Elizabeth Pollina, PhD

Assistant Professor of Developmental Biology

Research Interests

The Pollina Lab is broadly interested in identifying the molecular mechanisms that preserve longevity across the diverse cell types of the nervous system.

A fundamental mystery of biology is how the myriad neurons of the brain persevere for the lifespan of an organism. For most organisms, the vast majority of neurons generated at an individual’s birth must survive until its death, while also retaining a remarkable level of plasticity that facilitates learning, memory, and behavior.

As animals encounter new sensory stimuli and learn complex behaviors, these experiences trigger changes in neuronal activity patterns that lead to dynamic alterations to neuronal transcriptomes and epigenomes. Despite essential functions in promoting plasticity, neuronal activity presents a risk to the genome and epigenome, as activity-induced transcription proceeds via induction of DNA breaks at gene regulatory elements. The chromatin around activity-inducible genes is rapidly remodeled as the DNA itself is cut, unwound, and eventually re-sealed in a process that has the potential to create permanent mutations. How do neurons balance the need for plasticity with the relentless assault on their (epi)genomes that occurs in response to stimuli?  What mechanisms safeguard neuronal (epi)genomes, and how are these mechanisms adapted in organisms of vastly different lifespans? Can we identify the molecular basis of interventions that reverse (epi)genome damage to restore youthful neuronal function?

In the Pollina lab, we aim to identify mechanisms of transcriptional control and genome stability that preserve neuronal function over time and to understand how these mechanisms go awry to cause aging and neurological disease. Our lab tackles these questions using a multidisciplinary approach that integrates biochemistry, single-cell genomic assays, cell biology, and neuronal circuit function.

Specific Projects in the Pollina Lab Include:

Role of Neuronal-Specific Chromatin Complexes in Transcriptional Fidelity

We discovered an activity-dependent protein complex, NPAS4:NuA4, that both induces activity-dependent transcription and stimulates the repair of transcription-coupled DSBs. We aim to characterize how this complex and other repair factors work downstream of neuronal activity to preserve transcriptional fidelity and suppress mutational accumulation across a range of cell types in vivo. Using mouse models, we are examining how inactivation of the NPAS4:NuA4 complex components influences developmental and aging phenotypes.

Activity-Dependent DNA Repair Mechanisms in Humans

Unlike mice that live less than 3 years, human neurons must survive 80-100 years of repeated stimulation. The extended lifespan of humans compared to rodents suggests that neuronal (epi)genome preservation is especially essential for sustaining neuronal vitality and preventing disease. We are dissecting mechanisms of human-specific activity-dependent transcription and DNA repair using human brain tissue and IPSC-derived neuronal cultures.

Role of Sleep in Neuronal Rejuvenation and Nervous System Longevity

Neuronal function can be rejuvenated by a variety of interventions, such as diet and cognitive training, yet how the fundamental process of sleep preserves neuronal longevity remains largely unknown. Both acute and sustained loss of sleep increases the risk of developing degenerative diseases and can shorten lifespan across a variety of species. Why is sleep so critical and how does it restore function at the genome level in individual cell types of the nervous system? We are investigating the molecular factors that regulate sleep-dependent (epi)genome integrity across neuronal ensembles in the brain and body, using both genomic techniques and behavioral assays. We aim to test how re-activating restorative signaling pathways initiated during sleep may mitigate the effects of sleep loss on aspects of development and aging.