Theus Laboratory

Michelle H. Theus, PhD

Assistant Professor
Molecular and Cellular Neurobiology
Department of Biomedical Sciences & Pathobiology
Duck Pond Drive Research Complex

About the Lab

We are an interdisciplinary research team focused on novel translational medicine strategies for central nervous system (CNS) repair. Our research endeavors are an integral part of the Virginia Tech/Wake Forest Center for Veterinary Regenerative Medicine, which aims to develop and test novel therapies for CNS, cardiac, musculoskeletal, and vascular disorders in animal and human health as part of our One Health Initiative.

Research Interests

Mechanisms of CNS injury and Repair: Vascular Remodeling; Neurogenesis; 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 tissue regions leading to preservation of function following vascular perturbation.

Our laboratory uses 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, traumatic brain injury (TBI) and hindlimb ischemia. We are also evaluating the effects of our genetic perturbations on the neurogenic response in the dentate gyrus of the hippocampus, a highly vulnerable region involved in cognitive decline following TBI.

Toward our long-term translational goal, we have begun testing the effects of a novel Eph blocking peptide for its pro-arteriogenic and neuroprotective properties. We are simultaneously developing a nanoparticle system and testing delivery methods which by-pass the blood brain barrier (BBB). In addition, we and others are investigating the novel 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 identify highly relevant and potent cellular pathways which can be targeted for pharmacotherapy to prevent neural tissue damage, limit progressive injury, 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.