Publications by authors named "Dillon Gavlock"
Article Synopsis
- The study suggests that insulin resistance in the liver is a key factor leading to dysfunction in pancreatic islets, which is linked to Type 2 Diabetes Mellitus (T2DM) and Metabolic Associated Steatotic Liver Disease (MASLD).
- Researchers developed a microphysiological system combining liver and pancreatic models to better understand how these organ dysfunctions relate to each other. This system allows for the investigation of changes that occur when metabolic syndrome is present.
- Results showed that under metabolic syndrome conditions, the liver-pancreas system exhibited altered insulin secretion and signaling, indicating a direct connection between liver issues and islet dysfunction, which could help in developing personalized treatment strategies for affected patients.
Article Synopsis
- - MASLD is a global health issue affecting around 30% of the population, caused by a mix of genetics, lifestyle, and environmental factors, posing challenges for treatment development due to patient variability.
- - Creating effective therapeutic models is difficult because existing systems and animal models fail to fully reflect the complexities of MASLD progression, prompting the need for more precise experimental approaches.
- - The study utilized a liver acinus microphysiology system (LAMPS) with patient-derived cells to explore the effects of the PNPLA3 genetic variant on MASLD and tested the drug resmetirom, revealing significant changes in liver cell behavior indicative of disease progression.
Article Synopsis
- TM6SF2 rs58542926 (E167K) is linked to an increased risk of metabolic liver disease, prompting the need for a human model to study the mutation's effects due to conflicting animal study results.
- A human in vitro model was developed using gene editing on induced pluripotent stem cells, leading to observations of liver cell dysfunction, including lipid accumulation and reduced VLDL secretion associated with the mutation.
- The model demonstrated similarities to human conditions, facilitating future research on potential clinical interventions by addressing protein misfolding and ER stress related to the TM6SF2-E167K mutation.
Article Synopsis
- Metabolic dysfunction-associated steatotic liver disease (MASLD) affects about 30% of the global population, driven by a mix of genetic, lifestyle, and environmental factors, complicating treatment and clinical trial design.* -
- The study utilized a liver acinus microphysiology system (LAMPS) made from patient-derived cells to explore the effects of the PNPLA3 rs738409 genetic variant on MASLD progression, replicating various metabolic conditions.* -
- Results showed that the PNPLA3 GG variant led to increased liver fat, immune activation, and pro-fibrotic factor secretion compared to wild type cells, providing insights for future treatments like resmetirom.*
Article Synopsis
- Researchers found that problems in the liver can lead to issues in the pancreas, which affects blood sugar levels and can cause diabetes and a liver disease called MASLD.
- They created a special system that mimics human organs to study how these two organs affect each other when things go wrong, like during early metabolic syndrome.
- The results showed that when the liver is not working properly, it can send confusing signals to the pancreas, making it harder for the body to control insulin and blood sugar, which could help doctors understand these diseases better and create personalized treatments.
: COVID-19 pandemic has caused more than 6 million deaths worldwide. Co-morbid conditions such as Type 2 Diabetes (T2D) have increased mortality in COVID-19. With limited translatability of and small animal models to human disease, human organ-on-a-chip models are an attractive platform to model disease conditions and test potential therapeutics.
View Article and Find Full Text PDFMetabolic syndrome is a complex disease that involves multiple organ systems including a critical role for the liver. Non-alcoholic fatty liver disease (NAFLD) is a key component of the metabolic syndrome and fatty liver is linked to a range of metabolic dysfunctions that occur in approximately 25% of the population. A panel of experts recently agreed that the acronym, NAFLD, did not properly characterize this heterogeneous disease given the associated metabolic abnormalities such as type 2 diabetes mellitus (T2D), obesity, and hypertension.
View Article and Find Full Text PDFReciprocal coevolution of tumors and their microenvironments underlies disease progression, yet intrinsic limitations of patient-derived xenografts and simpler cell-based models present challenges towards a deeper understanding of these intercellular communication networks. To help overcome these barriers and complement existing models, we have developed a human microphysiological system (MPS) model of the human liver acinus, a common metastatic site, and have applied this system to estrogen receptor (ER)+ breast cancer. In addition to their hallmark constitutive (but ER-dependent) growth phenotype, different ESR1 missense mutations, prominently observed during estrogen deprivation therapy, confer distinct estrogen-enhanced growth and drug resistant phenotypes not evident under cell autonomous conditions.
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