Pediatric Cancer

Current Projects
Kiara C. Eldred, PhD

Dr. Eldred is focusing on retinoblastoma, a tumor of the eye that primarily occurs in children. She is developing three-dimensional tissue cultures that replicate the complexity of the human retina. Using these retinal “organoid” models, Dr. Eldred will generate mutations of the retinoblastoma (RB1) gene in previously healthy tissue to observe the effects of different mutations on the formation and growth of retinoblastoma. She hopes this will also shed light on the roles of tumor-causing oncogenes and tumor suppressors involved in retinoblastoma progression. A deeper understanding of specific RB1 mutations may guide the prevention, diagnosis, and development of individualized treatment plans for patients with retinoblastoma and other cancers involving mutations in the RB1 pathway.   

Project title: "Dissecting the mechanisms of tumorigenesis in the human retina"
Institution: University of Washington
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Thomas Reh, PhD
Cancer Type: Other Cancer, Pediatric, All Cancers
Research Area: Cell Biology
Katherine E. Gadek, PhD

Dr. Gadek focuses on the Sonic Hedgehog (Shh) signaling pathway, which can be altered in rhabdomyosarcoma (RMS) patients. RMS is the most common soft-tissue sarcoma in children, but survival rates and treatments for high-risk patients have not improved in three decades. Dr. Gadek will examine the timing of tumor development and the role of Shh signaling in tumor location and formation. This may lead to diagnostic markers and tools for identifying high-risk patients with altered Sonic Hedgehog signaling, which could improve treatment options and outcomes.

Project title: "Defining endothelial progenitor cell pliancy in rhabdomyosarcoma" 
Institution: St. Jude Children's Research Hospital
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Mark Hatley, MD, PhD, and Stacey Ogden, PhD
Cancer Type: Head and Neck Cancer, Pediatric, Sarcoma
Research Area: Developmental Biology
Jennifer M. Kalish, MD, PhD

Dr. Kalish is studying a rare hereditary syndrome called Beckwith-Wiedemann syndrome (BWS), which increases the risk of children developing kidney and liver cancers. These individuals have epigenetic changes on chromosome 11 that are found in other types of cancers. Epigenetic markers modify DNA so gene expression is turned on or off; changes in this process can cause cancer. By understanding how cancer is triggered in BWS, Dr. Kalish aims to identify pathways that can be targeted for the development of new treatments both for BWS patients and for others with cancers that have similar epigenetic changes. As a physician-scientist, Dr. Kalish established the BWS Registry, which compiles both clinical data and patient samples, and created the first human cell-based models of BWS.

Project title: "Epigenetic and genetic mechanisms of cancer in Beckwith-Wiedemann Syndrome"
Institution: Children's Hospital of Philadelphia
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Marisa S. Bartolomei, PhD, and Garrett M. Brodeur, MD
Cancer Type: Kidney and Bladder, Other Cancer, Pediatric
Research Area: Epigenetics
Birgit Knoechel, MD, PhD

Cancer cells harboring many genetic changes in their DNA often express novel proteins called neoantigens that activate the immune system to recognize and attack the tumor. Based on this mechanism, researchers are developing novel treatments to stimulate the immune system's response against a tumor, but this approach may not work for pediatric cancers that carry few genetic mutations. Dr. Knoechel's research is investigating alternative ways neoantigens can be generated, such as splicing or epigenetic changes, which occur frequently in leukemia and pediatric cancers. She is focusing on T-cell acute lymphoblastic leukemia (T-ALL), an aggressive blood malignancy in children and young adults that frequently stops responding to treatment causing relapse. Her research aims to identify mechanisms of immune "exhaustion" when T-cells stop fighting a tumor, define neoantigens generated by non-genetic mechanisms, and develop novel strategies to target non-genetic neoantigen expression. This research may lead to novel immunotherapy strategies for pediatric tumors.

Project title: "Mechanisms of CD8+ T-cell dysfunction and its therapeutic targeting in T-ALL"
Institution: Dana-Farber Cancer Institute
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Kimberly Stegmaier, MD, and Catherine J. Wu, MD
Cancer Type: Blood, Pediatric
Research Area: Immunotherapy
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
Anand G. Patel, MD, PhD

Dr. Patel studies rhabdomyosarcoma (RMS), a fast-growing childhood cancer that can spread from muscles to other parts of the body. Dr. Patel has discovered that each RMS tumor consists of different subpopulations of cells that mimic different stages of early muscle development. He will characterize how chemotherapy or radiation therapy selects for specific subpopulations of resistant cancer cells that survive treatment within both patient tissue and in patient-derived models of cancer. Using this information, Dr. Patel aims to test whether directing therapy against resistant cell subpopulations improves treatment outcomes. Ultimately, the goal of this research is to uncover novel therapeutic targets and drugs for the treatment of pediatric RMS.

Project title: "Targeting the developmental architecture of rhabdomyosarcoma"
Institution: St. Jude Children's Research Hospital
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Michael A. Dyer, PhD
Cancer Type: Pediatric, Sarcoma
Research Area: Chemoresistance
Zulekha A. Qadeer, PhD

Dr. Qadeer investigates the mechanisms underlying medulloblastoma (MB), the most common form of malignant brain tumors in children. Group 3 MB is a particularly aggressive subgroup, for which there are few actionable targets for therapies. Dr. Qadeer aims to understand how the genes and pathways regulated by the proteins MYC and TGFb mediate the transformation of neural precursor cells to malignant group 3 MB tumors. This work may also help elucidate tumor heterogeneity and resistance to current alkylating chemotherapies. The overall goal of this research is to identify more effective therapies to treat patients by targeting the mutations that drive tumor formation.

Project title: "Targeting TGFb pathway dependencies in Group 3 Medulloblastoma" 
Institution: University of California, San Francisco
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): William A. Weiss, MD, PhD
Cancer Type: Pediatric, Brain
Research Area: Invasion and Metastasis
Peng Wu, MD, PhD

Dr. Wu focuses on hepatoblastoma, the most common childhood liver malignancy and the cancer with the fastest growing incidence rate in children under the age of five years. Hepatoblastoma is characterized by a low overall mutational burden, but carries activating mutations in the Wnt signaling pathway. Using new techniques to culture cancer cells derived from patients, Dr. Wu aims to understand how abnormal Wnt activation drives cell proliferation and irregular differentiation in hepatoblastoma. The results of these studies may lead to new treatment strategies for liver cancer and other rare tumors.

Project title: "Understanding and modulating aberrant differentiation in hepatoblastoma" 
Institution: Stanford University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Roeland Nusse, PhD
Cancer Type: Other Cancer, Pediatric
Research Area: Cancer Genetics
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