Biology subjects

Munoz-Perez, J. P.

Publications and source records attributed to Munoz-Perez, J. P..

3 recordsLinked to original sources

bioRxiv2024

Spatio-temporal T cell tracking for personalized TCR-T designs in childhood cancer

Immune checkpoint inhibition (ICI) has revolutionized oncology, offering extended survival and long-term remission in previously incurable cancers. While highly effective in tumors with high mutational burden, lowly mutated cancers, including pediatric malignancies, present low response rate and limited predictive biomarkers. Here, we present a framework for the identification and validation of tumor-reactive T cells as a biomarker to quantify ICI efficacy and as candidates for a personalized TCR-T cell therapy. Therefore, we profiled a pediatric malignant rhabdoid tumor patient with complete remission after ICI therapy using deep single-cell T cell receptor (TCR) repertoire sequencing of the tumor microenvironment (TME) and the peripheral blood. Specifically, we tracked T cell dynamics longitudinally from the tumor to cells in circulating over a time course of 12 months, revealing a systemic response and durable clonal expansion of tumor-resident and ICI-induced TCR clonotypes. We functionally validated tumor reactivity of TCRs identified from the TME and the blood by co-culturing patient-derived tumor cells with TCR-engineered autologous T cells. Here, we observed unexpectedly high frequencies of tumor-reactive TCR clonotypes in the TME and confirmed T cell dynamics in the blood post-ICI to predict tumor-reactivity. These findings strongly support spatio-temporal tracking of T cell activity in response to ICI to inform therapy efficacy and to serve as a source of tumor-reactive TCRs for personalized TCR-T designs.

genomics↗

bioRxiv2021

Sea Turtle Facial Recognition Using Map Graphs of Scales

O_LIIndividual identification of sea turtles is important to study their biology and aide in conservation efforts. Traditional methods for identifying sea turtles that rely on physical or GPS tags can be expensive, and difficult to implement. Alternatively, the scale structure on the side of a turtles head has been shown to be specific to the individual and stable over its lifetime, and therefore can be used as the individuals "fingerprint". C_LIO_LIHere we propose a novel facial recognition method where an image of a sea turtle is converted into a graph (network) with nodes representing scales, and edges connecting two scales that share a border. The topology of the graph is used to differentiate species. C_LIO_LIWe additionally develop a robust metric to compare turtles based on a correspondence between nodes generated by a coherent point drift algorithm and computing a graph edit distance to identify individual turtles with over 94% accuracy. C_LIO_LIBy representing the special and topological features of sea turtle scales as a graph, we perform more accurate individual identification which is robust under different imaging conditions and may be adapted for a wider number of species. C_LI

ecology↗

bioRxiv2020

The Mystery of a Marine Monster: Morphological and Performance Modifications in the World's only Marine Lizard, the Galapagos Marine Iguana

Reptiles have repeatedly invaded and thrived in aquatic environments throughout history, however fewer than 8% of the 6000 extant species are primarily aquatic. The Galapagos Marine Iguana (Amblyrhynchus cristatus), the worlds only marine lizard, may have had one of the most unique and challenging transitions to aquatic life. Curiously, previous studies have identified relatively few physiological adaptations in Marine Iguanas, however, little is known about the extent of morphological specialisation and performance trade-offs associated with the marine environment. By examining the morphology and locomotory performance of the Marine Iguana in comparison to their closely related mainland ancestors, the Black Spiny-tailed iguana (Ctenosaura similis) and Green Iguana (Iguana iguana), we found variation reflected specialisation to ecological niches. However, variation was more pronounced among subspecies of Marine Iguana, suggesting that little morphological or performance modification is required for iguanids to successfully invade aquatic environments, thus raising the question why there are so few extant aquatic reptilian lineages. We found that specialisation for the marine environment resulted in a trade-off in sprint speed in a terrestrial environment, similar to that seen in extant crocodilians. Reduced performance in a terrestrial environment likely poses little risk to large-bodied apex predators, whereas in iguanids, a performance trade-off would likely incur increased predation. As such, we suggest that this may explain why iguanids and other ancestral lineages have not undergone transitions to aquatic life. Additionally, we found that the magnitude of morphological and performance variation was more pronounced between subspecies of Marine Iguana than between iguanid species. Summary StatementThe Marine Iguana has undergone a unique evolutionary transition to aquatic behaviour, we explore the extent of morphological and performance specialisation required and why there are so few extant marine reptiles. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

evolutionary biology↗