There are four major areas of research which I’m currently involved in 1) epigenetics of Alzheimer’s disease 2) Method to protect mitochondria from oligomeric abeta induced alterations (3) RNA sequencing of identified cells within a heterogeneous population of cells and 4) Chronic traumatic encephalopathy in retired NFL players.
Areas of research 1 and 2
Because there are a huge numbers of variables that change in Alzheimer’s disease, we focus on selected aspects of four of these: energy, epigenetics, chromatin structure and expression of genes related to synaptic structure and function. The basic model that we propose is that selected Abeta oligomers modulate mitochondrial and epigenetic function which then affects chromatin structure of genes related to synaptic structure and function. Because synaptic degeneration is one of the earliest pathological features and strongest correlate to cognitive decline in AD understanding the underlying mechanism is crucial in developing therapeutic tools like the novel Co-enzyme Q10 analogues developed by Sidney Hecht at ASU.
Area of research 3
Array expression data from many labs, including our own show large changes in expression of many glial, vascular and neuronal specific genes in Alzheimer’s disease (AD) compared to normal controls (NC). Although select glial, vascular and neuronal specific changes are distinguishable, there are thousands of genes that are not cell class-specific but play major roles in cell function. Examples include genes related to energetics, to epigenetics, and inflammation. In order to investigate disease and regional effects on gene expression on select classes of cells we have proposed to work with laser captured microglia, astrocytes, and neurons. This project proposes to delineate mechanistic interactions between neurons and glial cells in human neurological diseases. Such an effort is likely to generate a more comprehensive understanding of the composition(s) of the stroma in normal tissues as well as of the role(s) of the stroma in disease initiation, and progression.
Area of research 4
The overarching goals of this research is to prospectively collect standardized neurologic, neuropsychological, and neuropsychiatric data, as well as potential in vivo biomarkers (e.g., tissue and neuroimaging) on former NFL players with a history of high exposure to repetitive head impacts and a comparison group with limited or no history of repetitive head impacts or other brain trauma (i.e., professional baseball players). Participants will be followed longitudinally with standardized clinical testing until the time of death at which time an autopsy will be performed.