Columbia’s Edward P. Evans Center for Myelodysplastic Syndromes Awards Inaugural Grants and Fellowships
Four research teams at Columbia University have been awarded the inaugural Edward P. Evans Center for Myelodysplastic Syndromes (MDS) Pilot Awards and Fellowships.
The center, established by the Herbert Irving Comprehensive Cancer Center (HICCC) in December 2021, is dedicated to the study and treatment of MDS, a malignant disease that attacks bone marrow stem cells. Each year, more than 40,000 individuals are diagnosed with MDS, and roughly one-third will develop acute myeloid leukemia (AML), a severe and rapidly progressing form of blood cancer.
To support their research, each team will receive a one-year $100,000 grant for the Edward P. Evans Center Pilot Awards and a two-year $60,000/year grant for the fellowships. The two pilot projects are being led by principal investigators Pawel Muranski, MD, assistant professor of medicine and of pathology and cell biology at Columbia University Vagelos College of Physicians and Surgeons (VP&S); Amer Assal, MD, assistant professor of medicine at VP&S; and Raul Rabadan, PhD, professor of systems biology and of biomedical informatics at VP&S. The two fellowships have been awarded to Rossella Labella, PhD, postdoctoral research scientist in the Department of Physiology and Cellular Biophysics, and Junsong Zhou, PhD, associate research scientist in the Department of Rehabilitation and Regenerative Medicine.
About the award-winning projects:
Evans Pilot Awards
“Multi-Epitope Specific Cytotoxic CD4+ T Cells for Adoptive Immunotherapy of Myelodysplastic Syndrome”
Lead Investigators: Pawel Muranski, MD and Amer Assal, MD
Co-investigators: Azra Raza, MD, professor of medicine, director of the MDS clinical program, and co-director of the Edward P. Evans MDS Center; Markus Y. Mapara, MD, professor of medicine; Mithil K. Soni, PhD, associate research scientist at Columbia Center for Translational Immunology
Stem cell transplant provides a chance to cure MDS, but due to the treatment’s toxicity, only younger and healthier patients are eligible. For all others, therapeutic options are limited to hypomethylating agents that only offer modest survival benefits. The team plans to apply novel techniques, developed by Dr. Muranski, in the production of tumor-specific T cells directed against tumor-associated antigens that are known to be expressed by neoplastic cells in MDS. Dr. Muranski and his colleagues believe this project is of high relevance to MDS as it lays the groundwork for a novel therapeutic approach to treat this often-fatal illness, particularly in patients who are transplant ineligible.
“Systematic Protein Structure Characterization of Mis-spliced Transcripts in Myelodysplastic Syndromes”
Lead Investigator: Raul Rabadan, PhD
Co-Investigator: James Manley, PhD, professor of life sciences
RNA splicing is a process that transforms a precursor messenger RNA (mRNA) into a mature one. Dysfunction of the splicing machinery is a key contributor to many human diseases and disorders, including MDS. Despite interest in dissecting the pathogenic consequences of mis-spliced versions of mRNA in MDS, little is known about the structural and functional changes in protein products. The project combines the unique expertise of two labs — computational cancer genomics (Dr. Rabadan) and RNA splicing (Dr. Manley) — to examine the structures of proteins arising from mis-splicing to learn about their functional consequences and explore potential therapeutic targets for MDS.
“Functional-Dysfunctional Mitochondrial Exchange Between Mesenchymal and Dysplastic Stem Cells Drives MDS to AML Transformation”
Lead Investigator: Rossella Labella, PhD
In the last decades, significant efforts have been made to understand the development of MDS and its transformation to AML. Uncovering the mechanisms behind disease transformation is crucial to developing the means to prevent it. Dr. Labella previously found that AML cells transfer dysfunctional mitochondria to heathy mesenchymal stem cells (MSCs), while healthy MCSs provide their functional mitochondria to AML cells. As a result, mitochondrial function of AML cells improves. Dr. Labella aims to perform additional experiments to fully delineate the role of mitochondrial transfer in MDS to AML transformation and to identify the molecular mediators in this process.
“Understanding the Role of Epitranscriptional Regulation in MDS Pathogenesis”
Lead Investigator: Junsong Zhou, PhD
MDS originates from abnormal hematopoietic stem cells (HSCs) with accumulating genetic and epigenetic mutations. Understanding the novel molecular and cellular mechanisms underlying MDS pathogenesis is fundamental for devising novel therapies. Dr. Zhou aims to investigate parts of the epitranscriptome, which includes all the biochemical modifications of the RNA within a cell, for possible answers. Previously, he found that deletion of Mettl3, a type of modification enzyme, leads to HSC differentiation defects and other features of MDS such as hemorrhagic complications, due to thrombocytopenia (low platelet count) and platelet dysfunction. His next set of experiments will uncover a previously unappreciated contribution by epitranscriptional regulation to MDS and may lead to novel therapeutic targets.