenase 1 expression in mesenchymal stem cell-derived adipocytes decreases differentiation and lipid accumulation via upregulation of the canonical Wnt signaling cascade. Stem Cell Res Ther. 2013 Mar 12;4(2):28.
- Cao J, Puri N, Sodhi K, Bellner L, Abraham NG, Kappas A. Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway. Int J Hypertens. 2012;2012:628147.
- Burgess AP, Vanella L, Bellner L, Gotlinger K, Falck JR, Abraham NG, Schwartzman ML, Kappas A. Heme oxygenase (HO-1) rescue of adipocyte dysfunction in HO-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin. Cell Physiol Biochem. 2012;29(1-2):99-110.
- Vanella L, Li M, Kim D, Malfa G, Bellner L, Kawakami T, Abraham NG. ApoA1: mimetic peptide reverses adipocyte dysfunction in vivo and in vitro via an increase in heme oxygenase (HO-1) and Wnt10b. Cell Cycle. 2012 Feb 15;11(4):706-14.
- Burgess A, Vanella L, Bellner L, Schwartzman ML, Abraham NG. Epoxyeicosatrienoic acids and heme oxygenase-1 interaction attenuates diabetes and metabolic syndrome complications. Prostaglandins Other Lipid Mediat. 2012 Jan;97(1-2):1-16.
- Marrazzo G, Bellner L, Halilovic A, Li Volti G, Drago F, Dunn MW, Schwartzman ML. The role of neutrophils in corneal wound healing in HO-2 null mice. PLoS One. 2011;6(6):e21180.
- Bellner L, Patil KA, Castellano K, Halilovic A, Dunn MW, Schwartzman ML. Targeted suppression of HO-2 gene expression impairs the innate anti-inflammatory and repair responses of the cornea to injury. Mol Vis. 2011 Apr 29;17:1144-52.
- Halilovic A, Patil KA, Bellner L, Marrazzo G, Castellano K, Cullaro G, Dunn MW, Schwartzman ML. Knockdown of heme oxygenase-2 impairs corneal epithelial cell wound healing. J Cell Physiol. 2011 Jul;226(7):1732-40.
- Bellner L, Wolstein J, Patil KA, Dunn MW, Laniado-Schwartzman M. Biliverdin Rescues the HO-2 Null Mouse Phenotype of Unresolved Chronic Inflammation Following Corneal Epithelial Injury. Invest Ophthalmol Vis Sci. 2011 May 17;52(6):3246-53.
- Bellner L, Vitto M, Patil KA, Dunn MW, Regan R, Laniado-Schwartzman M. Exacerbated corneal inflammation and neovascularization in the HO-2 null mice is ameliorated by biliverdin. Exp Eye Res. 2008 Sep;87(3):268-78.
- Patil K, Bellner L, Cullaro G, Gotlinger KH, Dunn MW, Schwartzman ML. Heme oxygenase-1 induction attenuates corneal inflammation and accelerates wound healing after epithelial injury. Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3379-86.
- Seta F, Bellner L, Rezzani R, Regan RF, Dunn MW, Abraham NG, Gronert K, Laniado-Schwartzman M. Heme oxygenase-2 is a critical determinant for execution of an acute inflammatory and reparative response. Am J Pathol. 2006 Nov;169(5):1612-23.
PubMed Publications – Lars Bellner, Ph.D.