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Biography

Dr. Cross has a BSE in Aerospace Engineering and a PhD in Neuroscience from The University of Michigan. Her research passion is to make a significant impact on the therapeutic and diagnostic options for neurological disorders and dementia through imaging. During her graduate studies, Dr. Cross developed in vivo manganese-enhanced MRI to evaluate axonal transport in rodents. She was the first to demonstrate in vivo age-related decline in transport rates and recovery of axonal connections in the olfactory tract after brain injury using an intranasal administration of paramagnetic MR contrast. During Dr. Cross’ tenure as junior faculty, this research expertise expanded to use imaging in studies of Alzheimer’s disease and traumatic brain injury in humans and animal models. Her research innovation is demonstrated by investigations with diverse application such as a new therapeutic approach for brain injury and neurodegeneration using intranasal administration of microtubule-stabilizing agents. Also, in collaboration with researchers at the VA Puget Sound Dr. Cross has been investigating the underlying neuronal substrate for the mild but persistent cognitive deficits presenting in veterans with mild traumatic brain injury from explosive blasts and the results were recently featured in Science Translational Medicine. Another innovative project collaborating with researchers in Environmental Science used FDG-PET to investigate human face recognition in wild American crows. Dr. Cross has active service with several national and international scientific organizations including Radiological Society of North America (RSNA): Research and Education Study Section, Program Committee, the Educational Exhibits committee, and Molecular Imaging Abstract Review Subcommittee, the Society of Nuclear Medicine and Molecular Imaging (SNMMI): Vice Chair for the Scientific Program Committee (Neurosciences), the Society for Neuroscience (SfN) and International Society for Magnetic Resonance in Medicine (ISMRM). Dr. Cross has recently moved to Salt Lake City to continue her research efforts at the University of Utah.

Abstract

Approximately 1.7 million traumatic brain injuries (TBIs) occur per year in the United States. In addition, TBI is a significant environmental risk factor for the development of neurodegenerative diseases such as chronic traumatic encephalopathy (CTE) and Alzheimer’s disease (AD). In TBI, shear forces generated by impact cause cytoskeleton misalignment and disruption of axonal transport followed by a cascade of metabolic and neuroinflammatory events. We hypothesize that cytoskeletal injuries may synergistically increase the initiation and progression of the neurodegenerative process. However, there is no effective pharmacological intervention to improve outcome in TBI or slow the neurodegenerative progress of Alzheimer’s disease. We propose that microtubule-stabilizing drugs under use as chemotherapeutics, may be administered in low doses to stabilize the cytoskeleton and to maintain axonal transport known to be disrupted in TBI and AD. Although, taxanes such as paclitaxel do not significantly penetrate across blood brain barrier, this limitation may be overcome by intranasal delivery. This research used preclinical neuroimaging (FDG-PET and MRI) combined with neurocognitive testing in mouse models of TBI and AD to show the therapeutic efficacy of intranasal paclitaxel. In addition, immunohistochemistry for AD pathology supported in vivo findings and the ability of the drug to restore axonal transport was shown using in vitro kinetic analysis of axonal dynamics. This study provides evidence of the efficacy for intranasally administered paclitaxel to improve outcome following TBI and to slow cognitive decline and development of pathology in AD. The use of in vivo neuroimaging for therapeutic development aids clinical translation.