Richard Moss

Position title: Professor - Senior Associate Dean for Basic Research, Biotechnology and Graduate Studies, School of Medicine and Public Health

Email: rlmoss@wisc.edu

Phone: Phone: (608) 265-0523

Address:
RESEARCH INTERESTS - Heart and skeletal muscle physiology

Headshot of Richard Moss

 

Address: 4111 Health Sciences Learning Center – 750 Highland Avenue – Madison, WI 53705

PubMed

Education

Ph.D., Univ of Vermont
Postdoctoral Research, Boston Biomedical Research Institute

Research

My laboratory studies contractile processes in heart and skeletal muscles and alterations in contraction in diseases such as heart failure. A primary focus of our research is the set of mechanisms by which calcium, various physical factors and signal transduction pathways regulate myocardial contraction.

We use a range of investigative approaches including biophysics, biochemistry and molecular biology in our studies of these mechanisms. Most of our experiments involve measurements of contractile properties of single muscle cells in response to alteration in contractile protein composition, which is done by biochemical exchange, gene knock-outs, and expression of proteins on a null background. In this way, we are able to assess the roles of specific proteins in regulation and determine the roles of specific domains in protein function.

Another focus of our research is the molecular mechanisms that determine the work capabilities of myosin molecules, which is essentially a study of the kinetics of nucleotide turnover by myosin. Our interest in this problem is stimulated by the observation that different myosin isoforms have widely varying work rates, which gives rise to variable work rates among the muscles of the body. Even the same myosin isoform expressed in different species can have dramatically different turnover kinetics, and work rates can be dramatically slowed in disease states such as heart failure and ischemic heart disease.

Our investigations of this mechanism feature systematic mutation of myosin molecules, expression in a baculovirus/insect cell system, and measurement of function using an in vitro motility assay system. Studies such as these are probing the most fundamental processes of the actomyosin ATPase, and results will presumably also have implications for our understanding of altered contraction in diseased heart muscle.

In this regard, the laboratory is presently engaged in extensive studies of the basis for contractile dysfunction in animal models of heart failure (CREB-A133 dominant-negative mouse) and myocardial stunning.


Figure (above)
Foreground: A gene “knock-in” targeting strategy for the cardiac regulatory light chain (RLC) gene is shown. The targeting strategy makes use of homologous recombination in mouse embryonic stem cells in order to replace the wild type, endogenous gene with a gene bearing a specific mutation of interest. Chimeric mice are then bred to produce mice homozygous for the mutation. Functional effects of the mutation are assessed from the whole animal to the molecular level by using a variety of biochemical, histological, and mechanical assays.

Background: a single mouse myocyte is anchored to two pins connected to a force transducer and length control device in order to measure force and kinetics of activation.

Representative Publications

  • Wei L, Gregorich ZR, Lin Z, Cai W, Jin Y, McKiernan SH, McIlwain S, Aiken JM, Moss RL, Diffee GM, Ge Y. Novel Sarcopenia-related Alterations in Sarcomeric Protein Post-translational Modifications in Skeletal Muscles Identified by Top-down Proteomics. Mol Cell Proteomics. 2017 Oct 18. [Epub ahead of print]
  • Jin Y, Wei L, Cai W, Lin Z, Wu Z, Peng Y, Kohmoto T, Moss RL, Ge Y. Complete Characterization of Cardiac Myosin Heavy Chain (223 kDa) Enabled by Size-Exclusion Chromatography and Middle-Down Mass Spectrometry. Anal Chem. 2017 May 2;89(9):4922-4930.
  • Moss RL, Lynch TL 4th, Fitzsimons DP. Acting on an impulse (or two): Advantages of high-frequency tetanic onset in skeletal muscle. J Gen Physiol. 2017 Mar 6;149(3):297-300.
  • Kensler RW, Craig R, Moss RL. Phosphorylation of cardiac myosin binding protein C releases myosin heads from the surface of cardiac thick filaments. Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):E1355-E1364.
  • Moss RL. Cardiac myosin-binding protein C: A protein once at loose ends finds its regulatory groove. Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):3133-5.
  • Massengill MT, Ashraf HM, Chowdhury RR, Chrzanowski SM, Kar J, Warren SA, Walter GA, Zeng H, Kang BH, Anderson RH, Moss RL, Kasahara H. (2016) Acute heart failure with cardiomyocyte atrophy induced in adult mice by ablation of cardiac myosin light chain kinase. Cardiovasc Res. 111:34-43.
  • Gregorich ZR, Peng Y, Cai W, Jin Y, Wei L, Chen AJ, McKiernan SH, Aiken JM, Moss RL, Diffee GM, Ge Y. (2016) Top-Down Targeted Proteomics Reveals Decrease in Myosin Regulatory Light-Chain Phosphorylation That Contributes to Sarcopenic Muscle Dysfunction. J Proteome Res. 2016 Jul 13. [Epub ahead of print]
  • Moss RL. (2016). Cardiac myosin-binding protein C: A protein once at loose ends finds it regulatory groove. Proc Natl Acad Sci USA 113:3133-3135.
  • Chen YC, Ayaz-Guner S, Peng Y, Lane NM, Locher MR, Hohmoto T, Larsson L, Moss RL, Ge Y. (2015). Effective top-down LC/MS+ method for assessing actin isoforms as a potential cardiac disease marker. Anal Chem 87:8399-8406.
  • Zhao YT, Valdivia CR, Gurrola GB, Powers PP, Willis BC, Moss RL, Jalife J, Valdivia HH. (2015). Arrhythmogenesis in a catecholamine polymorphic ventricular tachycardia mutation that depresses ryanodine function. Proc Natl Acad Sci USA 112:E1669-1677.
  • Rosas PC, Liu Y, Abdalla MI, Thomas CM, Kidwell DT, Dusio GF, Mukhopadhyay D, Kumar R, Baker KM, Mitchell BM, Powers PA, Fitzsimons DP, Patel BG, Warren CM, Solaro RJ, Moss RL, Tong CW. (2015). Phosphorylation of cardiac myosin-binding protein-C is a critical mediator of diastolic function. Circ Heart Fail 8:582-594.
  • Tong CW, Wu X, Liu Y, Rosas PC, Sadayappan S, Hudmon A, Muthuchamy M, Powers PA, Valdivia HH, Moss RL. (2015). Phosphoregulation of cardiac inotropy via myosin binding protein-C during increased pacing frequency or b1-adrenergic stimulation. Circ Heart Fail 8:595-604.
  • Moss RL, Fitzsimons DP, Ralphe JC. (2015). Cardiac MyBP-C regulates the rate and force of contraction in mammalian myocardium. Circ Res 116:183-192.
  • Theis JL, Zimmermann MT, Larsen BT, Rybakova IN, Long PA, Evans JM, Middha S, de Andrade M, Moss RL, Wieben ED, Michels VV, Olson TM. (2014). TNNI3K mutation in familial syndrome of conduction system disease, atrial tachyarrhythmia and dilated cardiomyopathy. Hum Mol Genet 23:5793-5804.
  • Colson BA, Rybakova IN, Prochniewicz E, Moss RL, Thomas DD. (2012). Cardiac myosin binding protein-C restricts intrafilament torsional dynamics of actin in a phosphorylation-dependent manner. Proc Natl Acad Sci USA 109:20437-20442.
  • Ge Y, Moss RL. (2012). Nitroxyl, redox switches, cardiac myofilaments and heart failure: A prequel to novel therapeutics? Circ Res 111:954-956.