A deadly complication known as hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) can occur after bone marrow transplant, a curative therapy for malignancy. HSCT-TMA results in injury to small blood vessels throughout the body, preventing red blood cells from delivering oxygen to tissues. This can damage multiple organs, especially the kidneys. The cause of the disorder is unknown and there are limited effective drug therapies, making diagnosis and treatment difficult.

Choroid plexus carcinoma (CPC) is a rare, aggressive brain cancer arising from the choroid plexus (ChP), a highly complex tissue within the brain's ventricles that produces cerebrospinal fluid. CPC is most often diagnosed in young children, and the only hope for survival is usually total removal of the tumor through surgery. However, this surgery is often complicated due to large tumor size at diagnosis, tumor invasion of nearby brain tissue, and complicated networks of blood vessels in CPC that bleed significantly in the operating room.

Intrinsically disordered protein regions (IDRs), part of the “dark matter of biology”, are extremely abundant in the protein kingdom. How IDRs perform functions in the cell is not well understood due to a lack of tools to study them. Since numerous known disease mutations occur in IDRs, our lack of understanding of IDRs represents a major hurdle for developing therapeutics. My lab strives to understand how IDRs play a role in regulating gene transcription in the context of physiology and disease.

Ewing sarcoma (EwS) is a malignant cancer of bone and soft tissues that occurs mainly in children, adolescents and young adults. Currently, combinations of intensive chemotherapy, surgery and radiation are only 70% effective for localized tumors, and these therapies can cause lifelong health problems in survivors. If the tumors spread, fewer than 1/3 of patients will survive. New therapeutic advances are needed that are more effective with fewer toxic side effects.

Ewing sarcoma is an aggressive cancer that primarily affects children and adolescents. There are no targeted therapies for Ewing sarcoma and the prognosis upon relapse or metastasis is bleak for most patients. The major vulnerability of Ewing sarcoma, the fusion protein EWS::FLI1, has proven to be undruggable despite heroic efforts by many research groups. We are proposing an entirely novel approach that will uncover new, high-resolution structural insights about behavior and properties of the EWS::FLI1 fusion.