Zhen Yan, PhD

Program Focus

In my goal to provide scientific evidence for development of interventions to prevent non-communicable disease and promote human health and wellbeing, current projects include: machine learning-based multi-omics modeling and CRISPR/Cas9-mediated gene editing in elucidating molecular transducer of physical activity; exercise-induced mitophagy and its role in contractile and metabolic adaptations; exercise-induced mitophagy in hippocampal neurons against Alzheimer’s disease; exercise-induce mitophagy against HFpEF; exercise-induced EcSOD in skeletal muscle in disease prevention; a novel mitochondrial reporter gene, MitoTimer, for mitochondrial quantity and quality; epigenetic mechanism of maternal exercise-mediated protection against metabolic diseases in the offspring; exercise impacts on mitochondria and muscle function in Friedrich's ataxia; and molecular mechanism of resistance exercise-induced contractile and metabolic adaptations.

Program Focus

Non-communicable diseases, also known as chronic diseases, such as cardiovascular, metabolic and neurodegenerative diseases and cancer, account for more than 60% of the death in America, engulfing more than 75% of health care costs. On the contrary, regular exercise has profound health benefits and is the most effective intervention in prevention and treatment of chronic diseases. I employ the state-of-the-art molecular and imaging technologies in a variety of animal models to elucidate the underlying molecular and signaling mechanisms of exercise training-induced adaptations and their impacts on health and disease. My overarching goal is to provide scientific evidence for development of interventions to prevent non-communicable disease and promote human health and wellbeing.

Reviewed Journals

• Guan Y, Yan Z. Molecular Mechanisms of Exercise and Healthspan. Cells. 2022 Mar 3;11(5). doi: 10.3390/cells11050872. Review. PubMed PMID: 35269492; PubMed Central PMCID: PMC8909156.
• Spaulding HR, Yan Z. AMPK and the Adaptation to Exercise. Annu Rev Physiol. 2022 Feb 10;84:209-227. doi: 10.1146/annurev-physiol-060721-095517. Review. PubMed PMID: 35143330; PubMed Central PMCID: PMC8919726.
• Laker RC, Altıntaş A, Lillard TS, Zhang M, Connelly JJ, Sabik OL, Onengut S, Rich SS, Farber CR, Barrès R, Yan Z. Exercise during pregnancy mitigates negative effects of parental obesity on metabolic function in adult mouse offspring. J Appl Physiol (1985). 2021 Mar 1;130(3):605-616. doi: 10.1152/japplphysiol.00641.2020. Epub 2020 Dec 17. PMID: 33332990
• Drake JC, Wilson RJ, Laker RC, Guan Y, Spaulding HR, Nichenko AS, Shen W, Shang H, Dorn MV, Huang K, Zhang M, Bandara AB, Brisendine MH, Kashatus JA, Sharma PR, Young A, Gautam J, Cao R, Wallrabe H, Chang PA, Wong M, Desjardins EM, Hawley SA, Christ GJ, Kashatus DF, Miller CL, Wolf MJ, Periasamy A, Steinberg GR, Hardie DG, Yan Z. Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy. Proc Natl Acad Sci U S A. 2021 Sep 14;118(37). doi: 10.1073/pnas.2025932118. PubMed PMID: 34493662.
• Cui D, Drake JC, Wilson RJ, Shute RJ, Lewellen B, Zhang M, Zhao H, Sabik OL, Onengut S, Berr SS, Rich SS, Farber CR, Yan Z. A novel voluntary weightlifting model in mice promotes muscle adaptation and insulin sensitivity with simultaneous enhancement of autophagy and mTOR pathway. FASEB J. 2020 Apr 18;. doi: 10.1096/fj.201903055R. [Epub ahead of print] PubMed PMID: 32304342.
  
• Wilson RJ, Drake JC, Cui D, Lewellen BM, Fisher CC, Zhang M, Kashatus DF, Palmer LA, Murphy MP, Yan Z. Mitochondrial protein S-nitrosation protects against ischemia reperfusion-induced denervation at neuromuscular junction in skeletal muscle. Free Radic Biol Med. 2018 Mar;117:180-190. doi: 10.1016/j.freeradbiomed.2018.02.006. Epub 2018 Feb 9. PubMed PMID: 29432799; PubMed Central PMCID: PMC5896769.
  
• Call JA, Donet J, Martin KS, Sharma AK, Chen X, Zhang J, Cai J, Galarreta CA, Okutsu M, Du Z, Lira VA, Zhang M, Mehrad B, Annex BH, Klibanov AL, Bowler RP, Laubach VE, Peirce SM, Yan Z. Muscle-derived extracellular superoxide dismutase inhibits endothelial activation and protects against multiple organ dysfunction syndrome in mice. Free Radic Biol Med. 2017 Dec;113:212-223. doi: 10.1016/j.freeradbiomed.2017.09.029. Epub 2017 Oct 2. PubMed PMID: 28982599; PubMed Central PMCID: PMC5740866.
• Laker RC, Drake JC, Wilson RJ, Lira VA, Lewellen BM, Ryall KA, Fisher CC, Zhang M, Saucerman JJ, Goodyear LJ, Kundu M, Yan Z. Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy. Nat Commun. 2017 Sep 15;8(1):548. doi: 10.1038/s41467-017-00520-9. PubMed PMID: 28916822; PubMed Central PMCID: PMC5601463.
  

Conference Presentations

• Shute R, Shen W, Guan Y, Yan Z. Comparison of the impacts of voluntary weightlifting and wheel running in prevention of high-fat diet-induced obesity and insulin resistance in mice. International Biochemistry of Exercise Conference. Toronto, Canada. May 2022
• Guan Y, Wolf MJ, Epstein FH, Shah S, Zhang M, Yan Z. Phosphorylation of Ulk1 at S555 is Not Required in Exercise-mediated Protection against Diastolic Dysfunction and Exercise Intolerance in Diabetic Mice. The 18th International Biochemistry of Exercise Conference (IBEC). Toronto, Canada. May 2022.
• Drake, JC, Wilson RJ, Laker RC, Zhang M, Yan Z. Mitochondria-associated AMPK mediates mitochondrial quality control in skeletal muscle.  Cell Symposia: Exercise Metabolism. Sitges, Spain. May 2019.
• Guan Y, Thomas DA, Yan Z. Mitophagy in Exercise-induced Protection against Diastolic Dysfunction and Cardiac Atrophy in Diabetes. Annual Muscle Group at VT/FBRI Symposium, Virginia Polytechnic Institute & State University, Blacksburg, VA. April 2019.
• Guan Y, Thomas DA, Yan Z. Voluntary Wheel Running Reverses Cardiac and Skeletal Muscle Atrophy in Diabetic Mice. Advances in Skeletal Muscle Biology in Health and Disease Conference, Myology Institute, University of Florida, Gainesville, FL. February 2019.
  
• Wilson RJ, Drake JC, Cui D, Ritger ML, Guan Y, Call JA, Zhang M, Leitner LM, Geodeck A, Yan Z. Voluntary running protects against neuromuscular dysfunction following hindlimb ischemia-reperfusion in mice. Advances in Skeletal Muscle Biology in Health and Disease Conference, Myology Institute, University of Florida, Gainesville, FL. Feb. 2019.
• Drake JC., Wilson RJ, Laker RC, Zhang M., Yan Z. Mitochondria-associated AMPK mediates mitochondrial quality control in skeletal muscle.  Advances in Skeletal Muscle Biology in Health and Disease Conference, Myology Institute, University of Florida, Gainesville, FL. Feb. 2019.
  

Invited Lecture and Symposium Presentations

• 2/23 – Invited Speaker at Department of Public Health and Exercise Science, Appalachian State University
• 2/23 – Invited Speaker for Oklahoma Medical Research Foundation Research Forum, Oklahoma City, OK
  
• 3/23 – Invited Speaker for Advances in Skeletal Muscle Biology Conference, Gainesville, FL
  
• 4/23 – Invited Speaker for the Seminar Series at Center for Muscle Health and Neuromuscular Disorders at Ohio State University and Nationwide Children's Hospital, Columbus, OH
• 6/23 – Invited Lecturer of International Ph.D. Course -Skeletal Muscle Metabolism and Growth, Køge, Denmark
  
• 6/23 – Invited Speaker for August Krogh Mini Symposium, University of Copenhagen, Copenhagen, Denmark
  
• 8/23 – Invited Speaker at Shanghai University of Sport, Shanghai, China
  
• 9/23 –  Invited Speaker at Seminar Series in the Department of Biomedical Sciences at the University of Missouri-Columbia, Missouri
  
• 9/23 – Invited Speaker at Seminar Series in the Department of Physiology and Biophysics at the University of Illinois at Chicago