Tracy L. Hagemann, PhD

Position title: Associate Research Professor

Tracy L. Hagemann, PhD

PhD, Rush University

Contact Information

Waisman Center, Room 713A
1500 Highland Avenue
Madison, WI 53705
Alexander Disease Research

Research Statement

Our research focuses on the role of astrocytes in neurodegenerative disease and the cellular consequences of their dysfunction. Astrocytes have traditionally been thought of as support cells that maintain ion and neurotransmitter homeostasis in the central nervous system (CNS). However, research over the past few decades has revealed more complex functions including the regulation of neurogenesis, synaptogenesis, neurotransmission and remyelination. In addition, astrocytes control blood flow, maintain the blood brain barrier, and contribute to the distribution and clearance of compounds through the CNS glymphatic system.

Astrocytes take on another critical role of reacting to CNS injury by activating anti-stress and neuroinflammatory pathways in both acute insults and chronic disease. Reactive astrocytes are heterogeneous in their response and can either promote or prevent regeneration and repair. Given the complexities of astrocyte function in the healthy CNS and their sometimes paradoxical role in brain and spinal cord injury, it can be difficult to dissect the effects of astrogliosis on other neural cell types from the primary insult.

To better understand astrocyte function in neurodegenerative disease, we have focused on one of the few examples of a primary disorder of astrocytes, Alexander disease. Alexander disease (AxD) is caused by mutations in the gene for glial fibrillary acidic protein (GFAP), an astrocyte specific intermediate filament protein, that lead to protein aggregation, activation of stress response genes, including GFAP, and reactive gliosis. AxD can affect all ages but is most severe in children, who often present with seizures, motor and cognitive delay, and a general failure to thrive. We have generated several rodent models with missense mutations homologous to those found in patients with the disease. These models allow us to study the effects of astrocyte dysfunction on other cell types in the mammalian CNS, including neurons and oligodendrocytes and their progenitors. As with other injuries, the astrocyte response to mutant GFAP is also heterogeneous, and a second goal is to identify the molecular networks controlling regional differences in astrocyte reactivity.  Finally we hope that understanding the mechanisms behind Alexander disease pathology will lead to therapeutic strategies for this devastating disorder as well as other diseases with astropathology.

Selected Publications