Theus Laboratory

Michelle H. Theus, PhD

Associate Professor
Molecular and Cellular Neurobiology
Life Sciences I (MC0910)
970 Washington St. SW
Blacksburg, VA 24061

About the Lab

We are an interdisciplinary brain injury lab focused on discovering novel therapies for stroke and traumatic brain injuries. Our research endeavors are an integral part of Center for One Health and Regenerative Medicine, Integrated Health and Biomedical Sciences program and The VT School of Neuroscience.

Research Interests

Mechanisms of Brain injury and Repair: Cerebrovascular Remodeling, Neurogenesis and Innate Immunity

Leptomeningeal anastomoses or pial arteriole collaterals represent nature 'by-pass' vessels within the cerebrovascular network of the brain. Both their density and ability to remodel dictates the extent at which blood flow is restored to vulnerable brain regions following stroke.

Our laboratory uses a variety of unique cellular and molecular tools to investigate the mechanisms underlying the early pre-natal development and injury-induced remodeling of collaterals in the brain. Recently, we discovered that a member of the Eph RTK, notorious axon growth/guidance molecules, restricts collateral formation and perturbs key players involved in their outward growth and remodeling. We are currently investigating this novel suppressive pathway using a conditional gene targeted approach in murine models of stroke and traumatic brain injury (TBI). We are also evaluating the effects of our genetic perturbations on the immune regulation and aberrant neurogenic responses following cortical contusion and repeated diffuse mild TBI.

Toward our long-term translational goal, we have begun testing the effects of several novel Eph blocking molecules for their therapeutic potential in stroke and TBI. We are simultaneously developing a nanoparticle system and testing delivery methods which by-pass the blood brain barrier. In addition, we and others are testing the protective role of a newly discovered member of the NLR family in vascular function and innate immune activation following TBI.

The long-term goal of these studies is to better understand and target highly relevant pathways involved in brain injuries using novel genetic systems and state-of-the art pharmacotherapy to prevent tissue damage and promote functional recovery.

Facilities

Our surgical suite houses the eCCI device for TBI, multiple anesthesia units, stereoscopes, brain infusion pumps and stereotactic devices. It also houses a neurobehavioral core (Rotarod, beam balance, beam walk, novel object recognition and grip strength devices) and an x-ray irradiator for chimeric studies involving analysis of immune-derived regulation of vascular growth/remodeling.

We also employ a range of molecular and cellular techniques including but not limited to transgenic mouse models, gain- and reverse-of-function brain infusions, selective arteriole labeling, high resolution Laser Doppler imaging, confocal image analysis, and non-biased StereoInvestigator stereology.

Cerebrovascular labeling images
Cerebrovascular labeling. (A) Dye perfusion allows visualization of the pial collaterals. (B) Confocal image of dye labeled vessel and surrounding smooth muscle cell. (C-D) Endothleial cell-specific genetic labeling using double-reporter mice. (E-F) Histological and confocal analysis of reporter labeling.