Michael John Garabedian

Biosketch / Results /

Michael Garabedian

Professor, Department of Microbiology
Professor, Department of Urology

Course Director

Contact Info

Address
522 First Avenue
New York, NY 10016

212/263-7662
Michael.Garabedian@med.nyu.edu

Research Summary

Steroid hormone receptors are ligand-regulated transcription factors that control diverse physiological and developmental processes. In addition, estrogen and androgen receptors (ER and AR) are implicated in the etiology of breast and prostate cancer, respectively, whereas the glucocorticoid receptor (GR) is an important therapeutic target for cancer and inflammatory diseases. The goal of my laboratory is to elucidate the mechanism of signal transduction and transcriptional regulation by these receptors. Specifically, the lab is interested: 1) How molecular chaperones regulate steroid receptor action; 2) how transcriptional regulatory molecules (coactivators and corepressors) modulate ER, GR and AR transcriptional activity and the role of steroid receptor phosphorylation in the recruitment of coactivators and corepressors, 3) how Rho GTPases and the actin cytoskeleton regulate steroid receptor transcriptional response, and 4) the mechanism of GR-induced cell growth arrest and apoptosis. We are using genetic (mouse knock-outs and knock-ins), biochemical (microarrays and high-throughput screening of small molecules that disrupt receptor:coactivator interaction) as well as cell biological strategies (studying macromolecular complexes using color variants of GFP) to elucidate the mechanism of ER, AR and GR function in vivo. Understanding the mechanism of steroid receptor-regulated gene expression may reveal novel points of intervention to be exploited in the development of new therapies for steroid-dependent malignancies, such as breast and prostate cancer.


Research Interests

Signal Transduction and Transcriptional Regulation by Steroid Receptors

miRNA Targeting of Oxysterol-Binding Protein-Like 6 Regulates Cholesterol Trafficking and Efflux
Ouimet, Mireille; Hennessy, Elizabeth J; van Solingen, Coen; Koelwyn, Graeme J; Hussein, Maryem A; Ramkhelawon, Bhama; Rayner, Katey J; Temel, Ryan E; Perisic, Ljubica; Hedin, Ulf; Maegdefessel, Lars; Garabedian, Michael J; Holdt, Lesca M; Teupser, Daniel; Moore, Kathryn J. miRNA Targeting of Oxysterol-Binding Protein-Like 6 Regulates Cholesterol Trafficking and Efflux. Arteriosclerosis, thrombosis, & vascular biology. 2016 Mar 3;36(5):942-951 (2009452)

PARP-1 Represses LXR-mediated ABCA1 Expression and Cholesterol Efflux in Macrophages
Shrestha, Elina; Hussein, Maryem A; Savas, Jeffery N; Ouimet, Mireille; Barrett, Tessa J; Leone, Sarah; Yates, John R 3rd; Moore, Kathryn J; Fisher, Edward A; Garabedian, Michael J. PARP-1 Represses LXR-mediated ABCA1 Expression and Cholesterol Efflux in Macrophages. Journal of biological chemistry. 2016 Mar 29;291(21):11172-11184 (2059152)

Neurotrophic-priming of glucocorticoid receptor signaling is essential for neuronal plasticity to stress and antidepressant treatment
Arango-Lievano, Margarita; Lambert, W Marcus; Bath, Kevin G; Garabedian, Michael J; Chao, Moses V; Jeanneteau, Freddy. Neurotrophic-priming of glucocorticoid receptor signaling is essential for neuronal plasticity to stress and antidepressant treatment. Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2015 Nov 16;112(51):15737-15742 (1863502)

LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2
Hussein, Maryem A; Shrestha, Elina; Ouimet, Mireille; Barrett, Tessa J; Leone, Sarah; Moore, Kathryn J; Herault, Yann; Fisher, Edward A; Garabedian, Michael J. LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2. PLoS one. 2015 Aug 19;10(8):e0135218-e0135218 e0135218 (1732262)

MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia
Jones, Courtney L; Gearheart, Christy M; Fosmire, Susan; Delgado-Martin, Cristina; Evensen, Nikki A; Bride, Karen; Waanders, Angela J; Pais, Faye; Wang, Jinhua; Bhatla, Teena; Bitterman, Danielle S; de Rijk, Simone R; Bourgeois, Wallace; Dandekar, Smita; Park, Eugene; Burleson, Tamara M; Madhusoodhan, Pillai Pallavi; Teachey, David T; Raetz, Elizabeth A; Hermiston, Michelle L; Muschen, Markus; Loh, Mignon L; Hunger, Stephen P; Zhang, Jinghui; Garabedian, Michael J; Porter, Christopher C; Carroll, William L. MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia. Blood. 2015 Aug 31;126(19):2202-2212 (1761702)