Mohammad Ovais Azizzanjani

All Publications

• 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 human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture. Nature communications Vazquez, N., Lee, C., Valenzuela, I., Phan, T. P., Derderian, C., Chavez, M., Mooney, N. A., Demeter, J., Aziz-Zanjani, M. O., Cusco, I., Codina, M., Martinez-Gil, N., Valverde, D., Solarat, C., Buel, A., Thauvin-Robinet, C., Steichen, E., Filges, I., Joset, P., De Geyter, J., Vaidyanathan, K., Gardner, T. P., Toriyama, M., Marcotte, E. M., Drew, K., Roberson, E. C., Jackson, P. K., Reiter, J. F., Tizzano, E. F., Wallingford, J. B. 2025; 16 (1): 5701

  Abstract

  Cilia are essential organelles, and variants in genes governing ciliary function result in ciliopathic diseases. The Ciliogenesis and PLANar polarity Effectors (CPLANE) protein complex is essential for ciliogenesis, and all but one subunit of the CPLANE complex have been implicated in human ciliopathy. Here, we identify three families in which variants in the remaining CPLANE subunit CPLANE2/RSG1 also cause ciliopathy. These patients display cleft palate, tongue lobulations and polydactyly, phenotypes characteristic of Oral-Facial-Digital Syndrome. We further show that these alleles disrupt two vital steps of ciliogenesis, basal body docking and recruitment of intraflagellar transport proteins. Moreover, APMS reveals that Rsg1 binds CPLANE and the transition zone protein Fam92 in a GTP-dependent manner. Finally, we show that CPLANE is generally required for normal transition zone architecture. Our work demonstrates that CPLANE2/RSG1 is a causative gene for human ciliopathy and also sheds new light on the mechanisms of ciliary transition zone assembly.

  View details for DOI 10.1038/s41467-025-61005-8

  View details for PubMedID 40593758

• 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