Annet Kirabo, D.V.M., Ph.D.

Assistant Professor

annet.kirabo@vanderbilt.edu
Faculty Appointments
Assistant Professor of Medicine Assistant Professor in the Department of Molecular Physiology and Biophysics
Education
Ph.D., Physiology & Pharmacology, University of Florida, Gainesville, FloridaM.Sc., Saint Cloud State University , Saint Cloud, MinnesotaD.V.M., Makerere University, Uganda
Office Address
2220 Pierce Ave, P415C MRBIV
Nashville, TN 37232
Research Description
The current goal of my research program is to define the molecular mechanisms underlying activation of the immune system in response to hypertensive stimuli including excess dietary salt, sympathetic nerve outflow, and oxidative stress. We are attempting to uncover the mechanisms by which hypertensive stimuli lead to accumulation of isolevuglandins (IsoLGs) in antigen presenting cells and how these may activate the immune system. We are using novel cutting-edge methods to isolate MHC-associated peptides, and use mass spectrometry and proteomics to identify IsoLG-modified peptides presented by MHCs in hypertension. Our goal is to use these modified peptides to design immunotherapeutic approaches in hypertension and cardiovascular disease.
Research Keywords
Cardiovascular disease, Hypertension, Dendritic cells, Neo-antigens, Isolevuglandins
Publications
Kirabo A. A new paradigm of sodium regulation in inflammation and hypertension. Am. J. Physiol. Regul. Integr. Comp. Physiol [print-electronic]. 2017 Dec 12/1/2017; 313(6): R706-R710. PMID: 28931546, PMCID: PMC5814689, PII: ajpregu.00250.2017, DOI: 10.1152/ajpregu.00250.2017, ISSN: 1522-1490.

Barbaro NR, Foss JD, Kryshtal DO, Tsyba N, Kumaresan S, Xiao L, Mernaugh RL, Itani HA, Loperena R, Chen W, Dikalov S, Titze JM, Knollmann BC, Harrison DG, Kirabo A. Dendritic Cell Amiloride-Sensitive Channels Mediate Sodium-Induced Inflammation and Hypertension. Cell Rep. 2017 Oct 10/24/2017; 21(4): 1009-20. PMID: 29069584, PMCID: PMC5674815, PII: S2211-1247(17)31419-5, DOI: 10.1016/j.celrep.2017.10.002, ISSN: 2211-1247.

Barbaro NR, Kirabo A, Harrison DG. A New Role of Mister (MR) T in Hypertension: Mineralocorticoid Receptor, Immune System, and Hypertension [editorial]. Circ. Res. 2017 May 5/12/2017; 120(10): 1527-9. PMID: 28495982, PMCID: PMC5511376, PII: CIRCRESAHA.117.310985, DOI: 10.1161/CIRCRESAHA.117.310985, ISSN: 1524-4571.

Kirabo A, Ryzhov S, Gupte M, Sengsayadeth S, Gumina RJ, Sawyer DB, Galindo CL. Neuregulin-1ß induces proliferation, survival and paracrine signaling in normal human cardiac ventricular fibroblasts. J. Mol. Cell. Cardiol [print-electronic]. 2017 Apr; 105: 59-69. PMID: 28263756, PII: S0022-2828(17)30050-0, DOI: 10.1016/j.yjmcc.2017.03.001, ISSN: 1095-8584.

Dixon KB, Davies SS, Kirabo A. Dendritic cells and isolevuglandins in immunity, inflammation, and hypertension. Am. J. Physiol. Heart Circ. Physiol [print-electronic]. 2017 Mar 3/1/2017; 312(3): H368-H374. PMID: 27986660, PII: ajpheart.00603.2016, DOI: 10.1152/ajpheart.00603.2016, ISSN: 1522-1539.

Foss JD, Kirabo A, Harrison DG. Do high-salt microenvironments drive hypertensive inflammation?. Am. J. Physiol. Regul. Integr. Comp. Physiol [print-electronic]. 2017 Jan 1/1/2017; 312(1): R1-R4. PMID: 27903514, PMCID: PMC5283943, PII: ajpregu.00414.2016, DOI: 10.1152/ajpregu.00414.2016, ISSN: 1522-1490.

Itani HA, Xiao L, Saleh MA, Wu J, Pilkinton MA, Dale BL, Barbaro NR, Foss JD, Kirabo A, Montaniel KR, Norlander AE, Chen W, Sato R, Navar LG, Mallal SA, Madhur MS, Bernstein KE, Harrison DG. CD70 Exacerbates Blood Pressure Elevation and Renal Damage in Response to Repeated Hypertensive Stimuli. Circ. Res [print-electronic]. 2016 Apr 4/15/2016; 118(8): 1233-43. PMID: 26988069, PMCID: PMC4833561, PII: CIRCRESAHA.115.308111, DOI: 10.1161/CIRCRESAHA.115.308111, ISSN: 1524-4571.

Wu J, Saleh MA, Kirabo A, Itani HA, Montaniel KR, Xiao L, Chen W, Mernaugh RL, Cai H, Bernstein KE, Goronzy JJ, Weyand CM, Curci JA, Barbaro NR, Moreno H, Davies SS, Roberts LJ, Madhur MS, Harrison DG. Immune activation caused by vascular oxidation promotes fibrosis and hypertension. J. Clin. Invest [print-electronic]. 2016 Apr 4/1/2016; 126(4): 1607. PMID: 27035819, PMCID: PMC4811163, PII: 87425, DOI: 10.1172/JCI87425, ISSN: 1558-8238.

Wu J, Saleh MA, Kirabo A, Itani HA, Montaniel KR, Xiao L, Chen W, Mernaugh RL, Cai H, Bernstein KE, Goronzy JJ, Weyand CM, Curci JA, Barbaro NR, Moreno H, Davies SS, Roberts LJ, Madhur MS, Harrison DG. Immune activation caused by vascular oxidation promotes fibrosis and hypertension. J. Clin. Invest [print-electronic]. 2016 Jan; 126(1): 50-67. PMID: 26595812, PMCID: PMC4701546, PII: 80761, DOI: 10.1172/JCI80761, ISSN: 1558-8238.

Xiao L, Kirabo A, Wu J, Saleh MA, Zhu L, Wang F, Takahashi T, Loperena R, Foss JD, Mernaugh RL, Chen W, Roberts J, Osborn JW, Itani HA, Harrison DG. Renal Denervation Prevents Immune Cell Activation and Renal Inflammation in Angiotensin II-Induced Hypertension. Circ. Res [print-electronic]. 2015 Aug 8/28/2015; 117(6): 547-57. PMID: 26156232, PMCID: PMC4629828, PII: CIRCRESAHA.115.306010, DOI: 10.1161/CIRCRESAHA.115.306010, ISSN: 1524-4571.

McMaster WG, Kirabo A, Madhur MS, Harrison DG. Inflammation, immunity, and hypertensive end-organ damage. Circ. Res. 2015 Mar 3/13/2015; 116(6): 1022-33. PMID: 25767287, PMCID: PMC4535695, PII: CIRCRESAHA.116.303697, DOI: 10.1161/CIRCRESAHA.116.303697, ISSN: 1524-4571.

Saleh MA, McMaster WG, Wu J, Norlander AE, Funt SA, Thabet SR, Kirabo A, Xiao L, Chen W, Itani HA, Michell D, Huan T, Zhang Y, Takaki S, Titze J, Levy D, Harrison DG, Madhur MS. Lymphocyte adaptor protein LNK deficiency exacerbates hypertension and end-organ inflammation. J. Clin. Invest [print-electronic]. 2015 Mar 3/2/2015; 125(3): 1189-202. PMID: 25664851, PMCID: PMC4362266, PII: 76327, DOI: 10.1172/JCI76327, ISSN: 1558-8238.

Kamat NV, Thabet SR, Xiao L, Saleh MA, Kirabo A, Madhur MS, Delpire E, Harrison DG, McDonough AA. Renal transporter activation during angiotensin-II hypertension is blunted in interferon-¿-/- and interleukin-17A-/- mice. Hypertension [print-electronic]. 2015 Mar; 65(3): 569-76. PMID: 25601932, PMCID: PMC4326622, PII: HYPERTENSIONAHA.114.04975, DOI: 10.1161/HYPERTENSIONAHA.114.04975, ISSN: 1524-4563.

Trott DW, Thabet SR, Kirabo A, Saleh MA, Itani H, Norlander AE, Wu J, Goldstein A, Arendshorst WJ, Madhur MS, Chen W, Li CI, Shyr Y, Harrison DG. Oligoclonal CD8+ T cells play a critical role in the development of hypertension. Hypertension [print-electronic]. 2014 Nov; 64(5): 1108-15. PMID: 25259750, PMCID: PMC4191997, PII: HYPERTENSIONAHA.114.04147, DOI: 10.1161/HYPERTENSIONAHA.114.04147, ISSN: 1524-4563.

Kirabo A, Fontana V, de Faria AP, Loperena R, Galindo CL, Wu J, Bikineyeva AT, Dikalov S, Xiao L, Chen W, Saleh MA, Trott DW, Itani HA, Vinh A, Amarnath V, Amarnath K, Guzik TJ, Bernstein KE, Shen XZ, Shyr Y, Chen SC, Mernaugh RL, Laffer CL, Elijovich F, Davies SS, Moreno H, Madhur MS, Roberts J, Harrison DG. DC isoketal-modified proteins activate T cells and promote hypertension. J. Clin. Invest [print-electronic]. 2014 Oct; 124(10): 4642-56. PMID: 25244096, PMCID: PMC4220659, PII: 74084, DOI: 10.1172/JCI74084, ISSN: 1558-8238.

Jin X, Zhao W, Kirabo A, Park SO, Ho WT, Sayeski PP, Zhao ZJ. Elevated levels of mast cells are involved in pruritus associated with polycythemia vera in JAK2V617F transgenic mice. J. Immunol [print-electronic]. 2014 Jul 7/15/2014; 193(2): 477-84. PMID: 24920845, PII: jimmunol.1301946, DOI: 10.4049/jimmunol.1301946, ISSN: 1550-6606.

Wu J, Thabet SR, Kirabo A, Trott DW, Saleh MA, Xiao L, Madhur MS, Chen W, Harrison DG. Inflammation and mechanical stretch promote aortic stiffening in hypertension through activation of p38 mitogen-activated protein kinase. Circ. Res [print-electronic]. 2014 Feb 2/14/2014; 114(4): 616-25. PMID: 24347665, PMCID: PMC4186716, PII: CIRCRESAHA.114.302157, DOI: 10.1161/CIRCRESAHA.114.302157, ISSN: 1524-4571.

Kirabo A, Park SO, Wamsley HL, Gali M, Baskin R, Reinhard MK, Zhao ZJ, Bisht KS, Keseru GM, Cogle CR, Sayeski PP. The small molecule inhibitor G6 significantly reduces bone marrow fibrosis and the mutant burden in a mouse model of Jak2-mediated myelofibrosis. Am. J. Pathol [print-electronic]. 2012 Sep; 181(3): 858-65. PMID: 22796437, PMCID: PMC3432437, PII: S0002-9440(12)00439-7, DOI: 10.1016/j.ajpath.2012.05.033, ISSN: 1525-2191.

Majumder A, Magis AT, Park SO, Figueroa NC, Baskin R, Kirabo A, Allan RW, Zhao ZJ, Bisht KS, Keseru GM, Sayeski PP. A46, a benzothiophene-derived compound, suppresses Jak2-mediated pathologic cell growth. Exp. Hematol [print-electronic]. 2012 Jan; 40(1): 22-34. PMID: 22019628, PMCID: PMC3237899, PII: S0301-472X(11)00500-5, DOI: 10.1016/j.exphem.2011.10.003, ISSN: 1873-2399.

Kirabo A, Park SO, Majumder A, Gali M, Reinhard MK, Wamsley HL, Zhao ZJ, Cogle CR, Bisht KS, Keserü GM, Sayeski PP. The Jak2 inhibitor, G6, alleviates Jak2-V617F-mediated myeloproliferative neoplasia by providing significant therapeutic efficacy to the bone marrow. Neoplasia. 2011 Nov; 13(11): 1058-68. PMID: 22131881, PMCID: PMC3223609, ISSN: 1476-5586.

Majumder A, Kirabo A, Karrupiah K, Tsuda S, Caldwell-Busby J, Cardounel AJ, Keseru GM, Sayeski PP. Cell death induced by the Jak2 inhibitor, G6, correlates with cleavage of vimentin filaments. Biochemistry [print-electronic]. 2011 Sep 9/13/2011; 50(36): 7774-86. PMID: 21823612, PMCID: PMC3168676, DOI: 10.1021/bi200847n, ISSN: 1520-4995.

Kirabo A, Kearns PN, Jarajapu YP, Sasser JM, Oh SP, Grant MB, Kasahara H, Cardounel AJ, Baylis C, Wagner KU, Sayeski PP. Vascular smooth muscle Jak2 mediates angiotensin II-induced hypertension via increased levels of reactive oxygen species. Cardiovasc. Res [print-electronic]. 2011 Jul 7/1/2011; 91(1): 171-9. PMID: 21354995, PMCID: PMC3112021, PII: cvr059, DOI: 10.1093/cvr/cvr059, ISSN: 1755-3245.

Kirabo A, Oh SP, Kasahara H, Wagner KU, Sayeski PP. Vascular smooth muscle Jak2 deletion prevents angiotensin II-mediated neointima formation following injury in mice. J. Mol. Cell. Cardiol [print-electronic]. 2011 Jun; 50(6): 1026-34. PMID: 21420414, PMCID: PMC3092026, PII: S0022-2828(11)00100-3, DOI: 10.1016/j.yjmcc.2011.03.005, ISSN: 1095-8584.

Kirabo A, Embury J, Kiss R, Polgár T, Gali M, Majumder A, Bisht KS, Cogle CR, Keseru GM, Sayeski PP. The stilbenoid tyrosine kinase inhibitor, G6, suppresses Jak2-V617F-mediated human pathological cell growth in vitro and in vivo. J. Biol. Chem [print-electronic]. 2011 Feb 2/11/2011; 286(6): 4280-91. PMID: 21127060, PMCID: PMC3039371, PII: M110.200774, DOI: 10.1074/jbc.M110.200774, ISSN: 1083-351X.

Sayeski P, et al. A Potential Therapeutic Target for AT1 Receptor Mediated Cardiovascular Disease. Pharmaceuticals. 2010; 3(11): 3478-93.

Kiss R, Polgár T, Kirabo A, Sayyah J, Figueroa NC, List AF, Sokol L, Zuckerman KS, Gali M, Bisht KS, Sayeski PP, Keseru GM. Identification of a novel inhibitor of JAK2 tyrosine kinase by structure-based virtual screening. Bioorg. Med. Chem. Lett [print-electronic]. 2009 Jul 7/1/2009; 19(13): 3598-601. PMID: 19447617, PMCID: PMC2812898, PII: S0960-894X(09)00647-7, DOI: 10.1016/j.bmcl.2009.04.138, ISSN: 1464-3405.

McDoom I, Ma X, Kirabo A, Lee KY, Ostrov DA, Sayeski PP. Identification of tyrosine 972 as a novel site of Jak2 tyrosine kinase phosphorylation and its role in Jak2 activation. Biochemistry [print-electronic]. 2008 Aug 8/12/2008; 47(32): 8326-34. PMID: 18636744, PMCID: PMC3636534, DOI: 10.1021/bi800867d, ISSN: 1520-4995.