Research we fund

This project aims to enhance CAR T-cell therapy, a promising treatment for blood cancers, by leveraging the ketogenic diet and its key byproduct, beta-hydroxybutyrate (BHB). We found that BHB enhances the metabolism of CAR T cells, improving their effectiveness and durability in the body. Our study will explore this innovative approach using murine models of blood cancers and healthy donors, aiming to better understand how BHB can augment CAR T-cell function. The ultimate goal is to pave the way for more potent, accessible cancer therapies.

Despite an array of promising immunotherapies, the blood cancer multiple myeloma still remains without any known cure. Patients with high-risk disease in particular still relapse most frequently after current BCMA-targeting therapies such as CAR-T cells. Here we identify CD70 as an alternative CAR-T target in these high-risk patients who need new treatment options, and further use innovative artificial intelligence-inspired strategies to develop a best-in-class CAR-T design targeting CD70. The goal of our proposal is to perform additional validation studies to prove the efficacy and safety of this novel CAR-T cell, with the goal of moving toward near-term clinical trials in high-risk myeloma by the completion of the award period.

The overall focus of my research is improving outcomes with immunotherapy in multiple myeloma.  I will accomplish this through 1) novel clinical trials of bispecific antibodies and CAR-T therapy; 2) outcomes research including real world evidence and patient reported outcomes to understand the safety, efficacy and areas of unmet need with standard of care immunotherapy; and 3) correlative studies focused on understanding factors impacting the efficacy and toxicity of these therapies.

We will conduct a decentralized randomized controlled trial of a high-fiber plant-based dietary intervention among patients with multiple myeloma undergoing induction chemoimmunotherapy. The study will assess whether the intervention (meals and virtual coaching) leads to improved rates of complete response, and quality of life mediated by improvements in weight and insulin resistance. The study is expected to provide rigorous evidence of the effectiveness of this intervention in patients with newly diagnosed multiple myeloma and support the development of low-cost, minimal-risk nutrition as a strategy to improve cancer treatment outcomes.

Winship Cancer Institute is the only NCI-Designated Comprehensive Cancer Center in Georgia, the largest state by land area east of the Mississippi River, and 8th largest state by population. The Winship IMPACT program will leverage existing relationships throughout the state to bring hematology trials to patients in their communities. The goals are to strengthen our relationship with community sites and to increase opportunities for patients to access cutting edge trials throughout our state.

Our recent studies have identified specific bacteria that can potentially promote the growth of human myeloma tumor cells. We are now testing if eradicating these bacteria in MGUS patients will be effective for prevention of myeloma.

We have observed that non-glycosylated CST6 proteins suppress osteoclast differentiation and function without causing immunosuppression. We aim to determine whether BCMA-CAR-T cells which are engineered to secret CST6 proteins kill myeloma cells and suppress bone lytic lesions without immune suppressive effects in myeloma. Our ultimate goal is to develop a CAR-T-cell based immune therapy to prevent bone loss and disease progression in myeloma patients.

Despite remarkable progress in the last 20 years, multiple myeloma remains an incurable disease. In recent years, 2 CAR T cell products that target BCMA on the myeloma cell have been approved. These products result in remarkable initial responses however the duration of these responses has been disappointing. In this proposal, we will take a novel approach to isolate and characterize myeloma cells that interact with CAR T cells but are not killed by them as a potential resistance mechanism.

Immunotherapy using chimeric antigen receptor (CAR) T cells, or CARTs for short, holds great promise for improving outcomes and survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Next-generation “armored” CARTs that can overcome transforming growth factor beta (TGF-beta) dependent immune suppression in the tumor microenvironment may provide deeper and more durable disease control than the TGF-beta sensitive CART products currently in clinical use.

Telehealth could improve access for Medicaid patients with a blood cancer who experience barriers to specialty care, but not all specialists offer it. Using Medicaid data, this study will provide novel information on whether blood cancer specialists are continuing to use telehealth following the COVID-19 pandemic when telehealth use increased dramatically. This study will also examine if telehealth helps address inequities in access to specialists, including for racial/ethnic minoritized groups and those living in rural areas.