The MDS Foundation, Inc.’s Young Investigator Grant provides an investigator, aged 40 years or less, the opportunity to initiate, continue or complete a project that focuses on either basic or clinical management into the causation, epidemiology, molecular biology, cytogenetics, morphology, prognosis and treatment of the Myelodysplastic Syndromes.
Gilbert Bruce Smith Young Investigator Grant Winner
Funded by: MDS Foundation, Inc.
Grant Year: 2021-2023
Research Center: Albert Einstein College of Medicine
Research Title: STAT3 Degradation to Overcome Therapy Resistance in MDS
Summary: MDS arises from the accumulation of mutations in hematopoietic stem cells (HSC’s) & therapy resistance is invariable. We identified significant upregulation, increased expression of STAT3 in MDS-HSC’s that was predictive of adverse prognosis. KTX-21 & KTX-105 are two specific STAT3 degraders that decreased cellular proliferation, and caused significant downregulation of STAT3 as well as its target genes (MCL1) in multiple hypomethylating agent and venetoclax resistant leukemic lines. In Aim 1, we test the efficacy of the STAT3 degraders by treating a large cohort of therapy resistant primary patient samples and PDX’s. In Aim 2 we will evaluate the preclinical efficacy of STAT3 degradation alone and in combination with the clinically relevant MCL1 inhibitor AZD5991 in therapy resistant MDS.
Gilbert Bruce Smith Young Investigator Grant Winner
Funded by: MDS Foundation, Inc.
Grant Year: 2021-2023
Research Center: The Francis Crick Institute, Haematopoietic Stem Cell Laboratory
Research Title: Identification and functional screening to identify niche-related therapeutic targets in Myelodysplasia
Summary: Myelodysplastic syndrome are a collection of clonal haematopoietic stem cell (HSCs) disorders with very limited treatment options. We hypothesise that a combination of aging and genetic abnormalities in HSCs transmit disease cues to the bone marrow niche that in-turn provides nurturing signals for the sustenance of the disease. A combination of xenotransplantation, RNA sequencing and cytokine profiling will be used to delineate the interacting surface proteins between the MDS HSCs and niche mesenchymal stromal cells. Large-scale siRNA screening followed by targeted inducible shRNA lentiviral approach will be used to identify the receptor-ligands that can be potentially used as therapeutic targets.
If you would like to be notified about new grant opportunities, please complete the following information:
