Rhabdomyosarcoma is the most common soft tissue sarcoma in children and has no targeted treatment options. The most aggressive forms of rhabdomyosarcoma are caused when pieces of two chromosomes break off and fuse together and create an abnormal protein called PAX3-FOXO1. This new protein turns on and off hundreds–if not thousands–of genes, transforming a normal cell into a cancer cell. The exact mechanism of how PAX3-FOXO1 accomplishes this is unknown and insight into this process is hindered by the lack of models.
Principal Investigator Name:
Genevieve Kendall, PhD
Project Title:
Mechanisms of PAX3-FOXO1 and HES3 Cooperation in Rhabdomyosarcoma
Background: Medulloblastoma is the most common malignant brain tumor affecting children and comprises ~33% of pediatric brain cancers. Medulloblastoma is a tumor originating in the cerebellum and most of these tumors arise from unregulated proliferation of cerebellar granule cells. Current treatment strategies have not changed much over the years and are associated with high morbidity and mortality associated with recurrence. Thus, there is an urgent need for more effective and targeted therapies that reduce toxicity and prevent recurrence.
Principal Investigator Name:
Saikat Mukhopadhyay, MD/PhD
Project Title:
Role of Primary Cilium Signaling and Dynamics in Medulloblastoma Initiation and Progression
Background: My goal is to improve treatments for infant leukemia patients and genetic counseling efforts for their families. To realize this goal, we will develop mouse models to study the interactions between MLL translocations (the most common mutation in infant leukemia) and inherited genetic variants that potentially predispose to infant leukemia – in this case variants in the MLL3 gene. Mice are the optimal model for these studies because they are genetically tractable and mouse blood development closely approximates human blood development.
Principal Investigator Name:
Jeffrey Magee, MD/PhD
Project Title:
The Role of Inherited MLL3 Single Nucleotide Variants and Fetal Epigenetic Programming in Infant Leukemogenesis
Background: Genetic alterations and epigenetic mechanisms can alter the balance of normal blood development resulting in hematological malignancies. Acute myeloid leukemia represents approximately 20% of all childhood leukemias. Despite a better prognosis for childhood leukemia compared to adults, 30% of children eventually fail to respond to therapy. An altered differentiation program that is accompanied by uncontrolled cell growth defines these leukemias.
Principal Investigator Name:
Michael Kharas, PhD
Project Title:
Uncovering the Dysregulated RNA Binding Protein Network in Childhood Acute Myeloid Leukemia
Background: Outcome for children with glioblastoma (GBM) is extremely poor. It is highly resistant to conventional methods of cancer treatment and less than 16% of children survive more than five years after diagnosis. In addition, aggressive combined therapy causes significant harm. Recent advancements in cancer immunotherapy have enabled us to genetically engineer patients' own T cells to express artificial molecules called chimeric antigen receptors (CARs) that specifically recognize the GBM-associated protein, human epidermal growth factor receptor 2 (HER2).
Principal Investigator Name:
Meenakshi Hegde, MD
Project Title:
Engineering the CAR T Cells to Overcome Tumor Derived Immune-Inhibition in Glioblastoma
Viviana is a vibrant and fun-loving little girl. After showing several strange symptoms, Viviana was taken to the ER and was diagnosed with acute lymphoblastic leukemia soon after. Today her laughter is still contagious as she's in the midst of treatment!
