Department of Medicine
Faculty Profiles by Division

Division of Cardiology

Faculty Profiles
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photo Iain Scott, PhD

Cardiology

Associate Professor of Medicine

Email: scotti2@upmc.edu

Phone: 412-648-7691
Contact
Office: BST E1254
200 Lothrop Street
Pittsburgh, PA 15261
 
Phone: 412-648-7691
Fax: 412-648-5980
E-mail: scotti2@upmc.edu
Administrative Assistant:
Kathy Brickett
Address: 200 Lothrop Street; BST E1240
Pittsburgh, PA 15261
Phone: 412-624-3239
Fax: 412-648-5980
Education and Training
Education
PhD, University of St. Andrews (UK)
Research Interest
Mitochondria are ubiquitous organelles, playing a vital role in bioenergetics, metabolite biosynthesis and overall cellular homeostasis. Their activity needs to be tightly regulated, as evidenced by the growing number of pathologies in which mitochondrial dysfunction is a causative factor. Mitochondria are highly susceptible to environmental stresses, with overnutrition being a particular problem in the developed world. A high caloric intake leads to a surge in available acetyl-CoA (the final breakdown product of fats, carbohydrates and proteins in the mitochondria), which cannot be utilized for energetic or synthetic purposes. This excess acetyl-CoA is instead used as the substrate for acetylation (a post-translational modification of lysine residues), which acts to reduce the activity of a vast number of mitochondrial metabolic enzymes. Our work focuses on the intrinsic mechanisms that regulate mitochondrial protein acetylation, and how this fundamental alteration affects organelle function at the cellular and tissue level. In particular, we are interested in the coordination between acetylation levels and mitophagy, a quality control mechanism that mediates the removal of dysfunctional mitochondrial organelles. We have recently discovered that GCN5L1, a mitochondrial protein that promotes lysine acetylation, regulates the transcriptional machinery of mitophagy. Our future work will aim to elucidate the pathways that link nutritional inputs, GCN5L1-mediated lysine acetylation, and mitochondrial quality control systems. These findings will then be translated into studies involving metabolically-relevant disease models, such as heart failure and diabetes, in order to achieve a better understanding of the role played by dysfunctional mitochondria in these processes.
Educational Interest
Member, Molecular Pharmacology Graduate Training Program
Member, Cell and Molecular Pathology Graduate Training Program
Lecturer, Fundamentals of Bench Research (CLRES2700)
Module Leader and Lecturer, Molecular Pathobiology (MSCMP 2740) – Congestive Heart Failure
Publications
For my complete bibliography, Click Here.
Selected Publications:
Scott I, Wang L, Wu K, Thapa D, Sack MN. GCN5L/BLOS 1 Links Acetylation, Organelle Remodeling and Metabolism. Trends in Cell Biology. 2018; 28(5): 346-355.
Thapa D, Stoner MW, Zhang M, Xie B, Manning JR, Guimaraes D, Shiva S, Jurczak MJ, Scott I. Adropin regulates pyruvate dehydrogenase in cardiac cells via a novel GPCR-MAPK-PDK4 signaling pathway. Redox Biology. 2018; 18: 25-32.
McGarry A, McDermott M, Kieburtz K, deBlieck EA, Beal F, Marger K, Ross C, Shoulson I, Gilbert P, Mallonese WM, Guttman M, Wojcieszek J, Kumar R, LeDoux MS, Jenkins M, Rosas HD, Nanc M, Biglan K, Como P, Huntington Study Group 2CARE Investigators and Coordinators. A randomized, double-blind placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology. 2017; 88(2): 152-159.
Thapa D, Zhang M, Manning JR, Gulmaraes DA, Stoner MW, O'Doherty RM, Shiva S, Soctt I. Acetylation of mitochondrial proteins by GCNSL1 promotes enhanced fatty acid oxidation in the heart. American Journal of Physiology-Heart Circulatory Pysiology. 2017; 3(2): H265-H274.
Kumar A, Corey C, Scott I, Shiva S, D'Cunha J. Minnelide/Triptolide Impairs Mitochondrial Function by Regulating SIRT3 in P53-Dependent Manner in Non-Small Cell Lung Cancer. PLos One. 2016; 11(8): e0160783.
Wang L, Scott I, Zhu L, Wu K, Han K, Chen YT, Gucek M, Sack MN. GCN5L1 modulates cross-talk between mitochondria and cell signaling to regulate Fox01 stability and gluconeogenesis. Nature Communications. 2017; 8(1): 523.
Stoner MW, Thapa D, Zhang M, Gibson GA, Calderon MJ, St. Croix CM, Scott I. a-Lipoic Acid Promotes a-Tubulin Hyperacetylation and Blocks the Turnover of Mitochondria through Mitophagy. Biochemical Journal. 2016; 473: 1821-30.
Sponsored Research/Activities
Title: Novel Strategies to Resolve Metabolic Defects in the Diabetic Heart
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL147861
Start Year: 2020
End Year: 2024
Title: Novel Strategies to Resolve Metabolic Defects in the Diabetic Heart
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL147861
Start Year: 2020
End Year: 2024
Title: Tead1 and Cardiac Adaptation
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL147946
Start Year: 2019
End Year: 2024
Title: Endothelial Reprogramming in Pulmonary Hypertension
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL148712
Start Year: 2019
End Year: 2024
Title: Regulation of Fuel Utilization by Lysine Acetylation in the Failing Heart
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL132917
Start Year: 2017
End Year: 2021
Title: Regulation of Hepatic Mitochondrial Homeostasis and Fuel Metabolism by Acetylation
Role: Principal Investigator
Funding Agency: American Diabetes Association
Start Year: 2017
End Year: 2019
Title: Regulation of Fuel Utilization by Lysine Acetylation in the Failing Heart
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL132917
Start Year: 2017
End Year: 2021
Title: Regulation of Hepatic Mitochondrial Homeostasis and Fuel Metabolism by Acetylation
Role: Co-Investigator
Funding Agency: American Diabetes Association
Grant Number: RES
Start Year: 2017
End Year: 2019
Notable Achievements
Special Act Award, National Institutes of Health, 2014
Young Investigator Award, Society for Redox Biology and Medicine, 2012
Fellows Award for Research Excellence, National Institutes of Health, 2010

Division Websites

Cardiology

Endocrinology and Metabolism

Gastroenterology, Hepatology and Nutrition

General Internal Medicine

Geriatric Medicine
Hematology/Oncology

Infectious Diseases

Pulmonary, Allergy and Critical Care Medicine

Renal-Electrolyte

Rheumatology and Clinical Immunology

Contact

Department of Medicine
1218 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261
Email:  chairoff@pitt.edu
Phone:  412-648-9636
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