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.
Protein engineering for an optimized factor VIII for Hemophilia A therapy
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.
Reducing Severe Bleeding Symptoms in Hemophilia by Lowering Fibrinolysis
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.
Antibody-mediated FV/FVa resistance as a therapeutic approach for hemophilia
Dr. Sean Quinn is a postdoctoral fellow at the Children’s Hospital of Philadelphia in the laboratory of Dr. Rodney Camire. Dr. Quinn received his doctoral degree in Biochemistry/Biophysics from Rensselaer Polytechnic Institute in 2019. For his JGP project, Dr. Quinn will develop novel monoclonal antibodies (mAbs) that bind and protect FV or activated FV (FVa) to promote coagulation in the context of hemophilia. To accomplish this goal, Dr. Quinn will use biochemical and biophysical approaches to map the epitopes where lead candidate mAbs bind to FV/FVa. Moreover, he plans to assess the efficacy of these mAbs using a combination of in vivo approaches with an already established hemophilia mouse model. Long-term, Dr. Quinn’s goal is to become an independent investigator to develop approaches to modulate anticoagulant pathways to treat bleeding.
Roles of the B domain in regulating the synthesis and secretion of FVIII Year 2021-2023
Dr. Yuan Zhang obtained her Ph.D in microbiology from Wuhan University, China, in 2015. Her Ph.D work focused on creating new or more effective genetically engineered vaccines against human viruses. In 2016, she joined Dr. Bin Zhang’s group as a postdoctoral fellow at the Lerner Research Institute, Cleveland Clinic. She works on understanding the mechanism of receptor-mediated ER-Golgi transport of secreted glycoproteins. In her JGP project, she aims to identify B domain signals that direct FVIII into the LMAN1-MCFD2 secretory pathway, and investigate the importance of the B domain in FVIII biosynthesis and LMAN1-MCFD2 mediated secretion in mouse models. She hopes that her research will provide important information for guiding recombinant FVIII production and the design of hemophilia A gene therapies.
Rescue of FVIII mutant expression by translational and post-translational modulation using small molecule therapy
Vishal Srivastava is working as a postdoctoral fellow in Dr. Bin Zhang’s lab at the Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic. He received his Ph.D. from the CSIR-Central Drug Research Institute/Jawaharlal Nehru University, India. As a recipient of the JGP Fellowship, he will study the role of proteostasis regulators/chaperone-like small molecules and ribosomal readthrough compounds to correct protein impairments due to missense and nonsense mutations in hemophilia A (HA) patients. He hopes to develop innovative therapeutic approaches for treatment of HA patients based on their mutations.
The role of EPCR-FVIIa in the pathogenesis and treatment of hemophilic arthropathy
From University of Texas Health Science Center at Tyler (UTHSCT). Dr. Magisetty completed Ph.D. doctoral training on the evaluation of FVIIa-EPCR interactions in the management of hemophilic arthropathy and is enthusiastic looking forward to the postdoctoral training on the “Role of EPCR-FVIIa anti-inflammatory signaling in the pathogenesis and treatment of hemophilic arthropathy”.
The role of FVIIa-released endothelial extracellular vesicles in hemophilia therapy
I am currently working as a Postdoctoral Research Associate at the University of Texas Health Science Center at Tyler, Tyler, Texas, under the mentorship of Professor L. Vijaya Mohan Rao. My research focuses on elucidating novel mechanisms by which FVIIa provides hemostatic and anti-inflammatory effects and the relevance of these mechanisms in treating bleeding disorders and hemophilic arthropathy. I graduated from the University of Calcutta, India, in 2009 with a bachelor’s degree in Microbiology. My post-graduation was also in Microbiology from India in 2011. I completed my doctoral studies in 2019 from the Indian Association for the Cultivation of Science, India, where I focused on understanding the mechanistic details of tissue factor-factor VIIa-induced progression of human breast cancer. I published several peer-reviewed articles from my Ph.D. thesis work in journals, such as Journal of Biological Chemistry, Cellular Signaling, and Molecular Carcinogenesis. I enjoy playing video games, reading novels, and cooking various Indian foods.
Gene Therapy for Hemophilia: Patient Preferences and Shared-Decision Making
Dr. Thornburg graduated from Duke University Medical School, completed her pediatric residency at Duke University Medical Center, and completed her pediatric hematology/oncology fellowship at the University of Michigan. While at the University of Michigan, she completed a Master Degree in Clinical Research Design and Statistical Analysis. During her time in Michigan she focused her training on hemophilia and other bleeding disorders and was a NHF-Shire Clinical Fellow under the mentorship of Dr. Steven Pipe. Dr. Thornburg was on the faculty at Duke University from 2005-2013 where she directed the sickle cell and hemostasis and thrombosis programs.
Dr. Thornburg is committed to taking care of children with blood disorders including bleeding disorders, clotting disorders and inherited red blood cell disorders. She conducts clinical research to improve the care of individuals with blood disorders. Her NHF Innovative Investigator Research Award focuses on patient preferences and shared-decision making related to gene therapy for hemophilia.
In order to educate the next generation of physicians, Dr. Thornburg teaches medical students, residents and fellows and is the Director of the Pediatric Hemostasis and Thrombosis Fellowship at RCHSD, a site for the NHF-Takeda Clinical Fellowship program.
Dr. Thornburg is a member of NHF’s Medical and Scientific Advisory Council (MASAC).
In addition to her career in medicine, Dr. Thornburg enjoys spending time with her family, traveling and playing tennis.
Health Services Guide for Bleeding Disorder Camps
A professor and dual certified nurse practitioner in pediatrics and adults. She completed her PhD in Educational and Organizational Leadership and taught for 10 years specializing in camp nursing, service leadership, physiology, and hematology. Dr. Gaslin periodically works as a camp consultant and legal consultant and publishes the majority of her work in the areas of bleeding disorders, pediatric development, camp nursing, behavioral health, and leadership.
Dr. Gaslin served as the Medical Director at a special needs camp for six years where she directed care for children with chronic disease, disability and life-threatening illness. She currently serves as a nurse practitioner in a Hemophilia Treatment Center. She also serves as the Executive Director for the Association of Camp Nursing where she travels to different areas of the US and Canada educating healthcare providers about camp health services and the many benefits for children and adults. She recently (2020) co-authored a textbook: Camp Nursing; The Basics and Beyond. Dr Gaslin is passionate about every child having a camp experience and learning that they can achieve great things in life.
Pilot Study of Telemedicine vs In Person Physical Therapy Intervention for Hemophilia
Elizabeth Hall is the physical therapist for the Hemophilia and Thrombosis Treatment Center (HTC) at Rady Children’s Hospital San Diego (RCHSD). She has worked at RCHSD for over ten years and has worked closely with Dr. Thornburg for the past seven years. She has expertise in the evaluation and treatment of patients 0-21 years in inpatient, rehabilitation, and outpatient settings. She has developed particular expertise in the evaluation and management of children and adolescents with bleeding disorders. She is an active member of the Western States PT working group.
Increasing the efficacy of prophylactic infused FIX in hemophilia B patients by manipulating its binding to collagen IV
Dr. Xuejie Chen is a postdoctoral fellow in the laboratory of Dr. Darrel Stafford at the University of North Carolina at Chapel Hill. Before joining Dr. Stafford’s lab, she received her Ph.D. degree in Cell Biology from Beijing Normal University, P. R. China. In her JGP Fellowship project, Dr. Chen aims to study the contributions of extravascular factor IX (FIX) to blood coagulation and to search for FIX variants that could efficiently displace the endogenous dysfunctional FIX in hemophilia B patients. To achieve this goal, Dr. Chen will study the binding between FIX and the subendothelial basement membranes, mainly type IV collagen, and use the site-directed random mutagenesis library to screen for tighter binding FIX molecules. In doing so, she hopes to identify a FIX variant that can be used in hemophilia B patients for better coagulation therapies.
Post-Traumatic Stress Disorder (PTSD) and Posttraumatic Stress Symptoms (PTSS) Among Adults with Hemophilia A and B
Amanda Stahl, MSW, LICSW is the social worker for adult patients at the Boston Hemophilia Center at Brigham and Women’s Hospital, where she has been providing clinical services to patients with bleeding disorders since 2015. She participates in multiple national committees, joining the NHF Social Work Working Group in 2019, and the ATHN Access to Care Working Group also in 2019. For the past 2 years she has been a speaker at the NHF Bleeding Disorders Conference presenting on her research and information about Post-Traumatic Stress Symptoms for patients with acute and chronic illness. Amanda is a “double eagle” graduating with both her BA in 2006, and MSW in 2010, from Boston College.
Engineered Regulatory T-cell Therapy for Tolerance to FVIII
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.
Preclinical Development of Nuclease-Free Gene Editing for Lifeling Treatment of Bleeding Disorders
The Epitopes Recognized in the Early Immunue Response to Factor VIII
Identification of a Potential Novel Role for Factor IX Using a Zebrafish Model
Navigating Time and Space: Experiences of Aging with Hemophilia
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).
Functional Interpretation of Genetic Variants in Von Willebrand Factor
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.
Retrospective Chart Review of Joint Outcomes and Hospital Utilization for Persons with Hemophilia A (with and without inhibitors) Who Were Switched to Emicizumab for Treatment Prophylaxis
This research project will illustrate the improvements to joint range of motion and hospital utilization (which includes emergency room visits, hospital admissions, and central line infections) in persons with hemophilia A (with and without inhibitors) who switched to emicizumab for bleeding prevention.