Transitioning Pharmacogenomics into the Clinical Setting: Training Future Pharmacists

Pharmacogenomics, once hailed as a futuristic approach to pharmacotherapy, has transitioned to clinical implementation. Although logistic and economic limitations to clinical pharmacogenomics are being superseded by external measures such as preemptive genotyping, implementation by clinicians has met resistance, partly due to a lack of education. Pharmacists, with extensive training in pharmacology and pharmacotherapy and accessibility to patients, are ideally suited to champion clinical pharmacogenomics. This study aimed to analyze the outcomes of an innovative pharmacogenomic teaching approach. Second-year student pharmacists enrolled in a required, 15-week pharmaceutical care lab course in 2015 completed educational activities including lectures and small group work focusing on practical pharmacogenomics. Reflecting the current landscape of direct-to-consumer (DTC) genomic testing, students were offered 23andMe genotyping. Students completed surveys regarding their attitudes and confidence on pharmacogenomics prior to and following the educational intervention. Paired pre- and post-intervention responses were analyzed with McNemar's test for binary comparisons and the Wilcoxon signed-rank test for Likert items. Responses between genotyped and non-genotyped students were analyzed with Fisher's exact test for binary comparisons and the Mann-Whitney U-test for Likert items. Responses were analyzed for all student pharmacists who voluntarily completed the pre-intervention survey (N = 121, 83% response) and for student pharmacists who completed both pre- and post-intervention surveys (N = 39, 27% response). Of those who completed both pre- and post-intervention surveys, 59% obtained genotyping. Student pharmacists demonstrated a significant increase in their knowledge of pharmacogenomic resources (17.9 vs. 56.4%, p < 0.0001) and confidence in applying pharmacogenomic information to manage patients' drug therapy (28.2 vs. 48.7%, p = 0.01), particularly if the student had received genotyping. Student pharmacists understanding of the risks and benefits of using personal genome testing services significantly increased (55.3 vs. 86.8%, p = 0.001) along with agreement that personal genomics would likely play an important role in their future career (47.4 vs. 76.3%, p = 0.01), particularly among students who participated in genotyping. The educational intervention, including personal genotyping, was feasible, and positively enhanced students' reflections, and attitudes toward pharmacogenomics in a professional pharmacy program

Identifying genes that mediate anthracyline toxicity in immune cells

The role of the immune system in response to chemotherapeutic agents remains elusive. The interpatient variability observed in immune and chemotherapeutic cytotoxic responses is likely, at least in part, due to complex genetic differences. Through the use of a panel of genetically diverse mouse inbred strains, we developed a drug screening platform aimed at identifying genes underlying these chemotherapeutic cytotoxic effects on immune cells. Using genome-wide association studies (GWAS), we identified four genome-wide significant quantitative trait loci (QTL) that contributed to the sensitivity of doxorubicin and idarubicin in immune cells. Of particular interest, a locus on chromosome 16 was significantly associated with cell viability following idarubicin administration (p = 5.01 × 10−8). Within this QTL lies App, which encodes amyloid beta precursor protein. Comparison of dose-response curves verified that T-cells in App knockout mice were more sensitive to idarubicin than those of C57BL/6J control mice (p < 0.05). In conclusion, the cellular screening approach coupled with GWAS led to the identification and subsequent validation of a gene involved in T-cell viability after idarubicin treatment. Previous studies have suggested a role for App in in vitro and in vivo cytotoxicity to anticancer agents; the overexpression of App enhances resistance, while the knockdown of this gene is deleterious to cell viability. Further investigations should include performing mechanistic studies, validating additional genes from the GWAS, including Ppfia1 and Ppfibp1, and ultimately translating the findings to in vivo and human studies

Nonmurine animal models of food allergy.

Food allergy can present as immediate hypersensitivity [manifestations mediated by immunoglobulin (Ig)E], delayed-type hypersensitivity (reactions associated with specific T lymphocytes), and inflammatory reactions caused by immune complexes. For reasons of ethics and efficacy, investigations in humans to determine sensitization and allergic responses of IgE production to innocuous food proteins are not feasible. Therefore, animal models are used a) to bypass the innate tendency to develop tolerance to food proteins and induce specific IgE antibody of sufficient avidity/affinity to cause sensitization and upon reexposure to induce an allergic response, b) to predict allergenicity of novel proteins using characteristics of known food allergens, and c) to treat food allergy by using immunotherapeutic strategies to alleviate life-threatening reactions. The predominant hypothesis for IgE-mediated food allergy is that there is an adverse reaction to exogenous food proteins or food protein fragments, which escape lumen hydrolysis, and in a polarized helper T cell subset 2 (Th2) environment, immunoglobulin class switching to allergen-specific IgE is generated in the immune system of the gastrointestinal-associated lymphoid tissues. Traditionally, the immunologic characterization and toxicologic studies of small laboratory animals have provided the basis for development of animal models of food allergy; however, the natural allergic response in large animals, which closely mimic allergic diseases in humans, can also be useful as models for investigations involving food allergy

Nonmurine Animal Models of Food Allergy

Food allergy can present as immediate hypersensitivity [manifestations mediated by immunoglobulin (Ig)E], delayed-type hypersensitivity (reactions associated with specific T lymphocytes), and inflammatory reactions caused by immune complexes. For reasons of ethics and efficacy, investigations in humans to determine sensitization and allergic responses of IgE production to innocuous food proteins are not feasible. Therefore, animal models are used a) to bypass the innate tendency to develop tolerance to food proteins and induce specific IgE antibody of sufficient avidity/affinity to cause sensitization and upon reexposure to induce an allergic response, b) to predict allergenicity of novel proteins using characteristics of known food allergens, and c) to treat food allergy by using immunotherapeutic strategies to alleviate life-threatening reactions. The predominant hypothesis for IgE-mediated food allergy is that there is an adverse reaction to exogenous food proteins or food protein fragments, which escape lumen hydrolysis, and in a polarized helper T cell subset 2 (Th2) environment, immunoglobulin class switching to allergen-specific IgE is generated in the immune system of the gastrointestinal-associated lymphoid tissues. Traditionally, the immunologic characterization and toxicologic studies of small laboratory animals have provided the basis for development of animal models of food allergy; however, the natural allergic response in large animals, which closely mimic allergic diseases in humans, can also be useful as models for investigations involving food allergy. Key words: allergens, atopic dog, gastrointestinal food allergy, swine. Environ Healt