Research we fund

Blood cancers such as leukemia, lymphoma and myeloma may be caused by abnormal regulation of genes that control normal cell growth and development. Genes that are normally active can be silenced and/or genes normally not present in a blood cell are abnormally activated. The result can be an uncontrolled signal for continued cell growth or survival. Our group studies the molecular basis of this gene deregulation using cells cultured in the laboratory, human specimens, and animal models.

Project Term: January 1, 2019 - September 30, 2024

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.

Project Term: July 1, 2019 - June 30, 2024

We developed a chimeric antigen receptor (CAR) targeting an epitope of the myeloid associated antigen cathepsin G that is processed and presented in the contest of the MHC complex in myeloid leukemic cells. T cells expressing the cathepsin G specific CAR (CG1.CAR) recognize HLA-A2+ myeloid target cells expressing cathepsin G. We intend to study efficacy and safety of CG1.CAR-T cells in preclinical models in preparation of a phase I clinical study in patients with relapsed/refractory AML.

Project Term: July 1, 2021 - June 30, 2024

Bone marrow scar formation (fibrosis) is a hallmark of myelofibrosis and contributes significantly to the disease progression. We use mouse genetics to model myelofibrosis and understand the cellular and molecular makeup of the diseased microenvironment. We aim to understand the composition and alteration of the bone marrow microenvironment in myelofibrosis. This may provide novel therapeutic targets for myelofibrosis.

Project Term: July 1, 2019 - June 30, 2024

Clinical outcome of high-risk Myelodysplastic Syndrome (MDS) and AML with mutant (mt) RUNX1 is relatively poor. Supported by our preclinical data, we propose a Phase Ib clinical trial of omacetaxine mepisuccinate (OM) and venetoclax along with correlative science studies in patients with relapsed MDS or AML exhibiting mtRUNX1. Studies proposed will also determine pre-clinical activity of novel, OM-based combinations against mtRUNX1-expressing, patient-derived, pre-treatment AML cells.

Project Term: October 1, 2021 - September 30, 2024

My ultimate goal is to develop more effective, better tolerated, and individualized treatment for patients with AML. This project focuses on AML patients with IDH1 or IDH2 mutations, with a clinical trial evaluating a combination of three agents which are effective in IDH-mutated AML. While these therapies are not curative on their own, my hope is that this combination will lead to a practice changing all-oral, outpatient, and well-tolerated curative strategy for patients with IDH-mutated AML.

Project Term: October 1, 2021 - September 30, 2026

We will enroll transplant-eligible patients with intermediate-risk AML, and define mutation clearance after recovery from induction using deep exome sequencing. Patients who clear all mutations will be consolidated with chemotherapy only (HiDAC). Patients who fail to clear all mutations will be offered an allogeneic transplant. This prospective study may improve outcomes for intermediate-risk patients by more precisely using transplantation in first remission.

Project Term: April 1, 2021 - March 31, 2023

Dr. Madhav Dhodapkar, M.D., of Winship Cancer Institute of Emory University, Atlanta, leads a multi-institutional, multi-disciplinary LLS Specialized Center of Research team focused on advancing new immunotherapies for patients with multiple myeloma. Their goal is to improve the effectiveness of CAR T-cell immunotherapy, which engineers the patient’s T cells to find and kill cancer cells. The CAR-T they are studying targets a protein called BCMA found on the surface of all myeloma cells. BCMA-targeting therapies are showing tremendous promise for treating myeloma patients in clinical trials, but many patients eventually relapse. Dr. Dhodapkar’s group is working to understand the mechanisms that cause some patients to be resistant to the treatment. They are also investigating another type of immunotherapy that relies on natural killer T cells. His team includes researchers at Emory as well as Fred Hutchinson Cancer Center in Seattle.

Project Term: January 1, 2020 - December 31, 2024

We seek to optimize combination therapy for chronic lymphocytic leukemia with ibrutinib. We will address this question through 2 clinical trials combining ibrutinib with chemoimmunotherapy or an antibody. We will also examine the biology of CLL cells at a genetic and functional level to predict who will have the best response to therapy and to identify resistance mechanisms. Our goal is to develop curative combinations for CLL and to understand resistance in the patients who are not cured.

Project Term: July 1, 2018 - June 30, 2023

Nearly half of patients with diffuse large B-cell lymphoma (DLBCL), ultimately fail current therapies and die from their disease. Selective targeting of cyclin-dependent kinase 9 (CDK9) is a promising strategy, as evidenced by potent anti-tumor effects in preclinical models of DLBCL. Yet tumors evade therapy by developing resistance. This proposal seeks to both elucidate and circumvent the oncogenic events underlying this resistance in order to offer novel therapeutic approaches to treat DLBCL.

Project Term: October 1, 2021 - September 30, 2023

Mantle cell lymphoma (MCL) is an aggressive blood cancer which affects about 3,000 individuals in the United States annually. Despite advances of novel therapies in blood cancers, MCL remains incurable, and patients ultimately succumb to disease. We seek to evaluate longitudinal samples from patients with MCL treated with novel therapies to understand the mechanisms of drug resistance. We identify novel targets, with a particular focus on protein turnover pathways, to overcome drug resistance and improve survival of patients with MCL.

Project Term: July 1, 2018 - June 30, 2023

This project is aimed at investigating a pre-clinical “off-the-shelf” CAR (chimeric antigen receptor) T-cell immunotherapy approach where the CAR cells are generated directly in the patient’s body. Importantly, this product will be a truly off the shelf therapy that is ready instantaneously and can be used repeatedly without the restriction of time-consuming manufacturing processes.

Project Term: July 1, 2020 - June 30, 2023