Prerna Giri

All Publications

• Cryo-Electron Tomography Reveals Nanoscale Thick Filament Disorganization in MYH7 P710R Hypertrophic Cardiomyopathy Cardiomyocytes. ACS nano Zaoralová, M., Yoniles, J., Giri, P., Held, R. G., Vander Roest, A., Dahlberg, P. D., Bernstein, D., Dunn, A. R., Engel, L. 2026; 20 (34): 23748-23755

  Abstract

  Hypertrophic cardiomyopathy (HCM) is the most common monogenic inherited heart disease and is a major cause of sudden death in individuals under 35 years of age. HCM is associated with progressive tissue-level disarray and subcellular disorganization in individual cardiomyocytes. Mutations in β-cardiac myosin (MYH7), the second most common genetic cause of HCM, commonly result in changes in sarcomeric force production, but how this leads to altered cell- and tissue-level organization is unclear. Here, we use cryo-electron tomography (cryo-ET) to bridge the molecular and cellular scales by visualizing the nanoscale organization of individual myosin-containing thick filaments within sarcomeres of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Compared to isogenic wild-type controls, hiPSC-CMs expressing P710R MYH7 exhibit pronounced disruption of the hexagonal packing of thick filaments within individual sarcomeres, which would be difficult to visualize using conventional light microscopy or even room-temperature electron microscopy. We also observe ribosome infiltration into areas of sarcomeric disorder for both wild-type and P710R MYH7 hiPSC-CMs, suggesting that disordered regions may be sites of local proteostasis or remodeling. Together, these data illuminate how altered myosin activity can propagate to yield dramatic changes in sarcomeric organization in HCM.

  View details for DOI 10.1021/acsnano.6c03369

  View details for PubMedID 42689701

• Cryo-Electron TomographyReveals Nanoscale Thick FilamentDisorganization in MYH7 P710R Hypertrophic Cardiomyopathy Cardiomyocytes ACS NANO Zaoralova, M., Yoniles, J., Giri, P., Held, R. G., Vander Roest, A., Dahlberg, P. D., Bernstein, D., Dunn, A. R., Engel, L. 2026

  View details for DOI 10.1021/acsnano.6c03369

  View details for Web of Science ID 001852509700001

• Mechanisms of mechanosensing by MLP and α-actinin-2 in cardiac hypertrophy Bhat, A., Vera, C., Marang, C., Giri, P., Bernstein, D., Dunn, A. CELL PRESS. 2026: 327a

  View details for Web of Science ID 001717762500141

• Getting to the heart of hypertrophic cardiomyopathy with cryogenic electron tomography Yoniles, J., Zaoralova, M., Fajardo, G., Giri, P., Engel, L., Bernstein, D., Dunn, A. R., Dahlberg, P. D. CELL PRESS. 2026: 9a

  View details for Web of Science ID 001717073300042

• Cryo-electron tomography reveals the structural diversity of cardiac proteins in their cellular context. bioRxiv : the preprint server for biology Woldeyes, R. A., Nishiga, M., Vander Roest, A. S., Engel, L., Giri, P., Montenegro, G. C., Wu, A. C., Dunn, A. R., Spudich, J. A., Bernstein, D., Schmid, M. F., Wu, J. C., Chiu, W. 2023

  Abstract

  Cardiovascular diseases are a leading cause of death worldwide, but our understanding of the underlying mechanisms is limited, in part because of the complexity of the cellular machinery that controls the heart muscle contraction cycle. Cryogenic electron tomography (cryo-ET) provides a way to visualize diverse cellular machinery while preserving contextual information like subcellular localization and transient complex formation, but this approach has not been widely applied to the study of heart muscle cells (cardiomyocytes). Here, we deploy a platform for studying cardiovascular disease by combining cryo-ET with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). After developing a cryo-ET workflow for visualizing macromolecules in hiPSC-CMs, we reconstructed sub-nanometer resolution structures of the human thin filament, a central component of the contractile machinery. We also visualized a previously unobserved organization of a regulatory complex that connects muscle contraction to calcium signaling (the troponin complex), highlighting the value of our approach for interrogating the structures of cardiac proteins in their cellular context.

  View details for DOI 10.1101/2023.10.26.564098

  View details for PubMedID 37961228

  View details for PubMedCentralID PMC10634850

• The Z-disc: Mechanosensor at the interface between myosin biomechanics and hypertrophic signaling Giri, P., Roest, A., Lee, S., Heinrich, P., Dunn, A. R., Wu, S., Bernstein, D. CELL PRESS. 2023: 404A

  View details for Web of Science ID 000989629702211

• The Z-disc: Mechanosensor at the interface between myosin biomechanics and hypertrophic signaling. Biophysical journal Giri, P., Vander Roest, A. S., Lee, S., Heinrich, P., Dunn, A. R., Wu, S., Bernstein, D. 2023; 122 (3S1): 404a

  View details for DOI 10.1016/j.bpj.2022.11.2198

  View details for PubMedID 36784062