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						HOME
		Search Text: Home/< Back ToThe Science/Molecular Cardiology
  Molecular Cardiology
    The Laboratory of Molecular Cardiology, led by Dr. Robert S. Adelstein, is focused on the role of non-muscle myosin II (NM II) in development and disease.
    On This Page
    
          Robert Adelstein
  Robert Adelstein, M.D.
          Senior Investigator
          Email
      Meet the Team
            Contact us
  Senior Investigator Research Interests
            
  Research Interests
              As prototypical cellular motor proteins, most myosins convert the energy of ATP into movement. Contractile muscle myosin II proteins participate in the beating of the heart and movement of the body, while non-muscle myosin IIs play an integral role in cellular movement, shape regulation, and division. Dr. Adelstein’s laboratory is focused on the role of non-muscle myosin II (NMII) in development and disease.

Three genes—MYH9, MYH10, and MYH14—encode the heavy chains of the individual NMII proteins: NMII-A, NMII-B, and NMII-C, which are composed of both heavy and light chains. Dr. Adelstein and colleagues first described the phosphorylation and regulation of NMII ATPase activity in a seminal Nature paper in 1975. His laboratory has subsequently shifted its emphasis from predominantly biochemical approaches to transgenic mouse studies. By systematically ablating each of the heavy chain genes alone and in combination, Dr. Adelstein and his colleagues have discovered critical roles for NMII-A and NMII-B in early embryonic development, including a requirement for NMII-A in the visceral endoderm and placenta and for NMII-B in the normal development of the heart and brain. A combined KO of NM II-B and II-C in cardiac myocytes results in defects in karyokinesis.

It has been known for several years that single amino acid mutations in MYH9 lead to a human disease syndrome called MYH9-RD that includes abnormalities of the kidneys, platelets, lens of the eye, and the inner ear. Dr. Adelstein and his colleagues have generated transgenic mice that duplicate the human mutations and recapitulate the major features of the human disease. They use these animal models to study the molecular and cellular mechanisms that give rise to the specific defects.

Dr. Adelstein and colleagues first studied mutations in MYH10 that lead to strikingly abnormal heart development in the mouse—the heart develops outside of the body (ectopia cordis) due to a failure of ventral wall closure. In rare instances, children are born with and surgically treated for the same unusual defect. Coming full circle, Dr. Adelstein’s laboratory in collaboration with the University of Washington is carrying out whole exomic  sequencing on probands with the diagnosis of Pentalogy of Cantrell and their parents.

In vertebrates two of the paralogs (NM IIB and IIC) undergo alternative splicing. Studies of the mechanism responsible for splicing in the brain show that the Rbfox family of RNA binding proteins plays an essential role in NM IIB splice regulation. Characterization of these proteins demonstrates that they are required for neuronal differentiation during spinal cord development by regulating pre-mRNA splicing of Numb, a signaling adaptor protein. Recent work in this lab has shown a novel function for Rbfox in microRNA biogenesis.

Our present research projects include: the role of NM IIA in spermatogenesis; the function of NMIIs in cardiac development; using whole exomic sequencing to study causative genes for Pentalogy of Cantrell; understanding the role of NM IIA in squamous cell carcinoma; NMII and mechanotransduction; and studying the functions of the Rbfox  family of proteins.
  Featured Publications
                Nonmuscle Myosin IIA Regulates Intestinal Epithelial Barrier in vivo and Plays a Protective Role During Experimental Colitis.
            Authors:Naydenov NG, Feygin A, Wang D, Kuemmerle JF, Harris G, Conti MA, Adelstein RS, Ivanov A
                                                                                            
            Sci Rep
      
                2016 Jan 01;6:24161
        Read Publication
                      PKC412 normalizes mutation-related keratin filament disruption and hepatic injury in mice by promoting keratin-myosin binding.
            Authors:Kwan R, Chen L, Looi K, Tao GZ, Weerasinghe SV, Snider NT, Conti MA, Adelstein RS, Xie Q, Omary M
                                                                                                                        
            Hepatology
      
                2015 Dec 01;62(6):1858-69
        Read Publication
                      Limb body wall complex, amniotic band sequence, or new syndrome caused by mutation in IQ Motif containing K (IQCK)?
            Authors:Kruszka P, Uwineza A, Mutesa L, Martinez AF, Abe Y, Zackai EH, Ganetzky R, Chung B, Stevenson RE, Adelstein RS, Ma X, Mullikin JC, Hong SK, Muenke
                                                                                                                        
            Mol Genet Genomic Med
      
                2015 Sep 01;3(5):424-32
        Read Publication
                      Convergence and extrusion are required for normal fusion of the mammalian secondary palate.
            Authors:Kim S, Lewis AE, Singh V, Ma X, Adelstein R, Bush JO
                                                                                                                        
            PLoS Biol
      
                2015 Apr 01;13(4):e1002122
        Read Publication
                      Myosin II controls cellular branching morphogenesis and migration in three dimensions by minimizing cell-surface curvature.
            Authors:Elliott H, Fischer RS, Myers KA, Desai RA, Gao L, Chen CS, Adelstein RS, Waterman CM, Danuser G
                                                                                                                        
            Nat Cell Biol
      
                2015 Feb 01;17(2):137-47
        Read Publication
  Meet the Team

    Robert Adelstein

            Robert Adelstein, M.D.
                Senior Investigator
                Robert Adelstein graduated from Harvard Medical School with a M.D. in 1959. He did his internship at Bellevue Hospital in New York and Duke Hospital in Durham, NC, his junior medical residency at Bellevue, and his senior residency at Duke. He arrived at the NIH in 1961 as a Research Associate and worked with Wayne Kielley in Chris Anfinsen’s lab (NHLBI). He also conducted postdoctoral research with Edmond Fischer in the Department of Biochemistry at the University of Washington from 1966 to 1968 and was on sabbatical in Howard Cedar’s lab in Jerusalem from 1983 to 1984. He has been Chief of the Laboratory of Molecular Cardiology since 1981. Dr. Adelstein has authored or coauthored more than 200 papers. He has served as a member of the Editorial Board of the Journal of Biological Chemistry for over 15 years. Dr. Adelstein is a member of the Biophysical Society, American Society for Biochemistry and Molecular Biology, American Society for Clinical Investigation, American Association for Advancement of Science, and American Society for Cell Biology. He was a member of the Molecular Cytology NIH study section from 1981 to 1985, and was on the board of the American Heart Association’s Basic Cell Peer Review Committee. He is a past president of the Foundation for Advanced Education in the Sciences at the NIH.
    
          Contact the lab
    10 Center DrBethesda, MD 20814United States
        Phone:
                    301-496-1865
                Fax:
            301-402-1542
  Mary Anne Salmon
    
            Mary Anne Salmon, Ph.D.
        

    Scientific Support Staff

        maryanne.conti@nih.gov
            Sachiyo Kawamoto
    
            Sachiyo Kawamoto, M.D., Ph.D.
        

    Staff Scientist

        kawamots@nhlbi.nih.gov
            Xuefei Ma
    
            Xuefei Ma, Ph.D.
        

    Staff Scientist

        max3@mail.nih.gov
            Rachel Reed
    
            Rachel Reed
        

    Administrative Support Staff

        rreed@nih.gov
            Connie Lerma Cervantes
    
            Connie Lerma Cervantes
        

    Postbaccalaureate

        connie.lermacervantes@nih.gov
            Tingyi Wei
    
            Tingyi  Wei, Ph.D.
        

    Postdoctoral Fellow

        tingyi.wei@nih.gov
            Alexander Zhovmer
    
            Alexander  Zhovmer, Ph.D.
        

    Research Fellow

        alexander.zhovmer@nih.gov
            Thirupugal Govindarajan
    
            Thirupugal Govindarajan, Ph.D.
        

    Postdoctoral Fellow

        thirupugal.govindarajan@nih.gov
            Brittany MacTaggart
    
            Brittany  MacTaggart
        

    Postbaccalaureate

        brittany.mactaggart@nih.gov
            Derek Sung
    
            Derek Sung
        

    Postbaccalaureate

        derek.sung@nih.gov
            Mohsin Ahmad
    
            Mohsin Ahmad
        

    Post-baccalaureate

        mohsin.ahmad@nih.gov
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