Bio

Academic Appointments


Honors & Awards


  • AHA Career Development Award, American Heart Association (2018-2021)
  • Helena Anna Henzl-Gabor Travel Grant, Stanford School of Medicine (2018)
  • CVI Travel Award, Stanford University (2017)
  • NRSA F32 Postdoctoral Fellowship, NIH (2016-2018)
  • AHA Postdoctoral Fellowship, American Heart Association (2015-2016)
  • I3P Predoctoral Travel Award, CSIC (Spanish Research Council) (2008-2010)
  • I3P Predoctoral Fellowship, CSIC (Spanish Research Council) (2007-2011)

Patents


  • Christine Wahlquist, Mark Mercola, Agustin Rojas-Munoz, Alexandre Colas, Roger J. Hajjar, Dongtak Jeong. "United States Patent 20140243387 Methods for improving cardiac contractility", Sanford-Burnham Medical Research Institute, Icahn School Of Medicine At Mount Sinai

Publications

All Publications


  • EXOSOMAL MIR-106A-363 CLUSTER FROM THE HYPOXIC HUMAN IPSC-DERIVED CARDIOMYOCYTES RESTORE THE ISCHEMIC MYOCARDIUM Jung, J., Tada, Y., Bornstaedt, D., Wahlquist, C., Mercola, M., Woo, Y., Yang, P. ELSEVIER SCIENCE INC. 2018: 14
  • miR-25 Tough Decoy Enhances Cardiac Function in Heart Failure. Molecular therapy : the journal of the American Society of Gene Therapy Jeong, D., Yoo, J., Lee, P., Kepreotis, S. V., Lee, A., Wahlquist, C., Brown, B. D., Kho, C., Mercola, M., Hajjar, R. J. 2017

    Abstract

    MicroRNAs are promising therapeutic targets, because their inhibition has the potential to normalize gene expression in diseased states. Recently, our group found that miR-25 is a key SERCA2a regulating microRNA, and we showed that multiple injections of antagomirs against miR-25 enhance cardiac contractility and function through SERCA2a restoration in a murine heart failure model. However, for clinical application, a more stable suppressor of miR-25 would be desirable. Tough Decoy (TuD) inhibitors are emerging as a highly effective method for microRNA inhibition due to their resistance to endonucleolytic degradation, high miRNA binding affinity, and efficient delivery. We generated a miR-25 TuD inhibitor and subcloned it into a cardiotropic AAV9 vector to evaluate its efficacy. The AAV9 TuD showed selective inhibition of miR-25 in vitro cardiomyoblast culture. In vivo, AAV9-miR-25 TuD delivered to the murine pressure-overload heart failure model selectively decreased expression of miR-25, increased levels of SERCA2a protein, and ameliorated cardiac dysfunction and fibrosis. Our data indicate that miR-25 TuD is an effective long-term suppressor of miR-25 and a promising therapeutic candidate to treat heart failure.

    View details for PubMedID 29273502

  • Inhibition of miR-25 improves cardiac contractility in the failing heart NATURE Wahlquist, C., Jeong, D., Rojas-Munoz, A., Kho, C., Lee, A., Mitsuyama, S., Van Mil, A., Park, W. J., Sluijter, J. P., Doevendans, P. A., Hajjar, R. J., Mercola, M. 2014; 508 (7497): 531-?

    Abstract

    Heart failure is characterized by a debilitating decline in cardiac function, and recent clinical trial results indicate that improving the contractility of heart muscle cells by boosting intracellular calcium handling might be an effective therapy. MicroRNAs (miRNAs) are dysregulated in heart failure but whether they control contractility or constitute therapeutic targets remains speculative. Using high-throughput functional screening of the human microRNAome, here we identify miRNAs that suppress intracellular calcium handling in heart muscle by interacting with messenger RNA encoding the sarcoplasmic reticulum calcium uptake pump SERCA2a (also known as ATP2A2). Of 875 miRNAs tested, miR-25 potently delayed calcium uptake kinetics in cardiomyocytes in vitro and was upregulated in heart failure, both in mice and humans. Whereas adeno-associated virus 9 (AAV9)-mediated overexpression of miR-25 in vivo resulted in a significant loss of contractile function, injection of an antisense oligonucleotide (antagomiR) against miR-25 markedly halted established heart failure in a mouse model, improving cardiac function and survival relative to a control antagomiR oligonucleotide. These data reveal that increased expression of endogenous miR-25 contributes to declining cardiac function during heart failure and suggest that it might be targeted therapeutically to restore function.

    View details for DOI 10.1038/nature13073

    View details for Web of Science ID 000334741600038

    View details for PubMedID 24670661

    View details for PubMedCentralID PMC4131725

  • Synthesis and SAR of b-Annulated 1,4-Dihydropyridines Define Cardiomyogenic Compounds as Novel Inhibitors of TGF beta Signaling JOURNAL OF MEDICINAL CHEMISTRY Schade, D., Lanier, M., Willems, E., Okolotowicz, K., Bushway, P., Wahlquist, C., Gilley, C., Mercola, M., Cashman, J. R. 2012; 55 (22): 9946-9957

    Abstract

    A medium-throughput murine embryonic stem cell (mESC)-based high-content screening of 17000 small molecules for cardiogenesis led to the identification of a b-annulated 1,4-dihydropyridine (1,4-DHP) that inhibited transforming growth factor β (TGFβ)/Smad signaling by clearing the type II TGFβ receptor from the cell surface. Because this is an unprecedented mechanism of action, we explored the series' structure-activity relationship (SAR) based on TGFβ inhibition, and evaluated SAR aspects for cell-surface clearance of TGFβ receptor II (TGFBR2) and for biological activity in mESCs. We determined a pharmacophore and generated 1,4-DHPs with IC(50)s for TGFβ inhibition in the nanomolar range (e.g., compound 28, 170 nM). Stereochemical consequences of a chiral center at the 4-position was evaluated, revealing 10- to 15-fold more potent TGFβ inhibition for the (+)- than the (-) enantiomer. This stereopreference was not observed for the low level inhibition against Activin A signaling and was reversed for effects on calcium handling in HL-1 cells.

    View details for DOI 10.1021/jm301144g

    View details for Web of Science ID 000311461500045

    View details for PubMedID 23130626

  • Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Salomonis, N., Schlieve, C. R., Pereira, L., Wahlquist, C., Colas, A., Zambon, A. C., Vranizan, K., Spindler, M. J., Pico, A. R., Cline, M. S., Clark, T. A., Williams, A., Blume, J. E., Samal, E., Mercola, M., Merrill, B. J., Conklin, B. R. 2010; 107 (23): 10514-10519

    Abstract

    Two major goals of regenerative medicine are to reproducibly transform adult somatic cells into a pluripotent state and to control their differentiation into specific cell fates. Progress toward these goals would be greatly helped by obtaining a complete picture of the RNA isoforms produced by these cells due to alternative splicing (AS) and alternative promoter selection (APS). To investigate the roles of AS and APS, reciprocal exon-exon junctions were interrogated on a genome-wide scale in differentiating mouse embryonic stem (ES) cells with a prototype Affymetrix microarray. Using a recently released open-source software package named AltAnalyze, we identified 144 genes for 170 putative isoform variants, the majority (67%) of which were predicted to alter protein sequence and domain composition. Verified alternative exons were largely associated with pathways of Wnt signaling and cell-cycle control, and most were conserved between mouse and human. To examine the functional impact of AS, we characterized isoforms for two genes. As predicted by AltAnalyze, we found that alternative isoforms of the gene Serca2 were targeted by distinct microRNAs (miRNA-200b, miRNA-214), suggesting a critical role for AS in cardiac development. Analysis of the Wnt transcription factor Tcf3, using selective knockdown of an ES cell-enriched and characterized isoform, revealed several distinct targets for transcriptional repression (Stmn2, Ccnd2, Atf3, Klf4, Nodal, and Jun) as well as distinct differentiation outcomes in ES cells. The findings herein illustrate a critical role for AS in the specification of ES cells with differentiation, and highlight the utility of global functional analyses of AS.

    View details for DOI 10.1073/pnas.0912260107

    View details for Web of Science ID 000278549300035

    View details for PubMedID 20498046