Dana-Farber Cancer Institute

Dana-Farber Cancer Institute

44 Binney Street

Boston, MA 2115

United States

Therapeutic Reactivation of p53 to Overcome Apoptotic Resistance in Pediatric Leukemia

Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML)

p53 is a renowned tumor suppressor gene that is frequently mutated or deleted in cancer, resulting in the development, persistence, and chemoresistance of human cancers. In surveying the broad spectrum of cancers for genetic modification of p53, we have identified a series of pediatric leukemias that maintain expression of wild-type p53 despite the attendant risks to tumor cell survival. We hypothesized that mechanisms other than p53 mutation and deletion could be operational to neutralize p53 activity in these contexts, including negative regulation of p53 by HDM2 and/or HDMX.

Regulation of Tumor Debris Mediated Inflammation as a Therapeutic Modality in Medulloblastoma

Medulloblastoma

Background

Radiation and chemotherapy is the standard for most patients with cancer. The goal is to kill as many of the tumor cells as possible before resistance develops and the tumor stops responding. Our recent work has discovered that the release of the cellular content (cellular debris) of dead tumor cells into the tumor microenvironment provides the necessary factors that stimulate surviving tumor cells to grow.

Novel Nanoscale Phosphoproteomic Discovery of Therapeutic Targets in AML Stem Cells

Leukemia, Acute Myeloid Leukemia (AML)

Dr. Wang has moved and will be continuing his research at City of Hope's Beckman Research Institute in Duarte, CA. http://www.leowanglab.org/

Background

Acute myeloid leukemia (AML) is difficult to treat, relapses easily, and is often fatal. This is largely due to the existence of rare leukemia stem cells (LSCs), which are able to propagate the disease but are resistant to chemotherapy. Developing therapies that specifically target LSCs will improve AML cure rates dramatically.

The Role of DEF and SSU Processome in Neuroblastoma Pathogenesis

Neuroblastoma

Background

Neuroblastoma is the most common solid tumor of childhood, which accounts for 15% of childhood cancer deaths. Changes in the nucleolus and ribosome biogenesis are known to occur in malignant cells, which is due to the key role of the ribosome in cell growth and proliferation. In my graduate work, I have shown that a nucleolar factor Def plays a role in ribosomal RNA processing during zebrafish development as a component of the SSU processome.

Elucidating Mechanisms Driving Renal Medullary Carcinomas to Deliver a Rational Approach to Cancer Directed Therapy

Renal Cell Carcinoma

Background

Through the natural history of patients with sickle cell trait or disease, we have learned that they are at risk of a rare cancer, renal medullary carcinoma. With a very poor prognosis, it is critical that we understand the molecular underpinnings of this disease in order to devise improved therapeutic options. Unfortunately, there are no models available to study this cancer in the laboratory.

A Translational Approach to Identify Drugs with Specific Activity Against EZH2 Mutant High Risk T-ALLs and ETP ALLs that Overexpress the JDP2 bZIP Transcription Factor

Leukemia, Acute Lymphoblastic Leukemia (ALL)

Background

Outcomes for children with acute lymphoblastic leukemia (ALL), the most common childhood malignancy, have improved dramatically over the last 20 years. However, a subset of patients with ETP-ALL have an extremely poor prognosis. Very recently, it was discovered that many of these high-risk tumors and other high-risk T-ALLs have acquired disruptions of the EZH2 gene. We have shown that the JDP2 gene is upregulated in both ETP-ALL and other high-risk T-ALLs and is required for the growth and survival of these leukemia cells.

The Role of PARP3 in the Formation of Chromosomal Translocations

Ewing Sarcoma, Acute Lymphoblastic Leukemia (ALL), Non-Hodgkin Lymphoma

Background

Cancer cells have many abnormalities in their DNA. In a cell, DNA is divided into large structures called chromosomes. Chromosomes can be broken as a result of exposure to damaging environmental factors such as sunlight or cancer treatments such as chemotherapy. Broken chromosomes are very dangerous to the cell because essential genetic information can be lost or corrupted, ultimately resulting in death of the cell. Ideally, a cell with broken chromosomes is able to correctly rejoin the broken ends to restore the chromosomes to their original form.

Therapies for SHH-subtype Medulloblastoma

Brain Tumors, Medulloblastoma

Background

Brain tumors are now the leading cause of cancer death in children. One of the most common brain tumors in children is called medulloblastoma. Many mutations (changes in the DNA) that cause medulloblastoma have been identified, and a new type of specific, targeted therapy looks very promising for attacking tumors with particular mutations. However, some tumors with these mutations do not respond to the new specific drugs.

Role of LMO1 in Neuroblastoma Initiation and Maintenance: Analysis in the Zebrafish model of Childhood Neuroblastoma

Neuroblastoma

Targeting MYC/MYCN-driven Transcriptional Amplification in Pediatric Cancer

General Pediatric Cancer, Neuroblastoma

Alex's Lemonade Stand Foundation for Childhood Cancer