Biology subjects

Card, D. C.

Publications and source records attributed to Card, D. C..

4 recordsLinked to original sources

bioRxiv2026

mSWI/SNF complex inhibition sensitizes KRAS-mutant lung cancers to targeted therapies via epithelial-mesenchymal subversion

Targeted therapies for KRAS-mutant non-small lung cancer (NSCLC) have shown promising clinical results, however, incomplete tumoral responses and the inevitable emergence of therapeutic resistance remain critical challenges. Here we identify mSWI/SNF chromatin remodeling complexes as critical determinants of (EMT)-mediated KRAS inhibitor inefficacy and resistance in KRAS G12C lung cancers. Treatment with the clinical-grade SMARCA4/2 inhibitor, FHD-286, dampens EMT-mediated acquired resistance in drug-responsive models and similarly resensitizes drug-refractory models by rewiring mSWI/SNF chromatin localization and activities that modulate epithelial transcriptional programs and cell state. Further, synergistic mSWI/SNF and KRAS inhibitor combination treatment sensitizes non-G12C KRAS-mutant NSCLC cells to pan-RAS and G12D-specific inhibitors. Finally, FHD-286 and sotorasib combination treatment results in potent anti-tumor efficacy in both G12Ci-resistant and - sensitive organoid models and in vivo patient-derived xenograft (PDX) systems. These data nominate mSWI/SNF inhibition as a combination strategy to improve KRAS inhibitor efficacy, response duration, and to mitigate emergence of resistance.

cancer biology↗

bioRxiv2023

Diminishing growth of zoological natural history collections threatens future research in the life sciences and beyond

Natural history museums comprise a unique and important component of biological infrastructure worldwide, and underlie diverse research, education, and outreach in the natural sciences. Each museum is built around one or more biological collections that serve as a repository of important materials for study, which have contributed to scientific research in increasingly important areas ranging from understanding global climate change to developing new biotechnological applications. However, despite centuries of existence, global collections sizes have only been recently estimated, and aside from analyses of certain institutions or well-studied clades, little is known about how patterns of collecting activity across institutions, geographic regions, or taxonomic clades, or how these patterns vary across time. To address this important gap in our understanding of critical life sciences infrastructure, I gathered and analyzed zoological records associated with preserved specimens collected between 1900 and 2015 and housed in worldwide natural history collections using data from the Global Biodiversity Information Facility. My analysis indicated that global, museum-associated collecting activity focused on animals has varied greatly over time, peaking around 2000 and declining significantly since. By stratifying data by institution, nation, and taxonomic phylum and class, I also illuminated how individual data series contribute to these global patterns. Institutions and nations had either concentrated or dispersed periods of relatively high collecting activity that occurred over different time periods, although most growth occurred in the second half of the 20th century for both many individual institutions and globally. Certain taxonomic clades comprise the largest proportions of collections records over this time period, namely arthropods (especially insects) and chordates (especially vertebrates), underscoring the taxonomically biased collecting histories of many institutions. Altogether, my analyses provide a critical, early view of historical zoological collecting activity and, to help other museum stakeholders to explore the data and results in more depth, I also describe and release NHMinformatics, an interactive dashboard built using R Shiny. These resources, when combined with recommendations I have made for sustainable collections growth, will be helpful for establishing policy goals, provisioning museum infrastructure, and training curatorial personnel.

zoology↗

bioRxiv2019

Integrating natural history-derived phenomics with comparative genomics to study the genetic architecture of convergent evolution

Evolutionary convergence has been long considered primary evidence of adaptation driven by natural selection and provides opportunities to explore evolutionary repeatability and predictability. In recent years, there has been increased interest in exploring the genetic mechanisms underlying convergent evolution, in part due to the advent of genomic techniques. However, the current genomics gold rush in studies of convergence has overshadowed the reality that most trait classifications are quite broadly defined, resulting in incomplete or potentially biased interpretations of results. Genomic studies of convergence would be greatly improved by integrating deep vertical, natural history knowledge with horizontal knowledge focusing on the breadth of taxonomic diversity. Natural history collections have and continue to be best positioned for increasing our comprehensive understanding of phenotypic diversity, with modern practices of digitization and databasing of morphological traits providing exciting improvements in our ability to evaluate the degree of morphological convergence. Combining more detailed phenotypic data with the well-established field of genomics will enable scientists to make progress on an important goal in biology: to understand the degree to which genetic or molecular convergence is associated with phenotypic convergence. Although the fields of comparative biology or comparative genomics alone can separately reveal important insights into convergent evolution, here we suggest that the synergistic and complementary roles of natural history collection-derived phenomic data and comparative genomics methods can be particularly powerful in together elucidating the genomic basis of convergent evolution among higher taxa.

evolutionary biology↗

bioRxiv2017

Targeted capture of complete coding regions across divergent species

Despite continued advances in sequencing technologies, there is a need for methods that can efficiently sequence large numbers of genes from diverse species. One approach to accomplish this is targeted capture (hybrid enrichment). While these methods are well established for genome resequencing projects, cross-species capture strategies are still being developed and generally focus on the capture of conserved regions, rather than complete coding regions from specific genes of interest. The resulting data is thus useful for phylogenetic studies, but the wealth of comparative data that could be used for evolutionary and functional studies is lost. Here we design and implement a targeted capture method that enables recovery of complete coding regions across broad taxonomic scales. Capture probes were designed from multiple reference species and extensively tiled in order to facilitate cross-species capture. Using novel bioinformatics pipelines we were able to recover nearly all of the targeted genes with high completeness from species that were up to 200 myr divergent. Increased probe diversity and tiling for a subset of genes had a large positive effect on both recovery and completeness. The resulting data produced an accurate species tree, but importantly this same data can also be applied to studies of molecular evolution and function that will allow researchers to ask larger questions in broader phylogenetic contexts. Our method demonstrates the utility of cross-species approaches for the capture of full length coding sequences, and will substantially improve the ability for researchers to conduct large-scale comparative studies of molecular evolution and function.

evolutionary biology↗