Jonathan D. Brown, M.D.

Assistant Professor

jonathan.d.brown@vanderbilt.edu

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Faculty Appointments
Assistant Professor of Medicine Assistant Professor of BiochemistryAssistant Professor of Molecular Physiology & Biophysics
Education
M.D., New York Medical College, Valhalla, New YorkB.A., Classics with Departmental Honors, Brown University, Providence, Rhode Island
Research Description
Inflammation and stress signaling are critical determinants of cardiovascular and metabolic disease. Ultimately, these pathways converge in the nucleus to change chromatin structure and activate pathologic gene expression. A primary focus of the lab is to study how specific transcription factors and coregulators control these abnormal gene expression programs in cardiometabolic disease. In particular, the lab seeks to understand how chromatin-dependent signaling drives transcriptional programs that change cell state.

You are welcome to visit the Jon Brown Lab website @: https://www.jonbrownlab.com/ to learn more about my research.
Clinical Description
Jonathan Brown is trained in general clinical cardiology and CV disease prevention. He attends on the inpatient teaching service.
Research Keywords
Cardiometabolic disease, Epigenomics, Gene regulation, Chromatin, Transcription.
Publications
Tao H, Yancey PG, Blakemore JL, Zhang Y, Ding L, Jerome WG, Brown JD, Vickers KC, Linton MF. Macrophage SR-BI modulates autophagy via VPS34 complex and PPARa transcription of Tfeb in atherosclerosis. J Clin Invest. 2021 Apr 4/1/2021; 131(7): PMID: 33661763, PMCID: PMC8011903, PII: 94229, DOI: 10.1172/JCI94229, ISSN: 1558-8238.

Koblan LW, Erdos MR, Wilson C, Cabral WA, Levy JM, Xiong ZM, Tavarez UL, Davison LM, Gete YG, Mao X, Newby GA, Doherty SP, Narisu N, Sheng Q, Krilow C, Lin CY, Gordon LB, Cao K, Collins FS, Brown JD, Liu DR. In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice. Nature [print-electronic]. 2021 Jan; 589(7843): 608-14. PMID: 33408413, PMCID: PMC7872200, PII: 10.1038/s41586-020-03086-7, DOI: 10.1038/s41586-020-03086-7, ISSN: 1476-4687.

Perreault AA, Brown JD, Venters BJ. Erythropoietin Regulates Transcription and YY1 Dynamics in a Pre-established Chromatin Architecture. IScience. 2020 Oct 10/23/2020; 23(10): 101583. PMID: 33089097, PMCID: PMC7559257, PII: S2589-0042(20)30775-6, DOI: 10.1016/j.isci.2020.101583, ISSN: 2589-0042.

Antolic A, Wakimoto H, Jiao Z, Gorham JM, DePalma SR, Lemieux ME, Conner DA, Lee DY, Qi J, Seidman JG, Bradner JE, Brown JD, Haldar SM, Seidman CE, Burke MA. BET bromodomain proteins regulate transcriptional reprogramming in genetic dilated cardiomyopathy. JCI Insight [print-electronic]. 2020 Jun 6/30/2020; PMID: 32603312, PII: 138687, DOI: 10.1172/jci.insight.138687, ISSN: 2379-3708.

Hu JR, Duncan MS, Morgans AK, Brown JD, Meijers WC, Freiberg MS, Salem JE, Beckman JA, Moslehi JJ. Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer: Contemporary Meta-Analyses. Arterioscler. Thromb. Vasc. Biol [print-electronic]. 2020 Mar; 40(3): e55-e64. PMID: 31969015, PMCID: PMC7047549, DOI: 10.1161/ATVBAHA.119.313046, ISSN: 1524-4636.

Beckman JA, Doherty SP, Feldman ZB, Banks ES, Moslehi J, Jaffe IZ, Hamburg NM, Sheng Q, Brown JD. Comparative Transcriptomics of Ex Vivo, Patient-Derived Endothelial Cells Reveals Novel Pathways Associated With Type 2 Diabetes Mellitus. JACC Basic Transl Sci. 2019 Sep; 4(5): 567-74. PMID: 31768474, PMCID: PMC6872769, PII: S2452-302X(19)30181-0, DOI: 10.1016/j.jacbts.2019.05.012, ISSN: 2452-302X.

Guillermier C, Doherty SP, Whitney AG, Babaev VR, Linton MF, Steinhauser ML, Brown JD. Imaging mass spectrometry reveals heterogeneity of proliferation and metabolism in atherosclerosis. JCI Insight. 2019 Jun 6/6/2019; 4(11): PMID: 31167964, PMCID: PMC6629145, PII: 128528, DOI: 10.1172/jci.insight.128528, ISSN: 2379-3708.

Zhang Y, Federation AJ, Kim S, O'Keefe JP, Lun M, Xiang D, Brown JD, Steinhauser ML. Targeting nuclear receptor NR4A1-dependent adipocyte progenitor quiescence promotes metabolic adaptation to obesity. J. Clin. Invest [print-electronic]. 2018 Nov 11/1/2018; 128(11): 4898-911. PMID: 30277475, PMCID: PMC6205397, PII: 98353, DOI: 10.1172/JCI98353, ISSN: 1558-8238.

Brown JD, Feldman ZB, Doherty SP, Reyes JM, Rahl PB, Lin CY, Sheng Q, Duan Q, Federation AJ, Kung AL, Haldar SM, Young RA, Plutzky J, Bradner JE. BET bromodomain proteins regulate enhancer function during adipogenesis. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2018 Feb 2/27/2018; 115(9): 2144-9. PMID: 29444854, PMCID: PMC5834672, PII: 1711155115, DOI: 10.1073/pnas.1711155115, ISSN: 1091-6490.

Gupta RM, Hadaya J, Trehan A, Zekavat SM, Roselli C, Klarin D, Emdin CA, Hilvering CRE, Bianchi V, Mueller C, Khera AV, Ryan RJH, Engreitz JM, Issner R, Shoresh N, Epstein CB, de Laat W, Brown JD, Schnabel RB, Bernstein BE, Kathiresan S. A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of Endothelin-1 Gene Expression. Cell. 2017 Jul 7/27/2017; 170(3): 522-533.e15. PMID: 28753427, PMCID: PMC5785707, PII: S0092-8674(17)30768-7, DOI: 10.1016/j.cell.2017.06.049, ISSN: 1097-4172.

Duan Q, McMahon S, Anand P, Shah H, Thomas S, Salunga HT, Huang Y, Zhang R, Sahadevan A, Lemieux ME, Brown JD, Srivastava D, Bradner JE, McKinsey TA, Haldar SM. BET bromodomain inhibition suppresses innate inflammatory and profibrotic transcriptional networks in heart failure. Sci Transl Med. 2017 May 5/17/2017; 9(390): PMID: 28515341, PMCID: PMC5544253, PII: 9/390/eaah5084, DOI: 10.1126/scitranslmed.aah5084, ISSN: 1946-6242.

Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP, Roberts JM, Janiszewska M, Huh SJ, Liang Y, Ryan J, Doherty E, Mohammed H, Guo H, Stover DG, Ekram MB, Peluffo G, Brown J, D'Santos C, Krop IE, Dillon D, McKeown M, Ott C, Qi J, Ni M, Rao PK, Duarte M, Wu SY, Chiang CM, Anders L, Young RA, Winer EP, Letai A, Barry WT, Carroll JS, Long HW, Brown M, Liu XS, Meyer CA, Bradner JE, Polyak K. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature [print-electronic]. 2016 Jan 1/21/2016; 529(7586): 413-7. PMID: 26735014, PII: nature16508, DOI: 10.1038/nature16508, ISSN: 1476-4687.

Milstone DS, Ilyama M, Chen M, O'Donnell P, Davis VM, Plutzky J, Brown JD, Haldar SM, Siu A, Lau AC, Zhu SN, Basheer MF, Collins T, Jongstra-Bilen J, Cybulsky MI. Differential role of an NF-kB transcriptional response element in endothelial versus intimal cell VCAM-1 expression. Circ. Res. 2015 Jul 7/3/2015; 117(2): 166-77. PMID: 26034041, PII: CIRCRESAHA.117.306666, DOI: 10.1161/CIRCRESAHA.117.306666, ISSN: 1524-4571.

Brown JD. Bariatric surgery: "Roux"-minating on endothelial cell and high-density lipoprotein function [editorial]. Circulation [print-electronic]. 2015 Mar 3/10/2015; 131(10): 845-7. PMID: 25673671, PII: CIRCULATIONAHA.115.015343, DOI: 10.1161/CIRCULATIONAHA.115.015343, ISSN: 1524-4539.

Brown JD, Lin CY, Duan Q, Griffin G, Federation AJ, Paranal RM, Bair S, Newton G, Lichtman AH, Kung AL, Yang T, Wang H, Luscinskas FW, Croce KJ, Bradner JE, Plutzky J. NF-kB directs dynamic super enhancer formation in inflammation and atherogenesis. Mol. Cell. 2014 Oct 10/23/2014; 56(2): 219-31. PMID: 25263595, PMCID: PMC4224636, PII: S1097-2765(14)00679-0, DOI: 10.1016/j.molcel.2014.08.024, ISSN: 1097-4164.

Nallamshetty S, Le PT, Wang H, Issacsohn MJ, Reeder DJ, Rhee EJ, Kiefer FW, Brown JD, Rosen CJ, Plutzky J. Retinaldehyde dehydrogenase 1 deficiency inhibits PPARg-mediated bone loss and marrow adiposity. Bone. 2014 Oct; 67: 281-91. PMID: 25064526, PMCID: PMC4209126, PII: S8756-3282(14)00256-7, DOI: 10.1016/j.bone.2014.07.005, ISSN: 1873-2763.

Tatematsu S, Francis SA, Natarajan P, Rader DJ, Saghatelian A, Brown JD, Michel T, Plutzky J. Endothelial lipase is a critical determinant of high-density lipoprotein-stimulated sphingosine 1-phosphate-dependent signaling in vascular endothelium. Arterioscler. Thromb. Vasc. Biol [print-electronic]. 2013 Aug; 33(8): 1788-94. PMID: 23723371, PMCID: PMC3794714, PII: ATVBAHA.113.301300, DOI: 10.1161/ATVBAHA.113.301300, ISSN: 1524-4636.

Anand P, Brown JD, Lin CY, Qi J, Zhang R, Artero PC, Alaiti MA, Bullard J, Alazem K, Margulies KB, Cappola TP, Lemieux M, Plutzky J, Bradner JE, Haldar SM. BET bromodomains mediate transcriptional pause release in heart failure. 2013.

Liu S1, Brown JD, Stanya KJ, Homan E, Leidl M, Inouye K, Bhargava P, Gangl MR, Dai L, Hatano B, Hotamisligil GS, Saghatelian A, Plutzky J, Lee CH. A diurnal serum lipid intergates hepatic lipogenesis and peripheral fatty acid use. 2013.

Nallamshetty S, Wang H, Rhee EJ, Kiefer FW, Brown JD, Lotinun S, Le P, Baron R, Rosen CJ, Plutzky J. Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo. PLoS ONE. 2013; 8(8): e71307. PMID: 23951127, PMCID: PMC3739807, PII: PONE-D-13-12923, DOI: 10.1371/journal.pone.0071307, ISSN: 1932-6203.

Kiefer FW, Orasanu G, Nallamshetty S, Brown JD, Wang H, Luger P, Qi NR, Burant CF, Duester G, Plutzky J. Retinaldehyde dehydrogenase 1 coordinates hepatic gluconeogenesis and lipid metabolism. Endocrinology [print-electronic]. 2012 Jul; 153(7): 3089-99. PMID: 22555438, PMCID: PMC3380298, PII: en.2011-2104, DOI: 10.1210/en.2011-2104, ISSN: 1945-7170.

Kiefer FW, Vernochet C, O'Brien P, Spoerl S, Brown JD, Nallamshetty S, Zeyda M, Stulnig TM, Cohen DE, Kahn CR, Plutzky J. Retinaldehyde dehydrogenase 1 regulates a thermogenic program in white adipose tissue. Nat. Med. 2012 Jun; 18(6): 918-25. PMID: 22561685, PMCID: PMC3792792, PII: nm.2757, DOI: 10.1038/nm.2757, ISSN: 1546-170X.

Brown JD, Oligino E, Rader DJ, Saghatelian A, Plutzky J. VLDL hydrolysis by hepatic lipase regulates PPARd transcriptional responses. PLoS ONE [print-electronic]. 2011; 6(7): e21209. PMID: 21750705, PMCID: PMC3130023, PII: PONE-D-11-04131, DOI: 10.1371/journal.pone.0021209, ISSN: 1932-6203.

Chutkow WA, Birkenfeld AL, Brown JD, Lee HY, Frederick DW, Yoshioka J, Patwari P, Kursawe R, Cushman SW, Plutzky J, Shulman GI, Samuel VT, Lee RT. Deletion of the alpha-arrestin protein Txnip in mice promotes adiposity and adipogenesis while preserving insulin sensitivity. Diabetes [print-electronic]. 2010 Jun; 59(6): 1424-34. PMID: 20299477, PMCID: PMC2874703, PII: db09-1212, DOI: 10.2337/db09-1212, ISSN: 1939-327X.

Kanda T, Brown JD, Orasanu G, Vogel S, Gonzalez FJ, Sartoretto J, Michel T, Plutzky J. PPARgamma in the endothelium regulates metabolic responses to high-fat diet in mice. J. Clin. Invest [print-electronic]. 2009 Jan; 119(1): 110-24. PMID: 19065047, PMCID: PMC2613459, PII: 36233, DOI: 10.1172/JCI36233, ISSN: 0021-9738.

Brown JD, Plutzky J. Peroxisome proliferator-activated receptors as transcriptional nodal points and therapeutic targets. Circulation. 2007 Jan 1/30/2007; 115(4): 518-33. PMID: 17261671, PII: 115/4/518, DOI: 10.1161/CIRCULATIONAHA.104.475673, ISSN: 1524-4539.

Brown JD, DiChiara MR, Anderson KR, Gimbrone MA, Topper JN. MEKK-1, a component of the stress (stress-activated protein kinase/c-Jun N-terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional activation in endothelial cells. J. Biol. Chem. 1999 Mar 3/26/1999; 274(13): 8797-805. PMID: 10085121, ISSN: 0021-9258.

Topper JN, DiChiara MR, Brown JD, Williams AJ, Falb D, Collins T, Gimbrone MA. CREB binding protein is a required coactivator for Smad-dependent, transforming growth factor beta transcriptional responses in endothelial cells. Proc. Natl. Acad. Sci. U.S.A. 1998 Aug 8/4/1998; 95(16): 9506-11. PMID: 9689110, PMCID: PMC21368, ISSN: 0027-8424.

Available Postdoctoral Position Details
Posted: 5/4/2020

The Brown Laboratory is seeking a highly motivated candidate for a Postdoctoral Research Fellowship who will study chromatin-dependent gene regulation in cardiovascular and metabolic disease.  For more details about current laboratory projects or open positions, please visit the Brown laboratory website: jonbrownlab.com.