Lucile Packard Children’s Hospital at Stanford University School of Medicine

Lucile Packard Children’s Hospital at Stanford University School of Medicine

300 Pasteur Dr

Stanford, CA 94305

United States

Targeting Aberrant Hh Signaling with BET Bromodomain Inhibition as a Novel Therapeutic Strategy Against MB and DIPG

Medulloblastoma, Diffuse Intrinsic Pontine Glioma (DIPG), Brain Tumors

Background

The specific childhood cancers I am addressing in this proposal are medulloblastoma (MB) and diffuse intrinsic pontine glioma (DIPG), which are the two most common malignant pediatric brain tumors and the leading causes of pediatric brain tumor-related deaths. We propose to focus on an evolutionarily conserved signaling axis called the Hedgehog (Hh) pathway that is known to be aberrantly activated in these two cancers. Importantly, targeting this pathway has been shown to effectively inhibit the growth of these two types of tumors.

Investigation of Oncogenic Long Non-coding RNAs in Ewing sarcoma

Ewing Sarcoma

Background

Long non-coding RNAs (lncRNAs) are RNA sequences that do not encode proteins. In the past, they were regarded as having no biological functions. However, recent studies have shown that lncRNAs regulate a number of cellular activities. More importantly, lncRNAs are beginning to be recognized as key players in oncogenesis in various cancers.

Characterization of Noncanonical Mitochondrial Notch/PINK1 Interaction in Medulloblastoma Tumorigenesis

Brain Tumors

Oncogene Addiction and the Immune Response in Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia (ALL)

Next-Generation Therapies for Hedgehog Pathway-Dependent Tumors

Brain Tumors, Glioma, Medulloblastoma, Rhabdomyosarcoma

Background

Inappropriate activation of the Hedgehog signaling pathway can promote the onset and/or progression of several pediatric cancers, including medulloblastoma, rhabdomyosarcoma, diffuse intrinsic pontine glioma, and Ewing's sarcoma. Hedgehog pathway inhibitors therefore provide new hope to children afflicted with these diseases, and drugs that target the transmembrane signaling protein Smoothened have induced dramatic tumor regressions in the clinic.

Oncogenic Hedgehog Pathway Activation by a Putative Rho GTPase-Activating Protein

Brain Tumors

Background

Aberrant Hedgehog (Hh) pathway activity during postnatal life contributes to a subset of medulloblastomas, the most common malignant brain tumors in children.

Reversing the Oncogenic Roles of Misdirected Chromatin Remodeling in Synovial Sarcoma

Synovial Sarcoma

Background

Synovial sarcoma (SS) represents the most common non-rhabdomyosarcomatous soft-tissue malignancy in pediatric patients; 30% of all synovial sarcomas manifest during the first two decades of life with a median age of 13 years. These aggressive tumors are largely resistant to conventional chemotherapy-based forms of treatment, underscoring the need for an understanding of their pathogenesis and the development of disease-specific biologic agents which target the molecular hallmark, the SS18-SSX fusion protein, or its interactions.

Improving Thymus Function by RB Inactivation

General Pediatric Cancer, Leukemia, Retinoblastoma

Children with cancer face many health challenges before, during, and after treatment. In particular, one major side effect of most chemotherapeutic approaches as well as bone marrow transplantation strategies is depletion in immune cells. This decrease in immune function may increase the risk of opportunistic infections as well as cancer relapse.

Studying the clonal dynamics and evolution of leukemia using molecular barcodes

Leukemia

Background

When we give a cancer a name we imply that it is a homogeneous entity. It is well known, however, that by the time cancer reaches a size to become clinically detectable it is a complex and large heterogeneous mixture of cancer cells. It is likely that this underlying heterogeneity plays an important role in both the development of the cancer and its response to treatment.

Alex's Lemonade Stand Foundation for Childhood Cancer