Biology subjects

Panchal, H.

Publications and source records attributed to Panchal, H..

3 recordsLinked to original sources

bioRxiv2026

Hypoxic stress granules trigger immunogenic dormancy in lung cancer

Induction of the MHC class I antigen processing and presentation pathway (C1APP) is a critical part of the IFN-{gamma} response necessary for effective cytotoxic immunity against tumors of epithelial origin1,2. Loss of this response is associated with worse disease outcomes and renders patients refractory to immunotherapies3-6. Without C1APP induction, tumor cells cannot optimally process and present immunopeptides from tumor-associated antigens (TAA) and neoantigens to effector cytotoxic T cells7-9. Here, we show that physiologic levels of hypoxia block induction of the immunoproteasome (IP) and other C1APP components in cancer cells, including human non-small cell lung cancer (NSCLC). In A549 cells, this leads to impaired presentation of more than 73% of detectable immunopeptides, including TAA and neoantigen-derived immunopeptides. This effect is independent of HIF-1 or HIF-2 signaling, protein degradation, autophagy, or stimulus type. Instead, hypoxia induces translational arrest of C1APP mRNAs prior to complete monosome loading, along with sequestration into hypoxia-associated stress granules. This phenomenon is reversible with the epitranscriptomic compound 5-azacytidine. Consistent with these findings, IP expression is excluded from hypoxic regions in most human NSCLC tumors. Together, these results link tumor hypoxia to a state of "immunogenic dormancy" and identify stress granules as a previously unrecognized mechanism of immune escape.

cancer biology↗

bioRxiv2024

A novel Candida glabrata protein regulated by mating signaling pathway shapes inter-species interaction

During mixed-species invasive candidiasis - an emerging threat in healthcare - presence of Candida albicans is near-essential for host colonisation by C. glabrata. However, the molecular communication underlying such intriguing inter-species interaction is largely unexplored. Here, we show that C. glabrata secretes a unique small protein Yhi1 that induces hyphal growth in C. albicans, which is essential for host tissue invasion. Notably, this Yhi1-based inter-species interaction is specific to C. glabrata and C. albicans, when compared with other common species of Candida. Our structure-function analyses reveal a novel functional pentapeptide motif (AXVXH) required for the function of Yhi1. Interestingly, Yhi1 expression and efflux are regulated through the mating MAPK signalling pathway and the pheromone transporter CgSte6, respectively, in C. glabrata, despite its preferred asexual reproduction. Our findings shed light on how C. glabrata mating signalling pathway is repurposed to interact with C. albicans, and highlight the potential of Yhi1 as a biomarker and a template for a synthetic novel antifungal peptide.

microbiology↗

bioRxiv2024

Motor neurons are dispensable for the assembly of a sensorimotor circuit for gaze stabilization

Sensorimotor reflex circuits engage distinct neuronal subtypes, defined by precise connectivity, to transform sensation into compensatory behavior. Whether and how motor neuron populations specify the subtype fate and/or sensory connectivity of their pre-motor partners remains controversial. Here, we discovered that motor neurons are dispensable for proper connectivity in the vestibular reflex circuit that stabilizes gaze. We first measured activity following vestibular sensation in premotor projection neurons after constitutive loss of their extraocular motor neuron partners. We observed normal responses and topography indicative of unchanged functional connectivity between sensory neurons and projection neurons. Next, we show that projection neurons remain anatomically and molecularly poised to connect appropriately with their down-stream partners. Lastly, we show that the transcriptional signatures that typify projection neurons develop independently of motor partners. Our findings comprehensively overturn a long-standing model: that connectivity in the circuit for gaze stabilization is retrogradely determined by motor partner-derived signals. By defining the contribution of motor neurons to specification of an archetypal sensorimotor circuit, our work speaks to comparable processes in the spinal cord and advances our understanding of principles of neural development.

neuroscience↗