Research we fund

The field of cancer treatment has made remarkable progress with the adoption of targeted therapy; however, small molecule drugs have limitations such as drug resistance and off-target toxicities. To overcome these challenges, we have developed an innovative approach that enhances the potency and precision of small molecule drugs. Our cutting-edge high-precision pretargeted nanoparticles can deliver potent triple inhibitors that effectively combat drug-resistant mantle cell lymphoma and dual proteolysis targeting chimeras (PROTACs) for treatment of transformed follicular lymphoma. Our proposal is supported by extensive preliminary data, and we are excited to be at the forefront of this revolutionary novel treatment strategy.

Project Term: July 1, 2024 - June 30, 2027

The goal of our laboratory is to discover, study, and the translate new leukemia therapies to the clinic. In this project, we are studying a signaling pathway, called PI3 kinase gamma, that we believe is important in patients with AML and might lead to new treatments using drugs that target its activity.

Project Term: October 1, 2024 - September 30, 2027

CAR-T cells are made from a patient’s own immune cells, altered so that they specifically recognize and kill the patient’s cancer cells. They are effective in many but not all cases of B-acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL), among other blood cancers. In this proposal we seek to better understand ways to select T cells that will make better CAR-T cells as well as to treat CAR T cells them in ways to make them work better in the cancer patient.

Project Term: October 1, 2024 - September 30, 2027

Peripheral T-cell lymphomas are highly aggressive blood cancer that have very poor survival rate, highlighting the need for new therapies to improve patient survival. We aim to improve our understanding of the characteristics of the individual cancer cells and their interaction with surrounding cells in the tumor environment with the goal of identifying new drugs that we can validate in preclinical models and move into more efficient treatments for lymphoma patients.

Project Term: October 1, 2024 - September 30, 2027

Our goal is to perform high-resolution molecular characterization of human leukemia stem cells (LSCs). We have developed an integrated set of single-cell techniques that will assess transcriptional, genomic, and phenotypic features of primary LSC populations obtained from patients undergoing varying forms of treatment. We expect to create a molecular atlas of primary LSCs that will provide the leukemia research community with a powerful resource for the development of improved therapies.

Project Term: October 2, 2024 - September 30, 2027

Genetic changes of ASXL1 are very frequent in human blood cancers. We found that the altered forms of ASXL1 protein promote blood cancers through forming tiny liquid-like droplets in the cell. In this project, we aim to develop a method to specifically break these droplets to inhibit its activity in driving blood cancers.

Project Term: October 1, 2024 - September 30, 2027

Multiple myeloma is characterized by severe changes in chromosomes that result in gains or losses of genetic material. Several key events disrupt the genome of myeloma cells and are important in defining poor patient outcome, but the biological mechanisms of how they cause high-risk disease is not known. We will perform comprehensive genomic studies, involving six different cutting-edge techniques, to examine the interactions of these high-risk events and identify the mechanisms leading to them.

Project Term: October 1, 2024 - September 30, 2027

Blood cancers can be caused by aberrant regulation of genes that control cell growth and development. The root cause of this problem may be the presence of mutant regulator proteins in the cell and abnormal switching on or off of target genes. Our SCOR studies the molecular basis of this gene deregulation using cell cultured in the laboratory, in human specimen and animal models.Melnick will study the complex of proteins evolve in looping DNA segments to put gene regulatory sequences in proximity of genes critical for the development of antibody producing B cells. Abnormalities of this apparatus lead to lymphoma. Roeder will study multi-protein complexes involved in “bookmarking” chromatin (the complex of DNA and histones found in the cell nucleus) by chemical modification. He studies the proteins that initiate transcription of DNA into RNA and that assure the passage of the polymerase that creates messenger RNA across genes. Soto-Feliciano studies TRIM28, a protein essential for growth of acute leukemia will identify its mechanisms and target genes. Licht will study the role of chromatin regulators in the response of the immune system to multiple myeloma and how inhibitors of chromatin regulator inhibitors affect the tumor immune response. Patel will study in explore the three-dimensional structures of these protein complexes critical for gene regulation in blood malignancies to understand their mechanisms and develop new small molecules to modulate their action.

Project Term: October 1, 2024 - September 30, 2029

Most CLL patients treated with CAR T-cells that target the CD19 antigen on the cell do not achieve a complete remission. CLL cells express other molecules on their surface; one of them is the receptor for BAFF (BAFF-R), which is highly expressed. We propose a phase I trial investigating LMY-920 for treatment of CLL. LMY-920 is a different type of CAR T-cell because it does not rely on an antibody structure to identify BAFF-R, but uses the structure of the ligand BAFF itself, and this may help avoid resistance to CAR T-cells.We also aim to improve the quality of the CAR T-cell product by removing the circulating B cells with a monoclonal antibody prior to collecting lymphocytes for manufacture.

Project Term: July 1, 2024 - June 30, 2027

This Specialized Center of Research is focused on identifying the contributions of chromosome 21, which is present in three copies in individuals with Down syndrome (DS), to acute leukemia. Children with DS are at a 20-fold increased risk of leukemia compared to the overall pediatric population and frequently have other health issues that complicate leukemia treatment. Although acute myeloid leukemia in children with DS (ML-DS), which frequently evolves from transient abnormal myelopoiesis (TAM), has a better outcome than acute myeloid leukemia (AML) in children without DS, those who relapse following treatment face an extremely poor prognosis. Similarly, children with DS who develop B-ALL have a worse prognosis than those without DS due to excessive treatment-related mortality and increased risk of relapse. Our overarching, united goal is to develop novel therapies to cure DSassociated leukemias and to reduce the side effects of treatment in this vulnerable population. In addition to children with DS, our study has major implications in other cases of pediatric and adult leukemias. For example, chromosome 21 amplification is one of the most significant gains in several classes of malignancies, including certain subtypes of AML, hyperdiploid ALL, and iAMP21. Amplification of chromosome 21 is also a feature of the acute leukemia phase of a disease named myelofibrosis. Therefore, insights we gain from this research will impact a large group of patients with acute leukemia.

Project Term: October 1, 2024 - September 30, 2029

Although many patients with diffuse large B-cell lymphoma (DLBCL) are cured with standard therapy, others will die from their disease. Survival is significantly worse for African American (AA) patients and those with Epstein- Barr virus (EBV), which is common in patients from Latin America. The reasons behind these poor outcomes are not well understood, in part because most studies of molecular features in lymphomas have not included enough patients from these racial and ethnic groups.Lymphoma tumors include not just the cancer cells themselves, but also surrounding cells and proteins that help the cancer cells survive. To understand why AA DLBCL patients and those with EBV have worse outcomes, we will look at differences in genes and tumor make-up in a large collection of DLBCL samples with good representation of these patient groups. Our goal is to find the factors most important to target with new treatments to improve survival for AA and EBV+ patients. We will also build innovative models of DLBCL in the lab to (1) discover how tumor make-up and gene changes affect tumors’ response to treatment, and (2) test new therapies designed to benefit AA DLBCL patients and patients with EBV-associated DLBCL.Overall, our LLS SCOR Program seeks to bridge the knowledge gap in molecular features of DLBCL in underrepresented populations, and fast-track development of novel targeted therapies that can improve outcomes for these vulnerable patients.

Project Term: October 1, 2024 - September 30, 2029

In December 2024, LLS made an equity investment in Solu Therapeutics to "Support Preclinical and Clinical Development of STX-0712 in hematological malignancies, primarily in CMML."Solu Therapeutics is a biotechnology company dedicated to developing next-generation therapeutics to eliminate disease-driving cells in cancer, immunology and other therapeutic areas. The company’s proprietary CyTAC (Cytotoxicity Targeting Chimera) and TicTAC (Therapeutic Index Control Targeting Chimera) platforms enable the development of innovative medicines that combine the target-binding capability of small molecules with the therapeutic power of biologics.STX-0712 is a CyTAC targeting the GPCR CCR2, which is a selective marker expressed at high levels on pathogenic monocytes. Pathogenic monocytes expressing CCR2 have been shown to be the key drivers in some hematological malignancies. A Phase 1 trial is ongoing to assess the safety and efficacy of STX-0712 in patients with advanced CMML (NCT06950034).

Project Term: December 18, 2024 - TBD