Role of cGAS-STING pathway in aging and sexual dimorphism in diabetic kidney disease.

Diabetic kidney disease (DKD) is the leading cause of chronic renal pathology. Understanding the molecular underpinnings of DKD is critical to designing tailored therapeutic approaches. Here we focused on sex differences and the contribution of aging towards the progression of DKD.

Spatial Stochastic Model of the Pre-B Cell Receptor.

Survival and proliferation of immature B lymphocytes requires expression and tonic signaling of the pre-B cell receptor (pre-BCR). This low level, ligand-independent signaling is likely achieved through frequent, but short-lived, homo interactions. Tonic signaling is also central in the pathology of precursor B acute lymphoblastic leukemia (B-ALL).

Inorganic arsenic promotes luminal to basal transition and metastasis of breast cancer.

Inorganic arsenic (iAs/As O ) is an environmental toxicant found in watersheds around the world including in densely populated areas. iAs is a class I carcinogen known to target the skin, lungs, bladder, and digestive organs, but its role as a primary breast carcinogen remains controversial. Here, we examined a different possibility: that exposure to iAs promotes the transition of well-differentiated epithelial breast cancer cells characterized by estrogen and progesterone receptor expression (ER+/PR+), to more basal phenotypes characterized by active proliferation, and propensity to metastasis in vivo.

Effect of Spatial Inhomogeneities on the Membrane Surface on Receptor Dimerization and Signal Initiation.

Important signal transduction pathways originate on the plasma membrane, where microdomains may transiently entrap diffusing receptors. This results in a non-random distribution of receptors even in the resting state, which can be visualized as "clusters" by high resolution imaging methods. Here, we explore how spatial in-homogeneities in the plasma membrane might influence the dimerization and phosphorylation status of ErbB2 and ErbB3, two receptor tyrosine kinases that preferentially heterodimerize and are often co-expressed in cancer.

Theory and Experimental Validation of a Spatio-temporal Model of Chemotherapy Transport to Enhance Tumor Cell Kill.

Cancer treatment efficacy can be significantly enhanced through the elution of drug from nano-carriers that can temporarily stay in the tumor vasculature. Here we present a relatively simple yet powerful mathematical model that accounts for both spatial and temporal heterogeneities of drug dosing to help explain, examine, and prove this concept. We find that the delivery of systemic chemotherapy through a certain form of nano-carriers would have enhanced tumor kill by a factor of 2 to 4 over the standard therapy that the patients actually received.

Development of a diffusion-based mathematical model for predicting chemotherapy effects.

Mathematical modeling of drug transport can complement current experimental and clinical investigations to understand drug resistance mechanisms, which eventually will help to develop patient-specific chemotherapy treatments. In this paper, we present a general time- and space-dependent mathematical model based on diffusion theory for predicting chemotherapy outcome. This model has two important parameters: the blood volume fraction and radius of blood vessels divided by drug diffusion penetration length.

Simulating cancer growth with multiscale agent-based modeling.

There have been many techniques developed in recent years to in silico model a variety of cancer behaviors. Agent-based modeling is a specific discrete-based hybrid modeling approach that allows simulating the role of diversity in cell populations as well as within each individual cell; it has therefore become a powerful modeling method widely used by computational cancer researchers. Many aspects of tumor morphology including phenotype-changing mutations, the adaptation to microenvironment, the process of angiogenesis, the influence of extracellular matrix, reactions to chemotherapy or surgical intervention, the effects of oxygen and nutrient availability, and metastasis and invasion of healthy tissues have been incorporated and investigated in agent-based models.

The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation.

Transcription factors of the STAT family are critical in the cytokine-mediated functional differentiation of CD4(+) helper T cells. Signaling inhibitors of the SOCS family negatively regulate the activation of STAT proteins; however, their roles in the differentiation and function of helper T cells are not well understood. Here we found that the SOCS protein CIS, which was substantially induced by interleukin 4 (IL-4), negatively regulated the activation of STAT3, STAT5 and STAT6 in T cells.