Funded by Foundation

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.

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. 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. Parthasarathy's research will tackle two important biological issues in coagulation - namely how procofactor FVIII converts to the active cofactor form (FVIIIa) and binds to IX and X, and the location of FVIII in generating the active Xase complex. Results from this study will provide molecular and biochemical insights into the role of FVIIIa in regulating hemostasis and further elucidate the interactions between coagulation complexes. Dr. Parthasarathy obtained his Masters in Biotechnology from Jawaharlal Nehru University in New Delhi, India and received his Ph.D. in Biochemistry from the University of Kansas in 2011. He has been a postdoctoral researcher in the lab of Dr. Rodney Camire at The Children's Hospital of Philadelphia since July 2011. This award has been made possible through a generous donation from Hemophilia of Georgia, Inc.

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.

Per Dr. Fu, the JGP provided her with the opportunity to work on hemophilia, as well as von Willebrand disease. After the completion of her JGP project, Dr. Fu remained in the bleeding disorder field.

The goal of Dr. Chen's research is to examine a method for selectively expanding hematopoietic stem cells expressing the factor VIII transgene. She will also examine the immune consequences of this approach, based on the idea that gene transfer in platelets evades immune recognition. This research has the potential to elicit important clues to developing an approach for gene therapy of hemophilia A and hemophilia A with inhibitors.

Dr. Chen earned a PhD in hematology from Fujian Medical University in China. She already has more than 27 papers published in the Chinese medical literature. Her research in hemophilia and gene therapy will be under the mentorship of Dr. Qizhen Shi, MD, PhD, Associate Investigator at the Blood Research Institute and Assistant Professor of Pediatric Hematology at the Medical College of Wisconsin.

Dr. Yee earned his undergraduate Credentials from Rensselaer Polytechnic Institute before receiving his doctorate from Rice University. His eventual goal is to operate an independent research laboratory in the field of bioengineering with a focus on understanding molecular mechanisms of hemostasis, thrombosis and vascular diseases. Dr. Yee's research project deals with factor VIII and its adhesion to its chaperone protein, von Willebrand factor. In these experiments, fragments of von Willebrand factor are screened for optimal factor VIII stabilization. By further studying the architecture of the "Factor VIII-von Willebrand Factor" complex, Dr. Yee seeks to gain insight to improve designs of novel therapeutics.