Research We Fund
With hundreds of projects currently underway, we fund scientists through our academic grant programs and biotech partners through our strategic venture philanthropy initiative. Use the filters below to find an LLS-funded project.
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Fahmin Basher, MD, PhD
Duke University Medical Center
Durham, North CarolinaThe Role of the DNA Sensor AIM2 in B Cell Fate and Function After HCT
Altered B cell homeostasis plays a key role in the development of chronic graft-vs-host-disease (cGVHD) after hematopoietic stem cell transplantation (HCT). We hypothesize that the DNA sensor AIM2 plays a critical role in the fate of BCR-activated B cells after HCT. We will utilize novel mouse models to investigate AIM2-BCR modulation with clear translational implications in autoreactivity perpetuating cGVHD as well as functional humoral deficiency and vaccine hyporesponsiveness after HCT.
Program: Career Development ProgramProject Term: Start Date: July 1, 2024 End Date: June 30, 2027
Pooja Khandelwal, MD
Cincinnati Children’s Hospital Medical Center
Cincinnati, OhioA randomized clinical trial of oral vitamin A to reduce chronic graft versus host disease in BMT
Vitamin A is safe, well tolerated and positively affects gut immune health. Graft versus host disease (GVHD) is a life-threatening complication of bone marrow transplant (BMT) which happens due to inflammatory changes in the gut. We harnessed the anti-inflammatory properties of vitamin A by giving it to children before bone marrow transplant (BMT) and showed reduction in acute gut and moderate/severe chronic GVHD. We will validate our findings in this currently proposed study of an independent group of adult BMT patients. We will give vitamin A or placebo before BMT to adult BMT patients and observe for reduction of chronic GVHD in vitamin A recipients compared to placebo. This study will be a step forward in adoption of vitamin A as a universal strategy to prevent GVHD which is affordable ($1.25 for entire treatment), non-toxic, and doesn’t suppress the immune system.
Program: Academic Clinical Trials Program (ACT)Project Term: Start Date: October 1, 2024 End Date: September 30, 2027
Nicoletta Cieri, MD, PhD
Dana-Farber Cancer Institute
Boston, MassachusettsTCR-like CARs targeting GvL mHAgs for the treatment of post-transplant AML relapse
AML recurrence is a devastating event after allo-HCT. I hypothesize that it could be counteracted through targeting of leukemia-restricted mHAgs via TCR-like CARs. I will identify scFVs recognizing mHAg:HLA complexes using a cell-free nanobody screening platform, and test the anti-leukemia activity and safety of CAR-Ts bearing such scFVs in vitro and in vivo. Through this approach, I will build a library of CAR constructs able to provide population-scale coverage for at-risk allo-HCT patients.
Program: Career Development ProgramProject Term: Start Date: July 1, 2024 End Date: June 30, 2026
Armin Rashidi, MD PhD
Fred Hutchinson Cancer Center
Seattle, WashingtonFecal microbiota transplantation to prevent acute GVHD after allogeneic stem cell transplantation
In up to half of patients with hematologic malignancies undergoing allogeneic stem cell transplantation, the trajectory of a smooth recovery toward cure is disrupted by acute graft-versus-host disease (aGVHD). Inspired by the role of intestinal microbial communities in aGVHD pathogenesis, we recently completed the largest fecal microbiota transplantation (FMT) trial to date in transplant recipients. We established the safety of standardized third-party FMT and characterized FMT effects on the microbiota, leading to the proposed randomized, placebo-controlled phase 2 trial of FMT to prevent aGVHD.
Program: Academic Clinical Trials Program (ACT)Project Term: Start Date: July 1, 2023 End Date: October 31, 2026
Pietro Genovese, PhD
Boston Children's Hospital
Boston, MassachusettsTowards clinical testing of epitope editing to enable novel adoptive immunotherapies
Innovations in gene engineering have made it possible to reprogram immune cells to attack specific targets on cancer cells, allowing the first adoptive cellular immunotherapies, known as CAR T cells, to be approved by the FDA for the treatment B lymphoblastic leukemia. A similar approach is currently under development for AML, but in contrast to B-ALL, there is no leukemia-specific target which would be amenable to targeting by immune cells without incurring severe adverse effects. Here, we aim to modify normal bone marrow stem cells used for allogeneic transplantation to make them resistant to CAR-T cells, thus enabling targeting proteins essential for tumor survival without the risk of severe toxicity on the healthy tissue counterpart.
Program: Translational Research ProgramProject Term: Start Date: July 1, 2023 End Date: June 30, 2026
Adi Nagler, PhD
Dana-Farber Cancer Institute
Boston, MassachusettsThe microbiome-induced immune response role in bronchiolitis obliterans syndrome following allogeneic hematopoietic cell transplantation
The microbiome is increasingly recognized as contributing to chronic graft-versus-host disease (cGVHD). I hypothesize that microbial antigens drive the devastating complication of bronchiolitis obliterans syndrome (BOS). To determine if such antigen targets are at the heart of BOS pathology, I will integrate spatial transcriptomic approaches, immunopeptidome analysis, and direct antigen specificity testing of TCRs from biospecimens collected from preclinical models and patient biospecimens.
Program: Career Development ProgramProject Term: Start Date: July 1, 2023 End Date: June 30, 2026
Robert Soiffer, MD
Dana-Farber Cancer Institute
Boston, MassachusettsUnderstanding and Overcoming Mechanisms of Immune Evasion after Allogeneic Transplant
Outcomes for patients with acute myelogenous leukemia who relapse after transplantation are dismal. This SCOR brings together an international group of collaborators with deep expertise in genomics, epigenetics, antigen presentation, and immune-regulation. They will focus on mechanisms of immune evasion by leukemia cells, identifying effective T cell responses to those evasive processes, and providing critical insights into the optimal approaches to model new and promising targets for immunotherapy with a goal of eliminating leukemia recurrence.
Program: Specialized Center of Research Program
Project Term: Start Date: October 1, 2022 End Date: September 30, 2027
Kirk Schultz, MD
University of British Columbia
VancouverA Polyomic Approach to Chronic Graft-versus-Host Disease (cGvHD) Biomarkers in Adults
Our team is the first to develop a polyomic pediatric cGvHD biomarker test for assessing the risk of developing cGvHD. A cooperative adult phase III clinical trial, CTTC1901, between Canada and Australia, focused on decreasing cGvHD (N=350 patients), offers an ideal opportunity to validate adult cGvHD biomarkers. This proposal will utilize the pediatric polyomic approach to validate a cGvHD risk assignment and diagnostic algorithm in adult hematopoietic stem cell transplant (HSCT).
Program: Translational Research ProgramProject Term: Start Date: July 1, 2022 End Date: June 30, 2025
Ravi Bhatia, MD
The University of Alabama at Birmingham
Birmingham, AlabamaPrediction and prevention of therapy-related myeloid neoplasms following autologous transplantation
The proposed studies will identify alterations in hematopoietic regulation that predict for risk for therapy-related myeloid neoplasm (TMN) and improve understanding of disease evolution to guide strategies to prevent TMN in patients receiving autologous hematopoietic cell transplantation (aHCT) for lymphoma. They will investigate alterations in hematopoietic function in peripheral blood stem cell used for aHCT, and serial evolution of hematopoietic defects leading to development of TMN.
Program: Translational Research ProgramProject Term: Start Date: July 1, 2022 End Date: June 30, 2025
Jaroslaw Maciejewski, MD, PhD
Cleveland Clinic Foundation
Cleveland, OhioHLA Mutations, GvH Resistance and Relapse Following Allogeneic Hematopoietic Stem Cell Transplant
This project investigates immunogenetic determinants of relapse following allogeneic stem cell transplant for myeloid neoplasia. Herein we will determine molecular modes of inactivation of HLA immunodominant peptide-presentation including HLA mutations, deletion and down modulation as a means of immunoescape. We will also study immunogenetic predictors of the strength of graft vs. leukemia according to the HLA divergence in the context of relapse, TCR repertoire diversity and HLA mutations.
Program: Translational Research ProgramProject Term: Start Date: November 1, 2021 End Date: October 31, 2024
Michael Keller, MD
Children's Research Institute
Washington, District of ColumbiaT-cell immunotherapy for prevention of COVID-19 following bone marrow transplantation
SARS-Cov-2 infections may be prolonged in cancer patients and may enable intrahost development of virulent viral variants. Adoptive immunotherapy with virus-specific T-cells has been an effective treatment for refractory viral infections in immunocompromised patients following HSCT. We propose to study the functionality of coronavirus-specific T-cells (CSTs) from healthy donors, and utilize CSTs as preventative therapy for patients undergoing bone marrow transplant in a phase I study.
Program: Translational Research ProgramProject Term: Start Date: July 1, 2021 End Date: June 30, 2024
Rizwan Romee, MD
Dana-Farber Cancer Institute
Boston, MassachusettsCytokine induced memory-like NK cell immunotherapy to target post transplant relapse
Coming soon.
Program: Career Development ProgramProject Term: Start Date: July 1, 2021 End Date: June 30, 2026
Areej El-Jawahri, MD
Massachusetts General Hospital
Boston, MassachusettsRandomized Trial of a Sexual Dysfunction Intervention for Hematopoietic Stem Cell Transplant Survivors
Our goal is to improve sexual function and quality of life for patients with blood cancers undergoing hematopoietic stem cell transplantation. We will conduct a clinical trial to evaluate whether a multi-component intervention to address sexual health and intimacy concerns can improve sexual function and satisfaction as well as quality of life and mood in hematopoietic stem cell transplant survivors. We will also explore whether improvement in sexual function leads to improvement in quality of life in this population. By developing an innovative and potentially scalable model of care to address sexual health issues, we aim to improve the quality of life and survivorship care for patients with blood cancers.
Program: Career Development ProgramProject Term: Start Date: July 1, 2019 End Date: June 30, 2024