Epigenetics and Cancer Risk
Several initiatives are ongoing in our research program. These include analyzing data to determine what factors appear to be most associated with developing a substance use disorder so that these may be applied to prevention efforts for youth and future generations. Our focus is not just on the “hard wired’ genetic variation that we are born with but the epigenetic changes that occur because of our experiences, both good and bad. Epigenetic changes include DNA methylation and histone modification, processes that change how genes are expressed. Genes can be silenced or their expression enhanced by these epigenetic processes. Our environment has a lot to do with this process. Early childhood stress can modify expression of genes which in turn can make individuals more vulnerable to stress or even experience higher rates of disease.
We are especially interested in how alcohol and drug use affect risk for development of cancers and neurodegenerative diseases. A recent publication shows how use of substances may influence risk for developing these conditions in future generations. We believe that the excellent cooperation and support we have received from our families who have aided in developing the foundation of this work, along with continued study of these important questions will contribute greatly to public health initiatives.
Epigenetics and Cognitive Impairment
Alzheimer’s disease (AD) and Parkinson’s disease (PD) together are the most common causes of dementia and cognitive impairment in the elderly. Increasing evidence that α-synuclein is involved in both disorders suggests the importance of further study to determine under what conditions this protein is altered. Accumulation of α-synuclein results in formation of molecular complexes linked to PD. Although amyloid beta protein and tau have been the mainstay of AD investigations, recent studies demonstrate that α-synuclein has a role in AD. Methylation of α-synuclein is associated with presence of Lewy bodies and dementia. A dose-related effect of quantity of alcohol consumption on methylation of sites within the α-synuclein gene in adults shows a potential link between alcohol use and greater risk of dementia through the α-synuclein gene.
Identifying Children That Would Benefit from Intervention
The following work was proposed for federal funding and received an outstanding rating by peer review but was not funded by NIH. Funds are needed to initiate this work and provide a neuroscientific approach to preventing substance use disorders by targeting individuals during childhood.
Our young adult participants that were enrolled in our follow-up study now have children of their own that they can bring in to participate. We propose looking at brain white matter integrity and connectivity related to functioning of brain regions involved in emotion regulation.
The overarching goal is to identify how familial risk factors and within-family variation especially in high-risk families influences neural connectivity and clinical outcome, and to relate these to modifiable behaviors (mindfulness and decision-making capacity). Results of this study would aid in identifying children that are most likely to benefit from mindfulness intervention to prevent the development of substance use disorder later in life.