Understanding the genetics behind hemophilia could help develop new treatments for patients
As a hematologist, Qizhen Shi, MD, PhD, has made it her mission to study new therapies for patients with bleeding disorders—specifically, hemophilia A. She began her tenure at Versiti Blood Research Institute as a fellow under Senior Investigator Robert Montgomery, MD, whose research focuses on bleeding disorders like hemophilia and von Willebrand disease, the most common bleeding disorder. As one of the premier blood health research institutes in the country, Versiti Blood Research Institute attracts blood health experts from around the world to conduct their research at the facility. This critical mass of expertise promotes an environment of collaboration and knowledge sharing—something Dr. Shi attributes to her reason for joining the team and her inspiration for expanding her research interests to include topics like gene therapy in hemophilia, stem cells and immunology.
“This Institute is unique … The investigators within the Institute have a variety of interests, from hemostasis and vascular biology to immunology and stem cell biology,” Dr. Shi says. “It’s a very collaborative environment.”
Currently, Dr. Shi’s research focuses on gene therapy, which targets platelets and the proteins that cause hemophilia. Factor VIII is a protein that circulates in blood and helps blood to clot if an individual is injured. Too much factor VIII can cause dangerous blood clots, but too little factor VIII can result in a bleeding disorder. Patients with hemophilia A experience a deficiency of factor VIII, which means they bleed more easily and their blood doesn’t clot properly, putting them at risk for serious health concerns. Proteins like factor VIII have short lives, so patients often require regular factor infusions (a replacement of the missing factor VIII) to treat their disease.
But there’s a catch: repeated factor VIII infusions can cause approximately 30% of hemophilia A patients to develop antibodies to the replacement factor VIII, rendering it ineffective. These patients still need factor VIII to help their blood clot—so how do they replace it if the factor infusions don’t work?
Dr. Shi is interested in genetically engineering hematopoietic stem cells, which exist in the bone marrow and give rise to blood cells, including platelets, which can serve as both a storage depot and trafficking vehicle in circulation. She hopes that engineering hematopoietic stem cells with the factor VIII gene and directing factor VIII expression to platelets will provide a cure for all patients with hemophilia A—including the ones with antibodies—as platelets can then deliver factor VIII to the right place at the right time.
Dr. Shi is hopeful that similar genetic engineering methods could be used in the future to treat patients with other conditions, including autoimmune diseases.
Versiti Blood Research Institute Senior Investigator Qizhen Shi, MD, PhD, is also a professor of pediatric hematology in the Department of Pediatrics at the Medical College of Wisconsin.