NHF 70th: Pursuing Discovery of the Next Generation of Therapies
Since its founding 70 years ago, NHF has played a pivotal role in advancing breakthrough research into bleeding disorders—through $25 million in funding—and championing the careers of promising investigators. Continuing that legacy, the NHF Innovative Investigator Award was inaugurated last fall to support cutting-edge research projects that promote the development of novel technologies and/or therapies.
The first two award recipients are: Shannon L. Meeks, MD associate professor at the Emory University School of Medicine in Atlanta; and Jill M. Johnsen, MD, associate member of Bloodworks Northwest Research Institute and associate professor at the University of Washington in Seattle. In the first installment of a two-part series, Dr. Meeks discusses her project and why she decided to pursue a career in bleeding disorders research.
Describe the research you will conduct with this award.
This project serves to further develop a novel delivery system for factor VIII, a vital blood-clotting protein that was developed by Drs. Caroline Hansen and Wilbur Lam. In this system, a “carrier vehicle” called a polyelectrolyte multilayer (PEM) capsule is loaded with human factor VIII. On its surface, the PEM capsule has fibrinogen—a protein present in blood plasma that is essential for blood clot formation—so when injected intravenously platelets bind to form a platelet hybridized capsule. When the platelets are activated at the site of an injury, they contract, bursting the capsule and releasing the factor VIII contained within.
The PEM capsules have been shown to work in vitro—outside a living organism—so the next step in drug development is to put them into an animal model. We already have a well-established murine (mouse) model of hemophilia A in which we have evaluated a number of treatment methodologies for mice with and without inhibitors. This project will test the efficacy of these PEM capsules for the treatment of bleeding in hemophilia A mice with and without inhibitors. It will also provide some safety data about how the mice tolerate injections of the PEM capsules.
What ultimately are you hoping to achieve with this research?
My goal is to test the efficacy of this novel factor VIII delivery system in our mouse model. If the PEM capsule can treat bleeding in hemophilia A mice and/or hemophilia A mice with inhibitors, we can begin to work towards larger animal models and ultimately patients. One of the most intriguing parts of this delivery system is that it could easily be adapted to carry factor IX for patients with hemophilia B and other factors or drugs as well.
How do you believe this award will help advance your research?
The novel factor VIII delivery system I am studying looked extremely promising in the in vitro testing. However, initial studies of in vivo—within a living organism—safety and efficacy are needed to secure larger amounts of funding. NHF’s Innovative Investigator Award will provide us with the opportunity for these initial “first in animal” experiments that are critical for this project to move forward.
Why did you pursue the field of bleeding disorders and what keeps you in it?
My undergraduate degree is in mathematics and I was always drawn to solving complex puzzles. As a student at Duke University, I had the opportunity to spend a couple of summers working in the Mississippi Children’s Cancer Clinic. While there, I became intrigued by the intricate balance of the coagulation system and as I advanced in my training that curiosity grew. So by the time I was applying for fellowships, my focus was hemostasis and thrombosis. As a fellow, I also began pursuing basic laboratory research in the immune response to factor VIII and now continue as a physician-scientist. The ability to treat patients while taking questions and needs back from the bedside to the laboratory to attempt to learn more and improve treatments keeps me engaged in the field.
From your perspective as a physician-scientist, how important is NHF’s funding of research to the advancement of care for people with bleeding disorders?
NHF’s ongoing support of both physician training and novel research is crucial. And for researchers like me, this funding makes it possible for us to pursue the discovery of the next generation of therapies and what we hope will one day be cures.
On a personal note, this is my second award from NHF. Previously, I received an NHF Clinical Fellowship, which was the very first award of my career. That fellowship launched my work in the field of hemophilia, which has truly enriched my life. But my experience is not unique. NHF support has launched and sustained the work of many researchers through the years and, in so doing, has helped accelerate important advances in the field of bleeding disorders while ensuring that patients have access to highly trained experts in the field.