Biomedical subjects

Melissa Martinez

Publications and source records attributed to Melissa Martinez.

3 recordsLinked to original sources

PubMed2026

CD36 Influences Leukemia Progression in MLL-AF9-Driven AML by Modulating the Leukemia Immune Microenvironment.

CD36, a fatty-acid translocase, is increasingly implicated in acute myeloid leukemia biology and treatment resistance, yet its contribution to leukemogenesis is still unclear. Using the MLL-AF9 model, we transduced hematopoietic stem/progenitor cells (HSPCs) from Cd36-knockout (KO) or wild-type (WT) mice and assessed leukemic potential with in vitro assays, transplants, and transcriptomic, metabolomic, and immune profiling. Both Cd36KO- and Cd36WT-HSPCs underwent efficient MA9-driven transformation, with comparable colony formation and Hox/Meis1 pathway activation, indicating Cd36 is dispensable for leukemic initiation. However, Cd36 deletion markedly attenuated disease progression, reducing leukemic burden and extending survival in irradiated mice (median 22 vs. 15 days, P = 0.001). Effects were strikingly amplified in immunocompetent, non-irradiated recipients (median 63 vs. 22 days, P = 0.002), revealing immune-dependent suppression. Immune profiling showed enhanced CD4⁺ and CD8⁺ T cell infiltration, reduced CD4⁺CD25⁺ regulatory-like cells, and lower Tim-3 expression in Cd36KO-MA9 spleens, consistent with a less exhausted, more effective anti-leukemic T cell response. Despite enhanced T cell infiltration, TCR repertoires remained conserved, indicating functional reprogramming rather than clonal selection. Consistent with a suppressive leukemia immune microenvironment, RNA-seq gene set enrichment analysis identified upregulation of inflammatory (TNFα/NF-κB) and hypoxic pathways in Cd36WT-MA9 cells. Untargeted metabolomics revealed metabolic shifts in Cd36KO cells, involving a reduction in three key metabolites, UDP-GlcNAc, UDP-Galactose/UDP-Glucose, and O-Phospho-L-Serine, that likely support an immune evasion mechanism. These findings demonstrate that while Cd36 is not essential for MLL-AF9-mediated transformation, its cell-intrinsic expression in leukemic cells suppresses anti-leukemic immunity and accelerates progression. This positions CD36 as a promising target to enhance immune surveillance and limit AML aggressiveness.

Acute Myeloid Leukemia (AML)↗

PubMed2024

Vertebrate and invertebrate animal infection models of Candida auris pathogenicity.

Candida auris is an emerging fungal pathogen with several concerning qualities. First recognized in 2009, it has arisen in multiple geographically distinct genomic clades nearly simultaneously. C. auris strains are typically multidrug resistant and colonize the skin much better than most other pathogenic fungi; it also persists on abiotic surfaces, enabling outbreaks due to transmission in health care facilities. All these suggest a biology substantially different from the 'model' fungal pathogen, Candida albicans and support intensive investigation of C. auris biology directly. To uncover novel virulence mechanisms in this species requires the development of appropriate animal infection models. Various studies using mice, the definitive model, are inconsistent due to differences in mouse and fungal strains, immunosuppressive regimes, doses, and outcome metrics. At the same time, developing models of skin colonization present a route to new insights into an aspect of fungal pathogenesis that has not been well studied in other species. We also discuss the growing use of nonmammalian model systems, including both vertebrates and invertebrates, such as zebrafish, C. elegans, Drosophila, and Galleria mellonella, that have been productively employed in virulence studies with other fungal species. This review will discuss progress in developing appropriate animal models, outline current challenges, and highlight opportunities in demystifying this curious species.

Animals↗

PubMed2019

Discovering human transcription factor physical interactions with genetic variants, novel DNA motifs, and repetitive elements using enhanced yeast one-hybrid assays.

Identifying transcription factor (TF) binding to noncoding variants, uncharacterized DNA motifs, and repetitive genomic elements has been technically and computationally challenging. Current experimental methods, such as chromatin immunoprecipitation, generally test one TF at a time, and computational motif algorithms often lead to false-positive and -negative predictions. To address these limitations, we developed an experimental approach based on enhanced yeast one-hybrid assays. The first variation of this approach interrogates the binding of >1000 human TFs to repetitive DNA elements, while the second evaluates TF binding to single nucleotide variants, short insertions and deletions (indels), and novel DNA motifs. Using this approach, we detected the binding of 75 TFs, including several nuclear hormone receptors and ETS factors, to the highly repetitive Alu elements. Further, we identified cancer-associated changes in TF binding, including gain of interactions involving ETS TFs and loss of interactions involving KLF TFs to different mutations in the TERT promoter, and gain of a MYB interaction with an 18-bp indel in the TAL1 superenhancer. Additionally, we identified TFs that bind to three uncharacterized DNA motifs identified in DNase footprinting assays. We anticipate that these enhanced yeast one-hybrid approaches will expand our capabilities to study genetic variation and undercharacterized genomic regions.

Algorithms↗