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2021 Gerstner Awardees to investigate individualized medicine approaches for heart attack and leukemia
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Moritz Binder M.D., a physician-scientist in Mayo Clinic's divisions of Hematology and Oncology, and Satsuki Yamada, M.D., Ph.D., a physician-scientist in the division of Cardiovascular Diseases, are recipients of the 2021 Gerstner Family Career Development Awards.
The competitive awards are presented annually by Mayo Clinic Center for Individualized Medicine to researchers conducting innovative investigations to predict, prevent, treat and cure disease using individualized medicine approaches.
The Gerstner Family Career Development Awards is a benefactor-sponsored initiative that seeks to promote a specialized workforce for individualized medicine discovery, translation and application. Made possible by a grant from the Louis V. Gerstner, Jr. Fund at Vanguard Charitable, the award provides important seed money for early-stage investigators interested in launching a career in individualized medicine.
Targeting leukemia mutation in quest for novel individualized therapeutic approach
Dr. Binder is investigating mutation-specific therapeutic targets for chronic myelomonocytic leukemia, a cancer that starts in blood-forming cells of the bone marrow and invades the blood. Patients with chronic myelomonocytic leukemia frequently have mutations in a gene called ASXL1.
"We know from previous studies that ASXL1-mutant myeloid malignancies overexpress important genes that make the cancer grow faster and more resistant to treatment," Dr. Binder says. "Unfortunately, patients with ASXL1 mutations do not fare well and do not respond as well to the treatments we currently have."
Dr. Binder's previous studies suggested overexpressed genes may be under the control of regulatory elements in the genome called “enhancers." His recent data suggest that these enhancers are specific to ASXL1-mutant chronic myelomonocytic leukemia and may therefore represent novel therapeutic targets that are only functional in the cancer cells and not in normal blood cells.
In his study supported by the Gerstner Award, Dr. Binder plans to investigate whether targeting these enhancers can reverse the overexpression of important leukemia driver genes and overcome the adverse effect of ASXL1 mutations in chronic myelomonocytic leukemia. He says treating a cancer by targeting enhancer-gene interactions would be a new approach not currently pursued in the myeloid malignancies.
"This work is the critical next step on the path to developing individualized treatment strategies with epigenetic small molecule therapeutics that can target such enhancer-gene interactions," Dr. Binder says. "Patients with ASXL1-mutant CMML are in dire need of safe and effective therapies and our study aims to uncover a novel class of mutation-specific therapeutic targets that may be exploited for therapeutic benefit."
Dr. Binder studied Quantitative Methods at the Harvard School of Public Health before joining Mayo Clinic in 2014 for Internal Medicine residency training. After residency, he completed fellowship training at Mayo Clinic in Hematology and Medical Oncology. In 2020, he returned to Boston for postdoctoral training in Cancer Epigenomics at Dana-Farber Cancer Institute as a Mayo Clinic Scholar. He currently is a Senior Associate Consultant in the Division of Hematology and a member of the Center for Individualized Medicine Epigenomics Program.
Investigating biotherapy for cardiovascular disease
Dr. Yamada is working to develop a targeted regenerative biotherapy to restore cardiac function in individuals who have suffered a myocardial infarction, also known as a heart attack.
A heart attack causes varying degrees of tissue damage across infarcted (an area of tissue death), non-infarcted and border zones within the heart. The resulting non-coordinated wall motion leads to cardiac pumping failure, which is resistant to a traditional drug treatment.
In her study supported by the Gerstner Award, Dr. Yamada plans to investigate the use of a patient’s own stem cells as a new therapy to help reestablish and maintain a synchronized pumping motion in the infarcted heart. In combination, she plans to analyze high-resolution imaging and artificial intelligence to tailor treatment plans for each individual heart patient.
"Cardiac damage after infarction has been considered non-reversible," Dr. Yamada says. "Successful completion of this project could potentially contribute to advancing disease management from reactive to proactive."
Dr. Yamada says her study will bring principles of individualized medicine and regenerative medicine together in the setting of heart failure management post myocardial infarction.
“The proposed work will provide a translational foundation to achieve the most effective cardiac reparative therapy,” Dr. Yamada says.
Following clinical training in Japan, Dr. Yamada joined Mayo Clinic as a postdoctoral fellow in Cardiovascular Research. Dr. Yamada is currently an assistant professor and has pursued research focused on the determinants of cardiovascular disease susceptibility and gene/cell-based rescue.
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