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There are no effective treatments for Alzheimer’s disease (AD), a progressive brain disease that slowly destroys a person’s memory, cognitive skills and ability to carry out the simplest tasks. AD affects more than 5 million individuals in the United States and ranks as the sixth leading cause of death. The ε4 allele of the apolipoprotein-E (APOE) gene is the strongest genetic risk factor for sporadic or late-onset AD. Heterozygous carriers of the ε4 allele are at three-to-four times greater risk; homozygous carriers are at ten times greater risk.

Cell motility and membrane trafficking play important roles in regulating cell division, cell migration, cell death and autophagy. Impairment of these processes can result in enhanced cell proliferation and survival and increased migration and invasion leading to cancer. Several proteins involved in cell motility and membrane trafficking have been shown to be dysregulated in various cancers. There is therefore a need for development of animal models for studying the roles of these proteins in cancer and their responses to drug treatment in vivo.

Cancer immunotherapy approaches, such as adoptive cell transfer (ACT), proved effective against many cancer types. Yet, post-treatment analyses of ACT have suggested that efficacy may be enhanced by increasing the percentage of neoantigen-reactive T cells in the infused product. Neoantigens are new proteins that form on cancer cells when certain mutations occur in tumor DNA. Current techniques for identifying neoantigen-specific TCRs in T cell expression are labor-intensive, time-consuming and technically challenging.

There is no known cure for Alzheimer’s disease, a brain disorder that severely affects memory, thinking, learning, and organizing skills. It eventually decreases a person’s ability to carry out simple, daily activities. It is predicted that over 14 million Americans will develop Alzheimer’s without effective treatment options. Mild cognitive impairment (MCI) is a stage prior to Alzheimer’s when memory problems become noticeable. A patient’s ability to function and live independently remain intact as the brain compensates for disease-related changes.

Advanced colorectal carcinoma is currently incurable, and new therapies are urgently needed. Ephrin (Eph) receptors are a clinically relevant class of receptor tyrosine kinases. Related signaling pathways are associated with oncogenesis of a number of cancers. NCI investigators found that phosphotyrosine-dependent Eph receptor signaling sustains colorectal carcinoma cell survival, thereby uncovering a survival pathway active in colorectal carcinoma cells.

The Transforming Growth Factor Beta (TGF-ß) ligands (i.e., TGF-ß1, -ß2, -ß3) are key regulatory proteins in animal physiology. Disruption of normal TGF-ß signaling is associated with many diseases from cancer to fibrosis. In mice and humans, TGF-ß activates TGF-ß receptors (e.g., TGFBR1), which activates SMAD proteins that alter gene expression and contribute to tumorigenesis.  Reliable animal models are essential for the study of TGF-ß signaling.

Cytokines are a broad category of intercellular signaling proteins that are critical for intercellular communication in human health and disease. However, systematic profiling of cytokine signaling activities has remained challenging due to the short half-lives of cytokines, and the pleiotropic functions and redundancy of cytokine activities within specific cellular contexts.

The use of tumor transcriptomics for precision oncology has made significant advances, mainly by identifying cancer driver genes or actionable mutations for treatment with targeted therapies.  However, this strategy misses out on broader genetic interactions that could reveal additional biologically testable biomarkers for therapy response prediction and inform the selection of more effective drugs for targeted treatment.

The Corona virus disease, 2019 (COVID-19) pandemic is a worldwide public health crisis with over 153 million confirmed cases and 3.2 million deaths as of April 2021. COVID-19 is caused by a novel coronavirus called SARS-CoV-2. SARS-COV-2 infects hosts via its spike (S) protein, which has two portions, S1 that binds the cell and S2 that is involved in viral entry via fusion with the cell membrane. There are several vaccines available for COVID-19 patients that directly target SARS-CoV-2 by systemic immunization.

Tumor cell lines are important tools for the study of cancer. However, most tumor cell lines available today do not mimic physiological tumor development, progression, and host immune responses. Autochthonous tumors include spontaneously occurring tumors and chemical, viral, or physical carcinogen-induced tumors. They are considered to model human tumors more closely than transplanted tumors. Autochthonous tumors can be generated de novo in a model organism of interest and are thought to resemble physiological human tumor conditions.