Researcher - Ling Li, Ph.D.
Facility - City of Hope
Location - Duarte, CA
Amount - $50,000.00
Biography: Ling Li Ph.D. is an associate professor in Gehr Family Center for Leukemia Research and Department of Hematological Malignancies Translational Science within Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope. Dr. Li joined Beckman Research Institute of City of Hope in 2015 as a faculty member, and successfully pursued a NIH-K99/R00 Career Development Award which was granted in June 2014. Dr. Li is very active in the area of leukemia research especially FLT3-ITD AML. His research focuses on studying the aberrantly regulated epigenetics that initiate or maintain the leukemia specifically acute myeloid leukemia (AML). Dr. Li was the first to report aberrant activity of PRMTs (like PRMT1) contributing to survival of FLT3 activated acute leukemia. His laboratory is currently determining the epigenetic-related resistance mechanisms of FLT3-ITD LSC to the conventional treatments. The primary goal of this effort is to develop novel therapeutics to specifically target LSC and advance these strategies for clinical trials in AML. To achieve this goal, Dr. Li will use Genetic Engineered Mouse Model (GEMM), human AML lines and patient samples derived xenografts (PDX) for the preclinical studies. To date, Dr. Li’s laboratory work has been funded by NIH, American Cancer Society and other prestigious grant agencies.
Lay Description: Acute myeloid leukemia (AML) patients carrying the FMS-like-tyrosine-kinase3 gene internal-tandem-duplication (FLT3-ITD) experience poor outcomes, because residual cancer cells with stem cell properties persist after standard treatment. Those so-called leukemia stem cells drive disease reoccurrence by co-opting RNA translation mechanisms normal cells use to make proteins and instead promote an overabundance of cancer-associated proteins. Dr. Li’s laboratory discovered that PABP1 arginine methylation mediated by corresponding enzyme PRMT9 participates in this oncogenic protein synthesis process in FLT3-ITD+ AML and developed a novel drug to block its AML-promoting activity. His team including physician and scientist will test whether this drug eliminates FLT3-ITD+ AML leukemia stem cells in animal models/primary human specimens, as a step toward clinical trials in humans.
Researcher - Stephen Oh, MD, PhD
Facility - Washington University in St. Louis
Location - St. Louis, MA
Amount - $50,000.00
Biography: Stephen Oh, MD, PhD is Associate Professor of Medicine and Co-Chief of the Division of Hematology at Washington University School of Medicine. Dr. Oh’s clinical and laboratory research efforts are focused on myeloproliferative neoplasms (MPNs). His group employs patient samples and animal models to investigate fundamental mechanisms driving the initiation, development, and leukemic progression of MPNs. A major focus of the laboratory is to utilize mass cytometry and multiplex imaging approaches to interrogate dysregulated cytokine signaling networks in MPNs. Dr. Oh has extensive clinical experience in the diagnosis and management of MPN patients and has contributed to numerous clinical trials investigating novel targeted therapies for MPN patients. The long-term objective of his work is to translate the findings from his laboratory research into improved therapies for MPN patients and to prevent leukemic prevention.
Overview - The objective of this project is to decipher mechanisms driving transformation of chronic myeloproliferative neoplasms (MPNs) to secondary acute leukemia (sAML). In preliminary studies, we identified aberrantly increased expression of DUSP6, a phosphatase that regulates intracellular signaling pathways, in sAML patient cells. We found that DUSP6 targeting inhibited MPN cell proliferation in vitro, and in preliminary in vivo studies, DUSP6 inhibition ameliorated MPN disease features and extended survival. We therefore hypothesize that DUSP6 drives MPN disease progression, and that targeted inhibition of DUSP6 may represent a viable therapeutic strategy in MPNs and sAML. Our studies supported by the When Everyone Survives Foundation will delineate how DUSP6 modulates aberrant signaling pathways in MPN disease progression and determine how DUSP6 inhibition impacts MPN disease development and leukemic progression.
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