Funded by Foundation

Bhavya Doshi, MD, is a pediatric hematologist and just accepted a new faculty position at Emory University in Atlanta, GA where the hemophilia group has been well-established in the study of factor VIII inhibitors. Dr. Doshi specializes in caring for children with bleeding and clotting disorders. She completed her medical training and pediatric residency at Emory University School of Medicine in Atlanta, GA and her pediatric hematology/oncology fellowship at the Children’s Hospital of Philadelphia. Dr. Doshi is a physician scientist with expertise in basic and translational approaches to improving diagnostics and therapeutics for patients with bleeding and clotting disorders. Her laboratory conducts research focused on the development, persistence, and management of neutralizing antibodies to protein replacement therapy and gene therapy in hemophilia. Her work has identified hemophilia A patients with anti-factor VIII antibodies who may be amenable to alternative treatment modalities whether bypassing agents or immunosuppressive regimens. Dr. Doshi’s work aims to identify B cell signatures that are altered in patients with alloantibody responses to therapeutics and leverage these for therapeutic development.

Our research focuses on understanding why some people with hemophilia A develop inhibitors that make treatment less effective, especially with new non-factor therapies. We aim to uncover how certain immune responses, like cytokine and cell activity, contribute to the development of these inhibitors. Specifically, we are studying a protein called BAFF and its role in influencing immune cells, though it’s still unclear what causes high BAFF levels. Our findings could lead to new biomarkers and treatments for preventing inhibitor development.

Dr. Hollenhorst is Associate Physician at Brigham and Women’s Hospital, Division of Hematology, and Instructor of Medicine at Harvard Medical School. She is a physician and scientist with an interest in hemostasis and thrombosis.

Dr. Hollenhorst pursued combined MD and PhD training at Harvard University, where she received a PhD in Chemical Biology under the mentorship of Professor Christopher T Walsh. She subsequently completed a residency in Internal Medicine at Brigham and Women’s Hospital, a fellowship in Transfusion Medicine at Harvard Medical School, and a fellowship in Hematology at Stanford University. While at Stanford she worked in the laboratory of Professor Carolyn Bertozzi at the Chemistry, Engineering, and Medicine for Human Health (ChEM-H) Institute, and served on the clinical faculty in Hematology and Transfusion Medicine.

In 2023, Dr. Hollenhorst opened her laboratory at Brigham and Women’s Hospital and Harvard Medical School. Her lab uses chemical techniques to study glycoproteins that are important for bleeding and clotting disorders. She has a clinical practice focused on hemostasis and thrombosis.

His project aims to directly address current limitations of hemophilia A gene and protein therapy by the identification and characterization of new hyperactive factor VIII variants based on his previous studies of hyperactive factor IX variants. He will take a rational approach to identify such variants focused on amino acid substitutions that can enhance factor VIII cofactor activity while maintaining physiological regulation, which will facilitate their translation into therapeutics. In vivo murine studies of efficacy and immunogenicity will provide the basis for subsequent translational studies.

Dr. Ze Zheng is an Assistant Professor at the Medical College of Wisconsin and an Assistant Investigator at the Versiti Blood Research Institute (Blood Center of Wisconsin). She received her MBBS in Clinical Medicine from Jiamusi University in China, and her PhD in Molecular Medicine and Genetics, focusing on liver metabolism, from Wayne State University in Michigan. During her postdoctoral training in Dr. Ira Tabas lab at Columbia University, she found a novel source and regulation of basal plasma tissue-type plasminogen activator (tPA) derived from hepatocytes, which is important for fibrinolysis when a vessel injury occurs. Dr. Zheng recently joined the Medical College of Wisconsin in July 2020 and established her research laboratory in the Versiti Blood Research Institute with access to state-of-the-art facilities and group meetings with established investigators in hemostasis and bleeding disorders. Dr. Zheng has been the recipient of a Berrie Scholar Award, an ASH Scholar Award, an AHA Career Development Award, and a Cullen Run COVID-19 Rapid Response Grant. 

As the 2020 recipient of the NHF Career Development Award, Dr. Zheng will be studying the mechanism of increased fibrinolysis in severe hemophilia patients in collaboration with the Comprehensive Center for Bleeding Disorders at Versiti Blood Center of Wisconsin. This work will explore novel therapeutic strategies to reduce basal fibrinolysis and bleeding symptoms in severe hemophilia patients. 

Moanaro Biswas, PhD, is currently an Assistant Professor in the Gene and Cell Therapy Program at the Herman B Wells Center for Pediatric Research at Indiana University, Indianapolis. She was appointed to this position in May 2018. She received her Masters and PhD in Biotechnology from India. She joined the University of Florida in 2013 as a Postdoctoral Research Associate and was subsequently appointed a faculty position in the department of Pediatrics at UF in 2017. She is mentored by Dr. Roland W. Herzog, a distinguished professor with extensive expertise in gene therapy for hemophilia. While at the University of FLorida, she received the Henry A. Kokomoor Award for excellence in Pediatric Research in 2017. Dr. Biswas has been the recipient of an early career investigator award from Bayer in 2016. Dr. Biswas is interested in studying cell and gene therapy-based treatments for combating inhibitor formation in hemophilia, As the 2018 recipient of the NHF/Novo Nordisk Career Development Award, which is made possible by a generous gift from Novo Nordisk, Dr. Biswas will be researching engineered Treg therapy for tolerance induction in hemophilia A. Chimeric antigen receptor (CAR) expressing Tregs, made specific for FVIII, will be tested in a murine model of hemophilia A. She will explore at the cellular and molecular level, interactions between antigen-specific CAR-Tregs and immune cell types involved in the development of inhibitors to FVIII.

The National Hemophilia Foundation (NHF) is pleased to announce Christopher J. Ng, MD, Assistant Professor of Pediatrics, University of Colorado Denver, as the recipient of the 2017 NHF/Novo Nordisk Career Development Award (CDA). The overall objectives of the CDA are to advance bleeding disorders research by promoting the development of innovative studies among established investigators. The award funds basic, pre-clinical or clinical research approaches to yielding scientific information or answers contributing to better treatments for inheritable bleeding disorders.

Dr. Ng's CDA project is on "von Willebrand Factor (VWF) regulation in blood outgrowth endothelial cells from individuals with altered VWF levels”. By using blood outgrowth endothelial cells, Ng will identify the transcriptional and epigenetic modifiers that play a role in the regulation of VWF levels. He will also be utilizing novel assays for characterizing the effects. The proposed studies should shed light on our molecular understanding of VWD, advance other areas of investigation and potentially lead to better diagnostic and prediction algorithms for bleeding in VWD. Ng will be mentored on this award by Jorge DiPaola, MD, Director of Basic and Translational Research in Pediatric Hemostasis and Thrombosis at University of Colorado Denver.

Dr. Ng received his medical degree in 2008 from the Keck School of Medicine at the University of Southern California and completed his pediatric residency at the University of Washington–Seattle Children’s Hospital. Dr. Ng has the distinction of having received a several previous awards from NHF and others during the early stages in his career. He is a former NHF-Shire Clinical Fellow, having received the award in 2013 while training under the mentorship of Dr. Marilyn Manco-Johnson, Director of the Hemophilia and Thrombosis Center at UCD and Dr. DiPaola (see below). Ng has been the recipient of NHF’s Judith Graham Pool Postdoctoral Research Fellowship in 2015 for his project on a “Multi-system evaluation of von Willebrand factor function in Type 1 von Willebrand disease mutations” (see below). Ng also received a 2013 HTRS Mentored Research Award, the CSL Behring Professor Heimburger Award and the Hemophilia Association of New York Research Award.

Ng’s immediate focus is to continue building his career as a physician-scientist, through basic and translational studies on VWF for enhancing knowledge of hemostatic and thrombotic disorders while continuing to treat patients and providing clinical leadership at the University of Colorado Denver’s Hemophilia and Thrombosis Center. For the longer term, Ng hopes to one day have an independent, NIH-funded laboratory studying VWF and the biological factors that lead to varied clinical phenotypes in hemophilia and VWD.

Through the CDA, Ng will receive $70,000 per year for up to three years. This award was selected through a process of peer review conducted by NHF's Research Review Committee. This volunteer committee is made up of highly experienced and respected physicians and researchers working in the field of hematology. NHF wishes to thank the reviewers as well as Novo Nordisk, Inc. for their very generous support of this research award.

Dr. von Drygalski's research focuses on better understanding the mechanisms operating the anti-fibrinolytic system and how this process works in patients with hemophilia and specifically with joint bleeding. Accelerated fibrinolysis and clot instability are becoming increasingly recognized as contributing factors to bleeding in hemophilia. One important molecule that prevents fibrinolysis is called TAFI (Thrombin Activatable Fibrinolysis Inhibitor). Dr. von Drygalski will be studying the dual anti-fibrinolytic and anti-inflammatory functions of TAFI in hemophilia arthropathy and develop a therapeutic TAFI-based approach to improving the efficacy of FVIIa based bypassing strategies for acute bleeding and joint protection. Her mentors and collaborators are John H. Griffin, PhD, Laurent O. Mosnier, PhD and Martin Lotz, MD, distinguished researchers at UCSD -The Scripps Research Institute. Dr. von Drygalski received her M.D. from the Universities of Erlangen/Nurnberg and Munich in 1995 and her Pharm.D. from the University of Munich in 1988. She joined the faculty in July 2011 as Assistant Clinical Professor at UCSD and Director of the Adult Hemophilia and Thrombosis Treatment Center, Division of Hematology/Oncology, Department of Medicine. She also has an appointment as Adjunct Assistant Professor at the Scripps Research Institute (TSRI). The funding for this award is made possible thanks to a generous grant from Novo Nordisk.

Dr. Smith's research focuses on better understanding the development of factor VIII inhibitors. Specifically, she will focus on the effects of chemical signals, or cytokines, secreted by helper T cells on the development of inhibitor antibodies. She hypothesizes that certain cells, called Th17 cells, play an important role in the development of these antibodies by stimulating inflammation and driving the immune response toward inhibitor production. Dr. Smith received a BS from the University of Delaware before earning her Ph.D. from Montana State University. Prior to her appointment as an Assistant Professor at the University of Texas Medical School at Houston, she spent four years as a postdoctoral research fellow at the University of Michigan.

Dr. Flood earned her undergraduate degree from Harvard University in 1995 and her doctorate from Tufts University in 1999. She is board certified in pediatrics as well as pediatric hematology/oncology. She has been serving as an Assistant Professor at the Medical College of Wisconsin, where she has been performing research and seeing patients since 2006.

As part of her NHF Career Development Award, Dr. Flood will study the common variants and interactions of the von Willebrand factor molecule as a means to enhance overall understanding and eventually improve upon current methods of von Willebrand disease testing. Using mouse models, she will investigate diagnostic alternatives by examining the interaction between ristocetin and its ability to bind to von Willebrand factor. As Dr. Flood states in her summary, "Improved testing for VWD will prevent patients with normal VWF function from receiving unnecessary treatment, while allowing more accurate assessment of patients with true defects in VWD."