Damon Runyon News

Dr. Zimmerman studies neuroblastoma, a tumor of the peripheral sympathetic nervous system. In high-risk neuroblastoma tumors, which account for 15% of all childhood cancer deaths, the chromatin remodeling gene CHD5 is often deleted and its loss is associated with poor prognosis. The gene expression program regulated by CHD5 has strong tumor suppressive effects and has thus emerged as a very attractive target for potential anti-cancer therapeutics. CHD5 expression is also altered in other cancer types, indicating a potential role in many different adult and pediatric malignancies.

Dr. Woessner seeks to identify genetic changes that cause the most common type of childhood cancer, acute lymphoblastic leukemia (ALL). There are multiple subtypes of ALL, each with distinct genetic changes that drive disease development and influence success or failure of treatment. He has sequenced the genomes of over 1000 tumor cells from children with ALL and identified several hundred repeatedly mutated genes, for which the functions are currently unknown. He will use high throughput approaches to test the role of these changes in ALL.

Dr. Lin studies neuroblastoma cancers. Genetic amplification and aberrant expression of the oncogenes LIN28B and MYCN are associated with high-risk neuroblastoma and poor survival. Interestingly, these genes positively regulate each other and form a self-reinforcing feedback loop to drive neuroblastoma oncogenesis. His research aims to identify novel factors that interact with LIN28B/MYCN in tumor formation. He is characterizing a LIN28B-interacting long intergenic non-coding RNA (lincRNA) and will determine how the lincRNA functions to regulate neuroblastoma progression.

Dr. Sabnis is exploring novel treatment options for rhabdomyosarcomas, the most common pediatric soft tissue sarcomas. These sarcomas uniquely depend on the activity of "protein chaperones" that prevent newly made proteins from forming toxic clumps. His research focuses on small molecules that inhibit one class of chaperones called HSP70s. The goal of these studies is to identify a new target for drug development to help cure this disease.

Dr. Chu focuses on a promising new class of therapy that inhibits epigenetic regulators, proteins that control the expression and activity of genes through DNA sequence-independent chemical modifications. Much remains unknown about how these new drugs induce specific changes in tumors upon treatment or what their efficacy is in sustaining long-term, durable responses in patients. He plans to characterize the changes induced with the use of such inhibitors in animal and human models of leukemia.

Dr. Lu [Layton Family Fellow of the Damon Runyon-Sohn Foundation Pediatric Cancer Fellowship Award] is developing new methods for direct analyses of RNA structures and RNA-RNA interactions in living cells, which remain a major technical challenge. RNA helicases and RNA binding proteins interact with and remodel RNA structures to coordinate all aspects of RNA metabolism, and mutations in these proteins lead to many cancers such as medulloblastoma brain tumors.

Dr. Cooper focuses on developing novel therapies for acute myeloid leukemia (AML), which has an approximately 50% mortality rate. Her work focuses on C/EBPalpha, a protein that is decreased in more than half of all AML patients. By determining how the production of this protein is regulated, she aims to understand the mechanisms for its reduction in leukemia and to develop strategies to target C/EBPalpha as a novel therapy for AML.

Dr. Balboni Iniguez studies Ewing sarcoma, a rare pediatric solid tumor containing a characteristic chromosomal translocation that fuses the EWSR1 gene to the FLI1 gene. The resulting EWS/FLI fusion protein initiates an oncogenic gene expression program, thus promoting tumorigenesis. EWS/FLI represents an attractive tumor-specific therapeutic target; however, it has been difficult to pharmacologically inhibit. Her work will focus on elucidating a novel approach to selectively target EWS/FLI by utilizing a small-molecule inhibitor against the transcriptional regulator proteins CDK12/13.

Dr. Aksoy is establishing a human stem-cell based model of medulloblastoma brain tumors that can be rapidly manipulated, allowing insights into how genetic mutation contributes to medulloblastoma tumorigenesis and how these mutations cooperate in tumor formation. She will study the highest-risk subtype of medulloblastoma, with the goal of understanding the possible role of translational control in this cancer. She will test both novel and existing mTOR inhibitors as a potential therapeutic strategy for patients.

Dr. Vu is studying childhood acute myeloid leukemia (AML), a complex and heterogeneous disease. Despite exciting advances in our understanding of AML and the availability of more aggressive treatment regimens, ~30% of children still eventually relapse from this disease and there are yet no approved targeted therapies for children with AML. Her project aims to uncover the role of Syncrip, a novel RNA binding protein, in maintaining the leukemia stem cell in AML.