Safadi Pilot Grant Recipients 2018

Fifteen applications were received by the designated deadline, reviewed and scored by three senior neuroscientists, two from the university of Chicago and one extramural reviewer. Two applications tied for best composite score, reflecting summed grades on (1) innovation; (2) scientific rigor, (3) uniqueness of opportunity, infrastructure, milieu; (4) multidisciplinary perspective, broadening neuroscience; (5) translational potential, clinical and disease relevance; and (6) future direction, impact potential. Congratulations to our two awardees!

Le Shen, PhD

Cell biologist working in the Department of Surgery, in collaboration with research teams in Pathology and Digestive Diseases research.

EFFECT OF CEREBRAL CAVERNOUS MALFORMATION GENES ON INTESTINAL EPITHELIUM

LeShen.jpgCerebral cavernous malformation (CCM) is a cause of brain hemorrhage at young age. Mutations in CCM disease genes cause disruption of brain endothelial barrier, and leaky junctions between individual small blood vessel cells. Given potentially similar mechanisms maintaining gut epithelial barrier, Dr Shen proposes that patients with CCM mutations also have a leaky gut, and may be predisposed to inflammatory bowel disease. He will perform pilot studies to test if mutations of these genes also affect cell-cell connections in epithelium.LeShenSafadi.pngHe will initiate animal models of inflammatory bowel disease, where CCM mutations can be tested in mice, and he will show feasibility of analyzing the fecal specimens of patients with familial CCM disease, to confirm whether their microbiome reflects increased gut permeability. The research establishes novel collaborations between the neurosciences and the rich digestive and microbiome research communities at the University of Chicago. It promises to uncover a new mechanism of gut disease, through the actions of brain disease genes.

Sean Polster, MD

Neurosurgery resident, working in the Section of Neurosurgery, in collaboration with Neuropathology, and the Center for Research Informatics

DIFFERENTIAL TRANSCRIPTOME OF HUMAN CEREBRAL HEMORRHAGIC MICROANGIOPATHY

Polster.jpgHemorrhagic stroke results from the weakening of small brain blood vessels, often many years preceding the symptomatic event. Ample opportunities to prevent a lethal or disabling stoke are presented by known mechanisms governing the weakening of blood vessels, many of which are reflected by differentially expressed genes in weakened blood vessels. PolsterGrantImages.PNGDr Polster proposes to build on expertise and infrastructure in the Neurovascular Surgery Research laboratory with differential transcriptome of diseased endothelium, the lining of blood vessels, in genetic diseases predisposing to hemorrhagic stroke. He will use laser capture microdissection to isolate endothelium from sample autopsy specimens of human brain tissue with hemorrhagic brain lesions and isolate their RNA. He will analyze the differentially expressed genes in this tissue in comparison to normal human brain vessel lining, and datasets from the genetic diseases already studied. He hopes to define common genes defining leaky blood vessels, and these can serve to identify biomarkers of disease in future career development project.