Case Western Reserve University

Case Western Reserve University

10900 Euclid Ave

Cleveland, OH 44106

United States

Unraveling the Function of PAX3-FOXO1’s Activation Domain in Rhabdomyosarcoma

Rhabdomyosarcoma is a childhood cancer that often resurfaces after chemotherapy, making it a challenging disease to tackle. The main culprit is a fusion protein called PAX3-FOXO1 (P3F), which causes the cancer by meddling with our DNA. Imagine this protein as a small machine that tweaks the opening, closing and 3D folding of the DNA instructions in our cells, leading to the growth of cancer. One part of the machine binds DNA, but little is known about the other half of the machine.

Cdk5 Inhibition Leads to Enhanced Immune Sensitivity of Medulloblastoma via Changes in the Epigenetic Landscape

Brain Tumors

Mentor: Alex Huang

Mechanism of Integrin-Mediated M2 Polarization of Tumor-Associated Macrophages by Metastatic Osteosarcoma

Osteosarcoma

Mentor: Alex Huang

Time Dependency of Anti-PDL1 Checkpoint Blockade Efficacy Against PDL1-Negative Medulloblastoma

Medulloblastoma

Mentor: Dr. Alex Huang

Targeting Pediatric Brain Tumors Using PTPmu Nanochains with Radiofrequency-Releasable Therapeutics

Brain Tumors

Background

Site-specific Hyper-phosphorylation of IRF2BP2 Modulates Tumor PD-L1 Expression in Medulloblastoma

Brain Tumors, Medulloblastoma

Background

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.

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

Acute Lymphoblastic Leukemia (ALL)

Background

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.

Cure Osteosarcoma Lung Metastasis by Disrupting Tumor VCAM-1 Signaling with Macrophages

Osteosarcoma

Background: Osteosarcoma (OS) is the most common aggressive primary bone cancer in the pediatric and adolescent population. Half of all new cases of OS diagnosed in the U.S. occur in children and young adults, and about 20% of these patients have metastatic spread, while others developed lung metastasis after initiation of therapy. Lung metastasis in OS responds poorly to conventional chemotherapy, which accounts for most of the mortality.

The Phase I/II Trials Collaborative for Children, Adolescents, and Young Adults at UH Rainbow Babies & Children's Hospital and the Case Comprehensive Cancer Center

Brain Tumors, General Pediatric Cancer

Innovative pediatric developmental therapeutic programs are critical to the identification of novel agents that offer the prospect of more effective and less toxic therapies for pediatric cancers.

Developing Immune-modulatory Strategies Against Primary and Metastatic Tumors in the Central Nervous System

Brain Tumors, Medulloblastoma

Pediatric brain tumors have among the highest cancer incidence and are major contributor of mortality and morbidity. Among pediatric brain tumors, medulloblastoma constitutes the most common malignant brain tumors with metastatic potential. Despite aggressive therapy consisting of surgery, radiation, chemotherapy and bone marrow transplantation, survival in high-risk medulloblastoma patients is only about 60%.

Alex's Lemonade Stand Foundation for Childhood Cancer