Biology subjects

Palmiotti, A.

Publications and source records attributed to Palmiotti, A..

4 recordsLinked to original sources

bioRxiv2026

An in vivo platform to jointly monitor cellular and metabolic responses to chemotherapy.

How drug treatments reshape immune and metabolic states within intact tumors remains difficult to study with existing methods. We introduce a spatial pharmacology platform that enables parallel analysis of multiple agents within a single tumor, linking local drug exposure to immune and metabolic remodeling. Using a microdevice for localized drug delivery, we created a large-scale paired CyCIF-MALDI dataset spanning 1.5 million cells across 27 MMTV-PyMT tumor sections and nine treatment programs, enabling integrated spatial pharmacology at unprecedented scale. Metabolic signatures robustly predict proteomic spatial neighborhoods establishing metabolism as a powerful predictor of tumor organization and immune phenotype. Within this framework, we identify a dominant metabolic axis defined by the myeloid polarization between CSF1R+ tumor-associated macrophages and MPO+ infiltrating myeloid cells localized near regions of drug-induced tumor cell death. Finally, we detect putative lipid-associated macrophage (LAM)-like populations within drug-resistant treatment regions.

bioengineering↗

bioRxiv2025

Retinoic acid production via the ray-finned fish gene beta-carotene oxygenase 1-like is essential for juvenile development

In vertebrates, vitamin A (VA) is crucial for development, tissue homeostasis, vision, and immunity. Retinal, a form of VA, is produced via enzymatic cleavage of {beta}-carotene by beta-carotene oxygenase 1 (bco1) and bco1-like (bco1l). While bco1 is found across vertebrate taxa, bco1l is a paralog of bco1 that we discover to have evolved in the ray-finned fishes, the most abundant, speciose, and commercially important group of fishes. We investigated the function of bco1l in ray-finned Siamese fighting fish, commonly known as betta, an emerging model for genetics and development. Using CRISPR-Cas9 knockouts, we find that lack of bco1l results in reduced VA and elevated {beta}-carotene in larvae, starting when animals have exhausted their yolk supply of retinal, followed by stunted growth and death during juvenile development. Exogenous retinoic acid rescues the mutation, demonstrating its deficiency causes these defects. bco1l is 4x more abundant than bco1 in the intestine. This, coupled with the inability of bco1 to sustain VA production in the bco1l mutant, indicates that bco1l is the primary enzyme for dietary carotenoid conversion into retinal. Our results show that VA production by bco1l is required for post-embryonic development, and that bco1l became essential after evolving via duplication of bco1.

genetics↗

bioRxiv2025

Genetic modulation of mitochondrial NAD+ regeneration does not prevent dopaminergic neuron dysfunction caused by mitochondrial complex I impairment

Dysfunction of mitochondrial complex I (MCI) has been implicated in the degeneration of dopaminergic neurons in Parkinsons disease. Here, we report the effect of expressing MitoLbNOX, a mitochondrial-targeted version of the bacterial enzyme LbNOX, which increases regeneration of NAD+ in the mitochondria to maintain the NAD+/NADH ratio, in dopaminergic neurons with impaired MCI (MCI-Park mice). MitoLbNOX expression did not ameliorate the cellular or behavioral deficits observed in MCI-Park mice, suggesting that alteration of the mitochondrial NAD+/NADH ratio alone is not sufficient to compensate for loss of MCI function in dopaminergic neurons.

cell biology↗

bioRxiv2023

Genetic manipulation of betta fish

Betta splendens, also known as Siamese fighting fish or betta, are renowned for their astonishing morphological diversity and extreme aggressive behavior. Despite recent advances in our understanding of the genetics and neurobiology of betta, the lack of tools to manipulate their genome has hindered progress at functional and mechanistic levels. In this study, we outline the use of three genetic manipulation technologies, which we have optimized for use in betta: CRISPR/Cas9-mediated knockout, CRISPR/Cas9-mediated knockin, and Tol2-mediated transgenesis. We knocked out three genes: alkal2l, bco1l, and mitfa, and analyzed their effects on viability and pigmentation. Furthermore, we successfully knocked in a fluorescent protein into the mitfa locus, a proof-of-principle experiment of this powerful technology in betta. Finally, we used Tol2-mediated transgenesis to create fish with ubiquitous expression of GFP, and then developed a bicistronic plasmid with heart-specific expression of a red fluorescent protein to serve as a visible marker of successful transgenesis. Our work highlights the potential for the genetic manipulation of betta, providing valuable resources for the effective use of genetic tools in this animal model.

genetics↗