PROJECT SUMMARY
The purpose of this NIH F32 training application is to provide support for Dr. Devin Wahl’s research and
training that will prepare him to become an independent investigator studying brain aging, age-associated
cognitive dysfunction and Alzheimer’s disease (AD). Dr. Wahl is a first-year postdoctoral fellow in Dr.
Thomas LaRocca’s lab at Colorado State University. He has prior experience in pre-clinical rodent studies of
brain aging, but under this training plan, he will learn a variety of new techniques used routinely in the LaRocca
lab (e.g., bioinformatics) and work with co-mentors to develop expertise in pre-clinical AD studies (a new
field for him). This work will complement Dr. Wahl’s existing expertise and put him on a career path towards
research and professional independence. In this project, Dr. Wahl will investigate the role of repetitive
element (RE) transcripts (derived from non-coding repetitive sequences in the genome) in brain aging and
AD. RE are commonly overlooked in biomedical research on aging, but our published/preliminary data and
reports from other groups indicate that aging is associated with an accumulation of RE transcripts, and that
these transcripts may modulate several main ‘hallmarks of aging’, such as inflammation. It is unknown
whether RE transcript accumulation plays a role in brain aging (and consequently age-related AD), but Dr.
Wahl’s strong preliminary data and recent reports implicating RE in age-related neurodegenerative diseases
and neuroinflammation suggest this is likely the case. Therefore, in Aim 1 of this project, Dr. Wahl will learn
and use advanced bioinformatics approaches (e.g., RNA-seq) to explore the effects of various interventions
known to modulate brain aging on RE expression in mice, and he will probe existing datasets on human
subjects to determine if RE are linked with brain aging/AD. In Aim 2, he will combine these new skills with his
prior experience to conduct a pre-clinical pharmacological intervention study (using an established RE
inhibitor) to determine if suppressing RE inhibits neuroinflammation and brain aging/AD. The results of this
training grant may address several important research priorities at NIA, including the identification of novel
molecular modulators of brain aging/AD and potential therapeutic targets for improving brain health and
preventing age-related AD. The sponsor, Dr. LaRocca, is NIA-funded to study RE transcripts in aging and AD
and has a history of success in this area. He will guide Dr. Wahl on all aspects of the proposed study, and Dr.
Wahl will also be mentored by a team of technical/professional experts including Drs. Seals, Hoeffer, Moreno,
Hamilton and Link who will provide guidance on other aspects of Dr. Wahl’s research and career. Dr. Wahl
already has a strong track record in research on aging/brain aging. As such, with this team of expert mentors
he will be able to successfully complete the investigations outlined, and developing new skills along with this
novel line of investigation will accelerate him on the path to becoming a successful, independent investigator.