Honors & Awards

  • AHA Postdoctoral Fellowship, American Heart Association (2022-2024)
  • MCHRI Postdoctoral Fellowship, Stanford Maternal and Child Health Research Institute (2020-2022)
  • Dean's Postdoctoral Fellowship, Stanford University School of Medicine (2020)

Professional Education

  • Ph.D., National Centre for Biological Sciences, India, Biochemistry and Biophysics (2018)
  • M.Sc., University of Delhi, India, Biochemistry (2009)
  • B.Sc., University of Delhi, India, Biochemistry (2007)

Stanford Advisors

All Publications

  • Cryo-EM structure of the folded-back state of human β-cardiac myosin. Nature communications Grinzato, A., Auguin, D., Kikuti, C., Nandwani, N., Moussaoui, D., Pathak, D., Kandiah, E., Ruppel, K. M., Spudich, J. A., Houdusse, A., Robert-Paganin, J. 2023; 14 (1): 3166


    To save energy and precisely regulate cardiac contractility, cardiac muscle myosin heads are sequestered in an 'off' state that can be converted to an 'on' state when exertion is increased. The 'off' state is equated with a folded-back structure known as the interacting-heads motif (IHM), which is a regulatory feature of all class-2 muscle and non-muscle myosins. We report here the human β-cardiac myosin IHM structure determined by cryo-electron microscopy to 3.6 Å resolution, providing details of all the interfaces stabilizing the 'off' state. The structure shows that these interfaces are hot spots of hypertrophic cardiomyopathy mutations that are thought to cause hypercontractility by destabilizing the 'off' state. Importantly, the cardiac and smooth muscle myosin IHM structures dramatically differ, providing structural evidence for the divergent physiological regulation of these muscle types. The cardiac IHM structure will facilitate development of clinically useful new molecules that modulate IHM stability.

    View details for DOI 10.1038/s41467-023-38698-w

    View details for PubMedID 37258552

    View details for PubMedCentralID 3156359

  • Nanomechanical Phenotypes in Cardiac Myosin-Binding Protein C Mutants That Cause Hypertrophic Cardiomyopathy. ACS nano Suay-Corredera, C., Pricolo, M. R., Velazquez-Carreras, D., Pathak, D., Nandwani, N., Pimenta-Lopes, C., Sanchez-Ortiz, D., Urrutia-Irazabal, I., Vilches, S., Dominguez, F., Frisso, G., Monserrat, L., Garcia-Pavia, P., de Sancho, D., Spudich, J. A., Ruppel, K. M., Herrero-Galan, E., Alegre-Cebollada, J. 2021


    Hypertrophic cardiomyopathy (HCM) is a disease of the myocardium caused by mutations in sarcomeric proteins with mechanical roles, such as the molecular motor myosin. Around half of the HCM-causing genetic variants target contraction modulator cardiac myosin-binding protein C (cMyBP-C), although the underlying pathogenic mechanisms remain unclear since many of these mutations cause no alterations in protein structure and stability. As an alternative pathomechanism, here we have examined whether pathogenic mutations perturb the nanomechanics of cMyBP-C, which would compromise its modulatory mechanical tethers across sliding actomyosin filaments. Using single-molecule atomic force spectroscopy, we have quantified mechanical folding and unfolding transitions in cMyBP-C domains targeted by HCM mutations that do not induce RNA splicing alterations or protein thermodynamic destabilization. Our results show that domains containing mutation R495W are mechanically weaker than wild-type at forces below 40 pN and that R502Q mutant domains fold faster than wild-type. None of these alterations are found in control, nonpathogenic variants, suggesting that nanomechanical phenotypes induced by pathogenic cMyBP-C mutations contribute to HCM development. We propose that mutation-induced nanomechanical alterations may be common in mechanical proteins involved in human pathologies.

    View details for DOI 10.1021/acsnano.1c02242

    View details for PubMedID 34060810

  • Study of Hcm Causing beta-Cardiac Myosin Mutations Located at Different Structurally Significant Regions of the Myosin-Head Bhowmik, D., Nandwani, N., Ruppel, K., Liu, C., Spudich, J. A. CELL PRESS. 2020: 435A
  • Uncovering the Molecular and Structural Basis of Hypertrophic Cardiomyopathy-Causing Mutations in Myosin and Myosin Binding Protein-C Nandwani, N., Trivedi, D. V., Sarkar, S. S., Morck, M., Ruppel, K., Spudich, J. A. CELL PRESS. 2020: 435A
  • A five-residue motif for the design of domain swapping in proteins NATURE COMMUNICATIONS Nandwani, N., Surana, P., Negi, H., Mascarenhas, N. M., Udgaonkar, J. B., Das, R., Gosavi, S. 2019; 10: 452


    Domain swapping is the process by which identical monomeric proteins exchange structural elements to generate dimers/oligomers. Although engineered domain swapping is a compelling strategy for protein assembly, its application has been limited due to the lack of simple and reliable design approaches. Here, we demonstrate that the hydrophobic five-residue 'cystatin motif' (QVVAG) from the domain-swapping protein Stefin B, when engineered into a solvent-exposed, tight surface loop between two β-strands prevents the loop from folding back upon itself, and drives domain swapping in non-domain-swapping proteins. High-resolution structural studies demonstrate that engineering the QVVAG stretch independently into various surface loops of four structurally distinct non-domain-swapping proteins enabled the design of different modes of domain swapping in these proteins, including single, double and open-ended domain swapping. These results suggest that the introduction of the QVVAG motif can be used as a mutational approach for engineering domain swapping in diverse β-hairpin proteins.

    View details for DOI 10.1038/s41467-019-08295-x

    View details for Web of Science ID 000456828100001

    View details for PubMedID 30692525

    View details for PubMedCentralID PMC6349918

  • Amino-acid composition after loop deletion drives domain swapping PROTEIN SCIENCE Nandwani, N., Surana, P., Udgaonkar, J. B., Das, R., Gosavi, S. 2017; 26 (10): 1994–2002


    Rational engineering of a protein to enable domain swapping requires an understanding of the sequence, structural and energetic factors that favor the domain-swapped oligomer over the monomer. While it is known that the deletion of loops between β-strands can promote domain swapping, the spliced sequence at the position of the loop deletion is thought to have a minimal role to play in such domain swapping. Here, two loop-deletion mutants of the non-domain-swapping protein monellin, frame-shifted by a single residue, were designed. Although the spliced sequence in the two mutants differed by only one residue at the site of the deletion, only one of them (YEIKG) promoted domain swapping. The mutant containing the spliced sequence YENKG was entirely monomeric. This new understanding that the domain swapping propensity after loop deletion may depend critically on the chemical composition of the shortened loop will facilitate the rational design of domain swapping.

    View details for DOI 10.1002/pro.3237

    View details for Web of Science ID 000411179200009

    View details for PubMedID 28710790

    View details for PubMedCentralID PMC5606538

  • Rapidly fatal myeloproliferative disorders in mice with deletion of Casitas B-cell lymphoma (Cbl) and Cbl-b in hematopoietic stem cells PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Naramura, M., Nandwani, N., Gu, H., Band, V., Band, H. 2010; 107 (37): 16274–79


    Casitas B-cell lymphoma (Cbl)-family E3 ubiquitin ligases are negative regulators of tyrosine kinase signaling. Recent work has revealed a critical role of Cbl in the maintenance of hematopoietic stem cell (HSC) homeostasis, and mutations in CBL have been identified in myeloid malignancies. Here we show that, in contrast to Cbl or Cbl-b single-deficient mice, concurrent loss of Cbl and Cbl-b in the HSC compartment leads to an early-onset lethal myeloproliferative disease in mice. Cbl, Cbl-b double-deficient bone marrow cells are hypersensitive to cytokines, and show altered biochemical response to thrombopoietin. Thus, Cbl and Cbl-b play redundant but essential roles in HSC regulation, whose breakdown leads to hematological abnormalities that phenocopy crucial aspects of mutant Cbl-driven human myeloid malignancies.

    View details for DOI 10.1073/pnas.1007575107

    View details for Web of Science ID 000281799000055

    View details for PubMedID 20805496

    View details for PubMedCentralID PMC2941297

  • Reciprocal Regulation of AKT and MAP Kinase Dictates Virus-Host Cell Fusion JOURNAL OF VIROLOGY Sharma, N. R., Mani, P., Nandwani, N., Mishra, R., Rana, A., Sarkar, D. P. 2010; 84 (9): 4366-4382


    Viruses of the Paramyxoviridae family bind to their host cells by using hemagglutinin-neuraminidase (HN), which enhances fusion protein (F)-mediated membrane fusion. Although respiratory syncytial virus and parainfluenza virus 5 of this family are suggested to trigger host cell signaling during infection, the virus-induced intracellular signals dictating virus-cell fusion await elucidation. Using an F- or HN-F-containing reconstituted envelope of Sendai virus, another paramyxovirus, we revealed the role and regulation of AKT1 and Raf/MEK/ERK cascades during viral fusion with liver cells. Our observation that extracellular signal-regulated kinase (ERK) activation promotes viral fusion via ezrin-mediated cytoskeletal rearrangements, whereas AKT1 attenuates fusion by promoting phosphorylation of F protein, indicates a counteractive regulation of viral fusion by reciprocal activation of AKT1 and mitogen-activated protein kinase (MAPK) cascades, establishing a novel conceptual framework for a therapeutic strategy.

    View details for DOI 10.1128/JVI.01940-09

    View details for Web of Science ID 000276358000024

    View details for PubMedID 20164223

    View details for PubMedCentralID PMC2863742