Biology subjects

Quiroga-Barber, I.

Publications and source records attributed to Quiroga-Barber, I..

2 recordsLinked to original sources

bioRxiv2026

Aberrant chromatin looping by NUP98-HOXA9 is constrained by CTCF and facilitated by cohesin

The acute myeloid leukemia (AML) fusion protein NUP98-HOXA9 (NHA9) drives leukemogenesis by promoting aberrant chromatin loop formation through phase separation, yet the mechanisms underlying these interactions remain unclear. To address this, we dissect the interplay between NHA9 and individual loop extrusion factors using in situ Hi-C, CUT&RUN, RNA-seq, and Auxin-inducible degradation of CTCF or RAD21. CTCF was found to be dispensable for NHA9 loop formation, although CTCF binding constrained a subset of loops that emerged only upon CTCF depletion. In contrast, cohesin played a distance-dependent role where short-range NHA9 loops formed independently of RAD21, while long-range loops were strongly cohesin-dependent. Despite this requirement, RAD21 showed minimal enrichment at NHA9 loop anchors, indicating that NHA9 does not function as a canonical cohesin barrier. Instead, these findings support a non-canonical model in which cohesin transiently facilitates interactions between distal NHA9-bound loci, which are subsequently stabilized through NHA9 phase separation. Together, this work reveals a distinct mechanism of oncogenic chromatin looping in which NUP98-HOXA9 cooperates with canonical loop extrusion machinery to reprogram genome architecture in AML.

Molecular Biology↗

bioRxiv2024

TDP-43 pathology links innate and adaptive immunity in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is the most common fatal motor neuron disease. Approximately 90% of ALS patients exhibit pathology of the master RNA regulator, Transactive Response DNA Binding protein (TDP-43). Despite the prevalence TDP-43 pathology in ALS motor neurons, recent findings suggest immune dysfunction is a determinant of disease progression in patients. Whether TDP-43 pathology elicits disease-modifying immune responses in ALS remains underexplored. In this study, we demonstrate that TDP-43 pathology is internalized by antigen presenting cells, causes vesicle rupture, and leads to innate and adaptive immune cell activation. Using a multiplex imaging platform, we observed interactions between innate and adaptive immune cells near TDP-43 pathological lesions in ALS brain. We used a mass cytometry-based whole-blood stimulation assay to provide evidence that ALS patient peripheral immune cells exhibit responses to TDP-43 aggregates. Taken together, this study provides a novel link between TDP-43 pathology and ALS immune dysfunction, and further highlights the translational and diagnostic implications of monitoring and manipulating the ALS immune response.

cell biology↗