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Principal Investigator: Nam Y Lee
Organization: UNIVERSITY OF ARIZONA
Fiscal Year: 2024
Award: $367,649
Funding agency: National Institute of General Medical Sciences
ABSTRACT
TGF-β affects virtually all aspects of mammalian physiology starting from early embryonic development to adult
tissue homeostasis through regulation of diverse cellular functions including proliferation, differentiation, and
apoptosis. TGF-β signaling also plays an important role in cell metabolism, although there has been incremental
progress in understanding how it differentially regulates mitochondrial biogenesis, respiration, and organelle
destruction. While such varying effects are theorized to occur primarily through slow-acting contextual gene
regulation, TGF-β is also capable of inducing more rapid, direct, and reversible changes in mitochondrial shape
and function through largely unknown mechanisms− a key aspect that represents an important knowledge gap
in the field. Our research program has focused on two powerfully opposing mechanisms by which two major
TGF-β effectors, Smad2 and TAK1, control mitochondrial fusion/fission dynamics to achieve and maintain
metabolic homeostasis. We seek to understand mechanisms governing their organization, activation, and
regulation in mitochondrial remodeling and how they influence cell behavior using angiogenesis as a
developmental model system. Our studies will provide unique perspectives on how the complex TGF-β signaling
networks control mitochondrial dynamics to affect their metabolic, developmental and homeostatic roles in
vascular physiology.
Terms: <21+ years old><Adult><Adult Human><Adult-Onset Diabetes Mellitus><Affect><Apoptosis><Apoptosis Pathway><Autoregulation><Biogenesis><Biologic Models><Biological Models><Blood Vessels><Body Tissues><Bone-Derived Transforming Growth Factor><Cell Communication and Signaling><Cell Function><Cell Physiology><Cell Process><Cell Signaling><Cellular Function><Cellular Metabolic Process><Cellular Physiology><Cellular Process><Complex><Defect><Development><Embryo Development><Embryogenesis><Embryonic Development><Gene Action Regulation><Gene Expression Regulation><Gene Regulation><Gene Regulation Process><Homeostasis><Intracellular Communication and Signaling><Ketosis-Resistant Diabetes Mellitus><Knowledge><MAP kinase kinase kinase 7><MAP3K7><MAP3K7 gene><Maturity-Onset Diabetes Mellitus><Metabolic><Metabolic Diseases><Metabolic Disorder><Milk Growth Factor><Mitochondria><Model System><NIDDM><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Obesity><Organelles><Origin of Life><Oxidative Stress><Physiological Homeostasis><Physiology><Platelet Transforming Growth Factor><Play><Production><Programmed Cell Death><Proliferating><Regulation><Research><Respiration><Role><Shapes><Signal Transduction><Signal Transduction Systems><Signaling><Slow-Onset Diabetes Mellitus><Stable Diabetes Mellitus><Subcellular Process><T2 DM><T2D><T2DM><TAK1><TAK1a><TAK1b><TAK1c><TAK1d><TGF B><TGF-Beta Activated Kinase 1><TGF-beta><TGF-beta-activated kinase 1><TGF-β><TGFbeta><TGFβ><Thesaurismosis><Tissues><Transforming Growth Factor beta><Transforming Growth Factor-Beta Family Gene><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><adiposity><adult onset diabetes><adulthood><angiogenesis><biological signal transduction><cell behavior><cell metabolism><cellular behavior><cellular metabaolism><corpulence><developmental><ketosis resistant diabetes><maturity onset diabetes><metabolism disorder><mitochondrial><mitogen-activated protein kinase kinase kinase 7><novel><programs><respiratory mechanism><social role><theories><transforming growth factor-beta-activated kinase 1><type 2 DM><type II DM><type two diabetes><vascular><virtual>