NIH R01 - 07/15/2024 – 07/14/2029
Identifying and overcoming mechanisms of resistance to effectively target the TBL1/beta-catenin signaling axis for high-risk osteosarcoma
Goals: Our overall objectives are to (1) identify and transcriptionally characterize the clonal evolution of Tegavivint-resistant OS cells using complementary human and murine OS in vivo models, (2) assess rationale combinatorial therapeutic regimens that can quickly be translated to the care of high-risk sarcoma patients; and (3) using our lab’s OS genetically engineered mouse models (GEMM)-derived syngeneic models we will identify the extrinsic effects of targeting TBL1/β-catenin on the evolution of the tumor immune microenvironment (TiME).
Role: PI
NIH R01 - 08/01/2024 – 07/31/2029
Dissecting and targeting PAK4 for high-risk Ewing sarcoma
Goals: Pre-clinical evaluation of PAK4 inhibition as rational therapeutic approach for the treatment of high-risk Ewing sarcoma (ES). This aim will investigate the therapeutic potential of targeting PAK4 as monotherapy, and in combination using our expertise in clinically relevant orthotopic and metastatic sarcoma models of high-risk ES. SPECIFIC AIM 2. Identification of upstream and downstream regulators of PAK4 in ES. SPECIFIC AIM 3.Role of PAK4 in the direct regulation of transcriptional signatures and alternative splicing in ES The goal of this aim is to enhance our understanding into the molecular contributions of PAK4 in ES development and progression.
Role: PI
NIH/R21 - 01/2022-12/2024
Dissecting and Targeting the Role of Galnt14 in High-Risk Osteosarcoma
Goals: This study will lead to the identification of critical candidate therapeutic modalities for the treatment of high-risk OS
Role: PI
MPI: Kohler
Peach Bowl LegACy Fund - 07/01/2023-06/30/2026
A Phase 1b Study of Tegavivint,a TBL1 inhibitor, with Gemcitabine in Children, Adolescents, and Young Adults with Relapsed or Refractory Osteosarcoma
Goals: 1. Define the maximum tolerated dose and/or recommended phase 2 dose of Tegavivint in combination with gemcitabine. 2. Describe toxicities, in pediatic and AYA patients with relapsed or refractory osteosarcoma
Role: PI
MPI: Cash
MIB (Making it Better) Research Award - 08/2022-07/2024
Combinatorial therapies to improve immune-mediated approaches for osteosarcoma
Goals: 1. Assess the efficacy of targeting osteosarcoma development and progression with single agent targeted therapy and combination checkpoint inhibition on murine osteosarcoma models. 2. Assessment of cellular tumor evolution secondary to combinatorial targeted therapies on high-risk OS
Role: PI
Osteosarcoma Institute - 01/2023-12/2024
Use of Combinatorial Therapies to Improve Immune-Mediated Approaches for High-Risk Osteosarcoma
Goals: 1. Evaluate the antitumor activity and characterize the molecular and cellular responses to ICI and characterize the molecular and cellular landscape of OS tumors post-treatment with targeted therapy in our GEMM OS models. 2. Evaluate the antitumor activity and characterize the molecular and cellular responses to single agent vs combinatorial B7-H3-CAR T cell and targeted therapy in murine OS models
Role: PI
NIH/R01 - 12/2022-11/2027
Dissecting and Targeting Oncogenic Functions of PAK4 in High-Risk Rhabdomyosarcoma
Goals: Pre-clinical evaluation of PAK4 inhibition as rational therapeutic approach for the treatment of high-risk RMS. We will examine PAK4’s role as a novel regulator of AS and PAK4-mediated downstream transcriptomic and proteomic signatures that contribute to RMS progression through the use of our extensive inventory of highly relevant human and syngeneic murine pre-clinical models.
Role: PI
The Charlie Landers Foundation - 07/2023-06/2024
Dissecting and Targeting PAK4-Mediated Signaling in Ewing Sarcoma Development and Metastasis
Goals: 1. Pre-clinical evaluation of combination therapy incorporating PAK1 and PAK4 inhibition as a therapeutic approach for the treatment of high-risk Ewing sarcoma. 2. Defining the PAK4-proteo-transcriptomic signaling networks in primary and metastatic Ewing sarcoma
Role: PI
Rutledge Cancer Foundation - 08/2023-07/2024
Testing myr5A encapsulated cytotoxic compounds in xenograft models of Ewing sarcoma
Goals: Assessment of the efficacy of Myr5a targeted delivery of anti-tumor agents for the treatment of Ewing sarcoma. We will perform in vivo studies using our xenograft models of Ewing sarcoma.
Role: PI
DOMPE FARMACEUTICI - 01/2024-01/2025
Targeting CXCR1/2 in metastatic Ewing’s Sarcoma
Goals: In vitro testing of Ladarixin on Ewing sarcoma cells and In vivo testing of Ladarixin on Ewing sarcoma tumor development and progression using orthotopic model
Role: PI