Garabedian Lab - Microbiology

 

Garabedian

Michael J. Garabedian, PhD
Professor, Departments of Microbiology and Urology
Alexandria Center for Life Science – East Tower
450 East 29th Street
Office Rm. 324
Office: (212) 263-7662
Fax: (646) 501-4643
Lab: (212) 263-7968
Email: Michael.Garabedian@nyulangone.org

 

 

KEY INTERESTS:

Resolution of inflammation by nuclear receptors in innate and adaptive immune cells

New prostate cancer therapeutics (peptoid conjugates and immune checkpoint blockade inhibitors)

Molecular mechanism of glucocorticoid receptor action in neuronal function during stress

Transcriptional and epigenetic regulation by nuclear receptors in macrophages
 

BIOGRAPHIC DETAILS:

Graduate Education:

PhD in Biochemistry from Brandeis University

Postdoctoral Training:

UCSF -1989-1994

Academic Appointments:

1994-Assistant Professor of Microbiology
2000- Associate Professor of Microbiology & Urology
2008-Professor of Microbiology & Urology

Major Responsibilities:

 

Module Director, Infection and Immunity Module
Content Director Microbiology; Infection and Immunity Module
Chair, Advisory Board, High Throughput Biology Core
NYU Tenure Track Faculty Senate representative (School of Medicine)

RESEARCH INTERESTS:

The focus of the Garabedian lab is to understand the mechanism of signal transduction and transcriptional regulation by nuclear hormone receptors. Specific areas of research include 1) Regulation of Inflammation by of liver X receptor (LXR) alpha in atherosclerosis and obesity; 2) Regulation of neuronal function by the glucocorticoid receptor (GR) in stress adaptation, 3) Rational design approaches for targeting the androgen receptor (AR) in therapy resistant prostate cancer, and effects on immune micro environment.

We use state-of-the-art genetic approaches including CRISPR and siRNA screens, sophisticated knock in mouse models, as well as molecular, genomic (single cell RNA-seq, spatial transcriptomics, ChIP-seq and ATAC-seq), proteomic and metabolomic approaches to discover novel insights into the mechanisms of nuclear receptors and other transcriptional regulatory factors in disease. Our goal is to leverage this information for potential clinical applications in prostate cancer, atherosclerosis, stress related anxiety and depression.

The laboratory and training environment has always promoted an inclusive, safe, and supportive research environment. Our lab is also part of Dr. Susan Logan’s lab (Associate Professor of Urology and Biochemistry and Molecular Pharmacology).

PUBLICATIONS:

Persistence of learning-induced synapses depends on neurotrophic priming of glucocorticoid receptors.
Arango-Lievano M, Borie AM, Dromard Y, Murat M, Desarmenien MG, Garabedian MJ, Jeanneteau F.
Proc Natl Acad Sci U S A. 2019 Jun 25;116(26):13097-13106. doi: 10.1073/pnas.1903203116. Epub 2019 Jun 10.
PMID: 31182610

Impaired LXRα Phosphorylation Attenuates Progression of Fatty Liver Disease.
Becares N, Gage MC, Voisin M, Shrestha E, Martin-Gutierrez L, Liang N, Louie R, Pourcet B, Pello OM, Luong TV, Goñi S, Pichardo-Almarza C, Røberg-Larsen H, Diaz-Zuccarini V, Steffensen KR, O'Brien A, Garabedian MJ, Rombouts K, Treuter E, Pineda-Torra I.
Cell Rep. 2019 Jan 22;26(4):984-995.e6. doi: 10.1016/j.celrep.2018.12.094.
PMID: 30673619

Prostate-specific loss of UXT promotes cancer progression.
Wang Y, Schafler ED, Thomas PA, Ha S, David G, Adney E, Garabedian MJ, Lee P, Logan SK.
Oncotarget. 2019 Jan 22;10(7):707-716. doi: 10.18632/oncotarget.26573. eCollection 2019 Jan 22.
PMID: 30774773

 Phosphorylation of LXRα impacts atherosclerosis regression by modulating monocyte/macrophage trafficking.  
Shrestha E, Voisin M, Barrett TJ, Nishi H, Cantor DJ, Hussein MA, David G, Pineda-Torra I, Fisher EA, Garabedian MJ.
BioRxIV. 2018;363366.

Bridging the Gap between Brain-Derived Neurotrophic Factor and Glucocorticoid Effects on Brain Networks.
Jeanneteau F, Borie A, Chao MV, Garabedian MJ.
Neuroendocrinology. 2018 Dec 20. doi: 10.1159/000496392. [Epub ahead of print] Review.
PMID: 30572337

Design of Peptoid-peptide Macrocycles to Inhibit the β-catenin TCF Interaction in Prostate Cancer.
Schneider JA, Craven TW, Kasper AC, Yun C, Haugbro M, Briggs EM, Svetlov V, Nudler E, Knaut H, Bonneau R, Garabedian MJ, Kirshenbaum K, Logan SK.
Nat Commun. 2018 Oct 23;9(1):4396. doi: 10.1038/s41467-018-06845-3.
PMID: 30352998

Phosphorylation of the glucocorticoid receptor alters SMAD signaling in vocal fold fibroblasts.
Mukudai S, Hiwatashi N, Bing R, Garabedian M, Branski RC.
Laryngoscope. 2019 May;129(5):E187-E193. doi: 10.1002/lary.27570. Epub 2018 Oct 16.
PMID: 30325506

The mediator complex in genomic and non-genomic signaling in cancer.
Weber H, Garabedian MJ.
Steroids. 2018 May;133:8-14. doi: 10.1016/j.steroids.2017.11.007. Epub 2017 Nov 21. Review.
PMID: 29157917

Glucocorticoid receptor action in metabolic and neuronal function.
Garabedian MJ, Harris CA, Jeanneteau F.
F1000Res. 2017 Jul 24;6:1208. doi: 10.12688/f1000research.11375.1. eCollection 2017. Review.
PMID: 28781762

URI Regulates KAP1 Phosphorylation and Transcriptional Repression via PP2A Phosphatase in Prostate Cancer Cells.
Mita P, Savas JN, Briggs EM, Ha S, Gnanakkan V, Yates JR 3rd, Robins DM, David G, Boeke JD, Garabedian MJ, Logan SK.
J Biol Chem. 2016 Dec 2;291(49):25516-25528. Epub 2016 Oct 25.
PMID: 27780869

Multivalent Peptoid Conjugates Which Overcome Enzalutamide Resistance in Prostate Cancer Cells.
Wang Y, Dehigaspitiya DC, Levine PM, Profit AA, Haugbro M, Imberg-Kazdan K, Logan SK, Kirshenbaum K, Garabedian MJ.
Cancer Res. 2016 Sep 1;76(17):5124-32. doi: 10.1158/0008-5472.CAN-16-0385. Epub 2016 Aug 3.

Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation.
Savic D, Ramaker RC, Roberts BS, Dean EC, Burwell TC, Meadows SK, Cooper SJ, Garabedian MJ, Gertz J, Myers RM.
Genome Med. 2016 Jul 11;8(1):74. doi: 10.1186/s13073-016-0328-6.

Dynein axonemal heavy chain 8 promotes androgen receptor activity and associates with prostate cancer progression.
Wang Y, Ledet RJ, Imberg-Kazdan K, Logan SK, Garabedian MJ.
Oncotarget. 2016 Aug 2;7(31):49268-49280. doi: 10.18632/oncotarget.10284.

Poly(ADP-ribose) Polymerase 1 Represses Liver X Receptor-mediated ABCA1 Expression and Cholesterol Efflux in Macrophages.
Shrestha E, Hussein MA, Savas JN, Ouimet M, Barrett TJ, Leone S, Yates JR 3rd, Moore KJ, Fisher EA, Garabedian MJ.
J Biol Chem. 2016 May 20;291(21):11172-84. doi: 10.1074/jbc.M116.726729. Epub 2016 Mar 29.

Neurotrophic-priming of glucocorticoid receptor signaling is essential for neuronal plasticity to stress and antidepressant treatment.
Arango-Lievano M, Lambert WM, Bath KG, Garabedian MJ, Chao MV, Jeanneteau F.
Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15737-42. doi: 10.1073/pnas.1509045112. Epub 2015 Nov 16.

LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2.
Hussein MA, Shrestha E, Ouimet M, Barrett TJ, Leone S, Moore KJ, Hérault Y, Fisher EA, Garabedian MJ.
PLoS One. 2015 Aug 19;10(8):e0135218. doi: 10.1371/journal.pone.0135218. eCollection 2015.

Modulation of Macrophage Gene Expression via Liver X Receptor α Serine 198 Phosphorylation.
Wu C, Hussein MA, Shrestha E, Leone S, Aiyegbo MS, Lambert WM, Pourcet B, Cardozo T, Gustafson JA, Fisher EA, Pineda-Torra I, Garabedian MJ.
Mol Cell Biol. 2015 Jun 1;35(11):2024-34. doi: 10.1128/MCB.00985-14. Epub 2015 Mar 30.

Targeting the androgen receptor with steroid conjugates.
Levine PM, Garabedian MJ, Kirshenbaum K.
J Med Chem. 2014 Oct 23;57(20):8224-37. doi: 10.1021/jm500101h. Epub 2014 Jul 8. Review.

Brain-derived neurotrophic factor signaling rewrites the glucocorticoid transcriptome via glucocorticoid receptor phosphorylation.
Lambert WM, Xu CF, Neubert TA, Chao MV, Garabedian MJ, Jeanneteau FD.
Mol Cell Biol. 2013 Sep;33(18):3700-14. doi: 10.1128/MCB.00150-13. Epub 2013 Jul 22. Erratum in: Mol Cell Biol. 2013 Oct;33(20):4138.

Inhibition of androgen receptor and β-catenin activity in prostate cancer.
Lee E, Madar A, David G, Garabedian MJ, Dasgupta R, Logan SK.
Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15710-5. doi: 10.1073/pnas.1218168110. Epub 2013 Sep 9.

A genome-wide RNA interference screen identifies new regulators of androgen receptor function in prostate cancer cells.
Imberg-Kazdan K, Ha S, Greenfield A, Poultney CS, Bonneau R, Logan SK, Garabedian MJ.
Genome Res. 2013 Apr;23(4):581-91. doi: 10.1101/gr.144774.112. Epub 2013 Feb 12.

Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner.
Gertz J, Reddy TE, Varley KE, Garabedian MJ, Myers RM.
Genome Res. 2012 Nov;22(11):2153-62. doi: 10.1101/gr.135681.111. Epub 2012 Sep 26.

Phosphorylation of the androgen receptor by PIM1 in hormone refractory prostate cancer.
Ha S, Iqbal NJ, Mita P, Ruoff R, Gerald WL, Lepor H, Taneja SS, Lee P, Melamed J, Garabedian MJ, Logan SK.
Oncogene. 2013 Aug 22;32(34):3992-4000. doi: 10.1038/onc.2012.412. Epub 2012 Sep 17.

Androgen receptor antagonism by divalent ethisterone conjugates in castrate-resistant prostate cancer cells.
Levine PM, Lee E, Greenfield A, Bonneau R, Logan SK, Garabedian MJ, Kirshenbaum K.
ACS Chem Biol. 2012 Oct 19;7(10):1693-701. doi: 10.1021/cb300332w. Epub 2012 Aug 7.
 

LAB MEMBERS:
Maud Voisin, PhD
Prashanth Thevkar Nagesh, PhD
Hannah Weber (MD/PhD student)
Jeff Schneider, (MD/PhD student co mentored with Dr. Susan Logan)
Sophie Ruff (MD/PhD student co mentored with Dr. Susan Logan)
Rachel Ruoff, Lab Manager