NHF funds a broad range of research programs that seek to increase our understanding of the science behind bleeding disorders, how they affect people's lives, and pathways to better treatments and cures.

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Engineered Regulatory T-cell Therapy for Tolerance to FVIII

Year:
-
Grants:
Career Development Award
Tags:
Hemophilia A (Factor VIII/F8)
Inhibitors
Author(s):
Moanaro Biswas

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.

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Increasing the efficacy of prophylactic infused FIX in hemophilia B patients by manipulating its binding to collagen IV

Year:
-
Grants:
Judith Graham Pool Postdoctoral Research Fellowship
Tags:
Hemophilia B (Factor IX/F9)
Author(s):
Xuejie Chen
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Preclinical Development of Nuclease-Free Gene Editing for Lifeling Treatment of Bleeding Disorders

Year:
-
Grants:
Judith Graham Pool Postdoctoral Research Fellowship
Tags:
Gene Therapy
Hemophilia A (Factor VIII/F8)
Hemophilia B (Factor IX/F9)
Author(s):
Calvin J. Stephans
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The Epitopes Recognized in the Early Immunue Response to Factor VIII

Year:
-
Grants:
Judith Graham Pool Postdoctoral Research Fellowship
Tags:
Hemophilia A (Factor VIII/F8)
Inhibitors
Author(s):
Seema Patel
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Identification of a Potential Novel Role for Factor IX Using a Zebrafish Model

Year:
-
Grants:
Judith Graham Pool Postdoctoral Research Fellowship
Tags:
Hemophilia B (Factor IX/F9)
Author(s):
Raghunath Azhwar
Identifying novel hemostatic regulation through species-specific studies using zebrafish

Identifying novel hemostatic regulation through species-specific studies using zebrafish

Year:
-
Grants:
Judith Graham Pool Postdoctoral Research Fellowship
Tags:
Hemophilia A (Factor VIII/F8)
Hemophilia B (Factor IX/F9)
Author(s):
Kari Lavik, PhD

Dr. Kari Lavik is a postdoctoral fellow at the University of Michigan in the laboratory of Dr. Jordan Shavit. She received a B.A. in biology from Case Western Reserve University, and her Ph.D. in Biomedical Sciences from The University of Toledo. Her graduate work focused on the study of cancer motility and metastasis through which she became interested in using zebrafish as a model for human disease. In February of 2017, Dr. Lavik joined the Shavit Laboratory in the Department of Pediatrics at the University of Michigan to use zebrafish for the study of bleeding and clotting disorders. For her 2018 JGP fellowship project, she will model hemophilia in the zebrafish, looking for novel species-specific regulators of hemostasis. By delving deeper into the genetic mechanisms that underlie the intrinsic pathway in zebrafish, Dr. Lavik will look for novel gene interactions that can be therapeutically targeted in patients with hemophilia.

von Willebrand Factor (VWF) Regulation in Blood Outgrowth Endothelial Cells from Individuals with Altered VWF Levels

von Willebrand Factor (VWF) Regulation in Blood Outgrowth Endothelial Cells from Individuals with Altered VWF Levels

Year:
-
Grants:
Career Development Award
Tags:
Von Willebrand Disease
Author(s):
Christopher J. Ng

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.

Protein Engineering of Plasminogen Activator 1 to Develop Novel Regulators of the Fibrinolytic and Hemostatic Pathways

Protein Engineering of Plasminogen Activator 1 to Develop Novel Regulators of the Fibrinolytic and Hemostatic Pathways

Year:
-
Grants:
Judith Graham Pool Postdoctoral Research Fellowship
Tags:
Plasminogen Activator 1 (PA1)
Author(s):
Laura Haynes

Dr. Laura Haynes received her PhD in biochemistry from the University of Vermont where she studied how flow conditions throughout the vasculature affect thrombin generation, as well as the role of the platelet membrane in modulating the structure/function of the platelet associated prothrombinase complex. Dr. Haynes is currently a research fellow with Dr. David Ginsburg at the University of Michigan. During her JGP fellowship, she will use phage-display technology coupled with high throughput DNA sequencing to make an exhaustive index of the mutations in plasminogen activator inhibitor-1 (PAI-1) that prolong its half-life while not being deleterious in the inhibition of its canonical targets urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). In doing so, she hopes to identify a PAI-1 variant that can downregulate the fibrinolytic process. Dr. Haynes will also implement similar technology to engineer a PAI-1 variant that inhibits activated protein C (APC), thereby prolonging thrombin generation. She hopes that this research will lead to potential therapeutic agents to treat hemophilia and other bleeding disorders.

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Navigating Time and Space: Experiences of Aging with Hemophilia

Year: 2019
Grants:
Innovative Investigator Research Award
Tags:
Aging
Hemophilia A (Factor VIII/F8)
Hemophilia B (Factor IX/F9)
Author(s):
Tam E. Perry

Dr. Tam E. Perry is an associate professor at Wayne State University School of Social Work. Her research addresses urban aging from a life course perspective, focusing on how underserved older adults navigate their social and built environments in times of instability and change. She conducts translational research projects that address older adults’ well-being in urban communities such as the Flint water crisis, and older adults’ experiences of gentrification in Detroit, particularly examining the relationship of older adults to their homes. She is also co-principal investigator of a project entitled, “Older Adults’ Experiences and Understandings of the Flint Water Crisis,” which focuses on the intersection between housing and health. This project received the Betty J. Cleckley Minority Issues Research Award from the Aging and Public Health Section of American Public Health Association for this research. She also serves as research chair and vice-chair of strategic planning of a multi-agency coalition, Senior Housing Preservation-Detroit. Lastly, she co-directs the Community Liaison and Recruitment Core of the Michigan Center for Urban African American Aging Research (MCUAAAR).

Dissecting the Roles of Non-muscle Myosin IIA in May-Hegglin Platelet Disorders

Dissecting the Roles of Non-muscle Myosin IIA in May-Hegglin Platelet Disorders

Year:
-
Grants:
Judith Graham Pool Postdoctoral Research Fellowship
Tags:
Platelets
Author(s):
Kasturi Pal
Per Dr. Pal, receiving the JGP Fellowship was a major milestone in her academic career and has given her the confidence to apply for future extramural funding.
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Novel Therapeutics for Hemophilia

Year:
-
Grants:
Innovative Investigator Research Award
Tags:
Hemophilia A (Factor VIII/F8)
Author(s):
Shannon L. Meeks

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.

PiggyBac Mediated Gene Transfer for Coagulation Disorders

PiggyBac Mediated Gene Transfer for Coagulation Disorders

Year:
-
Grants:
Career Development Award
Tags:
Gene Therapy
Author(s):
Janice M. Staber
Dr. Staber received her undergraduate e degree in biochemistry from the University of Iowa. She received her MD from the Carver College of Medicine at the University of lowa. She received strong mentorship under the guidance of Drs. Paul McCray and Steven Lentz during her post-doctoral research in gene therapy and hemophilia studies. She was subsequently appointed a faculty position at the University of Iowa Children's Hospital in 2010 and became Assistant Professor of Pediatrics in the Division of Hematology/Oncology in 2013.
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Developing a Point-of-Care Testing for Hemophilia

Year:
-
Grants:
Innovative Investigator Research Award
Tags:
Hemophilia A (Factor VIII/F8)
Author(s):
Jill M. Johnsen

Dr. Jill Johnsen is scientist and physician at the Washington Center for Bleeding Disorders in Seattle, WA.  She is an Associate Member at the Bloodworks Research Institute and also an Associate Professor of Medicine in the Division of Hematology at the University of Washington. Her research focuses on the study of hereditary and acquired modifiers of blood traits, with particular emphasis on the genetics and biology of variation in blood group and coagulation factors such as factor VIII, factor IX, and von Willebrand Factor.  Dr. Johnsen is honored by this award and grateful for this support that will further the development of a test to enable patients and providers to determine factor levels much more quickly without needing to send blood to a lab.

Identification, Characterization and Therapeutic Targeting of Key Molecular Markers and Pathways Implicated in the Development of Hemophilic Arthropathy

Identification, Characterization and Therapeutic Targeting of Key Molecular Markers and Pathways Implicated in the Development of Hemophilic Arthropathy

Year:
-
Grants:
Judith Graham Pool Postdoctoral Research Fellowship
Tags:
Hemophilic Arthropathy
Pain
Hemophilia A (Factor VIII/F8)
Hemophilia B (Factor IX/F9)
Author(s):
Esther Cooke

Dr. Esther Cooke received her Ph.D. from the Leeds Institute of Cardiovascular and Metabolic Medicine at the University of Leeds, U.K., where she studied the role of fibrinogen phosphorylation in thrombosis. Dr. Cooke is currently a postdoctoral fellow in the laboratory of Dr. Annette von Drygalski, at the University of California San Diego, and in collaboration with the laboratory of Dr. Laurent Mosnier at the Scripps Research Institute. Dr. Cook's JGP Fellowship project will focus on pathological mechanisms associated with joint bleeding, re-bleeding, and the development of hemophilic arthropathy. Dr. Cooke will perform comprehensive gene expression analyses to explore key molecular markers and pathways that drive soft tissue inflammation and vascular changes in joints after bleeding. In this way, she hopes to identify new therapeutic targets and develop novel treatment strategies to down-regulate these processes, thereby reducing re-bleeding tendency and slowing the progression of hemophilic arthropathy.

Understanding of a Neurophenotype in Hemophilia A

Understanding of a Neurophenotype in Hemophilia A

Year: 2019
Grants:
Bridge Award
Tags:
Hemophilia A (Factor VIII/F8)
Author(s):
Janice M. Staber
The long-term goal of my work is to improve treatment options for patients with hemophilia and other heritable bleeding disorders. The goal of my current research is to understand the impact of factor VIII deficiency on brain structure and function as well as determine the mechanism behind these changes. In our previous studies investigating survival of hemophilia A mice, we observed unusual behavior. After investigation we discovered an anxiety-like phenotype as demonstrated by increased time in the periphery on open field and increased time in the dark on light/dark testing. In order to accomplish the goal of the current proposal, we will utilize quantitative neuroimaging techniques to assess change in brain structure including intracranial volume and we will measure glial activation and neuroinflammation to determine the mechanism of the underlying neurophenotype in hemophilia A mouse model. In addition, we will determine if factor VIII replacement via our established gene transfer methods reduces or resolves the anxiety-like behavior in the hemophilia A mouse model. As part of the Hemophilia and Thrombosis Center at Iowa, I have an intimate knowledge of the up and coming therapies in the field. I have generated the preliminary data including behavior studies with hemophilia A mice. Published data on piggyBac transposon liver-transduction including tissue cell work and in vivo testing demonstrates the feasibility of long-term factor VIII replacement in the hemophilia A mouse model . As an early stage investigator, I had strong mentorship under the guidance of Drs. Paul McCray and Steven Lentz to complete my post-doctoral research and training in gene therapy and hemophilia research. I have extensive experience with the phenotypic studies in mouse models including behavior studies, vector delivery systems both in vivo and in vitro, and multiple coagulation antigen and activity assays.
Functional Interpretation of Genetic Variants in Von Willebrand Factor

Functional Interpretation of Genetic Variants in Von Willebrand Factor

Year: 2019
Grants:
Innovative Investigator Research Award
Tags:
Von Willebrand Disease
Author(s):
Andrew Yee
Dr. Andrew Yee is an assistant professor of pediatrics within the Department of Pediatrics, Hematology-Oncology Section at Baylor College of Medicine. Dr. Yee earned his doctorate from Rice University where he studied the biological responses of endothelial cells to mechanical forces in the laboratory of Dr. Larry McIntire. He continued his research training as a Judith Graham Pool postdoctoral fellow in the laboratory of Dr. David Ginsburg at the University of Michigan where he studied the molecular biology of von Willebrand factor. At Baylor College of Medicine, Dr. Yee and his team investigate the mechanisms by which von Willebrand factor controls blood clotting and are developing innovative approaches for diagnosing bleeding disorders.
Development of Hematopoietic CRISPR/Cas9 Gene Activation for Hemophilia Therapy

Development of Hematopoietic CRISPR/Cas9 Gene Activation for Hemophilia Therapy

Year:
-
Grants:
Judith Graham Pool Postdoctoral Research Fellowship
Tags:
Gene Therapy
Hemophilia B (Factor IX/F9)
Author(s):
Satish Nandakumar

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.

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Analysis of Lower Extremity Joint Characteristics, Biomechanics, and Neuromotor Control during Gait in Patients with Hemophilia

Year: 2019
Grants:
Physical Therapy Excellence Fellowship
Author(s):
Lena Volland

Hemophilia causes repetitive bleeding episodes throughout the musculoskeletal system, primarily into joints, such as knees and ankles. This leads to significant joint damage resulting in increased pain reproduction, decreased functional abilities, such as walking, and negatively impacts quality of life. Traditionally the extend of joint damage has been examined via clinical assessments, such as the Hemophilia Joint Health Scores, x-rays, MRIs, and more recently musculoskeletal ultrasound (MSKUS). However, these modalities fail to establish the global impact of joint damage on the entire body of a person with hemophilia and their functional abilities. Analyzing joint motion and forces acting upon the joint during walking has been a widely established technique to gain understanding of abnormal three-dimensional movements and is a key factor in clinical decision making-processes. With the overall goal of establishing better treatment approaches for persons with hemophilia it is vital to understand the underlying functional joint limitations. Therefore, the purpose of this study is to investigate characteristics of damaged joints, joint motion and control as well as forces acting upon the joint during walking in persons with hemophilia.

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Kelly Tickle

Year:
-
Grants:
Nursing Excellence Fellowship
Author(s):
Kelly Tickle
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Women with Hemophilia: Gender-based Differences in the Delivery of Comprehensive Care

Year: 2018
Grants:
Physical Therapy Excellence Fellowship
Author(s):
Laura Fox

This study will evaluate hemophilia treatment center (HTC) services provided to women with hemophilia A or B (Factor VIII or Factor IX level [ 50%). The American Thrombosis and Hemostasis Network (ATHN) maintains a confidential national database for patients with bleeding and clotting disorders. Utilizing this existing ATHNdataset, the study will analyze the effect of gender on the delivery of comprehensive care in patients with hemophilia A and B. The project will focus on how gender impacts three specific components of care: identification of patients with factor VIII or IX deficiency, inclusion of patients in the comprehensive care model, and monitoring of joint bleeding as a key component of comprehensive care provided by HTCs. Demonstrating gender-based disparities in comprehensive care would provide evidence for making changes to improve the clinical care provided to women with hemophilia. This study will add to the knowledge regarding the care of women with hemophilia, helping to inform future studies of this under-researched population.