Biology subjects

Asante-Asamani, E.

Publications and source records attributed to Asante-Asamani, E..

4 recordsLinked to original sources

bioRxiv2025

Antigen presenting cells play a critical role in determining response to regulatory T cell therapy in type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease in which the immune system attacks pancreatic beta cells, leading to high blood glucose levels and requiring lifelong insulin therapy. There is no cure, and individuals with T1D may face a reduced lifespan of up to 12 years. Defects in regulatory T cells (Tregs) are a key contributor to disease onset and are being explored as a therapeutic avenue. However, the effectiveness of Treg therapy remains uncertain. Research is further limited by the inability to directly observe pancreatic and lymph node activity during the long presymptomatic stage of T1D. In this study, we develop a mathematical model for beta and T cell dynamics. We find both Treg quality and quantity affect disease progression, and that antigen-presenting cell (APC) dynamics play a central role. Notably, Treg therapy combined with APC depletion improves outcomes, especially with strong peptide-induced APC activation.

immunology↗

bioRxiv2025

Mathematical Model for the Progression of Rhegmatogenous Retinal Detachment (RRD)

The separation of the neural layer (NL) and the retinal pigmented epithelium (RPE), referred to as retinal detachment (RD), is a disease of vertebrate eyes affecting nearly twenty eight thousand individuals in the United States annually. The rate at which RD progresses--especially in response to constant eye movement--and the factors influencing this progression remain poorly understood. This lack of quantitative insight contributes to delays in treatment which can lead to permanent vision loss. In this work, we develop a mathematical model to investigate the progression of retinal detachment over two saccadic eye rotation. We explore how various model parameters--describing fluid properties, biomechanical properties of the retina, molecular properties of the bond between the NL and the RPE, as well as geometric and physical properties of the eye--affect disease progression.

biophysics↗

bioRxiv2025

A mathematical model for bleb expansion clarifies the role of TalA and actin dynamics in regulating bleb size and frequency

Eukaryotic cells, such as cancer and immune cells, migrate using either pressure-driven blebs or actin polymerization driven pseudopods, with cells preferring to bleb in confined environments where high protrusion forces are required for movement. Blebbing involves a separation of the cell membrane from the cortex, via the detachment of membrane-to-cortex linker proteins. The detached membrane then expands and stabilizes into a spherical cap as a new cortex is formed beneath the protruded membrane while the old one is completely degraded. The role of linker proteins in blebbing has mostly been associated with directing blebs to the leading edge of the cell, where linker enrichment is low, suggesting that cells devoid of linker proteins will bleb profusely. However, experimental work in this study involving talA null chemotaxing Dictyostelium discoideum cells shows the opposite effect, pointing to an alternative role for TalA. Our quantitative analysis of bleb size and frequency reveals that talA null cells produce fewer and smaller blebs in confined environments, pointing to a reduction in their intracellular pressure. A mathematical model of bleb expansion developed and validated with our experimental data supports the hypothesis that linker proteins help the cell maintain intracellular pressure during blebbing by limiting changes to its surface area when pressurized. Our model also identifies elastic and viscous properties of the cell, the assembly rate of the new cortex and disassembly rate of the old cortex as key modulators of change in bleb size induced by weakening the strength of membrane to cortex attachment. SIGNIFICANCEThis work analyzes the role of the membrane-to-cortex linker protein talA in regulating bleb size and frequency during bleb-based chemotaxis. We identified that this protein helps to regulate intracellular pressure by preventing pressure loss due to uniform membrane expansion around the cell. In particular, cells form smaller and less frequent blebs without TalA. Analysis of a mathematical model for bleb expansion demonstrates that weakening the strength of linker proteins is sufficient to reduce the size of blebs. Our model also identifies an important role for actin dynamics and the viscoelastic properties of the cell in regulating the percentage change in blebs due to weakening membrane to cortex attachment. Additionally, we find that cells can partially retract blebs without myosin II by regulating the ratio of polymerization and depolymerization of actin in the reforming cortex.

cell biology↗

bioRxiv2024

Evaluating the Importance of Glucagon in the Insulin-Glucose Regulatory System: A Mechanistic Modeling Approach

The dynamics of insulin and glucose are tightly regulated. The pancreatic islets of Langerhans contain both beta and alpha cells which produce insulin and glucagon, respectively. Insulin is the only hormone in the body that lowers blood glucose levels by acting like a key for glucose to enter cells. Without insulin, cells cannot utilize glucose, their primary source of energy. In contrast, glucagon functions as a hormone which elevates blood glucose levels by promoting the breakdown of glycogen in the liver. Maintaining blood glucose within a safe range is vital since both excessively high and low levels can be life-threatening (hyperglycemia and hypoglycemia, respectively), and these two hormones work together to achieve this balance. In this work we aim to underscore the significance of glucagon in the insulin-glucose regulatory system. We construct a three-compartment mechanistic model that includes insulin, glucose, and glucagon, which is then validated by fitting to publicly available from an intravenous glucose tolerance test (IVGTT). After model validation, we investigate how removing glucose feedback from insulin secretion, as seen in insulin-dependent diabetes, disrupts the regulation of glucose and glucagon. To do this, we simulate the model (a) when insulin secretion is reduced to mimic an insufficient dose of insulin, (b) when the peak of insulin action is delayed mimicking a dosing delay of insulin, and (c) when both occur simultaneously. Lastly, we test different half-lives of insulin to evaluate how an increased half-life of manufactured insulin may further disrupt the system. We find that when insulin secretion is decreased, glucagon still responds to high glucose levels by decreasing glucagon production. This suggests that in cases of type 2 diabetes, where glucagon secretion is elevated despite high levels of glucose, a lack of insulin response may not be the sole cause for glucagon dysfunction. We also find that delaying insulin secretion increases the risk of a hypoglycemic event through a suppression of glucagon production. Initially, the spike in glucose causes glucagon secretion to be reduced; this is then followed by the delay in insulin peak which then continues to suppress glucagon despite blood glucose levels falling, leading to a lack of response by glucagon and a subsequent hypoglycemic event. Furthermore, we find that a higher half-life of insulin causes it to remain longer in the blood stream, inhibiting glucagons response to severely low glucose levels (glucose levels less than 3.9 mmol/L). This sheds light on why patients taking exogenous insulin, which has a longer half-life than endogenous insulin, may have difficulty recovering from hypoglycemic events. Hence, our model suggests that keeping the half-life of exogenous insulin below 10 minutes and administering it immediately after meals could help reduce the risk of hypoglycemic events in patients with type 1 or insulin dependent diabetes. Overall, we highlight how a disruption in the feedback between insulin and glucose not only alters blood glucose levels, but also glucagon response, which may lead to further disruption of the system.

systems biology↗