Tim Hao Shi

The overarching goal of my research is to understand the biochemical basis of muscle function and how it contributes to animal growth and meat quality. Specifically, my research has been focused on three main areas:

1. muscle stem cell biology,
2. muscle metabolism and metabolic disorders, and
3. meat science.

Muscle stem cells, also referred to as satellite cells, are one of the major contributors to postnatal muscle growth in agriculturally important animals. Additionally, muscle stem cells are critical to maintain muscle health as our previous work has shown that myopathy in poultry such as woody breast may be caused by lack, or exhaustion, of muscle stem cells at the late stage of animal growth.

The second area of my research is to understand skeletal muscle as a metabolic tissue. By taking up to 70-90% glucose from the circulation for energy production and locomotion, skeletal muscle plays a central role in local and whole-body energy homeostasis. We have been working on a nutrient sensing pathway, O-GlcNAcylation, and investigating its role in muscle physiology and pathophysiology during diet-induced obesity using mouse and pig as animal models.

In collaboration with Dr. David E. Gerrard, my research in meat science is to understand the functional role of mitochondrion, an organelle that is responsible for oxidative phosphorylation, in postmortem muscle metabolism and meat quality in pigs and cattle.

Taken together, the three areas I mentioned are closely related in that muscle stem cells contribute to muscle growth and metabolism, which in turn, can influence muscle stem cell behavior by providing a physical and biochemical microenvironment. Furthermore, a better understanding of muscle biology and metabolism will help develop new approaches to improve the growth efficiency of meat animals and the ultimate quality of meat.

• Postdoc (Post-Doctoral Fellowship) in Pharmacology, Yale University, New Haven, CT, 2007-2013
• Ph.D. (Doctor of Philosophy) in Muscle Biology, Purdue University, West Lafayette, IN, 2000-2007
• M.S. (Master of Science) in Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, China, 1993-1996
• B.S. (Bachelor of Science) in Veterinary Medicine, Anhui Science & Technology University, Fengyang, China, 1989-1993

1.    Chen, L., Q. Lu, X. Mao, Z. Zhu, C. Zhang, H. Shi, J. Sun, and Z. Fan 1996. Chronic vascular catheterization into sheep fetus. Chinese Journal of Obstetrics and Gynecology 31:381-382 (in Chinese).

2.    Shi, H. and L. Chen 1996. Passive immunity and immune responses of the newborn animals. Animal Husbandry and Veterinary Medicine 15:47-49 (in Chinese).

3.    Rong, J., H. Shi, and L. Chen 1997. Functional role of neuropeptide Y in energy homeostasis. Journal of Anhui Agrotechnical Normal College 11:45-48 (in Chinese).

4.    Rong, J., H. Shi, and X. Mao 1997. Role of liver in the clearance of reactive oxygen species.  Animal Husbandry and Veterinary Medicine 16:50-51 (in Chinese).

5.    Li, X., Y. Zhuang, G. Wu, L. Shen, G. Zhou, C. Chang, Y. Yang, and H. Shi 1998. Kinetics of fetal blood flow in gelatin microsphere-induced fetal hypoxia. Chinese Journal of Obstetrics and Gynecology 33:363-364 (in Chinese).

6.    Li, X., Y. Zhuang, C. Chang, G. Wu, L. Shen, G. Zhou, Y. Yang, M. Lu, H. Shi, and H. Wang 1998. Effect of salvia miltiorrhiza on the kinetics of blood flow in umbilical artery of hypoxic sheep fetus. Chinese Journal of Integrated Traditional and Western Medicine 18:543-545 (in Chinese).

7.    Zhao, G., Y. Yang,  X. Li, H. Shi, M. Lu, W. Zhao, and P. Zhu 1998. Establishment of an animal model for fetal hypoxia. Shanghai Laboratory Animal Science 18:1-5 (in Chinese).

8.    Shi, H., X. Mao, G. Zhou and Y. Yang 1998. Effect of cholic acid overload on kinetics of antioxidant enzymes in rat liver.  Shanghai Laboratory Animal Science 18 (Z1):222 (in Chinese).

9.    Zhou, G., Q. Gao, Y. Yang,  W. Zhao, P. Zhu, J. Yang, and H. Shi 1998. Histological evaluation of the chronic toxicological effect of Longbikai compound on Wistar rat.  Shanghai Laboratory Animal Science 18 (Z1):225 (in Chinese).

10.  Zhao, G., Y. Yang,  X. Li, H. Shi, M. Lu, W. Zhao, and P. Zhu 1998. Sheep fetal hypoxic model via injection of microsphere into fetal abdominal aorta during late pregnancy. Chinese Journal of Laboratory Animal Science 8:129-134 (in Chinese).

11. Shi, H., M. Lu, and J. Tang 1998. Neuropeptide Y, hypothalamus and energy homeostasis. Foreign Medical Sciences (Pathophysiology and Clinical Medicie) 18:26-28 (in Chinese).

12. Shi, H., X Mao, and J. Rong 1998.  Developmental changes of liver function in rat fetus and neonates. Chinese Journal of Applied Physiology 14: 143, 165  (in Chinese).

13.  Shi, H., Z. Zhu and X. Mao 1999. Effects of cholic acid overload on the concentration of cholaneglycinate in sheep and rat serum.  Animal Husbandry and Veterinary Medicine 31:14-15 (in Chinese).

14.   Lu, Q., H. Shi, X. Mao, L. Chen, J. Sun and Z. Pan 1999. Effects of cholic acid overload on rat fetal growth and development. Chinese Journal of Applied Physiology 15:76,81 (in Chinese).

15.  Shi, H., K. Zhang, and X. Mao 1999.  Effects of exogenous cholic acid on liver functions in SD rats. Journal of Shanghai Agricultural College 17:26-29, 51  (in Chinese).

16.  Xu, L., Y. Yang, W. Zhou, H. Shi, and S. Chen 2001. Study on cardiac function of Macaca mulatta. Shanghai Laboratory Animal Science 21:115-116.

17.  Shi, H., C. Zeng, A. Ricome, K.M. Hannon, A.L. Grant, and D.E. Gerrard 2007. Extracellular signal-regulated kinase pathway is differentially involved in β-agonist-induced hypertrophy in slow and fast muscles.  American  Journal of Physiology Cell Physiology 292:C1681-1689.

18.  Shi, H., J.M. Scheffler, J.M. Pleitner, C. Zeng, S. Park, K.M. Hannon, A.L. Grant, and D.E. Gerrard 2008.  Modulation of skeletal muscle fiber type by mitogen-activated protein kinase signaling. The FASEB Journal 22:2990-3000.

19.  Park, S., T.L. Scheffler, A.M. Gunawan, H. Shi, C. Zeng, K.M. Hannon, A.L. Grant, and D.E. Gerrard 2008. Chronic elevated calcium blocks AMPK-induced GLUT-4 expression in skeletal muscle. American Journal of Physiology Cell Physiology 296:C106-115.

20.  Shi, H., J.M. Scheffler, J.M. Pleitner, C. Zeng, S. Park, K.M. Hannon, A.L.  Grant, and D.E. Gerrard 2009. Mitogen-activated protein kinase is necessary for the maintenance of skeletal muscle mass.  American Journal of physiology Cell Physiology 296: C1040-1048.

21.  Shi, H., E. Boadu, F. Mercan, L. Zhang, A.M. Le, R.J. Roth Flach, K.J. Tyner, B.B. Olwin, and A.M. Bennett 2010. MAP kinase phosphatase-1 deficiency impairs skeletal muscle regeneration and exacerbates muscular dystrophy. The FASEB J 24:2985-2997.

22.  Shi, H., M. Verma, L. Zhang, C. Dong, R.A. Flavell, and A. M. Bennett 2013. Improved regenerative myogenesis and muscular dystrophy in mice lacking Mkp5.  The Journal of Clinical Investigation, 123:2064-2077.

23. Shi, H*., F. Gatzke, J. M. Molle, H. B. Lee, E. T. Helm, J. J. Oldham, L. Zhang, D. E. Gerrard and A. M. Bennett 2015. Mice lacking MKP-1 and MKP-5 reveal hierarchical regulation of regenerative myogenesis.  Journal of Stem Cell and Regenerative Medicine 1: 1-7. * Corresponding author.

24. England, E.M., S.K. Matarneh, E.M. Oliver, A. Apaoblaza, T.L. Scheffler, H.Shi and D.E. Gerrard 2016. Excess glycogen does not resolve high ultimate pH of oxidative muscle. Meat Science 114:95-102.

25. Daughtry M.R., E. Berio, Z. Shen, E.J.R. Suess, N. Shah, A.E. Geiger, E.R. Berguson, R.A. Dalloul, M.E. Persia, H. Shi and D.E. Gerrard 2017. Satellite cell-mediated breast muscle regeneration decreases with broiler size. Poultry Science doi:10.3382/ps/pex068.

26. England E.M., H. Shi, S.K. Matarneh, E.M. Oliver, E.T. Helm, T.L. Scheffler, E. Puolanne, and D.E. Gerrard 2017. Chronic activation of AMP-activated protein kinase increases monocarboxylate transporter 2 and 4 expression in skeletal muscle. Journal of Animal Science 95:3552-3562.

27. Lee, H, K. Min, J.S. Yi, H. Shi, W. Chang, L. Jason and A.M. Bennett 2017. A phosphoproteomic screen identified a guanine nucleotide exchange factor for Rab3A protein as a mitogen-activated protein (MAP) kinase phosphatase-5-regulated MAP kinase target in interleukin 6 (IL-6) secretion and myogenesis. Journal of Biological Chemistry 292:3581-3590.

28. Patterson B.A., S.K. Matarneh, K.M. Stufft, E.M. England, T.L. Scheffler, R.H. Preisser, H. Shi, E.C. Stewart, S. Eilert and D.E. Gerrard 2017. Pectoralis major muscle of turkey displays divergent function as correlated with meat quality. Poultry Science 96:1492-1503.

29. Stufft K.M., J. Elgin, B.A. Patterson, S.K. Matarneh, R.H. Preisser, H. Shi, E.M. England, T.L. Scheffler, E.W.Mills and D.E. Gerrard 2017. Muscle characteristics only partially explain color variations in fresh hams. Meat Science 128:88-96.

30. Matarneh S.K., E.M. England, T.L. Scheffler, C.N. Yen, J.C. Wicks, H. Shi, and D.E. Gerrard 2017. A mitochondrial protein increases glycolytic flux. Meat Science 133:119-125.

31. England E.M., S.K. Matarneh, R.M. Mitacek, A. Abraham, A. Ramanathan, J.C, Wicks, H. Shi, T.L. Scheffler, E.M. Oliver, E.T. Helm, and D.E. Gerrard 2018. Presence of oxygen and mitochondria in skeletal muscle early postmortem. Meat Science 139:97-106.

32. Matarneh S.K., M. Beline, S. de Luz E Silver, H. Shi, and D.E. Gerrard 2018. Mitochondrial F1-ATPase extends glycolysis and pH decline in an in vitro model. Meat Science 137:85-91.

33. Shi H., A. Munk, T.S. Nielsen, M.R. Daughtry, L. Larson, S. Li, K.F. Hoyer, H.W. Geisler, K. Sulek, R. Kjobsted, T. Fisher, M.M. Andersen, Z. Shen, U.K. Hansen, E.M. England, Z. Cheng, K. Hojlund, J.F.P. Wojtaszewski, X. Yang, M.W. Hulver, R.F. Helm, J.T. Treebak, and D.E. Gerrard 2018. Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity. Molecular Metabolism 11:160-177.    

34.  Geiger A.E., M.R. Daughtry, C.M. Gow, P.B. Siegel, H. Shi, and D.E. Gerrard 2018. Long-term selection of chickens for body weight alters muscle satellite cell behaviors. Poultry Science 97:2557-2567.

35. Apaoblaza A., S.D. Gerrard, S.K. Matarneh, J.C. Wicks, L. Kirkpatrick, E.M. England, T.L. ScheffleR, S.K. Duckett, H. Shi, S.L. Silva, A.L. Grant, D.E 2020. Gerrard. Muscle from grass- and grain-fed cattle differs energetically. Meat Science 161:107996. doi: 10.1016/j.meatsci.2019.107996.

36. He R., Y. Kong, P. Fang, L. Li, H. Shi, and Z. Liu 2020. Integration of quantitative proteomics and metabolomics reveals tissue hypoxia mechanisms in an ischemic-hypoxic rat model. Journal of Proteomics 228:103924. doi: 10.1016/j.jprot.2020.103924.

37. Geiger, A.E., M.R. Daughtry, C.N. Yen, L.T. Kirkpatrick, H. Shi, and D.E. Gerrard 2020. Dual effects of obesity on satellite cells and muscle regeneration. Physiological Reports 8: e14511. doi:10.14814/phy2.14511.

38.  Zumbaugh, M.D., A.E. Geiger, J. Luo, Z. Shen, H. Shi, D.E. Gerrard 2021. O-GlcNAc transferase is required to maintain satellite cell function. Stem Cells. PMID: 33634918. doi: 10.1002/stem.3361.

39. Zumbaugh, M.D., C.N. Yen, J. S. Bodmer, H. Shi, and D.E. Gerrard 2021. Skeletal muscle O-GlcNAc transferase action on global metabolism is partially mediated through Interleukin-15. Frontiers in Physiology 12:682052. doi: 10.3389/fphys.2021.682052.

40. Zeng, C., H. Shi, L. Kirkpatrick, A. Ricome, S. Park, J.M. Scheffler, K.M. Hannon, A.L. Grant, and D.E. Gerrard 2022. Driving an oxidative phenotype protects Myh4 null mice from myofiber loss during postnatal growth. Frontiers in Physiology 12:785151. doi: 10.3389/fphys.2021.785151.

41. Kirkpatrick L.T., J.M. Elgin, S.K. Matarneh, J.C. Wicks, R.P. Daniels, C.N. Yen, J.S. Bodmer, M.D. Zumbaugh, S.W. El-Kadi, S.L. Silva, T.H. Shi, and D.E. Gerrard 2022. Inherent factors influence color variations in semimembranosus muscle of pigs. Meat Science 185:108721. doi: 10.1016/j.meatsci.2021.108721.

42. Zumbaugh M.D., S.E. Johnson, T.H. Shi, and D.E. Gerrard 2022. Journal of Animal Sciences 100:skac035 doi: 10.1093/jas/skac035.

43. Daniels R.P., J.C. Wicks, M.D. Zumbaugh, S.K. Matarneh, M.D. Venhuizen, J. Elgin, J. Bodmer, C.N. Yen, S.W. El-Kadi, H. Shi, S.L. Silva, and D.E. Gerrard. Reduced scale time does not influence ultimate pork quality 2022. Meat Science 194:108958.  doi: 10.1016/j.meatsci.2022.108958.

44. Kirkpatrick L.T., M.R. Daughtry, S. El-Kadi, T.H. Shi, and D.E. Gerrard. O-GlcNAcylation is a gatekeeper of porcine myogenesis 2022. Journal of Animal Sciences 100:skac326. doi: 10.1093/jas/skac326.

Shi, H and Bennett, A.M 2012. Mitogen-activated protein kinases and mitogen-activated protein kinase phosphatases in muscular dystrophy, in Muscular Dystrophy, ISBN 978-953-51-0603-6, M. Hegde and A. Ankala eds. (InTech), pp159-172.

Lawan, A., Shi, H., Gratzke, F. and Bennett, A.M 2013. Diversity of mitogen-activated protein kinase phosphatase-1 functions, Cellular and Molecular Life Sciences , 70:223-237

Geisler, H. W., Shi, H., & Gerrard, D. E. (2013). MAPK Pathway in Skeletal Muscle Diseases. Journal of Veterinary Science & Animal Husbandry, 1(1), 1.

MDA186936 (Shi).  Role of MAP Kinase Phosphatase-5 in Duchenne Muscular Dystrophy from the Muscular Dystrophy Association (2/2011-1/2014).  Role: Principal Investigator

USDA NIFA (Shi). Existence of A Time-Sensitive Window Postmortem For The Physical Manipulation Of Pork Quality (3/2019-3/2022). Role: Principal Investigator

USDA NIFA (Gerrard and Shi). O-GlcNAcylation Modulation of Skeletal Muscle Metabolism and Growth from USDA (6/2019-6/2022). Role: Co-PD/PI