Duygu Sağ Laboratory

Macrophage polarization in inflammatory diseases

 

Duygu Sağ duygu.sag@deu.edu.tr
dsag.ibg@gmail.com
Members
Duygu Ünüvar – Purcu, PhD Student
Meltem Altunay, MSc Student

 

OVERVIEW

Metabolic and immune responses are the most basic and important survival requirements in multicellular organisms. Recent studies by us and others have uncovered the strong mutual influence of metabolism and macrophage inflammatory responses. Identifying the underlying mechanisms is a fascinating and vibrant novel research area and its findings will be critical for the design of therapeutic treatments for both metabolic and inflammatory diseases.

RESEARCH INTERESTS

Our research is focused on the mechanisms linking metabolism and macrophage polarization. Macrophages are major players in the immune system. Recent studies by us and others have uncovered the strong mutual influence of metabolism and macrophage inflammatory responses. Identifying the underlying mechanisms is critical for the design of therapeutic treatments for both metabolic and inflammatory diseases.

Our several current projects investigate the role of ATP-binding Cassette Transporter G1 (ABCG1) in macrophage polarization and inflammatory diseases. ABCG1 promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis, which is crucial for survival and function of cells. We have recently made the novel discovery that absence of ABCG1 in macrophages inhibits tumor growth, metastasis and prolongs survival of mice through the modulation of macrophage function within the tumor. In particular, in the absence of ABCG1, the tumor-associated macrophages shift from a tumor-promoting M2 (anti-inflammatory) to a tumor-fighting M1 (proinflammatory) phenotype (Sag et al, Nature Communications, 2015).

Our goal is to (1) uncover the molecular mechanisms through which ABCG1-deficiency shifts macrophages to a tumor-fighting M1 phenotype and (2) investigate the role of ABCG1 in macrophage polarization in humans, particularly in human cancer.

Furthermore, we aim to investigate the impact of macrophage ABCG1 deficiency on other diseases in which macrophages play a key role, such as type II diabetes and obesity.

Duygu Sağ Şekil

Lab members:

Sağ lab is currently seeking highly motivated graduate students and post-docs. If interested, please contact dsag.ibg@gmail.com

Education/Research Experience
May 15 – present Assistant Professor; Izmir Biomedicine and Genome Center (IBG-Izmir), Dokuz Eylul University, Izmir, Turkey.
2009 – 2015 Postdoctoral fellow; La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, California, USA.
2004 – 2009 Graduate Research Assistant, University of Louisville School of Medicine, Department of Microbiology and Immunology, Louisville, Kentucky, USA.
2009 Ph.D. in Immunology, University of Louisville School of Medicine, Department of Microbiology and Immunology, Louisville, Kentucky, USA.
2003 B.Sc. in Biology (with honors), Middle East Technical University, Ankara, Turkey.
AWARDS AND RECOGNITION
• 2236 Co-Funded Brain Circulation Scheme Fellowship, The Scientific and Technological Research Council of Turkey (TUBITAK) / EU 7th Frame Work Marie Curie Actions (2015-2017)
• Young Investigator Travel Award, Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) Conference 2011, Chicago, Illinois, USA (2011)
• Graduate Dean’s Citation Award, University of Louisville, Louisville, Kentucky, USA (2009)
• Travel Award, The 41st Annual Meeting of the Society for Leukocyte Biology, Denver, Colorado, USA (2008)
• Pre-doctoral Fellowship, American Heart Association, Great Rivers Affiliate, USA (2007-2009)
• Presidential Trainee Award (second place), The 40th Annual Meeting of the Society for Leukocyte Biology, Cambridge, Massachusetts, USA (2007)
• Travel Award, University of Louisville International Center for the 13th International Congress of Immunology, Rio de Janeiro, Brazil (2006)
• Pre-doctoral Fellowship, Integrated Programs in Biomedical Sciences, University of Louisville School of Medicine, Louisville, Kentucky, USA (2004-2005)
PUBLICATIONS
Full list and citations: Google Scholar: Duygu Sag
• Hanna RN, Cekic C, Sag D, Tacke R, Thomas GD, Nowyhed H, Herrley E, Rasquinha N, Peluso E, McArdle S, Wu R, Metzger D, Ichinose H, Shaked I, Chodaczek G, Biswas SK, Hedrick CC, 2015. Patrolling Monocytes Control Tumor Metastasis to the Lung. Science, 350(6263):985-90.
• Wingender G, Sag D, Kronenberg M, 2015. NKT10 cells: a novel iNKT cell subset. Oncotarget,6(29):26552-3.
• Wingender G, Birkholz AM, Sag D, Farber E, Chitale S, Howell AR, Kronenberg M, 2015. Selective conditions are required for the induction of iNKT cell hypo-responsiveness by antigenic stimulation. The Journal of Immunology, 195(8):3838-48.
Sag D*1, Cekic C*, Wu R, Linden J, Hedrick CC1, 2015. The Cholesterol Transporter ABCG1 links cholesterol homeostasis and tumor immunity. Nature Communications, 6:6354 (* equal contribution, 1corresponding authors).
• Zhu Y, Brown J, Sag D, Zhang L, Suttles J, 2015. AMP-activated protein kinase regulates IL-10-mediated anti-inflammatory signaling pathways in macrophages. The Journal of Immunology, 186 (7), 3858-3865.
• Cekic C, Day YJ, Sag D, Linden J, 2014. Myeloid expression of Adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment. Cancer Research, 74 (24), 7250-7259.
Sag D, Krause P, Hedrick CC, Kronenberg M, Wingender G, 2014. IL-10-producing NKT10 cells are a distinct regulatory invariant NKT cell subset. The Journal of Clinical Investigation, 124(9):3725-40.
• Cekic C, Sag D, Day L, Linden J, 2013. Extracellular adenosine regulates naïve T cell development and peripheral maintenance. The Journal of Experimental Medicine, 210 (12): 2693.
Sag D, Wingender G, Nowyhed H, Wu R, Gebre AK, Parks JS, Kronenberg M, Hedrick CC, 2012. ATP-binding cassette transporter G1 intrinsically regulates invariant natural killer T cell thymic development. The Journal of Immunology, 189(11):5129-38.
• Cekic C, Sag D, Li Y, Theodorescu D, Strieter RM, Linden J, 2012. Adenosine A2B receptor blockade slows growth of bladder and breast tumors. The Journal of Immunology, 188(1):198-205.
• Cekic C, Casella CR, Sag D, Antignano F, Kolb J, Suttles J, Hughes M, Krystal G, Mitchell TC, 2011. MyD88-dependent SHIP1 regulates pro-inflammatory signaling pathways in dendritic cells after monophosphoryl lipid A stimulation of TLR4. The Journal of Immunology, 186(7):3858-65.
Sag D, Carling D, Stout RD, Suttles J, 2008. Adenosine 5′-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. The Journal of Immunology, 181(12):8633.

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