Bio


Premature birth is a leading cause of developmental and neuropsychiatric disorders in children. One of the factors causing these defects is lowered levels of available oxygen (hypoxia) in the newborn due to immature lungs. My research focuses on understanding the cellular and molecular mechanisms underlying hypoxia-induced developmental disorders of the nervous system due to preterm birth.

Program Affiliations


Professional Education


  • Doctor of Philosophy, Indian Institute of Science Educ&Research Pune (2021)
  • Master of Science, Indian Institute of Science Educ&Research Pune (2021)
  • Bachelor of Science, University Of Delhi (2014)
  • PhD, Indian Institute of Science Education and Research (IISER), Pune, India, Developmental Neuroscience (2021)

Stanford Advisors


Lab Affiliations


All Publications


  • Synthesis of Phosphorodiamidate Morpholino Oligonucleotides Using Trityl and Fmoc Chemistry in an Automated Oligo Synthesizer JOURNAL OF ORGANIC CHEMISTRY Kundu, J., Ghosh, A., Ghosh, U., Das, A., Pattanayak, S., Ghose, A., Sinha, S., Nagar, D. 2022; 87 (15): 9466-9478

    Abstract

    Phosphorodiamidate morpholino oligonucleotides (PMOs) constitute 3 out of the 11 FDA-approved oligonucleotide-based drugs in the last 6 years. PMOs can effectively silence disease-causing genes and modify splicing. However, PMO synthesis has remained challenging for a variety of reasons: inefficient deprotection and coupling methods and instability of monomers. Here, we report the development of a suitable combination of resin supports, deblocking and coupling reagents for synthesizing PMOs using either trityl or Fmoc-protected chlorophosphoramidate monomers. The synthesized PMOs using both the methods on a solid support have been validated for gene silencing in a zebrafish model. The protocol was successfully transferred into an automated DNA synthesizer to make several sequences of PMOs, demonstrating for the first time the adaptation of regular PMOs in a commercial DNA synthesizer. Moreover, PMOs with longer than 20-mer sequences, including FDA-approved Eteplirsen (30-mer), were achieved in >20% overall yield that is superior to previous reports. Hybridization study shows that PMOs exhibit a higher binding affinity toward complementary DNA relative to the DNA/DNA duplex (>6 °C). Additionally, the introduction of Fmoc chemistry into PMOs opens up the possibility for PMO synthesis in commercial peptide synthesizers for future development.

    View details for DOI 10.1021/acs.joc.2c00265

    View details for Web of Science ID 000830817900001

    View details for PubMedID 35839125

  • A Tale of Two Waves: Diverse Genomic and Transmission Landscapes Over 15 Months of the COVID-19 Pandemic in Pune, India Niveditha, D., et al MedRxiv. 2022
  • Antagonistic Activities of Fmn2 and ADF Regulate Axonal F-Actin Patch Dynamics and the Initiation of Collateral Branching Journal of neuroscience Kundu, T., Das, S. S., Sewatkar, . K., Kumar, D. S., Nagar, D., Ghose, A. 2022
  • Coupling of dynamic microtubules to F-actin by Fmn2 regulates chemotaxis of neuronal growth cones JOURNAL OF CELL SCIENCE Kundu, T., Dutta, P., Nagar, D., Maiti, S., Ghose, A. 2021; 134 (13)

    View details for DOI 10.1242/jcs.252916

    View details for Web of Science ID 000679478500006

  • The Formin Fmn2b Is Required for the Development of an Excitatory Interneuron Module in the Zebrafish Acoustic Startle Circuit ENEURO Nagar, D., James, T. K., Mishra, R., Guha, S., Burgess, S. M., Ghose, A. 2021; 8 (4)

    Abstract

    The formin family member Fmn2 is a neuronally enriched cytoskeletal remodeling protein conserved across vertebrates. Recent studies have implicated Fmn2 in neurodevelopmental disorders, including sensory processing dysfunction and intellectual disability in humans. Cellular characterization of Fmn2 in primary neuronal cultures has identified its function in the regulation of cell-substrate adhesion and consequently growth cone translocation. However, the role of Fmn2 in the development of neural circuits in vivo, and its impact on associated behaviors have not been tested. Using automated analysis of behavior and systematic investigation of the associated circuitry, we uncover the role of Fmn2b in zebrafish neural circuit development. As reported in other vertebrates, the zebrafish ortholog of Fmn2 is also enriched in the developing zebrafish nervous system. We find that Fmn2b is required for the development of an excitatory interneuron pathway, the spiral fiber neuron, which is an essential circuit component in the regulation of the Mauthner cell (M-cell)-mediated acoustic startle response. Consistent with the loss of the spiral fiber neurons tracts, high-speed video recording revealed a reduction in the short latency escape events while responsiveness to the stimuli was unaffected. Taken together, this study provides evidence for a circuit-specific requirement of Fmn2b in eliciting an essential behavior in zebrafish. Our findings underscore the importance of Fmn2 in neural development across vertebrate lineages and highlight zebrafish models in understanding neurodevelopmental disorders.

    View details for DOI 10.1523/ENEURO.0329-20.2021

    View details for Web of Science ID 000728393700003

    View details for PubMedID 34193512

    View details for PubMedCentralID PMC8272403

  • Development of motor neurons and motor activity in zebrafish requires F-actin nucleation by Fmn2b Nagar, D., et al BioRxiv. 2021
  • Clinical characteristics of AY. 4 infections are similar to B. 1.617. 2 infections: a preliminary study Indian Journal of Basic and Applied Medical Research Das, R., et al 2021