8 results on '"Jason A. Somarelli"'
Search Results
2. Inequitable distribution of plastic benefits and burdens on economies and public health
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Rachel Karasik, Nancy E. Lauer, Anne-Elisabeth Baker, Niki E. Lisi, Jason A. Somarelli, William C. Eward, Kathinka Fürst, and Meagan M. Dunphy-Daly
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Global and Planetary Change ,Ocean Engineering ,Aquatic Science ,Oceanography ,Water Science and Technology - Abstract
Plastic heterogeneously affects social systems – notably human health and local and global economies. Here we discuss illustrative examples of the benefits and burdens of each stage of the plastic lifecycle (e.g., macroplastic production, consumption, recycling). We find the benefits to communities and stakeholders are principally economic, whereas burdens fall largely on human health. Furthermore, the economic benefits of plastic are rarely applied to alleviate or mitigate the health burdens it creates, amplifying the disconnect between who benefits and who is burdened. In some instances, social enterprises in low-wealth areas collect and recycle waste, creating a market for upcycled goods. While such endeavors generate local socioeconomic benefits, they perpetuate a status quo in which the burden of responsibility for waste management falls on downstream communities, rather than on producers who have generated far greater economic benefits. While the traditional cost-benefit analyses that inform decision-making disproportionately weigh economic benefits over the indirect, and often unquantifiable, costs of health burdens, we stress the need to include the health burdens of plastic to all impacted stakeholders across all plastic life stages in policy design. We therefore urge the Intergovernmental Negotiating Committee to consider all available knowledge on the deleterious effects of plastic across the entire plastic lifecycle while drafting the upcoming international global plastic treaty.
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- 2023
3. Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition
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Divya L. Dayanidhi, Jason A. Somarelli, John B. Mantyh, Gabrielle Rupprecht, Roham Salman Roghani, Sophia Vincoff, Iljin Shin, Yiquan Zhao, So Young Kim, Shannon McCall, Jiyong Hong, and David S. Hsu
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General Medicine - Abstract
Colorectal cancer (CRC) is the third most prevalent form of cancer in the United States and results in over 50,000 deaths per year. Treatments for metastatic CRC are limited, and therefore there is an unmet clinical need for more effective therapies. In our prior work, we coupled high-throughput chemical screens with patient-derived models of cancer to identify new potential therapeutic targets for CRC. However, this pipeline is limited by (1) the use of cell lines that do not appropriately recapitulate the tumor microenvironment, and (2) the use of patient-derived xenografts (PDXs), which are time-consuming and costly for validation of drug efficacy. To overcome these limitations, we have turned to patient-derived organoids. Organoids are increasingly being accepted as a “standard” preclinical model that recapitulates tumor microenvironment cross-talk in a rapid, cost-effective platform. In the present work, we employed a library of natural products, intermediates, and drug-like compounds for which full synthesis has been demonstrated. Using this compound library, we performed a high-throughput screen on multiple low-passage cancer cell lines to identify potential treatments. The top candidate, psymberin, was further validated, with a focus on CRC cell lines and organoids. Mechanistic and genomics analyses pinpointed protein translation inhibition as a mechanism of action of psymberin. These findings suggest the potential of psymberin as a novel therapy for the treatment of CRC.
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- 2022
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4. A transdisciplinary approach to reducing global plastic pollution
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Zoie Diana, Rachel Karasik, Greg B. Merrill, Margaret Morrison, Kimberly A. Corcoran, Daniel Vermeer, Evan Hepler-Smith, Nishad Jayasundara, Jeremy Pare, John Virdin, William C. Eward, Jason A. Somarelli, Meagan M. Dunphy-Daly, and Daniel Rittschof
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Global and Planetary Change ,Ocean Engineering ,Aquatic Science ,Oceanography ,Water Science and Technology - Published
- 2022
5. Mapping phenotypic heterogeneity in melanoma onto the epithelial-hybrid-mesenchymal axis
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Maalavika Pillai, Gouri Rajaram, Pradipti Thakur, Nilay Agarwal, Srinath Muralidharan, Ankita Ray, Dev Barbhaya, Jason A. Somarelli, and Mohit Kumar Jolly
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Cancer Research ,Oncology - Abstract
Epithelial to mesenchymal transition (EMT) is a well-studied hallmark of epithelial-like cancers that is characterized by loss of epithelial markers and gain of mesenchymal markers. Melanoma, which is derived from melanocytes of the skin, also undergo phenotypic plasticity toward mesenchymal-like phenotypes under the influence of various micro-environmental cues. Our study connects EMT to the phenomenon of de-differentiation (i.e., transition from proliferative to more invasive phenotypes) observed in melanoma cells during drug treatment. By analyzing 78 publicly available transcriptomic melanoma datasets, we found that de-differentiation in melanoma is accompanied by upregulation of mesenchymal genes, but not necessarily a concomitant loss of an epithelial program, suggesting a more “one-dimensional” EMT that leads to a hybrid epithelial/mesenchymal phenotype. Samples lying in the hybrid epithelial/mesenchymal phenotype also correspond to the intermediate phenotypes in melanoma along the proliferative-invasive axis - neural crest and transitory ones. As melanoma cells progress along the invasive axis, the mesenchymal signature does not increase monotonically. Instead, we observe a peak in mesenchymal scores followed by a decline, as cells further de-differentiate. This biphasic response recapitulates the dynamics of melanocyte development, suggesting close interactions among genes controlling differentiation and mesenchymal programs in melanocytes. Similar trends were noted for metabolic changes often associated with EMT in carcinomas in which progression along mesenchymal axis correlates with the downregulation of oxidative phosphorylation, while largely maintaining glycolytic capacity. Overall, these results provide an explanation for how EMT and de-differentiation axes overlap with respect to their transcriptional and metabolic programs in melanoma.
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- 2022
6. The Hallmarks of Cancer as Ecologically Driven Phenotypes
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Jason A. Somarelli
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0301 basic medicine ,Evolution ,Population ,Context (language use) ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,QH359-425 ,metastasis ,tumor microenvironment ,education ,QH540-549.5 ,Ecology, Evolution, Behavior and Systematics ,education.field_of_study ,Ideal free distribution ,Ecology ,Reproductive success ,ideal free distribution ,niche construction theory ,Phenotype ,fitness ,Niche construction ,Multicellular organism ,030104 developmental biology ,The Hallmarks of Cancer ,Evolutionary biology ,030220 oncology & carcinogenesis - Abstract
Ecological fitness is the ability of individuals in a population to survive and reproduce. Individuals with increased fitness are better equipped to withstand the selective pressures of their environments. This paradigm pertains to all organismal life as we know it; however, it is also becoming increasingly clear that within multicellular organisms exist highly complex, competitive, and cooperative populations of cells under many of the same ecological and evolutionary constraints as populations of individuals in nature. In this review I discuss the parallels between populations of cancer cells and populations of individuals in the wild, highlighting how individuals in either context are constrained by their environments to converge on a small number of critical phenotypes to ensure survival and future reproductive success. I argue that the hallmarks of cancer can be distilled into key phenotypes necessary for cancer cell fitness: survival and reproduction. I posit that for therapeutic strategies to be maximally beneficial, they should seek to subvert these ecologically driven phenotypic responses.
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- 2021
7. From the Clinic to the Bench and Back Again in One Dog Year: How a Cross-Species Pipeline to Identify New Treatments for Sarcoma Illuminates the Path Forward in Precision Medicine
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Sneha R. Rao, Jason A. Somarelli, Erdem Altunel, Laura E. Selmic, Mark Byrum, Maya U. Sheth, Serene Cheng, Kathryn E. Ware, So Young Kim, Joseph A. Prinz, Nicolas Devos, David L. Corcoran, Arthur Moseley, Erik Soderblom, S. David Hsu, and William C. Eward
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,tumor evolution ,Cancer Research ,comparative oncology ,precision medicine ,Proteomics ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,tumor heterogeneity ,medicine ,Exome sequencing ,Original Research ,Genetic heterogeneity ,business.industry ,Bortezomib ,Cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Precision medicine ,030104 developmental biology ,030220 oncology & carcinogenesis ,cancer therapy ,Sarcoma ,Personalized medicine ,business ,medicine.drug - Abstract
Cancer drug discovery is an inefficient process, with more than 90% of newly-discovered therapies failing to gain regulatory approval. Patient-derived models of cancer offer a promising new approach to identify new treatments; however, for rare cancers, such as sarcomas, access to patient samples is limited, which precludes development of patient-derived models. To address the limited access to patient samples, we have turned to pet dogs with naturally-occurring sarcomas. Although sarcomas make up
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- 2020
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8. Bioengineering a Future Free of Marine Plastic Waste
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Maya U. Sheth, Sarah K. Kwartler, Emma R. Schmaltz, Sarah M. Hoskinson, E. J. Martz, Meagan M. Dunphy-Daly, Thomas F. Schultz, Andrew J. Read, William C. Eward, and Jason A. Somarelli
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0106 biological sciences ,Global and Planetary Change ,lcsh:QH1-199.5 ,010504 meteorology & atmospheric sciences ,polymer ,010604 marine biology & hydrobiology ,Ocean Engineering ,lcsh:General. Including nature conservation, geographical distribution ,Aquatic Science ,Oceanography ,01 natural sciences ,Toxic chemical ,Bioremediation ,PETase ,bioremediation ,Marine debris ,pollution ,lcsh:Q ,Plastic waste ,Biochemical engineering ,lcsh:Science ,degradation ,0105 earth and related environmental sciences ,Water Science and Technology - Abstract
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.
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- 2019
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