Pediatric Cancer

Current Projects
Maxim Pimkin, MD, PhD

Dr. Pimkin is identifying and characterizing the most critical transcription factors (proteins that regulate the function of genes), called core regulatory circuitries (CRCs), in various types of AML. This will provide new insights into the most critical mechanisms of AML survival and identify new targets for drug development. Preliminary data show that CRCs can accurately and reliably predict critical genes necessary for AML cancer cell survival, suggesting a practical way of identifying potential therapeutic targets. Dr. Pimkin hopes to create a unified understanding of the common and different ways in which AML subtypes arise, as well as create an unprecedented way of predicting common and subtype-specific AML vulnerabilities. 

Project title: Divergent core transcriptional circuitries highlight context-specific vulnerabilities in AML
Institution: Harvard Medical School
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Stuart Orkin, MD
Cancer Type: Blood, Pediatric
Research Area: Genomics
Cara A. Rabik, MD, PhD

Dr. Rabik is examining how mutations in the WT1 gene result in methylation changes in acute myeloid leukemia (AML). WT1 recruits the machinery necessary for demethylation to its target genes, ultimately regulating gene expression. When WT1 is mutated, these genes remain methylated and inactive, preventing normal hematopoiesis. She is identifying WT1 target genes and mapping their methylation landscape both in leukemic and normal settings. She will also test drugs designed to cause demethylation to evaluate if these drugs can treat the leukemia caused by mutations in WT1.

Project title: "Determination of the role of WT1 in hematopoiesis and leukemogenesis"
Institution: The Johns Hopkins University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Patrick A. Brown, MD
Cancer Type: Blood, Pediatric
Research Area: Epigenetics
Marissa Rashkovan, PhD

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, accounting for 10-15% of pediatric and 25% of adult ALL cases. While survival rates have improved with intensified treatment regimens, 25% of pediatric T-ALL cases still relapse because of refractory disease. Furthermore, the intensity of these treatment regimens has led to increased secondary effects in these children later in life. This underscores the need for the development of efficient, targeted and highly specific anti-leukemic therapies to treat T-ALL. Dr. Rashkovan studies a distinct subgroup of immature T-ALL, ETP-ALL, which phenotypically resembles early thymic progenitors (ETPs), has been associated with early relapse, and poor prognosis. There is a particularly urgent need for targeted therapies for ETP-ALL, which is notoriously difficult to treat. She will assess the metabolic vulnerabilities of ETP-ALL in order to propose new, targeted therapies which could be beneficial for the treatment of this high-risk leukemia group.

Project title: "Targeting metabolic vulnerabilities in ETP-ALL"
Institution: Columbia-Presbyterian Medical Center
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Adolfo A. Ferrando, MD, PhD
Cancer Type: Blood, Pediatric
Research Area: Cancer Genetics
Jay F. Sarthy, MD, PhD

Dr. Sarthy is developing new easy-to-use and affordable methods for studying DNA packaging and epigenetics (modification of gene expression) in pediatric cancers with a special focus on diffuse midline gliomas and neuroblastoma. These methods may help explain the drivers of pediatric malignancies and allow clinicians to better monitor response to treatment with the goal of developing new drugs that restore the cell’s ability to package DNA correctly.

Project title: Characterization of the epigenomic landscape of diffuse midline gliomas
Institution: Fred Hutchinson Cancer Research Center
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Steven Henikoff, PhD
Cancer Type: Other Cancer, Pediatric, Brain
Research Area: Epigenetics
Yadira M. Soto-Feliciano, PhD

Pediatric acute myeloid leukemia (AML) has the lowest survival rate among all pediatric cancers. MLL gene rearrangements (MLL-r) occur in about 20% of children diagnosed with AML. This subtype of leukemia is exquisitely sensitive to inhibition of the interaction between MLL and the chromatin adaptor Menin. Dr. Soto-Feliciano is combining genetic, genomics, and mouse modeling approaches to identify factors that regulate the function of Menin in MLL-r and non-MLL-r leukemia. The identification of cellular mechanisms that mediate the response to Menin-MLL inhibitor-based therapies (already in pre-clinical studies), will inform us about the molecular mechanisms driving acute leukemia. She anticipates that the results of these experiments will provide a better understanding of gene expression programs and chromatin landscapes governing the leukemic state. In addition, this project has the potential to identify novel dependencies that can lead to development of novel drug targets for the treatment of pediatric leukemia.

Project title: "Dissecting the role of Menin in acute leukemia"
Institution: The Rockefeller University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): C. David Allis, PhD
Cancer Type: Blood, Pediatric
Research Area: Epigenetics
Kathryn R. Taylor, PhD

Dr. Taylor is investigating the impact of neural activity on pediatric high-grade glioma (pHGG) invasion. The innate ability of pHGGs to diffusely infiltrate healthy brain tissue is a classical hallmark of the disease, which represents a major contributor to the devastating prognosis. Using optogenetic techniques to stimulate neuronal activity, she will directly and noninvasively test the effect of activity-dependent secreted proteins on tumor cell invasion in human cancer cells and animal models. She plans to confirm the pro-infiltrative effect of candidate proteins on pHGG and subsequently uncover the mechanisms by which they alter the molecular dynamics of the tumor cell. Her hope is to highlight a novel means by which the neural microenvironment drives glioma progression and most importantly identify a new set of therapeutic targets to limit glioma spread.

Project title: "The effect of neuronal activity on pediatric glioma invasion"
Institution: Stanford University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Michelle L. Monje, MD, PhD
Cancer Type: Other Cancer, Pediatric, Brain
Research Area: Developmental Biology
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