Program in Molecular Medicine
University of Utah
Project Title: “CRISPR/CAS9 Gene Editing Identified a Novel Role of Actin Bundling Protein L-plastin in Platelet Production”
Project Summary: The functional relevance of L-plastin is not well understood in megakaryocytes (MKs) and platelets. L-plastin negatively regulates MK proplatelet formation and platelet count. MK L-plastin knockdown induced more podosomes, actin rich structures that initiates proplatelets. This proposal will investigate how L-plastin regulates podosome function and explore utility of L-plastin CRISPR/CAS9 gene edited human MKs as a novel cellular therapy for transfusion.
Leland Stanford Junior University
Project Title: “Personalized Tr1 Cell-Based Therapy for Graft-vs-Host Disease”
Project Summary: Allogeneic (allo-HSCT) is a life-saving procedure for patients with chemotherapy-resistant leukemias and lymphomas, bringing protective, healthy donor immune cells that kill tumor cells and prevent infections. However, these donor immune cells can attack patient tissues, causing dangerous graft-vs-host disease (GvHD). We designed a cell therapy that, unlike other existing GvHD therapies, suppresses GvHD but not protective immunity. This proposal aims to increase its clinical potency.
University of California, San Francisco
Project Title: “New Approaches to Study and Treat Alloantibody-Mediated Diseases Resulting from Blood Transfusions”
Project Summary: Using new antibody engineering techniques, in vivo models and assays using patient samples we aim to identify how alloantibodies activate the complement cascade, which is a key event in several diseases that result from blood transfusions. We will then test novel approaches to prevent complement-dependent alloantibody-mediated disease.
Assistant Professor in Pediatrics
Gene Therapy Program
Dana-Farber/Boston Children’s Cancer and Blood Disorder Center
Dana-Farber Cancer Institute
Project Title: “Engineering Immunotherapy Resistant Hematopoiesis to Treat High-Risk Acute Myeloid Leukemia”
Project Summary: AML is the most common hematologic malignancy but, despite diffuse use of allogeneic stem cell transplantation, it still has the lowest survival rate of all leukemias. Adoptive immunotherapies are currently hampered by the absence of specific targets, most of which are often shared with healthy tissues and thus lead to immunosuppression/toxicity. Here, we will develop new gene editing strategies to generate a stealth hematopoiesis that is resistant to immunoglobulin-based drugs/CAR-T cells.
Project Title: “Eliminating Senescent Bone Marrow-Derived Mesenchymal Stem Cells Using Microfluidics”
Project Summary: Cellular senescence, one of the hallmarks of organismal aging and age-related disorders, impairs the function of adult stem cells, limiting their therapeutic efficacy. Here, we will employ innovative microfluidic devices to separate non-senescent from senescent stem cells. This will reveal a simple, innovative, and clinically-relevant method to isolate a senescence-free subpopulation of stem cells, thereby increasing the efficacy of stem cells for cellular therapies and anti-aging treatments.
Department of Pathology
University of Pittsburgh School of Medicine
Project Title: “A Stochastic, Multicompartment, Dynamic Model of Hemostasis and Oxygenation During Trauma Resuscitation: Building a Platform for in Silico Trials of Transfusion Strategies”
Project Summary: In silico models offer an innovative approach to evaluating the comparative effectiveness of hemostatic resuscitation strategies in trauma. In this project, we will extend our earlier model of trauma resuscitation by incorporating hemodynamic, hemostatic, resuscitation, biomarker and tissue-oxygenation domains into a single comprehensive model of trauma resuscitation, using a stochastic design to select parameters for patient and blood component/ pharmaceutical agent variates.
Those who complete their NBF early-career grant-funded research are named NBF Scholars.
Arunoday Bhan, PhD
Boston Children’s Hospital
Avital Mendelson, PhD
Head, Laboratory of Stem Cell Biology & Engineering Research
Lindsley F. Kimball Research Institute
New York Blood Center
Antonella Nai, PhD
Regulation of Iron Metabolism Unit
Division of Genetics and Cell Biology
Ospedale San Raffaele
Hideyuki Oguro, PhD, MSc, BSc
Assistant Professor, Department of Cell Biology
University of Connecticut Health Center
Adjunct faculty, The Jackson Laboratory