Seale Innovation Fund

Improving Patient Outcomes After Heart Surgery

Scott Johnstone

Restoring blood flow to the heart surgically can be complicated by smooth muscle cells in the blood vessel wall dividing continuously afterward, eventually blocking blood flow again. The Johnstone lab has developed peptides that can block proteins that promote cell division, but peptides are poor agents for therapeutics. This research will design and test novel nanobodies, based on those peptides, that will be engineered to limit cell division. These therapeutic agents will act as a prototype for translational research aimed at improving patients’ lives after surgery.

Title: Identification of Cell-Permeable Nanobodies to Reduce Smooth Muscle Proliferation

Exploring Novel Treatments for Glioblastoma, Other Cancers

Samy Y. Lamouille

Glioblastoma cancer stem cells are resistant to radiation and chemotherapy. Failure to significantly eradicate these cells results in recurrence, making glioblastoma one of the most lethal diseases, with an average patient survival of 15 months. New treatment options are critically needed for this devastating disease. Lamouille will employ cutting edge molecular and microscopy techniques and clinically relevant models in vitro and in vivo to test a novel therapeutic approach specifically eradicating cancer stem cells. Because cancer stem cells are not unique to glioblastoma, this approach has broad implications in treating other types of cancer and preventing disease progression.

Title: Viral Vector-mediated Expression of a Therapeutic Peptide to Ablate Glioblastoma Cancer Stem Cells
Co-Investigator: James Weger-Lucarelli, Virginia-Maryland College of Veterinary Medicine

Investigating Stem Cell Dysregulation in Early Brain Development

Thomas Maynard

During development of the outer layer of tissue in the human brain, stem cells proliferate and diversify to eventually form the neural circuits that underlie cognitive behaviors. There’s a careful balance at play, and regulation of that balance is a target for better understanding a range of developmental disorders, including autism spectrum disorder and schizophrenia. This research investigates the connection between neural stem cell dysregulation and clinically defined neurodevelopmental disorders.

Title: A New Approach to Identify Cortical Stem Cell Pathology in Neurodevelopmental Disorders
Co-Investigator:  Anthony LaMantia, Fralin Biomedical Research Institute at VTC

Changing How We Study the Rhythms of Life

Steve Poelzing

Rhythmic electrical activity in excitable cells is necessary for life as we know it; some spontaneously excite on their own. Scientific understanding of this activity arises from studying what happens inside isolated cells, which has prevented the development of effective therapies to treat abnormal electrical activity in the brain (epilepsy), the heart (sudden cardiac death), the gut (intestinal pseudo-obstruction), and the uterus (premature birth). This research seeks to determine whether the outside of the cell, rather than the inside, can provide a more complete understanding of the rhythms of life and point toward new therapies.

Title: An Outside-In View on Cellular Automaticity: Changing How We Study the Rhythms of Life
Co-Investigator:  Gregory Hoeker, Sharon Swanger, Fralin Biomedical Research Institute at VTC

Developing a Better Understanding of Stress, Inflammation, and Chronic Pain

Sora Shin

Numerous studies have shown that stress, including early life trauma in the form of child abuse or neglect, induces long-lasting changes in the immune system. Specifically, researchers are interested in stress-induced altered sensitivity to pain, as many people who suffer from chronic pain also experienced early life trauma. This research seeks to better understand the neural circuits and connections between trauma, abuse and changes in an individual’s pain response and is a novel exploration of the impact of specific neurons on inflammation and chronic pain.

Title: Role of the Midline Thalamic Network in Top-Down Control Of Stress-Induced Hyperalgesia

Novel Therapies to Treat Heart Failure in Patients with Type 2 Diabetes

Junco Warren

Heart failure is a leading cause of death and hospitalization in the United States, and diabetes is a major risk factor. Patients with type 2 diabetes often suffer from heart failure in which the left ventricle is too stiff to function properly. While the number of patients with the diagnosis has increased, the treatment of those patients has been challenging, in part due to the complexity of the way the disease develops. Warren's work seeks novel therapies to treat heart failure in patients with type 2 diabetes.

Title: Novel Therapeutic Approach to Treat Heart Failure Patients with Type 2 Diabetes

Taking Aim at Deadly Pediatric Brain Cancer

Jia-Ray Yu

Diffuse midline glioma is  the  most  aggressive  form  of  pediatric  brain  cancer, with  no  effective therapy. The five-year survival rate is less than 1 percent. Development of targeted therapies is a challenge because the condition’s mutations are unsuitable for drug therapy. Researchers have identified two enzymes that show promise as targets for combination therapies, however. The objective of this research is to investigate the biology of those enzymes and uncover potential targets for combination therapies to treat this uncurable disease.

Title: Synthetic Lethality Screening for Druggable Factors that Amplify a Cancer Dependency in Diffuse Midline Glioma
Co-Investigator:  Wei Li, Javad Nazarian, Children’s National Research Institute