Browsing by Author "Nambiar, Annika"

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    Expansion of a neural crest gene signature following ectopic MYCN expression in sympathoadrenal lineage cells in vivo
    (Public Library of Science, 2024) Ibarra-García-Padilla, Rodrigo; Nambiar, Annika; Hamre, Thomas A.; Singleton, Eileen W.; Uribe, Rosa A.
    Neural crest cells (NCC) are multipotent migratory stem cells that originate from the neural tube during early vertebrate embryogenesis. NCCs give rise to a variety of cell types within the developing organism, including neurons and glia of the sympathetic nervous system. It has been suggested that failure in correct NCC differentiation leads to several diseases, including neuroblastoma (NB). During normal NCC development, MYCN is transiently expressed to promote NCC migration, and its downregulation precedes neuronal differentiation. Overexpression of MYCN has been linked to high-risk and aggressive NB progression. For this reason, understanding the effect overexpression of this oncogene has on the development of NCC-derived sympathoadrenal progenitors (SAP), which later give rise to sympathetic nerves, will help elucidate the developmental mechanisms that may prime the onset of NB. Here, we found that overexpressing human EGFP-MYCN within SAP lineage cells in zebrafish led to the transient formation of an abnormal SAP population, which displayed expanded and elevated expression of NCC markers while paradoxically also co-expressing SAP and neuronal differentiation markers. The aberrant NCC signature was corroborated with in vivo time-lapse confocal imaging in zebrafish larvae, which revealed transient expansion of sox10 reporter expression in MYCN overexpressing SAPs during the early stages of SAP development. In these aberrant MYCN overexpressing SAP cells, we also found evidence of dampened BMP signaling activity, indicating that BMP signaling disruption occurs following elevated MYCN expression. Furthermore, we discovered that pharmacological inhibition of BMP signaling was sufficient to create an aberrant NCC gene signature in SAP cells, phenocopying MYCN overexpression. Together, our results suggest that MYCN overexpression in SAPs disrupts their differentiation by eliciting abnormal NCC gene expression programs, and dampening BMP signaling response, having developmental implications for the priming of NB in vivo.
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    The Value of Interviews in Representing the Long-Term Effects of Radiation in Kazakhstan
    (2024-03) Nambiar, Annika
    Semipalatinsk, Kazakhstan was once the Soviet Union’s carefully concealed testing site for nuclear weapons, unbeknown even to nearby residents. In 1989, information about radioactive contamination became public knowledge, causing outcry. As a result, Semipalatinsk and its surrounding areas have high rates of structural and systemic health issues from nuclear testing, which were exacerbated by the dissolution of the Soviet Union. The long-term effects of this testing continue to burden the Kazakhstan healthcare system and its people today. In 1995, the American International Health Alliance (AIHA) formed the Houston-Semipalatinsk Partnership (HSP) to support better outcomes through systemic changes in affected regions following their independence from the former USSR. This paper, “The Value of Interviews in Representing the Long-Term Effects of Radiation in Kazakhstan,” discusses the subset of a collection of interviews about radiation effects and events involving hospital and healthcare administrators from the Texas Medical Center (TMC) Library and Kazakhstan who participated in the HSP. These interviews demonstrate how first-person sources highlight the voice and experience of the individual, conserve nonverbal information, and serve as a dynamic and engaging method to share history with the public. This work draws from interviews that the author and other Rice undergraduates conducted. These interviews are available online through Rice University’s Woodson Research Center and the TMC Library for the public to learn about these efforts in depth.