Ian F. Kimbrough
- B.S. in Molecular Biology, University of Alabama
- Ph.D. in Neurobiology, University of Alabama at Birmingham
Dr. Kimbrough joined the Virginia Tech School of Neuroscience in February 2016. The main focus of his research is investigating the role of the gliovascular interface in neurobiology and neurological disease.
Prior to starting his PhD graduate training at the University of Alabama at Birmingham (UAB), Dr. Kimbrough initially began his professional career in digital media. Ultimately, however, he was drawn to a more scientific and research focused-career, culminating in his obtaining a doctorate in Neuroscience. Transitioning to a research career, he has translated his advanced technical skills and passion for digital media design into the field of neurobiology, specifically in microscopy, image analysis, and image processing.
Specializing in live in vivo imaging, Dr. Kimbrough uses multi-channel multi-photon laser scanning microscopy to investigate cerebral vasculature biology and pathology in various neurological disease models, including brain tumors and Alzheimer’s disease. Incorporating his technical background during his graduate and postdoctoral training, he established novel in vivo and ex vivo imaging techniques, as well as analysis protocols, allowing greater insight into the pathogenesis of these diseases. His current interest is investigating the mechanisms and consequences of gliovascular uncoupling and the resulting breakdown of the blood-brain barrier that commonly occur in neurological disease
- The main focus of my research is to better understand the biology of the gliovascular unit and how its dysfunction contributes to neurological disease.
- Our current focus is exploring the role of vascular amyloid in the pathogenesis and progression of Alzheimer’s disease. Vascular amyloidosis, the pathological accumulation of amyloid beta on the vasculature, is prevalent in the Alzheimer’s brain, especially in advance stages of the disease. Buildup of this amyloid progressively impairs distinct aspects of neurovascular function. We have discovered that the presence of vascular amyloid decreases astrocytic vasoregulation and cerebral blood flow, creating areas of brain tissue that are inadequately perfused, and consequently, at risk of dying. Additionally, amyloid causes displacement of astrocytic endfeet, which are responsible for ensuring expression of endothelial tight junction proteins that form the blood-brain barrier (BBB). Displacement of these endfeet from blood vessels causes a breach in the BBB, exposing the brain to blood-born toxins, including albumin and glutamate. Astrocytes are also instrumental in communicating the neuronal energy demand to the vasculature, regulating the constriction or dilation of blood vessels through the local release of 20-HETE and prostaglandin-E2, respectively. Overall, the loss of astrocytic endfeet interaction with the vasculature due to amyloid buildup impairs the BBB integrity, interferes with astrocyte-mediated vascular regulation, and may also lead to seizures and neuronal toxicity due to unregulated entrance of toxic molecules from the periphery.
- To further explore the role of the BBB in neurological disease, we investigated the interaction of glioma (brain tumor) cells with the vasculature. Using our xenoline glioma model, we found that glioma cells are able to intercalate between astrocytic endfeet and the vasculature, similar to amyloid beta in Alzheimer’s disease. However, not only does the presence of glioma cells on the blood vessels interrupt the astrocytic endfoot placement causing a disruption of the BBB and astrocytic vascular regulation, we discovered that these malignant cells are able to usurp functional control of the vessels. In order for glioma cells to grow and survive, they require access to a nutrient source, which can become challenging in a fast growing tumor mass. Their ability to control vascular regulation enhances their ability to access blood-derived nutrients, ensuring better survival. Additionally, glioma cell metastasis in the limited extracellular space of the brain requires space for cells to move. We know that glioma cells preferentially migrate along the vasculature, and the ability to vasoregulate independently of astrocytes allow them to constrict blood vessels as needed, creating space for migration and metastasis. Once these cells establish a new site to set up a satellite tumor, they are then able to vasodilate the vasculature, increasing their nutrient availability. In order to further elucidate these mechanisms, we have developed a novel epicortical xenograft method of intracranial tumor implantation in conjunction with in vivo multi-photon and ex vivo confocal laser scanning microscopy. Understanding the mechanisms of glioma-mediated vascular co-option is important to better understand glioma biology and may offer new and effective treatment options for patients.
- Guo Y, Shan Jiang, Benjamin Grena, Kimbrough IF, Emily G. Thompson, Yoel Fink, Harald Sontheimer, Tatsuo Yoshinobu and Xiaoting Jia. Polymer composite with carbon nanofibers aligned during thermal drawing as a microelectrode for chronic neural interfaces. ACS Nano. 2017 Jul 25;11(7):6574-6585. doi: 10.1021/acsnano.6b07550. Epub 2017 Jun 13. PMID: 28570813
- Kimbrough IF*, Robel S*, Roberson E, Sontheimer H. (2015). Vascular amyloidosis impairs the gliovascular unit in the hAPPJ20 mouse model of Alzheimer disease. BRAIN. PMID: 26598495
- Watkins S, Robel S, Kimbrough IF, Robert SM, Ellis-Davies G, Sontheimer H. Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells. Nat Commun. 2014 Jun 19;5:4196.
doi: 10.1038/ncomms5196. PMID: 24943270
For a full list of Dr. Kimbrough's publications, visit PubMed.
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Translational Neuroscience Laboratory
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