Troy Hornberger

troy.hornberger@wisc.edu

Department of Comparative Biosciences
Office: 4256
Website

Troy Hornberger

Titles and Education

  1. Assc. in Chemistry, Lake Superior State University, 1996
  2. B.S. in Biology, Lake Superior State University, 1996
  3. M.A. in Kinesiology, University of Texas at Austin, 1999
  4. Ph.D. in Kinesiology, University of Illinois-Chicago, 2004

Research

     It is known that mechanical stimuli play a major role in regulation of skeletal muscle mass, and the maintenance of muscle mass contributes significantly to disease prevention and quality of life. Although the link between mechanical signals and the control of muscle mass has been recognized for decades, the mechanisms involved in converting mechanical information into the molecular events that control this process remain ill defined. Thus, the primary focus of our research is to determine how skeletal muscles sense mechanical information and convert this stimulus into the molecular events that regulate changes in mass (mechanotransduction).

     Our studies in the field of mechanotransduction and the regulation of skeletal muscle mass have led us to focus on a protein kinase called the mammalian target of rapamycin (mTOR). We are interested in mTOR because our previous work has established that: i) mechanical stimuli can robustly activate mTOR signaling; ii) mTOR signaling is necessary for a mechanically-induced increase in muscle fiber size (hypertrophy); and iii) the activation of mTOR signaling, in and of itself, is sufficient to induce hypertrophy. Since mechanical stimuli activate mTOR signaling, it follows that a mechanotransduction pathway must exist for converting mechanical information into the biochemical events that activate mTOR. Based on our recent work, it appears that the late endosomal / lysosomal system (LEL) may be a central component of this pathway. Therefore, to test this concept, we are currently pursuing the following hypotheses: 1) Raptor is necessary for the targeting of mTOR to the LEL and, in turn, the mechanical activation of mTOR signaling; 2) the mechanical activation of mTOR signaling is due, in part, to a diacylglycerol kinase ζ (DGKζ)-dependent increase in phosphatidic acid (PA) at the LEL; and 3) mechanical stimuli induce an increase in the phosphorylation of tuberin (TSC2), which causes it to dissociate from the LEL, and as a result, Rheb at the LEL becomes activated and stimulates mTOR signaling. In addition to testing these hypotheses, we are also in the process of defining the extent to which Raptor, DGKζ/PA and TSC2/Rheb contribute to mechanically-induced changes in protein synthesis and the induction of hypertrophy.

   The work in our lab involves the use of a wide variety of molecular, cellular and animal based techniques (e.g. cloning, mutagenesis, Western blotting, microscopy, metabolic tracers, in-vivo transfections, tissue specific inducible knockout transgenic mice and several models of mechanical loading). Furthermore, our lab is in the early stages of using a state-of-the-art mass spectrometry technique (NeuCode) to globally map the mechanically-regulated proteome / phosphoproteome. This is a new and particularly exciting direction that will enable us to dramatically expand our knowledge of the events that are mediated downstream versus upstream / parallel to the mechanical activation of mTOR signaling. 

   In summary, the long-term goal of our research is to identify targets for therapies that are aimed at mimicking the effects of mechanical stimuli and, in turn, prevent the loss of muscle mass that occurs during conditions such as immobilization, bed rest, cachexia, muscular dystrophies and aging. Moreover, it is known that mTOR signaling contributes to several diseases such as diabetes, aging and cancer, and thus, our research is also expected to benefit the ongoing efforts that are aimed at treating these diseases.

   To learn more about these projects, please visit the lab website: http://www.vetmed.wisc.edu/lab/hornberger/


 

Responsibilities

Professor

  • Physiology
  • Metabolic and Molecular Basis of Medicine (MMBM)

Clinical Interests

Factors that impact skeletal muscle mass

Compensatory growth of the lung

Graduate Training

Recent Publications

  1. 1. Steinert ND, Jorgenson KW, Lin KH, Hermanson JB, Lemens JL, Hornberger TA. A novel method for visualizing in-vivo rates of protein degradation provides insight into how TRIM28 regulates muscle size. iScience. 2023 Apr 21;26(4):106526. https://www.sciencedirect.com/science/article/pii/S258900422300603X?via%3Dihub
  2. 2. Zhu WG, Hibbert JE, Lin KH, Steinert ND, Lemens JL, Jorgenson KW, Newman SM, Lamming DW, Hornberger TA. Weight Pulling: A Novel Mouse Model of Human Progressive Resistance Exercise. Cells. 2021; 10(9):2459. https://doi.org/10.3390/cells10092459
  3. 3. Steinert ND, Potts GK, Wilson GM, Klamen AM, Lin KH, Hermanson JB, McNally RM, Coon JJ, Hornberger TA. Mapping of the Contraction-Induced Phosphoproteome Identifies TRIM28 as a Significant Regulator of Skeletal Muscle Size and Function. Cell Reports. 2021 Mar 2;34(9): 108796. * Recommended by the Faculty of 1000. https://pubmed.ncbi.nlm.nih.gov/33657380/
  4. 4.  Jorgenson KW, Phillips SM, and Hornberger TA. Identifying the Structural Adaptations that Drive the Mechanical Load-Induced Growth of Skeletal Muscle: A Scoping Review. Cells. 2020 Jul 9;9(7):E1658. * Obtained an Altmetric attention score of 125 (4th highest ever for the journal) within 1 month of publication. https://www.mdpi.com/2073-4409/9/7/1658/htm
  5. 5. You, JS†, McNally RM†, Jacobs BL*, Privett RE, Gundermann DM, Lin KH, Steinert ND, Goodman CA, and Hornberger TA. The role of raptor in the mechanical load-induced regulation of mTOR signaling, protein synthesis, and skeletal muscle hypertrophy. FASEB J. 2019 Mar;33(3):4021-4034. * Obtained an Altmetric attention score of 102 (top 2%) within 7 days of publication. † equal contribution.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404572/
  6. For a complete list of publications click herehttp://www.ncbi.nlm.nih.gov/sites/myncbi/troy.hornberger.1/bibliograpahy/40044484/public/?sort=date&direction=ascending