My project is to determine why hyper-phosphorylation of IRF2BP2 in the absence of Cdk5 prolongs the IRF2BP2 protein half-life. This leads to reduced ability of the tumor cells to up-regulate immune checkpoint molecule PDL1 (programmed death ligand 1) during immune attack. PD-L1 is a cell surface molecule produced by tumor cells that tells T cells that it is part of the person's body so the immune system ignores it. Interferon-gamma enhances the expression of PD-L1 on tumor cells, allowing the tumor cells to resist immune attack.
Principal Investigator Name:
Daniel Kingsley
Project Title:
Site-specific Hyper-phosphorylation of IRF2BP2 Modulates Tumor PD-L1 Expression in Medulloblastoma
I will determine the potential role of Cdk5 during the transformation of Notch1-induced T-cell leukemia from hematopoietic progenitor cells and its role in granting the ability of the leukemic cells to seed in the central nervous system (CNS). My mentor's laboratory identified a novel role of Cdk5 in T cell activation and function. We hypothesize that Cdk5 will also play a crucial role in regulating Notch1-induced transcriptome.
Principal Investigator Name:
Nimisha Swali
Project Title:
To Examine the Role of Cdk5 in T-cell Leukemia in Altering a Tumor's Ability to Seed CNS or Altering Immune Sensitivity to the Host's Immune System
T cells transduced with CD19 chimeric antigen receptors (CARs) have had dramatic therapeutic effects in children with B cell acute lymphoblastic leukemia (ALL). This strategy has now progressed to licensing trials. However, utilizing CARs to target T cell malignancies is challenging due to shared expression of most targetable antigens between malignant and normal T cells. This potentially leads to killing CAR expressing T cells.
Principal Investigator Name:
Benjamin Brenner
Project Title:
Optimizing a CD5 CAR Approach to Treat Children with T cell Leukemia and Lymphoma
Our laboratory is interested in finding better treatments for osteosarcoma (OS), the most common malignant primary bone tumor in children and adolescents. Survival rates for patients with OS have not changed for more than 30 years. We have been studying a rare genetic disorder called Rothmund-Thomson syndrome (RTS) as a model for OS development, where 2/3 of patients have germline mutations in a gene called RECQL4 (Type II RTS). These patients have an extremely high and specific risk for developing OS.
The tumor suppressor caspase-2’s levels are decreased in the childhood forms of acute leukemia, including T-lineage acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). The main role of caspase-2 is to induce a form of cell death called apoptosis but it has also been shown to prevent cell division. Therefore, caspase-2 may protect against leukemia by apoptosis or by stopping cell division.
Principal Investigator Name:
Kevin Dunne
Project Title:
Investigating the Role of Nucleophosmin as a Novel Caspase-2 Target in Pediatric Leukemia
T-cells have proved safe and effective for the treatment of certain types of cancer. However, T-cell efficacy against most solid tumors is limited by the immunosuppressive microenvironment generated by tumor cells and their infiltrating stroma. Myeloid-derived cells are potent controllers of the tumor microenvironment and can alter the fate of tumor-specific T-cells.
Principal Investigator Name:
Ari Morgenstern
Project Title:
Combining Oncolytic Adenovirus (OncAd) with Tumor Directed, Adenovirus-specific T-cells for the Treatment of Neuroblastoma: Effects of OncAds on Immunosuppressive Myeloid Cells
Sylvia loves volunteering and being active and artistic. After an MRI revealed a brain tumor instead of a suspected food allergy, Sylvia's entire life changed. She had surgery two days later and then began treatment. Thankfully today, she is cancer-free!