Ana Kojic

All Publications

• Generation of two induced pluripotent stem cell lines from healthy patients of African American ancestry. Stem cell research Mullen, M., Kojic, A., Alamana, C., Canel, G., Lai, C., Knowles, J. W., Wu, J. C. 2024; 76: 103322

  Abstract

  Stem cells are a resourceful tool for investigating cardiovascular disease in the context of race and gender. Once derived from blood or skin cells, the reprogrammed induced pluripotent stem cells (iPSCs) adopt an embryonic-like pluripotent state, enabling researchers to develop drug screening or disease modeling platforms. Here, we generated two iPSC lines from peripheral blood mononuclear cells (PBMCs) of two healthy African American patients. Both lines display the usual morphology of pluripotent stem cells, demonstrate elevated expression of pluripotent markers, show normal karyotype, and differentiate into all three germ layers in vitro.

  View details for DOI 10.1016/j.scr.2024.103322

  View details for PubMedID 38359472

• Structurally distinct PARP7 inhibitors provide new insights into the function of PARP7 in regulating nucleic acid-sensing and IFN-(3 signaling CELL CHEMICAL BIOLOGY Sanderson, D. J., Rodriguez, K. M., Bejan, D. S., Olafsen, N. E., Bohn, I. D., Kojic, A., Sundalam, S., Siordia, I. R., Duell, A. K., Deng, N., Schultz, C., Grant, D. M., Matthews, J., Cohen, M. S. 2023; 30 (1): 43-+

  Abstract

  The mono-ADP-ribosyltransferase PARP7 has emerged as a key negative regulator of cytosolic NA-sensors of the innate immune system. We apply a rational design strategy for converting a pan-PARP inhibitor into a potent selective PARP7 inhibitor (KMR-206). Consistent with studies using the structurally distinct PARP7 inhibitor RBN-2397, co-treatment of mouse embryonic fibroblasts with KMR-206 and NA-sensor ligands synergistically induced the expression of the type I interferon, IFN-β. In mouse colon carcinoma (CT-26) cells, KMR-206 alone induced IFN-β. Both KMR-206 and RBN-2397 increased PARP7 protein levels in CT-26 cells, demonstrating that PARP7's catalytic activity regulates its own protein levels. Curiously, treatment with saturating doses of KMR-206 and RBN-2397 achieved different levels of PARP7 protein, which correlated with the magnitude of type I interferon gene expression. These latter results have important implications for the mechanism of action of PARP7 inhibitors and highlights the usefulness of having structurally distinct chemical probes for the same target.

  View details for DOI 10.1016/j.chembiol.2022.11.012

  View details for Web of Science ID 000994359000001

  View details for PubMedID 36529140

  View details for PubMedCentralID PMC9868104

• Generation of two induced pluripotent stem cell lines from dilated cardiomyopathy patients caused by heterozygous mutations in the HCN4 gene. Stem cell research Yildirim, Z., Kojic, A., Yan, C. D., Wu, M. A., Vagelos, R., Wu, J. C. 2022; 65: 102951

  Abstract

  Dilated cardiomyopathy (DCM) is a progressive heart muscle disease that can culminate with heart failure and death. Mutations in several genes can cause DCM, including hyperpolarization-activated cyclic nucleotide-gated channel (HCN4), which has a critical function in the autonomic control of the heart rate. Here, we generated two human induced pluripotent stem cell (iPSC) lines generated from two DCM patients carrying variants in the HCN4 gene (c.2587G > T and c.2846G > A). Both lines display normal karyotype, typical morphology of pluripotent stem cells, and differentiate into all three germ layers in vitro. These lines are valuable resources for studying the pathological mechanisms of DCM.

  View details for DOI 10.1016/j.scr.2022.102951

  View details for PubMedID 36332467

• Generation of two induced pluripotent stem cell lines from dilated cardiomyopathy patients carrying heterozygous FLNC mutations. Stem cell research Kojic, A., Kim, H., Guevara, J. V., Ravada, S., Sallam, K., Wu, J. C. 2022; 64: 102928

  Abstract

  Dilated cardiomyopathy (DCM) is a heterogeneous cardiac disorder characterized by left ventricular dilatation and dysfunction. Mutations in dozens of cardiac genes have been connected to the development of DCM including the filamin C gene (FLNC). We generated two induced pluripotent stem cell (iPSCs) lines from DCM patients carrying single missense heterozygote FLNC mutations (c.6689G > A and c.3745G > A). Both lines expressed high levels of pluripotency markers, differentiated into derivatives of the three germ layers and possessed normal karyotypes. The derived iPSC lines can serve as powerful tools to model DCM in vitro and as a platform for therapeutic development.

  View details for DOI 10.1016/j.scr.2022.102928

  View details for PubMedID 36194907