Funded by Foundation

Swimming is an important life skill that benefits hemophilia patients medically and psychosocially. The goal of this project is to provide inner city children and teenagers the opportunity to learn how to swim. The swim program will be held at the Detroit Medical Center, where a team of professionals will teach the basics of swimming with the goal of independent swimming by the end of the program. The team will measure the children's progress medically and psychosocially throughout the program. This program will provide children and teenagers at our HTC with an amazing opportunity and also a very important life skill. We will also be using adult hemophilia patients to teach the children how to swim, which will provide them with work experience and community involvement.

Dr. Satish Nandakumar is currently a postdoctoral fellow in the laboratory of Dr. Vijay Sankaran at the Boston Children's Hospital. Previously, he did his graduate work at the St. Jude's Children's Research Hospital in Memphis, Tennessee. In his JGP Fellowship project, Dr. Nandakumar aims to develop a novel gene therapy approach for hemophilia that involves activation of the endogenous factor VIII or IX genes within hematopoietic stem cells by taking advantage of the CRISPR/Cas9 gene activation system. This work has the potential to benefit patients with mild hemophilia mutations.

Dr. Meeks is an Associate Professor of Pediatrics in the Department of Pediatrics at the Emory University School of Medicine and the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta. She obtained a Bachelor of Science in Mathematics from Duke University where she was elected to Phi Beta Kappa. After earning her medical degree from the University of Mississippi, she completed her clinical training at the University of Virginia and Emory University. Dr. Meeks has a basic, translational, and clinical research interest in the development of inhibitors in hemophilia A. Her work has focused on the early immune response to factor VIII and the diversity of the B-cell response to factor VIII. She is a former NHF clinical fellow who currently has funding to pursue these projects from the Hemostasis and Thrombosis Research Society and the National Institutes of Health.

The purpose of this project is to request support for the development of a Virtual Reality Environment (VRE) study program for pediatric patients diagnosed with hemophilia. The VRE program proposed was developed and created for children and includes interactive imagery, character avatars and colorful visual environments. This VRE program will be deployed by the child in a clinical setting and is proposed to help decrease, anxiety and needle phobia during intravenous factor infusions. Outcome measures will include an anxiety scale before and after each infusion, collection of biophysiologic data, pain score and visual analogue evaluation. The expected result of this nursing project is to monitor the use of a VRE in the pediatric population with a reduction of fear, anxiety and pain experienced with intravenous factor infusions.

Preliminary work done by Dr. Riten Kumar and colleagues has documented that moderate intensity exercise is associated with a significant improvement in multiple coagulation parameters in post-adolescent males with mild-moderate hemophilia A. As a continuation to our previous work, we now hope to compare the impact of moderate intensity exercise to DDAVP on laboratory coagulation parameters in post-adolescent males with mild hemophilia A. We also hope to investigate the impact of sequentially administering these interventions on hemostatic indices. Our over-arching hypothesis is that increase in coagulation parameters (particularly FVIII:C) with moderate intensity aerobic exercise would be non-inferior to DDAVP. We additionally hypothesize that we will appreciate an additive effect of sequentially administering clinical implications for patients with MHA. It may negate the use of DDAVP pre- exercise and could potentially lead to clinicians advising patients to appropriately warm-up (e g running), to raise their FVIII/VWF levels prior to undertaking more rigorous sports. It will also lay the foundation for future studies investigating the interaction between aerobic exercise and hemostasis in subjects with bleeding disorders these interventions. Should our hypothesis be correct, our study would have significant clinical implications for patients with MHA. It may negate the use of DDAVP pre-exercise and could potentially lead to clinicians advising patients to appropriately warm-up to raise their FVIII/VWF levels prior to undertaking more rigorous sports. It will also lay the foundation for future studies investigating the interaction between aerobic exercise and hemostasis in subjects with bleeding disorders.

It is unknown if there are differences in attitudes and behaviors between mothers of sons with hemophilia who have a known family history of hemophilia compared to mothers without a known family history. To capture these differences, this study will measure mothers' perceived vulnerability of their sons, protective behaviors toward their sons and reported stress in the mother-son relationship. Sixty mothers will complete the following surveys: Parent Protection Scale, Child Vulnerability Scale and Parenting Stress Index/Short Form. The results of this data will influence clinic social work practice in the comprehensive care model at hemophilia treatment centers.

Dr. Tine Wyseure obtained her Master’s degree in Drug Discovery and Development, and earned her Ph.D. in Pharmaceutical Sciences at the University of Leuven, Belgium. Since 2015, she has been a research associate in the lab of Dr. Laurent Mosnier at The Scripps Research Institute in San Diego. Dr. Wyseure’s 2016 JGP research fellowship award project is focused on investigating the effects of impaired TAFI activation in hemophilia on the progression of hemophilic joint disease. The lack of active TAFI worsens joint bleeding and chronic inflammation and drives the striking development of fragile blood vessels in diseased joints. In search of the missing link, Dr. Wyseure has discovered a novel paradigm on how the formation of new blood vessels is controlled by TAFI and suggests that patients with hemophilia may lack this control switch, causing the formation of unstable and leaky blood vessels.

Klaus Bonazza received his Ph.D. in chemistry from Vienna University of Technology. He is currently a postdoctoral researcher at Boston Children's Hospital and appointed at Harvard Medical School, mentored by Dr. Timothy Springer. His field of interest is the ultra-large concatemeric protein von Willebrand factor (VWF), which accounts for the adaptability of hemostasis to different flow conditions in the blood vessels.

At moderate, physiological flow VWF has a packed, "bird nest's" shape whereas strong elongational flow conditions, occurring downstream of vascular restrictions or injuries, induce a transition to a threat-like, elongated state. On top of this overall unpacking, tensile forces, which are exerted on the chain and transmitted by its A1 domain, cause local conformational changes which activate binding of thrombocyte receptor Glycoprotein Ib (GPIbα) to initiate coagulation. With his JGP fellowship award, Dr. Bonazza will pioneer a new method to obtain structural insights into force dependent VWF unpacking, A1 deformation and GPIbα binding based on hydrogendeuterium exchange under elongational flow conditions.

Dr. Megan Rost is a postdoctoral fellow at the University of Michigan. She received a B.S in biochemistry and biotechnology from Michigan State University, and her Ph.D. in molecular and developmental biology at the University of Cincinnati - Cincinnati Children's Hospital Medical Center. Her graduate work focused on understanding vascular endothelial development using zebrafish as a model organism. In July 2015, she joined the lab of Dr. Jordan Shavit in the Department of Pediatrics and Hematology/Oncology at University of Michigan. For her 2016 JGP research fellowship project, she will be using the zebrafish model to analyze blood clot structure and function in the presence and absence of von Willebrand Factor. In studying this, Dr. Rost will be elucidating how arterial thrombus formation occurs in the absence of VWF, aiding in uncovering possible new therapeutic targets for VWD treatment.

The project's ultimate goal is to expand nursing knowledge of hemarthrosis/soft-tissue bleeding detection by presenting our HTC's experience with how MSKUS improves accurate diagnosis and guides treatment of bleeding and other pain etiologies. By completing the retrospective data review, we hope that the experience of a large center HTC spanning both adults and pediatrics will be made available. We believe that the current restraints of MSKUS implementation include cost of equipment, operator certification, and quality of interpretation to guide interventions. Therefore, partnering with radiology experts may be helpful for other HTCs around the country when using this modality in the future. Our center's experience will show that collaboration with radiologists for real-time imaging is successful with nursing evaluation and coordination.

Social workers have been active members of the multidisciplinary teams of hemophilia treatment centers for many years, but the roles of these social workers may differ greatly from center to center. Social workers are often the advocate for patients and a primary source of assistance, information and referral. In many HTCs, they also provide counseling and therapy services to patients and consultation to staff. Indeed, these social workers appear to provide a wide variety of psychosocial and case management services to patients with bleeding disorders and their families. This research project will attempt to describe the various role tasks of hemophilia treatment center social workers, describe these tasks and identify the influences of the role in each HTC. An online survey will be developed and emailed to the approximately 135 HTC social workers across the nation. Data will be analyzed and shared with the social worker community through sessions and posters and the NHF annual meeting.

Dr. Laura Sommerville graduated cum laude from Messiah College and then obtained her MS and PhD degrees in cellular and molecular biology from Temple University. Her graduate work and doctoral dissertation produced several awards and publications in peer reviewed publications. She has been a postdoctoral fellow in the laboratory of Dr. Maureane Hoffman at Duke University since July 2014. Dr. Sommerville's 2015 JGP research fellowship award project is on understanding the loss of perivascular tissue factor during angiogenesis in hemophilia.

Dr. Christopher Ng was a pediatric hematology/oncology fellow at the University of Colorado - Anschutz Medical Campus. Dr. Ng attended medical school at the Keck School of Medicine at the University of Southern California and completed his pediatrics residency at the University of Washington/Seattle Children's Hospital. Dr. Ng received the NHF-Baxalta Clinical Fellowship in 2013. Dr. Ng's 2015 JGP research fellowship award project focused on a multi-system evaluation of von Willebrand factor function in Type 1 von Willebrand Disease mutations.

Dr. Noh's research will utilize induced pluripotent stem cells (iPSC) and manipulate them in vitro to expand production of megakaryocytes and platelets that express therapeutic proteins, including FVIII. The project will further determine whether this system of autologous platelets which overexpress FVIII can be delivered directly to the site of injury and hemorrhage, thereby circumventing and evading neutralization by alloantibody inhibitors in hemophilia A. Dr. Noh received her Ph.D. in Preventive Pharmacology from Seoul National University in South Korea. She has been a postdoctoral fellow in Dr. Mitchell Weiss' lab at The Children's Hospital of Philadelphia since 2012. Dr. Noh is currently being mentored in this JGP project by Dr. Mortimer Poncz at CHOP.

Dr. Chappell's research project will develop a model for characterizing bleeding in hemophilia and particularly in joints. Using mouse models of hematoma formation and knee joint bleeding, Dr. Chappell will use 3D fluorescent imaging technology in "living" hemophilia B mice to better trace bleeding over time- from induction of a bleed to its resolution. This project will provide additional insights on the basic science underlying hemophilic bleeds, not to mention the optimal interventions and timing of treatment to potentially prevent damage caused by bleeds. Dr. Chappell earned her Ph.D. in Pharmaceutical Sciences from UNC Chapel Hill in 2013. She will pursue her research under the mentorship of Dr. Dougald Monroe, Professor in the Division of Hematology/Oncology, UNC School of Medicine and the UNC McAllister Heart Institute.