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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Stephen Oh, PhD, MD
Washington University in St. Louis
St. Louis, MissouriExploiting Novel Therapeutic Vulnerabilities in Chronic Myelomonocytic Leukemia
The overall objective of this project is to identify novel pathways that may be targeted for therapeutic benefit in CMML. We have identified abnormal inflammation mediated by RSK1 in CMML patient cells, and we hypothesize that RSK1 drives CMML disease development. We thus propose studies to determine how RSK1 contributes to CMML pathogenesis, and to evaluate the therapeutic potential of RSK1 inhibition for CMML patients.
Program: CMML InitiativeProject Term: Start Date: November 1, 2023 End Date: October 31, 2026
Sam Butterworth, PhD
University of Manchester
ManchesterDevelopment of peptide-drug conjugates for the treatment of Chronic Myelomonocytic Leukaemia (CMML)
We are aiming to bring a new treatment option to patients with chronic myelomonocytic leukemia (CMML) by utilising CCL2-drug conjugates that specifically target and eliminate cancerous cells. Our leading conjugate shows potent and selective efficacy in killing CMML cells. The proposed work will help us understand how this drug works, which patients are most likely to benefit and how it can be combined with current treatments to achieve the greatest patient benefit.
Program: CMML InitiativeProject Term: Start Date: November 1, 2023 End Date: October 31, 2026
Ravindra Majeti, PhD, MD
Stanford
Palo Alto, CaliforniaTargeting the inflammatory GM-CSF pathway in high risk CMML
Chronic myelomonocytic leukemia (CMML) is a rare but poorly understood blood cancer often presenting with crippling inflammatory symptoms that frequently evolves into acute leukemia. In an ongoing clinical trial, we have compelling molecular and clinical data that this disease responds effectively to blockade of GM-CSF with lenzulimab, a well-tolerated and safe antibody, in combination with azacitidine. Here, we propose an integrated research program to investigate targeting of the GM-CSF pathway in high risk CMML using our carefully matched patient samples, proprietary GM-CSF tools, and humanized in vivo CMML models.
Program: CMML InitiativeProject Term: Start Date: November 1, 2023 End Date: October 31, 2028
Elliot Stieglitz, MD
University of California, San Francisco
San Francisco, CaliforniaCLL-1 CAR-T cells and trametinib for the treatment of Ras-mutated CMML and JMML
We hypothesize that demonstrating activity of CLL-1 CAR-T (CLL1CART) cell therapy with or without trametinib in pre-clinical models of chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML) is the most efficient method to bring cellular therapy to patients with these orphan diseases. In Aim 1, we will determine the in vitro and vivo efficacy of CAR-T cells redirected against CLL-1 using patient-derived xenograft (PDX) models of CMML and JMML. In Aim 2, we will evaluate the role of combining trametinib with CLL1CART cells. Based on our preliminary data, we hypothesize that trametinib will have direct antileukemia activity and will increase the efficacy of CLL1CART by decreasing T-cell exhaustion and augmenting T-cell fitness.
Program: CMML InitiativeProject Term: Start Date: November 1, 2023 End Date: October 31, 2026
Eric Padron, MD
Moffitt Cancer Center
Tampa, FloridaAdvancing the therapeutic landscape for Chronic Myelomonocytic Leukemia (CMML)
CMML is a universally lethal blood cancer characterized by increased monocytes (a type of white blood cell) in the peripheral blood and abnormal appearing cells within the bone marrow. Most CMML patients are clinically asymptomatic and remain so for weeks to months following diagnosis, with disease progression remaining inevitable. Despite therapeutic advances in similar blood cancers, no specific molecularly targeted therapies currently exist to treat CMML. Our team aims to identify new therapies and repurpose existing therapies to address the emergent unmet need for new treatments that meaningfully improve, and extend, the lives of patients with CMML.
Program: CMML InitiativeProject Term: Start Date: November 1, 2023 End Date: October 31, 2027
Huda Salman, MD
Indiana University
Indianapolis, IndianaDevelopment of cellular therapy for CMML and the Immune landscape of response and resistance
We will test the efficacy of CAR T cell therapy for CMML. We will modify the tumor microenvironment to enhance their efficacy. and we will upscale CAR T cells to the next level in terms of their genetic structure.
Program: CMML InitiativeProject Term: Start Date: November 1, 2023 End Date: October 31, 2028
Amit Verma, MBBS
Albert Einstein College of Medicine
Bronx, New YorkTargeting the inflammasome in CMML
Overactivation of the inflammasome is seen in CMML and leads to worsening of this condition. We will explore the potential of a new inflammasome inhibitor drug, HT-6184, in CMML patient samples and in animal models. Our preliminary results show that this drug can decrease inflammation and improve red cell development in CMML models. The new drug is approved for clinical trial use and our work will potentially lead to its use in clinical investigations in CMML.
Program: CMML Initiative
Project Term: Start Date: November 1, 2023 End Date: October 31, 2026