Pediatric Cancer

Current Projects
Özlem Aksoy, PhD

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.

Project title: "Understanding the role of translational control in humanized mouse models for medulloblastoma"
Institution: University of California, San Francisco
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Davide Ruggero, PhD
Cancer Type: Pediatric, Brain
Research Area: Cancer Genetics
Challice L. Bonifant, MD, PhD

Dr. Bonifant is studying how best to direct the immune system to combat acute myeloid leukemia (AML), a blood cancer of both children and adults. By specifically directing T immune cells to AML, she hopes to make therapy stronger and more effective, while also reducing toxicity. She is exploring the activity of T cells targeting multiple AML-specific antigens that do not affect normal cells. The ultimate goal of the work is to develop new strategies to treat AML.

Project title: "Dual-antigen targeting by ENG-T cells as improved anti-AML therapy"
Institution: University of Michigan, Ann Arbor
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Pavan Reddy, MD
Cancer Type: Blood, Pediatric, All Cancers
Research Area: Immunotherapy
Robert L. Bowman, PhD

Dr. Bowman focuses on acute myeloid leukemia (AML), which can be characterized by successive development of genetic mutations. While some mutations are found in nearly every cell of the disease, others are found in sub-populations and are thought to arise at later stages of disease development. It remains unclear if these late mutations are necessary for leukemic progression and are actionable therapeutic targets. He aims to develop models to test the oncogenic dependency of one of the most commonly mutated genes in AML, FLT3. Further models will be developed to understand the role of mutation order in disease development.

Project title: "Interrogating the subclonal architecture and functional contributions of mutation order in FLT3-ITD mutant AML"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Sohn Fellow
Cancer Type: Blood, Pediatric
Research Area: Animal Models/Mouse Models
Srinjoy Chakraborti, PhD

Dr. Chakraborti is developing technologies to facilitate the rapid identification of individual, specific, safely targetable tumor antigens, and to engineer tumor chimeric antigen receptors (CARs) to specifically recognize and kill cancer cells within a clinically relevant timeline. Dr. Chakraborti also plans to use these technologies to investigate the role of helper T cells in enhancing the activity of anti-cancer killer T cells. These technologies, although applicable to adult cancers as well, will focus on antigens derived from pediatric cancer tissues because conventional therapies (such as chemotherapy and radiation) hold long-term health risks. 

Project title: Mining pHLA and T cell receptors (TCR) specificities by phage display for de novo TCR engineering and personalized cancer therapy
Institution: Albert Einstein College of Medicine
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Jonathan R. Lai, PhD
Cancer Type: Other Cancer, Pediatric
Research Area: Immunotherapy
Stacy L. Cooper, MD

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.

Project title: "The Cebpa +37kb enhancer is a critical target of transformation in acute myeloid leukemia"
Institution: The Johns Hopkins University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Alan D. Friedman, MD
Cancer Type: Blood, Pediatric
Research Area: Epigenetics
Adam D. Durbin, MD, PhD

Dr. Durbin is developing new ways to target neuroblastoma, using chemical inhibitors and genetic techniques to disrupt small RNA species and enzymes that neuroblastoma cells require for survival. These new factors will also be inhibited in animal models of human neuroblastoma, alone and in combination with drugs similar to those entering clinical trials. These studies aim to identify new levels of gene regulation and methods to inhibit the genes involved in formation of neuroblastoma, with minimal side effects.

Project title: Interrogation of neuroblastoma dependencies and non-coding RNAs on the core-regulatory circuitry for therapeutic inhibition
Institution: Dana-Farber Cancer Institute
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): A. Thomas Look, MD
Cancer Type: Other Cancer, Pediatric
Research Area: Epigenetics
Amanda Balboni Iniguez, PhD

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. This research will contribute to our understanding of Ewing sarcoma cell biology and has important clinical implications for other cancers driven by similar transcription factor fusion proteins.

Project title: "Targeting the EWS-FLI oncoprotein in Ewing sarcoma with CDK12/13 inhibitors"
Institution: Dana-Farber Cancer Institute
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Kimberly Stegmaier, MD
Cancer Type: Pediatric, Sarcoma
Research Area: Experimental Therapeutics
Michael A. Koldobskiy, MD, PhD

Dr. Koldobskiy studies the ways that cancer cells rely on “epigenetic” modifications, or chemical marks that modify the expression of genes without a change in the genetic sequence itself. Variability of epigenetic marks allows cancer cells flexibility in turning genes on and off, and may account for resistance to treatment. By dissecting the mechanisms of epigenetic modification in pediatric acute lymphoblastic leukemia (ALL), the most common cancer in children, he aims to identify new targets for treatment.

Project title: "DNA methylation stochasticity in pediatric pre-B cell acute lymphoblastic leukemia"
Institution: The Johns Hopkins University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Andrew P. Feinberg, MD
Cancer Type: Blood, Pediatric
Research Area: Epigenetics
Loretta S. Li, MD

Approximately 10-15% of pediatric and adult patients with B-cell acute lymphoblastic leukemia (B-ALL) have a high-risk form of the disease characterized by rearrangements of a gene called CRLF2. Alterations of this gene result in increased expression of the CRLF2 protein and promote leukemia development. When treated with conventional chemotherapy, patients with CRLF2 gene alterations do poorly. Their leukemias are dependent on an enzyme called JAK2 for survival, yet no targeted therapies with proven efficacy are currently available. Dr. Li has unique access to a new drug called CHZ868, which turns off JAK2 enzyme activity, potently kills B-ALL cells, and improves overall survival in mice with JAK2-dependent B-ALL. Treatment with CHZ868 alone is not curative, however, and all mice eventually succumb to progressive leukemia. Using JAK2-dependent B-ALL cells and mouse models, she will study how leukemia becomes resistant to JAK2 inhibitors. Her goal is to identify combinations of agents that can prevent or overcome resistance to a single therapy and also guide the development of new JAK2 inhibitors for patients.

Project title: "Mechanisms of disease and resistance in CRLF2-rearranged B-cell acute lymphoblastic leukemia"
Institution: Dana-Farber Cancer Institute
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): David M. Weinstock, MD
Cancer Type: Blood, Pediatric
Research Area: Cancer Genetics
Sarah Naomi Olsen, PhD

Dr. Olsen is investigating new therapeutic options to treat acute myeloid leukemia (AML), an aggressive form of childhood cancer. One subtype of AML is characterized by a chromosomal translocation involving the MLL (KMT2A) and the AF9 gene, resulting in an abnormal MLL-AF9 fusion protein. Dr. Olsen is targeting the MLL-AF9 fusion protein using a newly developed protein degradation approach. Characterizing the consequences of direct MLL-AF9 degradation will provide important mechanistic insight into how this mutant protein modulates leukemia and help guide the development of combination therapeutic approaches for long-term responses in pediatric AML patients.

Project title: Targeted degradation of the MLL-AF9 fusion oncoprotein in acute myeloid leukemia
Institution: Dana-Farber Cancer Institute
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Scott A. Armstrong, MD, PhD
Cancer Type: Blood, Pediatric
Research Area: Epigenetics
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