Dr. Selenica performed her graduate studies in Sweden where she studied the role of amyloid beta and tau proteins in Alzheimer Disease. Directly after her PHD, she received a postdoctoral fellowship at the laboratory of Drs. Dave Morgan and Marcia Gordon, University of South Florida, where she studied therapeutic approaches in tauopathy utilizing mouse models of AD/FTD.

Dr. Selenica joined College of Pharmacy at University of South Florida (2013) as a founding faculty member and basic scientist. As an independent PI, Dr. Selenica focuses in the pathological mechanisms behind TDP-43 and tauopathy in neurodegenerative disorders. In 2019 Selenica lab relocated to the University of Kentucky, Sanders-Brown Center (SBCoA), where they joined the Alzheimer’s disease Center (UK-ADC) and a collaborative group of neuroscientist and neurologist experts focused on Aging and dementia.

Learn more about Dr. Selenica atSCHOLARS@UK

TDP-43 (transactive response DNA binding protein of 43 kDa), a nuclear RNA/DNA binding protein is associated with a spectrum of neurodegenerative diseases. TDP-43 Neuropathologic Changes (NC) are present in ~50% of demented individuals, including Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE) and Alzheimer’s disease (AD).

Overall, our laboratory focusses on elucidating underlying cellular mechanisms that impact TDP-43 structure-to-function relationship at the protein and cellular level, in animal models, and in TDP-43 retinopathies. We have identified TDP-43 citrullination as a bona-fide modification of TDP-43 and found “the disease-specific signatures of LATE and AD+LATE. Additionally, our research focuses on the PAD enzymes responsible for TDP-43 citrullination in the brain, which offers the potential to guide the development of new therapeutic treatment modalities and biomarker agents to LATE and related dementias (ADRDs).

Co-morbidities such as those contributing to metabolic diseases (e.g., diabetes) are known risk factors for dementia and contribute to disease severity. Notably, regional decline in glucose metabolic rate in the brain and reduced blood flow are one of the earliest and most consistent features of Alzheimer’s Disease. Our laboratory has identified hypusination of eukaryotic translation initiation factor 5A (eIF5AHyp), as a novel pathway upstream of synaptic plasticity impairments, cerebral metabolic dysfunction, and cognitive decline—cascades linked to the irreversible stages of dementia. We reported on the effects of reduced hypusination via pharmacological inhibition of deoxyhypusine synthase enzyme (DHS), on decreased TDP-43 phosphorylation and accumulation in the cytoplasm and stress granules in a cellular stress model (Smeltzer et al., 2021).

The current focus in our laboratory is to elucidate strategies that reduce aberrant and sustained eIF5AHyp and restore brain metabolism and neuronal mitochondrial bioenergetics. These approaches will establish the eIF5AHyp pathway and the singly hypusine moiety as a therapeutic target for TDP-43 in Alzheimer's Disease and Related Dementias (ADRD) and Limbic-predominant age-related TDP-43 encephalopathy (LATE).

Glial and innate immune activation are hallmarks of AD and TDP-43 proteinopathies although contribution to the etiopathology of the diseases is unclear. Microglia, are found in a highly activated state in the diseased brain as indicated by morphological alterations, proliferation, cell surface receptors, and secretion of cytokines and chemokines. In disease models, microglial activation can precede the emergence of TDP-43, Aβ and tau pathology, suggesting that inflammation is an early event.
Our laboratory investigates the role of inflammation in disease progression in tau and TDP-43 animal models.