Tso-Pang Yao
Professor of Pharmacology and Cancer Biology
Overview
My laboratory studies the regulatory functions of protein acetylation in cell signaling and human disease. We focus on a class of protein deacetylases, HDACs, which we have discovered versatile functions beyond gene transcription. We wish to use knowledge of HDAC biology to develop smart and rational clinical strategies for HDAC inhibitors, a growing class of compounds that show potent anti-tumor and other clinically relevant activities. Currently, there two major research major areas in the laboratory: aging/age-related disease, and mitochondrial biology/cancer metabolism.
(1) Quality control (QC) autophagy in aging and neurodegenerative disease. The accumulation of damaged proteins and mitochondria is prominently linked to aging and age-associated disease, including neurodegeneration, metabolic disorders and cancer. Autophagy has emerged as specialized degradation machinery for the disposal of damaged protein aggregates and mitochondria, two common denominators in neurodegenerative diseases. We have discovered that this form of quality control (QC) autophagy is controlled by a ubiquitin-binding deacetylase, HDAC6. Using both mouse and cell models, we are investigating how HDAC6 enforces QC autophagy and its importance in neurodegenerative disease and metabolic disorders. The potential of HDAC6 as a therapeutic target is being actively pursued.
(2) HDAC in mitochondria function and quality control. Acetyl-CoA is the donor of acetyl group for protein acetylation and numerous metabolic reactions. Remarkably, many mitochondrial enzymes and proteins are subject to acetylation. We are interested in characterizing the roles of HDAC in mitochondrial adaptation to changing metabolic demands and elucidating the intimate relationship between metabolism and protein acetylation.
(3) HDAC, skeletal muscle remodeling, regeneration and neuromuscular disease. Skeletal muscle undergoes active remodeling in response to change in neural inputs or damage. Loss in neural input causes dramatic muscle dysfunction and disease, such as ALS. We have discovered that neural activity controls muscle phenotype through HDAC4, whose activity becomes deregulated in ALS patients. We have characterized this novel HDAC4-dependent signaling pathway and are evaluating modulators of this pathway for potential clinical utility in motor neuron disease.
Positions
Professor of Pharmacology and Cancer Biology in the School of Medicine
2012 School of Medicine
Assistant Professor in Radiation Oncology in the School of Medicine
2020 School of Medicine
Member of the Duke Cancer Institute in the School of Medicine
1998 School of Medicine
Education
Ph.D. 1994
1994 University of California - San Diego
Publications, Grants & Awards
- Grants (15)
- Academics Articles (97)
- Conference Pages (4)
- Book Sections (2)
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institute of Environmental Health Sciences
St. Baldrick's Foundation
National Cancer Institute
National Institutes of Health
National Institutes of Health
National Institutes of Health
National Institutes of Health
Advanced Science (Weinheim, Baden Wurttemberg, Germany)
Journal of Medicinal Chemistry
Hum Mol Genet
J Cachexia Sarcopenia Muscle
Frontiers in Cell and Developmental Biology
Cell Death Differ
Neuropharmacology
Frontiers in Aging Neuroscience
Biochemical and Biophysical Research Communications
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Protein & Cell
Advances in Experimental Medicine and Biology
Neurodegener Dis
Molecular Biology of the Cell
Nature Communications
Mol Cell
Antioxid Redox Signal
Essays Biochem
The Embo Journal
Handbook of Experimental Pharmacology
Handbook of Experimental Pharmacology
The Journal of Cell Biology
Autophagy
The Journal of Biological Chemistry
The Embo Journal
Molecular and Cellular Biology
Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology
Biochemical and Biophysical Research Communications
The Journal of Biological Chemistry
Eukaryot Cell
The Journal of Biological Chemistry
Molecular and Cellular Biology
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Genes & Development
Journal of Molecular Biology
Nature
Journal of Cell Science
Oncogene
The Journal of Biological Chemistry
Journal of Neuroscience
The Journal of Biological Chemistry
Molecular Cancer Research : Mcr
Molecular and Cellular Biology
Molecular and Cellular Biology
Molecular Cell
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Science'S Stke : Signal Transduction Knowledge Environment
The Journal of Biological Chemistry
Novartis Foundation Symposium
The Journal of Biological Chemistry
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Science (New York, N.Y.)
The Embo Journal
Proceedings of the National Academy of Sciences of the United States of America
Genes & Development
Molecular Cell
The Journal of Biological Chemistry
Nature
Proceedings of the National Academy of Sciences of the United States of America
Genes & Development
Proceedings of the National Academy of Sciences of the United States of America
Molecular and Cellular Biology
Proceedings of the National Academy of Sciences of the United States of America
The Journal of Biological Chemistry
Nature Communications
Journal of Neurochemistry
Journal of Neurochemistry
Molecular Biology of the Cell
Autophagy and Signaling
Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging
Offices & Contact
Durham, NC
27710 Duke Box 3813
Durham, NC
27710