Michael J. Greenberg, Ph.D.

Associate Professor
Biochemistry and Molecular Biophysics

Biochemistry, Biophysics, and Structural Biology Program
Molecular Cell Biology Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314 362-8670

  • 314 362-7434

  • 314 362-7183

  • 253 McDonnell Medical Sciences Building

  • greenberg@wustl.edu

  • http://glab.biochem.wustl.edu/

  • heart disease, single molecule, optical trapping, cardiac muscle, stem cells, tissue engineering, cytoskeletal molecular motors, mechanobiology, computational modeling, precision medicine

  • The Greenberg lab seeks to understand the molecular and cellular biophysics of heart disease, with the goal of engineering disease models and precision therapeutics

Research Abstract:

Our lab is interested in understanding molecular motors and their role in mechanobiology. Currently, the lab is studying mutations in contractile proteins that cause familial cardiomyopathies, the leading cause of sudden cardiac death in people under 30 years old. The presentation and prognosis in patients depends on the exact mutation, and therefore these diseases are excellent candidates for a precision medicine approach.

The lab uses an array of biochemical, biophysical, cell biological, and engineering techniques to decipher how these mutations affect the mechanobiology of heart contraction across scales from the level of single molecules to the level of engineered tissues. We are using insights gleaned from our studies to develop novel therapies for pediatric and adult heart failure.

Mentorship and Commitment to Diversity Statement:
I have a strong commitment to training the next generation of scientists and helping them to achieve their career goals. Both of my parents and two of my siblings are teachers, so education is really a family business. I have extensive teaching experience, having taught classes from the middle school to the graduate school levels. I have organized discussion groups and journal clubs as forums for trainees to hone their communication skills. I am a member of the admissions committee for the Biochemistry, Biophysics, and Structural Biology Program and the co-chair of the Postdoc Support and Recruitment Committee in the Department of Biochemistry and Molecular Biophysics. For my mentoring efforts, I received the Undergraduate Mentor of the Year award. Beyond my teaching and mentoring at the university, I have served as an educational consultant to MacMillian Publishing, developing content that is used to teach physics and chemistry at high schools and colleges across the country. I have also acted as a science ambassador at an elementary school in an underprivileged school district.

The Greenberg lab is committed to providing trainees with personalized career development and support for a wide variety of career paths. We appreciate that each trainee is unique with their own set of talents, interests, strengths, and challenges. We strongly believe that tackling the problems of the future will require creativity that comes from bringing together diverse teams of individuals, where each person can draw from their unique background. We strive to create an inclusive, supportive environment where trainees from diverse background can realize their potential and work collaboratively to address important questions. Our team includes developmental biologists, engineers, biophysicists, physician scientists, and chemists, each with their own unique backgrounds. I believe that diversity is critical to the success of the lab, and I am committed to creating an inclusive environment to help each person achieve their unique potential.

I am committed to providing trainees with personalized training in a wide range of skills that extend beyond lab skills. I work with each trainee to develop research projects that will provide them with specific technical training necessary for their future career goals. Moreover, each trainee has an individualized development plan that they develop with me and revisit frequently. This plan includes training beyond the lab. Members of my lab have been encouraged to pursue training including obtaining teaching certificates, attending professional conferences unrelated to the lab’s research, taking coursework to learn new skills, performing outreach to underprivileged communities, and working with consulting groups. Taken together, the Greenberg lab provides individualized training to help prepare trainees for a wide range of career paths.

Selected Publications:

*Denotes Greenberg Lab Members

*Barrick SK, *Greenberg MJ. Cardiac myosin contraction and mechanotransduction in health and disease. J Biol Chem. 2021 Oct 9;297(5):101297. doi: 10.1016/j.jbc.2021.101297. Epub ahead of print. PMID: 34634306; PMCID: PMC8559575.

Papadaki M, Kampaengsri T, *Barrick SK, Campbell SG, von Lewinski D, Rainer PP, Harris SP, *Greenberg MJ, Kirk JA. Myofilament glycation in diabetes reduces contractility by inhibiting tropomyosin movement, is rescued by cMyBPC domains. J Mol Cell Cardiol. 2021 Sep 3;162:1-9. doi: 10.1016/j.yjmcc.2021.08.012. Epub ahead of print. PMID: 34487755.

Wong NR, Mohan J, Kopecky BJ, Guo S, Du L, Leid J, Feng G, Lokshina I, Dmytrenko O, Luehmann H, Bajpai G, Ewald L, Bell L, Patel N, Bredemeyer A, Weinheimer CJ, Nigro JM, Kovacs A, Morimoto S, Bayguinov PO, Fisher MR, *Stump WT, *Greenberg MJ, Fitzpatrick JAJ, Epelman S, Kreisel D, Sah R, Liu Y, Hu H, Lavine KJ. Resident cardiac macrophages mediate adaptive myocardial remodeling. Immunity. 2021 Jul 21:S1074-7613(21)00289-2. doi: 10.1016/j.immuni.2021.07.003. Epub ahead of print. PMID: 34320366.

*Barrick SK, *Greenberg L, *Greenberg MJ. A Troponin T Variant Linked with Pediatric Dilated Cardiomyopathy Reduces the Coupling of Thin Filament Activation to Myosin and Calcium Binding. Mol Biol Cell. 2021 Jun 23:mbcE21020082. doi: 10.1091/mbc.E21-02-0082. Epub ahead of print. PMID: 34161147.

*Clippinger SR, *Cloonan PE, Wang W, *Greenberg L, *Stump WT, *Angsutararux P, Nerbonne JM, *Greenberg MJ. Mechanical dysfunction of the sarcomere induced by a pathogenic mutation in troponin T drives cellular adaptation. J Gen Physiol. 2021 May 3;153(5):e202012787. doi: 10.1085/jgp.202012787. PMID: 33856419; PMCID: PMC8054178.

Bailey AL, Dmytrenko O, *Greenberg L, Bredemeyer AL, Ma P, Liu J, Penna V, Winkler ES, Sviben S, Brooks E, Nair AP, Heck KA, Rali AS, Simpson L, Saririan M, Hobohm D, Stump WT, Fitzpatrick JA, Xie X, Zhang X, Shi PY, Hinson JT, Gi WT, Schmidt C, Leuschner F, Lin CY, Diamond MS, *Greenberg MJ, Lavine KJ. SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. JACC Basic Transl Sci. 2021 Apr;6(4):331-345. doi: 10.1016/j.jacbts.2021.01.002. Epub 2021 Feb 26. PMID: 33681537; PMCID: PMC7909907.

*Greenberg MJ, Tardiff JC. Complexity in genetic cardiomyopathies and new approaches for mechanism-based precision medicine. J Gen Physiol. 2021 Mar 1;153(3):e202012662. doi: 10.1085/jgp.202012662. PMID: 33512404; PMCID: PMC7852459.

*Blackwell T, *Stump WT, *Clippinger SR, *Greenberg MJ. Computational Tool for Ensemble Averaging of Single-Molecule Data. Biophys J. 2021 Jan 5;120(1):10-20. doi: 10.1016/j.bpj.2020.10.047. Epub 2020 Nov 26. PMID: 33248132; PMCID: PMC7820714.

Lavine KJ, *Greenberg MJ. Beyond genomics-technological advances improving the molecular characterization and precision treatment of heart failure. Heart Fail Rev. 2021 Mar;26(2):405-415. doi: 10.1007/s10741-020-10021-5. Epub 2020 Sep 3. PMID: 32885327; PMCID: PMC7897225.

Porter JR, Meller A, Zimmerman MI, *Greenberg MJ, Bowman GR. Conformational distributions of isolated myosin motor domains encode their mechanochemical properties. Elife. 2020 May 29;9:e55132. doi: 10.7554/eLife.55132. PMID: 32479265; PMCID: PMC7259954.

Ezekian JE, *Clippinger SR, *Garcia JM, Yang Q, Denfield S, Jeewa A, Dreyer WJ, Zou W, Fan Y, Allen HD, Kim JJ, *Greenberg MJ, Landstrom AP. Variant R94C in TNNT2-Encoded Troponin T Predisposes to Pediatric Restrictive Cardiomyopathy and Sudden Death Through Impaired Thin Filament Relaxation Resulting in Myocardial Diastolic Dysfunction. J Am Heart Assoc. 2020 Mar 3;9(5):e015111. doi: 10.1161/JAHA.119.015111. Epub 2020 Feb 26. PMID: 32098556; PMCID: PMC7335540.

*Clippinger SR, *Cloonan PE, *Greenberg L, *Ernst M, *Stump WT, *Greenberg MJ. Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy. Proc Natl Acad Sci U S A. 2019 Sep 3;116(36):17831-17840. doi: 10.1073/pnas.1910962116. Epub 2019 Aug 19. PMID: 31427533; PMCID: PMC6731759.

*Barrick SK, *Clippinger SR, *Greenberg L, *Greenberg MJ. Computational Tool to Study Perturbations in Muscle Regulation and Its Application to Heart Disease. Biophys J. 2019 Jun 18;116(12):2246-2252. doi: 10.1016/j.bpj.2019.05.002. Epub 2019 May 7. PMID: 31126584; PMCID: PMC6588827.

Porter JR, Moeder KE, Sibbald CA, Zimmerman MI, Hart KM, *Greenberg MJ, Bowman GR. Cooperative Changes in Solvent Exposure Identify Cryptic Pockets, Switches, and Allosteric Coupling. Biophys J. 2019 Mar 5;116(5):818-830. doi: 10.1016/j.bpj.2018.11.3144. Epub 2019 Jan 25. PMID: 30744991; PMCID: PMC6400826.

*Greenberg MJ, Daily NJ, Wang A, Conway MK, Wakatsuki T. Genetic and Tissue Engineering Approaches to Modeling the Mechanics of Human Heart Failure for Drug Discovery. Front Cardiovasc Med. 2018 Sep 19;5:120. doi: 10.3389/fcvm.2018.00120. PMID: 30283789; PMCID: PMC6156537.

Woody MS, *Greenberg MJ, Barua B, Winkelmann DA, Goldman YE, Ostap EM. Positive cardiac inotrope omecamtiv mecarbil activates muscle despite suppressing the myosin working stroke. Nat Commun. 2018 Sep 21;9(1):3838. doi: 10.1038/s41467-018-06193-2. PMID: 30242219; PMCID: PMC6155018.

*Greenberg MJ, Shuman H, Ostap EM. Measuring the Kinetic and Mechanical Properties of Non-processive Myosins Using Optical Tweezers. Methods Mol Biol. 2017;1486:483-509. doi: 10.1007/978-1-4939-6421-5_19. PMID: 27844441; PMCID: PMC5506543.

Woody MS, Lewis JH, *Greenberg MJ, Goldman YE, Ostap EM. MEMLET: An Easy-to-Use Tool for Data Fitting and Model Comparison Using Maximum-Likelihood Estimation. Biophys J. 2016 Jul 26;111(2):273-282. doi: 10.1016/j.bpj.2016.06.019. PMID: 27463130; PMCID: PMC4968482.

*Greenberg MJ, Arpağ G, Tüzel E, Ostap EM. A Perspective on the Role of Myosins as Mechanosensors. Biophys J. 2016 Jun 21;110(12):2568-2576. doi: 10.1016/j.bpj.2016.05.021. PMID: 27332116; PMCID: PMC4919425.

*Greenberg MJ, Lin T, Shuman H, Ostap EM. Mechanochemical tuning of myosin-I by the N-terminal region. Proc Natl Acad Sci U S A. 2015 Jun 30;112(26):E3337-44. doi: 10.1073/pnas.1506633112. Epub 2015 Jun 8. PMID: 26056287; PMCID: PMC4491760.

Kee AJ, Yang L, Lucas CA, *Greenberg MJ, Martel N, Leong GM, Hughes WE, Cooney GJ, James DE, Ostap EM, Han W, Gunning PW, Hardeman EC. An actin filament population defined by the tropomyosin Tpm3.1 regulates glucose uptake. Traffic. 2015 Jul;16(7):691-711. doi: 10.1111/tra.12282. Epub 2015 Apr 29. PMID: 25783006; PMCID: PMC4945106.

*Greenberg MJ, Shuman H, Ostap EM. Inherent force-dependent properties of β-cardiac myosin contribute to the force-velocity relationship of cardiac muscle. Biophys J. 2014 Dec 16;107(12):L41-L44. doi: 10.1016/j.bpj.2014.11.005. PMID: 25517169; PMCID: PMC4269798.

Shuman H, *Greenberg MJ, Zwolak A, Lin T, Sindelar CV, Dominguez R, Ostap EM. A vertebrate myosin-I structure reveals unique insights into myosin mechanochemical tuning. Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2116-21. doi: 10.1073/pnas.1321022111. Epub 2014 Jan 27. PMID: 24469830; PMCID: PMC3926069.

*Greenberg MJ, Ostap EM. Regulation and control of myosin-I by the motor and light chain-binding domains. Trends Cell Biol. 2013 Feb;23(2):81-9. doi: 10.1016/j.tcb.2012.10.008. Epub 2012 Nov 29. PMID: 23200340; PMCID: PMC3558615.

*Greenberg MJ, Lin T, Goldman YE, Shuman H, Ostap EM. Myosin IC generates power over a range of loads via a new tension-sensing mechanism. Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):E2433-40. doi: 10.1073/pnas.1207811109. Epub 2012 Aug 20. PMID: 22908250; PMCID: PMC3443183.

Last Updated: 11/22/2021 9:05:39 PM

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