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Aileen Ugurbil

Publications and source records attributed to Aileen Ugurbil.

3 recordsLinked to original sources
PubMed2026

Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features.

Cancer arises from genetic and epigenetic alterations that reshape chromatin, transcriptional regulation, and malignant cell states. To chart cancer-intrinsic regulatory programs, we build a pan-cancer single-cell atlas of 60 cancer cell lines spanning 16 tissue origins and 20 cancer types, comprising 240,957 snRNA-seq and 223,347 snATAC-seq profiles. Integrative analyses reveal cell-state heterogeneity, core gene-regulatory networks, and a conserved EMT axis transcending tissue of origin; copy-number analysis identifies transcription factor amplification and hyperactivation as drivers of state reprogramming. Comparing cutaneous melanoma with acral melanoma, a rare subtype underrepresented in previous studies, uncovers a universal inflammation-suppressive program in acral and an inflamed landscape in cutaneous melanoma, with JAK-STAT activity as the central discriminator. Integrating data across models and patient cohorts links tumor-intrinsic regulation to microenvironmental composition and therapeutic response. By profiling rare alongside common subtypes, this atlas offers a resource for mapping pan-cancer and subtype-specific regulatory programs shaping cell-state plasticity.

Humans↗
PubMed2026

Ossification variants of the distal femoral condyle: longitudinal 3 T MRI evidence of progression to juvenile osteochondritis dissecans in asymptomatic siblings of patients with JOCD.

OBJECTIVE: Ossification variants (OVs) of the femoral condyles are traditionally regarded as benign developmental findings distinct from juvenile osteochondritis dissecans (JOCD). We aimed to characterize the longitudinal MRI behavior of OVs and JOCD lesions in asymptomatic siblings of JOCD patients. MATERIALS AND METHODS: In this HIPAA-compliant longitudinal pilot study, seven asymptomatic siblings of JOCD patients underwent serial 3&#xa0;T bilateral knee MRI. Two fellowship-trained musculoskeletal radiologists independently assessed 56 studies for bone marrow edema, lesion location, and MRI-defined category (OV or JOCD). RESULTS: OV and MRI-defined JOCD lesions were identified in 21 of 28 condyles (75%, 95% CI: 56.6-87.3%), while 7 condyles (25%, 95% CI: 12.7-43.4%) remained normal throughout follow-up. Six condyles demonstrated MRI-defined JOCD lesions at one or more timepoints. Three OV lesions evolved over time: two progressed to MRI-defined JOCD but remained clinically silent, and one progressed from OV to MRI-defined JOCD and subsequently to clinically manifest JOCD requiring surgery. Using Generalized Linear Mixed model, a statistically significant association was found between bone marrow edema and MRI-defined category (F&#x2009;=&#x2009;31.73, p&#x2009;<&#x2009;0.001). OV lesions showed absent or trace edema, whereas JOCD showed definite edema. Inter-reader agreement using Cohen's Kappa was moderate to substantial between the radiologists (&#x3ba;&#x2009;=&#x2009;0.479-0.739, 95% CI: 0.314-0.633, 0.644-0.845, p&#x2009;<&#x2009;0.001). CONCLUSIONS: In siblings of patients with JOCD, OV lesions are common and may represent dynamic MRI phenotypes along a continuum of epiphyseal ossification abnormalities, with occasional progression to MRI-defined JOCD and rare progression to clinically manifest JOCD.

Humans↗
PubMed2026

Mapping convergent regulators of melanoma drug resistance by PerturbFate.

High-throughput genomic studies have uncovered associations between diverse genetic alterations and disease phenotypes. However, elucidating how perturbations in functionally disparate genes give rise to convergent cellular states remains challenging. Here we present PerturbFate, a high-throughput, cost-effective, combinatorial-indexing single-cell platform that enables systematic interrogation of massively parallel CRISPR interference1 perturbations across the full spectrum of gene regulation, from chromatin remodelling and nascent transcription to steady-state transcriptomic phenotypes. Using PerturbFate, we profiled more than 300,000 cultured melanoma cells to characterize multimodal phenotypic and gene regulatory responses to perturbations in more than 140 vemurafenib resistance-associated genes. We uncovered a shared dedifferentiated cell state marked by convergent cooperative transcription factor activities across diverse genetic perturbations. We further dissected phenotypic responses to perturbations in Mediator complex components, linking module-specific biochemical properties to convergent transcriptional activations. We identified common regulatory nodes that drive similar phenotypic outcomes across distinct genetic perturbations. We also delineated how perturbations in functionally unrelated genes reshape cell state. Thus, PerturbFate establishes a versatile platform for identifying key molecular regulators by anchoring multimodal regulatory dynamics to disease-relevant phenotypes.

Humans↗