@article{gunady_ware_plumlee_devos_corcoran_prinz_misetic_ciccarelli_harrison_thorne_et al._2022, title={Exome sequencing of hepatocellular carcinoma in lemurs identifies potential cancer drivers A pilot study}, volume={10}, ISSN={["2050-6201"]}, DOI={10.1093/emph/eoac016}, abstractNote={Abstract Background and objectives Hepatocellular carcinoma occurs frequently in prosimians, but the cause of these liver cancers in this group is unknown. Characterizing the genetic changes associated with hepatocellular carcinoma in prosimians may point to possible causes, treatments and methods of prevention, aiding conservation efforts that are particularly crucial to the survival of endangered lemurs. Although genomic studies of cancer in non-human primates have been hampered by a lack of tools, recent studies have demonstrated the efficacy of using human exome capture reagents across primates. Methodology In this proof-of-principle study, we applied human exome capture reagents to tumor–normal pairs from five lemurs with hepatocellular carcinoma to characterize the mutational landscape of this disease in lemurs. Results Several genes implicated in human hepatocellular carcinoma, including ARID1A, TP53 and CTNNB1, were mutated in multiple lemurs, and analysis of cancer driver genes mutated in these samples identified enrichment of genes involved with TP53 degradation and regulation. In addition to these similarities with human hepatocellular carcinoma, we also noted unique features, including six genes that contain mutations in all five lemurs. Interestingly, these genes are infrequently mutated in human hepatocellular carcinoma, suggesting potential differences in the etiology and/or progression of this cancer in lemurs and humans. Conclusions and implications Collectively, this pilot study suggests that human exome capture reagents are a promising tool for genomic studies of cancer in lemurs and other non-human primates. Lay Summary Hepatocellular carcinoma occurs frequently in prosimians, but the cause of these liver cancers is unknown. In this proof-of-principle study, we applied human DNA sequencing tools to tumor–normal pairs from five lemurs with hepatocellular carcinoma and compared the lemur mutation profiles to those of human hepatocellular carcinomas.}, number={1}, journal={EVOLUTION MEDICINE AND PUBLIC HEALTH}, author={Gunady, Ella F. and Ware, Kathryn E. and Plumlee, Sarah Hoskinson and Devos, Nicolas and Corcoran, David and Prinz, Joseph and Misetic, Hrvoje and Ciccarelli, Francesca D. and Harrison, Tara M. and Thorne, Jeffrey L. and et al.}, year={2022}, month={Jan}, pages={221–230} }
 @article{dewitt_plumlee_brighton_sivaraj_martz_zand_kumar_sheth_floyd_spruance_et al._2022, title={Loss of ATRX promotes aggressive features of osteosarcoma with increased NF-KB signaling and integrin binding}, volume={7}, ISSN={["2379-3708"]}, DOI={10.1172/jci.insight.151583}, abstractNote={Osteosarcoma (OS) is a lethal disease with few known targeted therapies. Here, we show that decreased ATRX expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypic changes correspond with activation of NF-κB signaling, extracellular matrix remodeling, increased integrin αvβ3 expression, and ETS family transcription factor binding. Here, we characterize these changes in vitro, in vivo, and in a data set of human OS patients. This increased aggression substantially sensitizes ATRX-deficient OS cells to integrin signaling inhibition. Thus, ATRX plays an important tumor-suppression role in OS, and loss of function of this gene may underlie new therapeutic vulnerabilities. The relationship between ATRX expression and integrin binding, NF-κB activation, and ETS family transcription factor binding has not been described in previous studies and may impact the pathophysiology of other diseases with ATRX loss, including other cancers and the ATR-X α thalassemia intellectual disability syndrome.}, number={17}, journal={JCI INSIGHT}, author={DeWitt, Suzanne Bartholf and Plumlee, Sarah Hoskinson and Brighton, Hailey E. and Sivaraj, Dharshan and Martz, E. J. and Zand, Maryam and Kumar, Vardhman and Sheth, Maya U. and Floyd, Warren and Spruance, Jacob V. and et al.}, year={2022}, month={Aug} }
 @article{allen_cullen_hawkey_mochizuki_nguyen_schechter_borst_yoder_freedman_patierno_et al._2021, title={A Zebrafish Model of Metastatic Colonization Pinpoints Cellular Mechanisms of Circulating Tumor Cell Extravasation}, volume={11}, ISSN={["2234-943X"]}, DOI={10.3389/fonc.2021.641187}, abstractNote={Metastasis is a multistep process in which cells must detach, migrate/invade local structures, intravasate, circulate, extravasate, and colonize. A full understanding of the complexity of this process has been limited by the lack of ability to study these steps in isolation with detailed molecular analyses. Leveraging a comparative oncology approach, we injected canine osteosarcoma cells into the circulation of transgenic zebrafish with fluorescent blood vessels in a biologically dynamic metastasis extravasation model. Circulating tumor cell clusters that successfully extravasated the vasculature as multicellular units were isolated under intravital imaging (n = 6). These extravasation-positive tumor cell clusters sublines were then molecularly profiled by RNA-Seq. Using a systems-level analysis, we pinpointed the downregulation of KRAS signaling, immune pathways, and extracellular matrix (ECM) organization as enriched in extravasated cells (p < 0.05). Within the extracellular matrix remodeling pathway, we identified versican (VCAN) as consistently upregulated and central to the ECM gene regulatory network (p < 0.05). Versican expression is prognostic for a poorer metastasis-free and overall survival in patients with osteosarcoma. Together, our results provide a novel experimental framework to study discrete steps in the metastatic process. Using this system, we identify the versican/ECM network dysregulation as a potential contributor to osteosarcoma circulating tumor cell metastasis.}, journal={FRONTIERS IN ONCOLOGY}, author={Allen, Tyler A. and Cullen, Mark M. and Hawkey, Nathan and Mochizuki, Hiroyuki and Nguyen, Lan and Schechter, Elyse and Borst, Luke and Yoder, Jeffrey A. and Freedman, Jennifer A. and Patierno, Steven R. and et al.}, year={2021}, month={Sep} }
 @misc{sheth_kwartler_schmaltz_hoskinson_martz_dunphy-daly_schultz_read_eward_somarelli_2019, title={Bioengineering a Future Free of Marine Plastic Waste}, volume={6}, ISSN={["2296-7745"]}, DOI={10.3389/fmars.2019.00624}, abstractNote={Plastic waste has reached epidemic proportions worldwide, and the production of plastic continues to rise steadily. Plastic represents a diverse array of commonly-used synthetic polymers that are extremely useful as durable, economically-beneficial alternatives to other materials; however, despite the wide-ranging utility of plastic, the increasing accumulation of plastic waste in the environment has had numerous detrimental impacts. In particular, plastic marine debris can transport invasive species, entangle marine organisms, and cause toxic chemical bioaccumulation in the marine food web. The negative impacts of plastic waste have motivated research on new ways to reduce and eliminate plastic. One unique approach to tackle the plastic waste problem is to turn to nature’s solutions for degrading polymers by leveraging the biology of naturally-occurring organisms to degrade plastic. Advances in metagenomics, next generation sequencing, and bioengineering have provided new insights and new opportunities to identify and optimize organisms for use in plastic bioremediation. In this review, we discuss the plastic waste problem and possible solutions, with a focus on potential mechanisms for plastic bioremediation. We pinpoint two key habitats to identify plastic-biodegrading organisms: 1) habitats with distinct enrichment of plastic waste, such as those near processing or disposal sites, and 2) habitats with naturally-occurring polymers, such as cutin, lignin, and wax. Finally, we identify directions of future research for the isolation and optimization of these methods for widespread bioremediation applications.}, journal={FRONTIERS IN MARINE SCIENCE}, author={Sheth, Maya U. and Kwartler, Sarah K. and Schmaltz, Emma R. and Hoskinson, Sarah M. and Martz, E. J. and Dunphy-Daly, Meagan M. and Schultz, Thomas F. and Read, Andrew J. and Eward, William C. and Somarelli, Jason A.}, year={2019}, month={Oct} }