Yan Laboratory
Molecular
Exercise Physiology

Center for Skeletal Muscle Research
Robert M. Berne Cardiovascular Research Center
University of Virginia School of Medicine
409 Lane Road, MR4 - 6041A
Charlottesville, VA 22908
Phone: 434-982-4477
Fax: 434-982-3139
E-mail:
zhen.yan@virginia.edu

Funding

Federal funding
R01AR040849                                     Williams (PI)                 07/01/01–03/31/07      Completed
NIH/NHLBI                   
Molecular Genetics of Muscle Specialization                                     
The project intends to define the mechanisms of beneficial physiological adaptations in skeletal muscle following exercise training.
Role: Co-Investigator
Annual direct costs: $250,000

R01DK065954                                     Haystead (PI)              04/01/06–03/31/11      Completed   
NIH/NHLBI                               
Calcium desensitization in smooth muscle
The goal of this study is to define the functional role of Chasm in muscle contractile function.
Role: Co-investigator
Annual direct costs: $205,000

R01 AR050429-01                              Yan (PI)                       07/01/05–06/30/11        Completed
NIH/NIAMS
Exercise-Induced Mitochondrial Biogenesis
This study was designed to ascertain the functional role of the p38 MAPK pathway in regulation of the Pgc-1α gene in voluntary running-induced skeletal muscle adaptation in mice.
Role: PI
Annual direct costs: $160,000

R21AR060444-01                               Yan (PI)                       09/01/11–08/31/13      Completed
NIH/NIAMS
NO-dependent SOD3 protection against cachexia
The studies focus on NO-dependent regulation of SOD3 in protection against catabolic wasting in skeletal muscle.
Role: PI
Annual direct costs: $135,000

F32DK095559-01                                Greene (PI)                  07/01/12­06/30/13       Completed
NIH/NIDDK                                                                               
Atg6 in Protection Against Insulin Resistance
Studies focused on potential of targeting autophagic degradation through Atg6/Beclin1 as a means to removed damaged cell materials in the protection against high fat diet-induced insulin resistance.
Role: Mentor
Annual direct costs: $35,000

R21HD068953-01                                Lynch (PI)                    11/01/11–10/30/13        Completed
NIH/NICHD                                                                                           
Mitochondrial Lipid Kinase
This project investigates the mechanisms whereby sphingolipids accumulate in mitochondria and their impact on mitochondrial reactive oxygen species production in the context of insulin resistance.
Role: Co-Investigator
Annual direct costs: $125,000

R01AR050429-07                               Yan (PI)                       07/01/11–06/30/16      Active
NIH/NIAMS
p38 MAPK a regulator of muscle contractile and metabolic functions
The proposed studies focus on molecular mechanism and functional role of p38 MAPK in skeletal muscle metabolic and contractile function in cachexia and type 2 diabetes.
Role: PI
Annual direct costs: $225,000

K99AR067287-01                             Call (PI)                          09/01/14-08/31/19       Received fundable score and rejected for accepting faculty position at Univ of Georgia.                NIH/NIAMS                  
Mitophagy and muscle regeneration
The study focuses on the role of autophagy in mitochondrial and contractile apparatus remodeling during functional muscle regeneration.
Role: Mentor
Annual direct costs: $170,000

R01GM109473                                    Yan (PI)                       04/01/15 - 03/31/20     Active
NIH/NIGMS
Muscle-derived EcSOD in protection against multiple organ dysfunction syndrome
The study focuses on elucidating the role and mechanism by which muscle-derived EcSOD provides protection against multiple organ dysfunction syndrome in mouse models of sepsis.
Role: PI
Annual direct costs: $190,000

3R01CA166458-03S1                         Bullock (PI)                  06/01/15-12/31/17       Active
NIH
BLIMP-1 mediated regulation of CD8+ TIL. 
The goals are to identify the mechanistic basis for defects in CD8+ TIL glycolytic activity; to ascertain whether metabolic manipulation of TIL improves their function; to define whether TIL function can be regained by manipulating mitochondrial fission and fusion; and to delineate whether targeting tumor metabolism allows re-invigoration of TIL metabolism.
Role: Co-investigator
Total direct costs: $XXXX
5% effort

Private fundations
9960102Y Beginning Grant-in-Aid      Yan (PI)                       07/01/99–12/31/00      Terminated for SDG
AHA Texas-Affiliate   
Phosphorylation and dephosphorylation of human Cdc6 regulates DNA replication
The study focused on post-translational modification of human Cdc6 in control of DNA replication in mammalian cells.
Role: PI
Annual direct costs: $50,000

0130261N SDG                                   Yan (PI)                       01/01/01–12/31/04      Completed
American Heart Association  
Phosphatase regulation of mammalian DNA replication
The goal of this study is to determine the role of PP2A in control of DNA replication through dephosphorylation of Cdc6 in mammalian cells.
Role: PI
Annual direct costs: $65,000

Medical Student Research Fellowship Ajijola (PI)                   07/01/03-06/31/04       Completed
HHMI                                                                           
Exercise on atherosclerosis
The proposed area of researched focused on role of exercise as modulator of systemic inflammation and atherosclerotic burden.
Role: Mentor
Annual direct costs: $35,000

0625518U Postdoctoral fellowship     Li (PI)                           07/01/06-06/30/07       Completed
AHA­Mid Atlantic Affiliate                                          
IGF-1 receptor function in myofiber susceptibility to atrophy
The proposed study is to understand the role of muscle fiber type specific distribution of IGF-1 receptor in prevention of muscle atrophy caused by heart failure.
Role: Mentor
Annual direct costs: $35,000

0555426U                                            Yan (PI)                       07/01/05–06/30/07      Completed
AHA Mid-Atlantic Affiliate      
Skeletal Muscle Maladaptation in CHF
The study uses genetic approaches to enhance mitochondrial biogenesis or angiogenesis in fast-twitch skeletal muscles to test the possibility of preventing heart failure-induced exercise intolerance.
Role: PI
Annual direct costs: $66,000

Medical Student Research Fellowship Pogozelski (PI)           07/01/06-06/30/07       Completed
HHMI                                                                           
IGF-1R in the Prevention of Skeletal Muscle Atrophy
The proposed study focuses on the role of IGF-1R in prevention of skeletal muscle atrophy.
Role: Mentor
Annual direct costs: $36,000

7-06-RA-165                                       Yan (PI)                       07/01/06–12/31/09      Completed
American Diabetes Association                                             
Exercise and diet-induced insulin resistance
The study focuses on the mechanism by which endurance exercise reverses skeletal muscle insulin resistance through enhancing mitochondrial function.
Role: PI
Annual direct costs: $100,000
10% effort

Partners’ Fund                         Yan (PI)                       07/01/09–6/30/10        Completed
The Robert M. Berne Cardiovascular Research Centers at the University of Virginia
Epigenetic influence of exercise on offspring’s susceptibility to type 2 diabetes
This study determine if exercise in pregnancy reduces offspring’s susceptibility to diet-induced insulin resistance in mice and identify candidate genes that are epigenetically regulated and potentially responsible for the protection by exercise in pregnancy.
Role: PI
Annual direct costs: $25,000

Thelma R. Swortzel Award                Yan (PI)                       01/01/10–6/30/11        Completed   
University of Virginia
Maternal exercise and calorie restriction on epigenomics of cardiovascular function
This study focuses on maternal exercise and calorie restriction in pregnancy on the epigenetic regulation of high-fat diet-induced cardiovascular dysfunction in the offspring.
Role: PI
Annual direct costs: $50,000

Postdoctoral Fellowship                      Lira (PI)                        07/-01/11-06/31/13     Completed
American Physiological Society                                             
Muscle autophagy and prevention against insulin resistance
The proposed project focus on the role of PGC-1alpha in regulating exercise-induced autophagy in skeletal muscle in the context of diet-induced insulin resistance.
Role: Mentor
Annual direct costs: $74,000

1-11-BS-181 (Yan)                             Yan (PI)                       01/01/11–12/31/13      Completed
American Diabetes Association                                             
Mitochondrial permeability transition and mitophagy in type 2 diabetes
The study focuses on the importance of mitochondrial maintenance in skeletal muscle in the development of type 2 diabetes.
Role: PI
Annual direct costs: $100,000

1-11-JF-17 Junior Faculty Award       Hoehn (PI)                   01/01/11-12/31/13       Completed
American Diabetes Association                                             
The role of the mitochondrial permeability pore (mPTP) in the etiology of insulin resistance
This project tests the hypothesis that mitochondrial superoxide production modifies the mitochondrial permeability pore and increases its susceptibility to opening to drive insulin resistance
Role: PI
Annual direct costs: $140,600

12POST12030231                               Call (PI)                        07/01/12-06/30/14       Completed
AHA­Mid Atlantic Affiliate, Postdoctoral Fellowship                                      
Skeletal muscle-heart crosstalk in prevention of diabetic cardiomyopathy
The proposed studies focus on the necessity and sufficiency of extracellular superoxide dismutase in exercise training prevention of diabetic cardiomyopathy. 
Role: Mentor
Annual direct costs: $40,000
0% effort

Thelma R. Swortzel Award                Saucerman (MPI)         06/01/14–12/31/15        Active
University of Virginia
MitoTimer reporter in human fibroblasts for diagnosis of mitochondrial diseases
This study focuses on using MitoTimer in human fibroblasts as a diagnostic tool for human mitochondrial diseases.
Role: MPI
Annual direct costs: $50,000

14POST20450061                               Laker (PI)                     07/01/14-06/30/16       Active
AHA­Mid Atlantic Affiliate, Postdoctoral Fellowship                                      
Epigenetic influence of maternal exercise on offspring metabolic and cardiovascular outcomes The proposed studies focus on the impact of maternal exercise training on offspring from obese dams during pregnancy.
Role: Mentor
Annual direct costs: $43,000

14PRE20380254                                  Wilson (PI)                   07/01/14-06/30/16       Terminated due to move to University of Copenhagen           
AHA­Mid Atlantic Affiliate, Predoctoral Fellowship                            
Protein S-nitrosylation Protects Against Ischemia-Reperfusion Injury in Skeletal Muscle
The proposed studies focus on the role of protein s-nitrosylation in protection against Ischemia-Reperfusion induced mitochondrial oxidative stress in skeletal muscle.
Role: Mentor
Annual direct cost: $25,000

FARA 183                                           Yan (PI)                       12/15/14 – 12/14/16    Active                        
FARA, General Research Grant                                                                    
Exercise Impacts on Mitochondria and Muscle Function in Friedreich’s Ataxia
The objective of this proposal is to elucidate how exercise affects mitochondria in skeletal muscle and the heart and their function in a mouse model of Friedreich's Ataxia.
Role: PI
Annual direct costs: $125,000