Anushweta Asthana

All Publications

• Strategies for multimodal spatiotemporal profiling of phosphorylation in cilia biology. Journal of cell science Turn, R. E., Aziz-Zanjani, M. O., Asthana, A., Jackson, P. K. 2025; 138 (20)

  Abstract

  This Opinion piece highlights recent advances in technical approaches to dissect the mechanisms coupling cell cycle and ciliogenesis during G0/quiescence and the importance of transient post-translational modifications (PTMs) as dynamic regulators of these processes. We discuss the latest technologies enabling real-time monitoring of context-dependent phosphoproteomics and emerging concepts in PTM-driven control of ciliary function. Additionally, we outline major unanswered questions and propose future research directions. A better understanding of G0 regulatory pathways might both spur the development of clinical interventions for human cilia-linked pathologies and set the stage for future research linking cell quiescence to cancer and tissue regeneration.

  View details for DOI 10.1242/jcs.264159

  View details for PubMedID 41171145

• Metabolic STAMP for deciphering GPCR-regulated insulin secretion by pancreatic β cells. bioRxiv : the preprint server for biology Aziz-Zanjani, M. O., Turn, R. E., Hang, Y., Asthana, A., LaBrie, L. E., Mobedi, M., Xu, L. A., Krawitzky, M., Kim, S. K., Jackson, P. K. 2025

  Abstract

  Pancreatic β cells integrate glucose and metabolic cues to regulate insulin secretion, a process disrupted in T2D. GPCRs play a critical role in fine-tuning insulin release, yet the mechanisms by which ciliary (e.g., FFAR4) and non-ciliary (e.g., GLP1-R) GPCRs coordinate GSIS remains unclear. In this study, we employed Metabolic-STAMP (Synchronized Temporal-Spatial Analysis via Microscopy and Phosphoproteomics) in both mouse β cells (MIN6) and primary human islets to map the dynamic signaling networks governing GSIS and to link transient phosphorylation events to their functional outcomes. We systematically interrogated GPCR-mediated phosphorylation events through selective pharmacological inhibitors, resolving signaling hierarchies and consensus patterns across multiple pathways. Our multi-modal approach uncovered key insulin-secretion-associated PTMs, linked phosphorylation targets with phenotypic organelle dynamics, and provided mechanistic insights into how GLP1-R versus FFAR4 modulates GSIS through shared and GPCR-specific phospho-signatures. We highlighted key examples of stimulus-specific regulation by high glucose alone versus GPCR stimulation, including context-specific activation of the classic ERK signaling pathway, compartmentalized PKA signaling, pathway specificity in organelle dynamics and inter-organellar contacts, and HDAC6/ATAT-mediated regulation of microtubule acetylation. Collectively, these findings provided a blueprint for deconvolving pathway specificity of β cell GPCR signaling, illuminated regulatory nodes that program insulin release, and offered new therapeutic targets to enhance β-cell function.

  View details for DOI 10.1101/2025.10.03.680349

  View details for PubMedID 41256453

  View details for PubMedCentralID PMC12621840

• A genome-wide, CRISPR-based screen reveals new requirements for translation initiation and ubiquitination in driving adipogenic fate change. Genes & development Turn, R. E., Hilgendorf, K. I., Johnson, C. T., Han, K., Aziz-Zanjani, M. O., Swails Bollinger, S., Domizi, P., Cheng, R., Rabiee, A., Zhu, Y., Jiang, Z., Asthana, A., Demeter, J., Svensson, K. J., Bassik, M. C., Jackson, P. K. 2025

  Abstract

  In response to excess nutrients, white adipose tissue expands by both generating new adipocytes and upregulating lipogenesis in existing adipocytes. Here, we performed a genome-wide functional CRISPR screen to identify regulators of adipogenesis in the mouse 3T3-L1 preadipocyte model. In this pooled screening strategy, we used FACS to isolate populations based on lipid content, gating for fluorescence intensity of lipophilic fluorescent BODIPY dye. Additionally, we categorized whether the gene functions primarily during mitotic clonal expansion, lipogenesis, or both. We found that translation initiation and ubiquitin-dependent protein stability regulators drive both adipogenic fate change and lipogenesis. We further supported these findings with proteomics, demonstrating that essential changes in protein reprogramming can drive or inhibit 3T3-L1 adipogenesis independent of transcription. Furthermore, we demonstrated that specific branches of the hypusination pathway, a conserved regulator of translation initiation, are critical for translating adipogenic inducers of mitotic clonal expansion and that the neddylation/ubiquitin pathway modulates insulin sensitivity during lipogenesis.

  View details for DOI 10.1101/gad.352779.125

  View details for PubMedID 40675820

• The complex role of brain cilia in feeding control. Science (New York, N.Y.) Asthana, A., Jackson, P. K. 2025; 388 (6751): 1026-1027

  Abstract

  Variants in a ciliary receptor are associated with obesity.

  View details for DOI 10.1126/science.ady6368

  View details for PubMedID 40472110

• Synchronized temporal-spatial analysis via microscopy and phosphoproteomics (STAMP) of quiescence. Science advances Azizzanjani, M. O., Turn, R. E., Asthana, A., Linde-Garelli, K. Y., Xu, L. A., Labrie, L. E., Mobedi, M., Jackson, P. K. 2025; 11 (17): eadt9712

  Abstract

  Coordinated cell cycle regulation is essential for homeostasis, with most cells in the body residing in quiescence (G0). Many pathologies arise due to disruptions in tissue-specific G0, yet little is known about the temporal-spatial mechanisms that establish G0 and its signaling hub, primary cilia. Mechanistic insight is limited by asynchronous model systems and failure to connect context-specific, transient mechanisms to function. To address this gap, we developed STAMP (synchronized temporal-spatial analysis via microscopy and phosphoproteomics) to track changes in cellular landscape occurring throughout G0 transition and ciliogenesis. We synchronized ciliogenesis and G0 transition in two cell models and combined microscopy with phosphoproteomics to order signals for further targeted analyses. We propose that STAMP is broadly applicable for studying temporal-spatial signaling in many biological contexts. The findings revealed through STAMP provide critical insight into healthy cellular functions often disrupted in pathologies, paving the way for targeted therapeutics.

  View details for DOI 10.1126/sciadv.adt9712

  View details for PubMedID 40279433

• Metabolic STAMP for deciphering GPCR-regulated insulin secretion by pancreatic β cells bioRxiv Aziz-Zanjani, M., Turn, R. E., Hang, Y., Asthana, A., LaBrie, L., Mobedi, M., Xu, L. A., Kim, S. K., Jackson, P. K. 2025

  View details for DOI 10.1101/2025.10.03.680349

• Ciliary localization of GPR75 promotes fat accumulation in mice JOURNAL OF CLINICAL INVESTIGATION Chavez, M., Asthana, A., Jackson, P. K. 2024; 134 (19)

  Abstract

  Obesity is a growing public health concern that affects the longevity and lifestyle of all human populations including children and older individuals. Diverse factors drive obesity, making it challenging to understand and treat. While recent studies highlight the importance of GPCR signaling for metabolism and fat accumulation, we lack a molecular description of how obesogenic signals accumulate and propagate in cells, tissues, and organs. In this issue of the JCI, Jiang et al. utilized germline mutagenesis to generate a missense variant of GRP75, encoded by the Thinner allele, which resulted in mice with a lean phenotype. GPR75 accumulated in the cilia of hypothalamic neurons. However, mice with the Thinner allele showed defective ciliary localization with resistance to fat accumulation. Additionally, GPR75 regulation of fat accumulation appeared independent of leptin and ADCY3 signaling. These findings shed light on the role of GPR75 in fat accumulation and highlight the need to identify relevant ligands.

  View details for DOI 10.1172/JCI185059

  View details for Web of Science ID 001333356000013

  View details for PubMedID 39352389

  View details for PubMedCentralID PMC11444157