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Related Research Units

Infectious Diseases Research

Research Overview

Dr. Wessels’ research is concerned with understanding the molecular interactions between pathogen and host in infections due to Streptococcus pyogenes (group A Streptococcus or GAS), the etiologic agent of streptococcal pharyngitis (strep throat) and severe invasive infections such as necrotizing fasciitis and streptococcal toxic shock. These bacteria can colonize mucosal surfaces as harmless commensals, but they have the potential to produce local infection or systemic, life-threatening disease.

The lab is particularly interested in the molecular dialog between the bacteria and the human host, and how signaling between them affects the outcome of infection. Specific virulence factors such as the secreted toxin streptolysin O and its co-toxin NAD-glycohydrolase (NADase) inhibit uptake and killing of GAS by professional phagocytes (macrophages and neutrophils) and epithelial cells. Recent work in the lab has discovered that SLO and NADase prevent intracellular killing of GAS by blocking maturation of autophagosomes in epithelial cells and by inhibiting phagosomal acidification in macrophages. Current studies are focused on identifying receptors for SLO and NADase and understanding how specific interactions with host cell surface molecules and between the toxins control intoxication of target cells. Research in collaboration with the laboratory of Isaac Chiu is investigating how streptolysin S stimulates pain neurons during invasive infection and impairs host defense.

The expression of these and other virulence determinants is regulated by the CsrRS (CovRS) two-component system in response to specific environmental signals including the human cathelicidin antimicrobial peptide LL-37. Paradoxically, stimulation of LL-37 secretion as part of the host innate immune response appears to signal through CsrRS to upregulate multiple GAS virulence factors, thereby promoting a transition from asymptomatic mucosal colonization to invasive infection. The lab is investigating how the CsrRS system activates expression of certain genes and represses others, and how additional regulatory proteins modulate CsrRS-mediated control of gene expression.

Research Background

Michael Wessels received his MD from Duke University. He completed internship and residency at Beth Israel Hospital, Boston and a fellowship at Beth Israel and Brigham and Women's Hospitals.

 

Education

Medical School

Duke University
1979 Durham

Internship

Internal Medicine Beth Israel Deaconess Medical Center
1980 Boston MA

Residency

Internal Medicine Beth Israel Deaconess Medical Center
1982 Boston MA

Fellowship

Beth Israel Deaconess Medical Center
1982 Boston MA

Fellowship

Infectious Diseases Brigham & Women's Hospital/Beth Israel Deaconess Medical Center
1985 Boston MA

Publications

  1. Bacterial Sphingolipids Exacerbate Colitis by Inhibiting ILC3-derived IL-22 Production. Cell Mol Gastroenterol Hepatol. 2024; 18(2):101350. View Abstract
  2. Interplay between human STING genotype and bacterial NADase activity regulates inter-individual disease variability. Nat Commun. 2023 07 06; 14(1):4008. View Abstract
  3. Streptococcus pyogenes can support or inhibit growth of Haemophilus influenzae by supplying or restricting extracellular NAD. PLoS One. 2022; 17(9):e0270697. View Abstract
  4. Simultaneous Late, Late-Onset Group B Streptococcal Meningitis in Identical Twins. Clin Pediatr (Phila). 2023 02; 62(2):96-99. View Abstract
  5. Structure of the Streptococcus pyogenes NAD+ Glycohydrolase Translocation Domain and Its Essential Role in Toxin Binding to Oropharyngeal Keratinocytes. J Bacteriol. 2022 01 18; 204(1):e0036621. View Abstract
  6. Identification of Group A Streptococcus Genes Directly Regulated by CsrRS and Novel Intermediate Regulators. mBio. 2021 08 31; 12(4):e0164221. View Abstract
  7. Improved transformation efficiency of group A Streptococcus by inactivation of a type I restriction modification system. PLoS One. 2021; 16(4):e0248201. View Abstract
  8. RocA Binds CsrS To Modulate CsrRS-Mediated Gene Regulation in Group A Streptococcus. mBio. 2019 07 16; 10(4). View Abstract
  9. Streptolysin O Induces the Ubiquitination and Degradation of Pro-IL-1ß. J Innate Immun. 2019; 11(6):457-468. View Abstract
  10. Capsular Polysaccharide of Group A Streptococcus. Microbiol Spectr. 2019 01; 7(1). View Abstract
  11. Blocking Neuronal Signaling to Immune Cells Treats Streptococcal Invasive Infection. Cell. 2018 05 17; 173(5):1083-1097.e22. View Abstract
  12. Binding of NAD+-Glycohydrolase to Streptolysin O Stabilizes Both Toxins and Promotes Virulence of Group A Streptococcus. mBio. 2017 09 12; 8(5). View Abstract
  13. Inhibition of Inflammasome-Dependent Interleukin 1ß Production by Streptococcal NAD+-Glycohydrolase: Evidence for Extracellular Activity. mBio. 2017 07 18; 8(4). View Abstract
  14. NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus. PLoS Pathog. 2016 Mar; 12(3):e1005468. View Abstract
  15. Group A streptococcal bacteremia without a source is associated with less severe disease in children. Pediatr Infect Dis J. 2015 Apr; 34(4):447-9. View Abstract
  16. Choosing an antibiotic for skin infections. N Engl J Med. 2015 Mar 19; 372(12):1164-5. View Abstract
  17. Case records of the Massachusetts General Hospital. Case 6-2015. A 16-year-old boy with coughing spells. N Engl J Med. 2015 Feb 19; 372(8):765-73. View Abstract
  18. The human antimicrobial peptide LL-37 binds directly to CsrS, a sensor histidine kinase of group A Streptococcus, to activate expression of virulence factors. J Biol Chem. 2014 Dec 26; 289(52):36315-24. View Abstract
  19. Streptolysin O and NAD-glycohydrolase prevent phagolysosome acidification and promote group A Streptococcus survival in macrophages. mBio. 2014 Sep 16; 5(5):e01690-14. View Abstract
  20. BsaB, a novel adherence factor of group B Streptococcus. Infect Immun. 2014 Mar; 82(3):1007-16. View Abstract
  21. Streptolysin O and its co-toxin NAD-glycohydrolase protect group A Streptococcus from Xenophagic killing. PLoS Pathog. 2013; 9(6):e1003394. View Abstract
  22. Vitamin D and the human antimicrobial peptide LL-37 enhance group a streptococcus resistance to killing by human cells. mBio. 2012 Oct 23; 3(5). View Abstract
  23. CsrRS and environmental pH regulate group B streptococcus adherence to human epithelial cells and extracellular matrix. Infect Immun. 2012 Nov; 80(11):3975-84. View Abstract
  24. Regulation and function of pilus island 1 in group B streptococcus. J Bacteriol. 2012 May; 194(10):2479-90. View Abstract
  25. Signal transduction through CsrRS confers an invasive phenotype in group A Streptococcus. PLoS Pathog. 2011 Oct; 7(10):e1002361. View Abstract
  26. Clinical practice. Streptococcal pharyngitis. N Engl J Med. 2011 Feb 17; 364(7):648-55. View Abstract
  27. Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus. mBio. 2011; 2(1):e00332-10. View Abstract
  28. Inhibition of dendritic cell maturation by group A Streptococcus. J Infect Dis. 2009 Oct 01; 200(7):1152-61. View Abstract
  29. CsrRS regulates group B Streptococcus virulence gene expression in response to environmental pH: a new perspective on vaccine development. J Bacteriol. 2009 Sep; 191(17):5387-97. View Abstract
  30. Case records of the Massachusetts General Hospital. Case 2-2009. A 25-year-old man with pain and swelling of the right hand and hypotension. N Engl J Med. 2009 Jan 15; 360(3):281-90. View Abstract
  31. Induction of group A Streptococcus virulence by a human antimicrobial peptide. Proc Natl Acad Sci U S A. 2008 Oct 28; 105(43):16755-60. View Abstract
  32. PerR confers phagocytic killing resistance and allows pharyngeal colonization by group A Streptococcus. PLoS Pathog. 2008 Sep 05; 4(9):e1000145. View Abstract
  33. Burden and economic cost of group A streptococcal pharyngitis. Pediatrics. 2008 Feb; 121(2):229-34. View Abstract
  34. Variation in the group B Streptococcus CsrRS regulon and effects on pathogenicity. J Bacteriol. 2008 Mar; 190(6):1956-65. View Abstract
  35. Mg(2+) signalling defines the group A streptococcal CsrRS (CovRS) regulon. Mol Microbiol. 2007 Aug; 65(3):671-83. View Abstract
  36. The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn. J Immunol. 2006 Aug 01; 177(3):1956-66. View Abstract
  37. Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-alpha production in vitro and in vivo. Pediatr Res. 2006 Aug; 60(2):205-9. View Abstract
  38. Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells. Blood. 2006 Aug 15; 108(4):1284-90. View Abstract
  39. Enhancement of streptolysin O activity and intrinsic cytotoxic effects of the group A streptococcal toxin, NAD-glycohydrolase. J Biol Chem. 2006 Mar 24; 281(12):8216-23. View Abstract
  40. Changing epidemiology of acute rheumatic fever in the United States. Clin Infect Dis. 2006 Feb 15; 42(4):448-50. View Abstract
  41. The apoptotic response to pneumolysin is Toll-like receptor 4 dependent and protects against pneumococcal disease. Infect Immun. 2005 Oct; 73(10):6479-87. View Abstract
  42. Role of NADase in virulence in experimental invasive group A streptococcal infection. Infect Immun. 2005 Oct; 73(10):6562-6. View Abstract
  43. Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome". Proc Natl Acad Sci U S A. 2005 Sep 27; 102(39):13950-5. View Abstract
  44. Extracellular group A Streptococcus induces keratinocyte apoptosis by dysregulating calcium signalling. Cell Microbiol. 2005 Jul; 7(7):945-55. View Abstract
  45. Streptolysin S. J Infect Dis. 2005 Jul 01; 192(1):13-5. View Abstract
  46. Structural and genetic diversity of group B streptococcus capsular polysaccharides. Infect Immun. 2005 May; 73(5):3096-103. View Abstract
  47. Cytolysin-dependent evasion of lysosomal killing. Proc Natl Acad Sci U S A. 2005 Apr 05; 102(14):5192-7. View Abstract
  48. Regulation of virulence by a two-component system in group B streptococcus. J Bacteriol. 2005 Feb; 187(3):1105-13. View Abstract
  49. Interaction between complement regulators and Streptococcus pyogenes: binding of C4b-binding protein and factor H/factor H-like protein 1 to M18 strains involves two different cell surface molecules. J Immunol. 2004 Dec 01; 173(11):6899-904. View Abstract
  50. Selective impairment of TLR-mediated innate immunity in human newborns: neonatal blood plasma reduces monocyte TNF-alpha induction by bacterial lipopeptides, lipopolysaccharide, and imiquimod, but preserves the response to R-848. J Immunol. 2004 Oct 01; 173(7):4627-34. View Abstract
  51. Critical role of the complement system in group B streptococcus-induced tumor necrosis factor alpha release. Infect Immun. 2003 Nov; 71(11):6344-53. View Abstract
  52. The CsrR/CsrS two-component system of group A Streptococcus responds to environmental Mg2+. Proc Natl Acad Sci U S A. 2003 Apr 01; 100(7):4227-32. View Abstract
  53. Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. Proc Natl Acad Sci U S A. 2003 Feb 18; 100(4):1966-71. View Abstract
  54. Cytotoxic effects of streptolysin o and streptolysin s enhance the virulence of poorly encapsulated group a streptococci. Infect Immun. 2003 Jan; 71(1):446-55. View Abstract
  55. Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae. Proc Natl Acad Sci U S A. 2002 Sep 17; 99(19):12391-6. View Abstract
  56. NAD+-glycohydrolase acts as an intracellular toxin to enhance the extracellular survival of group A streptococci. Mol Microbiol. 2002 Apr; 44(1):257-69. View Abstract
  57. Group A Streptococcus tissue invasion by CD44-mediated cell signalling. Nature. 2001 Dec 06; 414(6864):648-52. View Abstract
  58. Absence of a cysteine protease effect on bacterial virulence in two murine models of human invasive group A streptococcal infection. Infect Immun. 2001 Nov; 69(11):6683-8. View Abstract
  59. Regulation of capsule gene expression by group A Streptococcus during pharyngeal colonization and invasive infection. Mol Microbiol. 2001 Oct; 42(1):61-74. View Abstract
  60. Functional analysis in type Ia group B Streptococcus of a cluster of genes involved in extracellular polysaccharide production by diverse species of streptococci. J Biol Chem. 2001 Jan 05; 276(1):139-46. View Abstract
  61. Human granulocytic ehrlichiosis presenting as facial diplegia in a 42-year-old woman. Clin Infect Dis. 2000 Nov; 31(5):1288-91. View Abstract
  62. CD44 as a receptor for colonization of the pharynx by group A Streptococcus. J Clin Invest. 2000 Oct; 106(8):995-1002. View Abstract
  63. Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection. Cell Microbiol. 2000 Aug; 2(4):283-92. View Abstract
  64. Characterization of the linkage between the type III capsular polysaccharide and the bacterial cell wall of group B Streptococcus. J Biol Chem. 2000 Mar 17; 275(11):7497-504. View Abstract
  65. Regulation of virulence factor expression in group A streptococcus. Trends Microbiol. 1999 Nov; 7(11):428-30. View Abstract
  66. Role of complement component C1q in the IgG-independent opsonophagocytosis of group B streptococcus. J Immunol. 1999 Sep 01; 163(5):2761-8. View Abstract
  67. Measurement of human antibodies to type III group B Streptococcus. Infect Immun. 1999 Aug; 67(8):4303-5. View Abstract
  68. Safety and immunogenicity of capsular polysaccharide-tetanus toxoid conjugate vaccines for group B streptococcal types Ia and Ib. J Infect Dis. 1999 Jan; 179(1):142-50. View Abstract
  69. Identification of csrR/csrS, a genetic locus that regulates hyaluronic acid capsule synthesis in group A Streptococcus. Mol Microbiol. 1998 Oct; 30(1):209-19. View Abstract
  70. Molecular analysis of the capsule gene region of group A Streptococcus: the hasAB genes are sufficient for capsule expression. J Bacteriol. 1998 Sep; 180(18):4955-9. View Abstract
  71. Molecular analysis of the role of the group A streptococcal cysteine protease, hyaluronic acid capsule, and M protein in a murine model of human invasive soft-tissue infection. J Clin Invest. 1998 Aug 01; 102(3):550-60. View Abstract
  72. Antibody responses in invasive group B streptococcal infection in adults. J Infect Dis. 1998 Aug; 178(2):569-72. View Abstract
  73. Structural properties of group B streptococcal type III polysaccharide conjugate vaccines that influence immunogenicity and efficacy. Infect Immun. 1998 May; 66(5):2186-92. View Abstract
  74. Hyaluronic acid capsule modulates M protein-mediated adherence and acts as a ligand for attachment of group A Streptococcus to CD44 on human keratinocytes. J Clin Invest. 1998 Apr 15; 101(8):1708-16. View Abstract
  75. Structure of the has operon promoter and regulation of hyaluronic acid capsule expression in group A Streptococcus. Mol Microbiol. 1998 Apr; 28(2):343-53. View Abstract
  76. Biology of streptococcal capsular polysaccharides. J Appl Microbiol. 1997 Oct; 83(S1):20S-31S. View Abstract
  77. Relative contributions of hyaluronic acid capsule and M protein to virulence in a mucoid strain of the group A Streptococcus. Infect Immun. 1997 Jan; 65(1):64-71. View Abstract
  78. Hyaluronic acid capsule modulates interactions of group A streptococci with human epidermal keratinocytes. Adv Exp Med Biol. 1997; 418:517-23. View Abstract
  79. Glycolipid intermediates in biosynthesis of group B streptococcal capsular polysaccharide. Adv Exp Med Biol. 1997; 418:623-5. View Abstract
  80. Role of complement and complement receptor C1qR in the antibody-independent killing of group B streptococcus. Adv Exp Med Biol. 1997; 418:941-3. View Abstract
  81. Regulation of hyaluronic acid capsule production by the has operon promoter in group A streptococci. Adv Exp Med Biol. 1997; 418:975-8. View Abstract
  82. Biology of streptococcal capsular polysaccharides. Soc Appl Bacteriol Symp Ser. 1997; 26:20S-31S. View Abstract
  83. Immune response to type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine. J Clin Invest. 1996 Nov 15; 98(10):2308-14. View Abstract
  84. Hyaluronic acid capsule and the role of streptococcal entry into keratinocytes in invasive skin infection. J Clin Invest. 1996 Nov 01; 98(9):1954-8. View Abstract
  85. Hyaluronate capsule and surface M protein in resistance to opsonization of group A streptococci. Infect Immun. 1996 May; 64(5):1495-501. View Abstract
  86. Characterization of cpsF and its product CMP-N-acetylneuraminic acid synthetase, a group B streptococcal enzyme that can function in K1 capsular polysaccharide biosynthesis in Escherichia coli. Mol Microbiol. 1996 Feb; 19(3):555-63. View Abstract
  87. Studies of group B streptococcal infection in mice deficient in complement component C3 or C4 demonstrate an essential role for complement in both innate and acquired immunity. Proc Natl Acad Sci U S A. 1995 Dec 05; 92(25):11490-4. View Abstract
  88. Cloning, sequence analysis and expression of the group A streptococcal guaB gene encoding inosine monophosphate dehydrogenase. Gene. 1995 Nov 07; 165(1):57-60. View Abstract
  89. Immunogenicity and protective activity in animals of a type V group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine. J Infect Dis. 1995 Apr; 171(4):879-84. View Abstract
  90. Identification of a gene similar to ABC transporters near the capsule synthesis region of the group A streptococcal chromosome. Dev Biol Stand. 1995; 85:231-5. View Abstract
  91. Characterization of the capsular polysaccharide genes of group B streptococci. Dev Biol Stand. 1995; 85:237-44. View Abstract
  92. Critical role of the group A streptococcal capsule in pharyngeal colonization and infection in mice. Proc Natl Acad Sci U S A. 1994 Dec 06; 91(25):12238-42. View Abstract
  93. Characterization of CMP-N-acetylneuraminic acid synthetase of group B streptococci. J Bacteriol. 1994 Dec; 176(23):7372-4. View Abstract
  94. Neonatal mouse protection against infection with multiple group B streptococcal (GBS) serotypes by maternal immunization with a tetravalent GBS polysaccharide-tetanus toxoid conjugate vaccine. Infect Immun. 1994 Aug; 62(8):3236-43. View Abstract
  95. Functional activity of antibodies to the group B polysaccharide of group B streptococci elicited by a polysaccharide-protein conjugate vaccine. Infect Immun. 1994 May; 62(5):1593-9. View Abstract
  96. Effects on virulence of mutations in a locus essential for hyaluronic acid capsule expression in group A streptococci. Infect Immun. 1994 Feb; 62(2):433-41. View Abstract
  97. Stimulation of protective antibodies against type Ia and Ib group B streptococci by a type Ia polysaccharide-tetanus toxoid conjugate vaccine. Infect Immun. 1993 Nov; 61(11):4760-6. View Abstract
  98. Capsular polysaccharide regulates neutrophil complement receptor interactions with type III group B streptococci. Infect Immun. 1993 Jul; 61(7):2866-71. View Abstract
  99. The changing spectrum of group B streptococcal disease. N Engl J Med. 1993 Jun 24; 328(25):1843-4. View Abstract
  100. Improving choice of prescribed antibiotics through concurrent reminders in an educational order form. Med Care. 1993 Jun; 31(6):552-8. View Abstract
  101. Identification of cpsD, a gene essential for type III capsule expression in group B streptococci. Mol Microbiol. 1993 May; 8(5):843-55. View Abstract
  102. Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism of type III group B streptococci. Infect Immun. 1992 Oct; 60(10):3986-93. View Abstract
  103. Group B Streptococcus type II polysaccharide-tetanus toxoid conjugate vaccine. Infect Immun. 1992 Oct; 60(10):4009-14. View Abstract
  104. Group B streptococcal opacity variants. J Bacteriol. 1992 Jun; 174(11):3739-49. View Abstract
  105. Identification of a genetic locus essential for capsule sialylation in type III group B streptococci. Infect Immun. 1992 Feb; 60(2):392-400. View Abstract
  106. Effects of chain length on the immunogenicity in rabbits of group B Streptococcus type III oligosaccharide-tetanus toxoid conjugates. J Clin Invest. 1992 Jan; 89(1):203-9. View Abstract
  107. Development of a vaccine against group B Streptococcus. An Esp Pediatr. 1991 Dec; 35 Suppl 47:125-6. View Abstract
  108. Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci. Proc Natl Acad Sci U S A. 1991 Oct 01; 88(19):8317-21. View Abstract
  109. The alpha-L-(1----2)-trirhamnopyranoside epitope on the group-specific polysaccharide of group B streptococci. Infect Immun. 1991 May; 59(5):1690-6. View Abstract
  110. Structural determination and immunochemical characterization of the type V group B Streptococcus capsular polysaccharide. J Biol Chem. 1991 Apr 15; 266(11):6714-9. View Abstract
  111. Correct structure of repeating unit of group B Streptococcus type III capsular polysaccharide. J Infect Dis. 1990 Dec; 162(6):1412. View Abstract
  112. Immunogenicity in animals of a polysaccharide-protein conjugate vaccine against type III group B Streptococcus. J Clin Invest. 1990 Nov; 86(5):1428-33. View Abstract
  113. Changing surgical antimicrobial prophylaxis practices through education targeted at senior department leaders. Infect Control Hosp Epidemiol. 1990 Nov; 11(11):578-83. View Abstract
  114. An oligosaccharide-tetanus toxoid conjugate vaccine against type III group B Streptococcus. J Biol Chem. 1990 Oct 25; 265(30):18278-83. View Abstract
  115. Molecular analysis of two group B streptococcal virulence factors. Semin Perinatol. 1990 Aug; 14(4 Suppl 1):22-9. View Abstract
  116. Definition of a bacterial virulence factor: sialylation of the group B streptococcal capsule. Proc Natl Acad Sci U S A. 1989 Nov; 86(22):8983-7. View Abstract
  117. Effect of hospitalwide change in clindamycin dosing schedule on clinical outcome. Rev Infect Dis. 1989 Jul-Aug; 11(4):619-24. View Abstract
  118. Antibody recognition of the type 14 pneumococcal capsule. Evidence for a conformational epitope in a neutral polysaccharide. J Exp Med. 1989 Jun 01; 169(6):2121-31. View Abstract
  119. Isolation and characterization of type IV group B Streptococcus capsular polysaccharide. Infect Immun. 1989 Apr; 57(4):1089-94. View Abstract
  120. Reduction of incorrect antibiotic dosing through a structured educational order form. Arch Intern Med. 1988 Aug; 148(8):1720-4. View Abstract
  121. A model of high-affinity antibody binding to type III group B Streptococcus capsular polysaccharide. Proc Natl Acad Sci U S A. 1987 Dec; 84(24):9170-4. View Abstract
  122. Transposon mutagenesis of type III group B Streptococcus: correlation of capsule expression with virulence. Proc Natl Acad Sci U S A. 1987 Oct; 84(20):7208-12. View Abstract
  123. Structure and immunochemistry of an oligosaccharide repeating unit of the capsular polysaccharide of type III group B Streptococcus. A revised structure for the type III group B streptococcal polysaccharide antigen. J Biol Chem. 1987 Jun 15; 262(17):8262-7. View Abstract
  124. Immunochemical analysis of the types Ia and Ib group B streptococcal polysaccharides. J Immunol. 1985 Dec; 135(6):4164-70. View Abstract
  125. Molecular size affects antigenicity of type III, group B Streptococcus capsular polysaccharide. Trans Assoc Am Physicians. 1985; 98:384-91. View Abstract
  126. Selective alteration in high affinity agonist binding: a mechanism of beta-adrenergic receptor desensitization. Mol Pharmacol. 1979 Jul; 16(1):10-20. View Abstract

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