Colin K. Combs, Ph.D.
Project: Novel Strategies for Attenuating the Inflammatory Contribution to Alzheimer’s Disease
Mentor: Colin K. Combs, Ph.D.
Professor and Chair, Department of Biomedical Sciences
Research Aims: This project’s goal is to determine the mechanisms by which immune cells in the periphery interact with brain resident immune cells to influence brain function during aging and Alzheimer’s disease (AD). Population and single cell transcriptomic analysis of brain resident immune cells, microglia, clearly demonstrate that these cells change their phenotype during AD. Moreover, numerous epidemiologic and GWAS studies support a critical role for inflammatory changes during disease. Although some of these changes are related to the microenvironment of the brain, the influence of peripheral immune cell behavior on the phenotype of microglia has become increasingly understood during disease. Our prior work has shown that selectively manipulating peripheral immune cell behavior with immunomodulatory strategies is sufficient to provide protective changes in microglial phenotype. Using a transgenic mouse model of Alzheimer’s disease, this project seeks to understand the cross-talk between peripheral immune cells and microglia to better define molecular signals influencing the inflammatory changes that regulate disease progression. Specific pharmacologic interventions using non brain-penetrant biologic and small molecule approaches will be tested for their ability to attenuate the peripheral to brain communication of inflammatory changes.
Techniques: Students will learn rodent husbandry, genotyping and drug delivery via intravenous/intraperitoneal injection and oral gavage. In addition, they will become familiar with PK/PD related to rodent therapeutic testing. Finally, students will learn enzymatic assays, ELISAs, flow cytometry, immunohistochemistry, mass spectrometry, and microscopy techniques relevant to brain along with statistical analysis, hypothesis testing, and scientific writing skills.
Student Independence: The SURF student will work with Dr. Combs to design a particular drug delivery paradigm to administer novel immunomodulatory therapeutics to control and AD mice. The student will also be responsible for literature review and suggestion of possible analyses of immune markers from the brain. Once the student has been trained by lab staff and passes an in-lab certification for the particular drug delivery paradigm and animal collection, he/she will be responsible for scheduling and delivering drugs and final brain and blood collections. The student will be expected to help plan the particular series of analyses from the collected tissue and present findings at weekly lab meetings. At all times, the student will have access to Dr. Combs, a lab manager, multiple post-docs, graduate students, and additional undergraduate students for any assistance that is needed.
