Jennifer J. Trowbridge, Ph.D.
2020 Funding recipient
Discovery of Mechanisms by Which the Aging Bone Marrow Microenvironment Drives Progression of Clonal Hematopoiesis to MDS
Discovery Research Grant 2020
Aging is a major risk factor for developing myelodysplastic syndrome (MDS). We currently do not have reliable clinical tests to determine which individuals in our population are at greatest risk of developing MDS. We also do not have any therapies that can prevent MDS from occurring in these individuals. The proposed project will use a new mouse model of aging associated MDS that we have created to determine what changes occur with aging that contribute to the risk of developing MDS. We will study whether chronic inflammation, which is associated with aging, can directly cause MDS to develop. We will also study whether specific changes that accumulate with aging in the bone marrow environment cause or contribute to MDS. The information gained in this study can be used to develop new methods for screening individuals, as they age, to determine their risk of MDS development. Furthermore, this information can also be used to engineer new therapies for prevention of MDS development or relapse.
SanMiguel JM, Eudy E, Loberg MA, Miles LA, Stearns T, Mistry JJ, Rauh MJ, Levine RL, Trowbridge JJ, Cell Origin–Dependent Cooperativity of Mutant Dnmt3a and Npm1 in Clonal Hematopoiesis and Myeloid Malignancy, Blood Advances, 2022, 6 (12), 3666–3677 DOI: 10.1182/bloodadvances.2022006968
SanMiguel JM, Eudy E, Loberg MA, Young KA, Mistry JJ, Mujica KD, Schwartz LS, Stearns TM, Challen GA, Trowbridge JJ, Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness versus Lineage Output in Dnmt3a -Mutant Clonal Hematopoiesis, Cancer Discovery, 2022, OF1–OF11 DOI: 10.1158/2159-8290.CD-22-0086