Publications Pubmed Listings 1. Morad M, Cleemann L, Menick DR. NCX1 phosphorylation dilemma: a little closer to resolution. Focus on “Full-Length cardiac Na+/Ca2+ exchanger 1 protein is not phosphorylated by protein kinase A”. Am J Physiol Cell Physiol 2011 May; 300 (5):C970-3 [Epub 2011 Mar 9]. (Review) 2. Crosson CE, Mani SK, Husain S, Alsarraf O, Menick DR. Inhibition of histone deacetylase protects the retina from ischemic injury. Invest Ophthal Vis Sci 2010 Jul; 51(7):3639-45 [Epub 2010 Feb 17]. PMCID: PMC2904015. 3. Cheng G, Takahashi M, Shunmugavel A, Wallenborn JG, DePaoli-Roach AA, Gergs U, Neumann J, Kuppuswamy D, Menick DR, Cooper G IV. Basis for MAP4 dephosphorylation-related microtubule network densification in pressure overload cardiac hypertrophy. J Biol Chem 2010 Dec 3; 285(49): 38125-40 [Epub 2010 Oct 2]. PMCID: PMC2992246. 4. Kammili RK, Taylor DG, Xia J, Osuala K, Thompson K, Menick, DR, Ebert SN. Generation of novel reporter stem cells and their application for molecular imaging of cardiac-differentiated stem cells in vivo. Stem Cells Dev 2010 Sep; 19(9):1437-48. PMCID: PMC3121874. 5. Kern CB, Wessels A, McGarity J, Dixon LJ, Alston E, Argraves WS, Geeting D, Nelson CM, Menick DR, and Apte SS. Reduced versican cleavage due to Adamts9 haploinsufficiency is associated with cardiac and aortic anomalies. class="jrnl"Matrix Biol class="src1" 2010 May;29(4):304-16 class="src1". PMCID: PMC2862783. 6. Chinnakkannu P, Samanna V, Cheng G, Ablonczy Z, Baicu CF, Bethard JR, Menick DR, Kuppuswamy D, Cooper GIV, Site Specific MAP4 Dephosphorylation Causes Microtubule Network Densification in Pressure Overload Cardiac Hypertrophy. J Biol Chem. 2010 285(28):21837-48. PMCID 20436166. 7. Xu L, Kappler CS, Mani SK, Shepherd NR, Renaud L, Snider P, Conway SJ, Menick, DR. Chronic administration of KB-R7943 induces up-regulation of cardiac NCX1. J Biol Chem 2009 Oct 2; 284 (40):27265-72 [Epub 2009 Aug 6]. PMCID: PMC2785654. 8. Snider P, Hinton RB, Moreno-Rodriguez RA, Wang J, Rogers R, Lindsley A, Li F, Ingram DA, Menick D, Field L, Firulli AB, Molkentin JD, Markwald R, and Conway SJ. Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart. Circ Res 102:752-760, 2008. PMCID: PMC2754697 9. Xu L, Renaud L, Müller JG, Baicu CF, Bonnema DD, Zhou H, Kappler CS, Kubalak SW, Zile MR, Conway SJ, Menick DR. Regulation of NCX1 expression: Identification of regulatory elements mediating cardiac specific expression and upregulation. J. Biol. Chem., 281:34430-34440, 2006. 10. Muller JG, Isomatsu Y, Koushik SV, O'Quinn M, Xu L, Kappler CS, Hapke E, Zile MR, Conway SJ, and Menick DR. Cardiac-specific expression and hypertrophic upregulation of the feline Na(+)-Ca(2+) exchanger gene H1-promoter in a transgenic mouse model. Circ Res 90:158-164, 2002. |
My laboratory is focused on the analysis of signaling and gene regulatory pathways, which play a role in cardiac failure. Recently, others and we have demonstrated that protein acetylation, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), plays a significant role in modulating gene expression in cardiac pathologies. Importantly, treatment with HDAC inhibitors preserves ventricular remodeling and cardiac function in models of cardiac hypertrophy, myocardial infarction (MI) and heart failure. We have demonstrated that the acetylation state of specific transcription factors affects their interaction with co-activators and co-repressors. Therefore, HDACs can facilitate gene activation via the direct deacetylation of transcription factors allowing for recruitment of co-activators to the promoter. We utilize both isolated adult cardiac myocytes as well as animal models of hypertrophy, MI and heart failure to determine the signals that regulate HDACs and HATs and how the resulting changes in protein acetylation modulate cardiomyocyte and ventricular function. Our goal is to translate our basic and pre-clinical discoveries into important new therapies for patients with heart disease.
