ABOUT THE RESEARCHER

OVERVIEW

Robert Husson is interested in understanding the molecular pathogenesis of Mycobacterium tuberculosis infection, particularly the means by which the bacterium adapts to its host. Understanding the means by which the bacterium adapts to the host can identify novel anti-bacterial targets for the design of new therapeutics. The Husson laboratory has focused on two aspects of microbial adaptation:

  • A major area of research in the Husson laboratory is the regulation of transcription by M. tuberculosis. We have characterized several sigma factors of M. tuberculosis, including SigE and SigH that are important in the response to oxidative and other stresses. Ongoing work indicates that these regulators are important in the response to starvation, oxidative and nitrosative stresses, and other challenges that are likely to be encountered during infection.
  • The second major area of Dr. Husson's research focuses on signal transduction pathways of M. tuberculosis. In addition to the typical bacterial two-component signal transduction systems, the bacterium has genes encoding 11 eukaryotic-like serine/ threonine kinases. We are investigating two of these kinases, which are essential and appear to regulate cell division. We are working to identify the in vivo targets of these kinases, the signals that activate them, and to determine the function of these molecules in M. tuberculosis physiology. Using chemical biology and genetic approaches we are investigating the broad effects of these kinases on M. tuberculosis physiology.

In addition to this research on gene regulation and signal transduction, we have collaborated with the Woychik laboroatory at Rutgers to characterize several toxin-antitoxin systems of M. tuberculosis that play a role in growth arrest. The Husson laboratory has also undertaken translational research relevant to new approaches for the diagnosis and treatment of tuberculosis.

BACKGROUND

Robert Husson received his MD from Harvard Medical School. He completed an internship, residency, and fellowship at Boston Children's Hospital. He undertook additional research training at Whitehead Institute and the National Institutes of Health prior to returning Boston Children’s Hospital.

Selected Publications

  1. Kang C-M, Abbott DW, Park ST, Dascher CC, Cantley LC, Husson RN. The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape. Genes Dev 2005; 19: 1692-1704.
  2. Park ST, Kang C-M, Husson RN. Regulation of the SigH stress response regulon by an essential protein kinase in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 2008; 105:13105-13110.
  3. Prisic A, Dankwa S, Schwartz D, Chou MF, Locasale J, Kang C-M, Bemis G, Church GM, Steen S, Husson RN. Extensive phosphorylation with overlapping specificity by Mycobacterium tuberculosis serine/threonine protein kinases Proc Natl Acad Sci USA 2010: 107:7521-7526. PMID: 20368441
  4. Mir M, Asong J, Li X, Cardot J, Boons G-J, Husson RN. The Extracellular domain of the Mycobacterium tuberculosis Ser/Thr Kinase PknB binds specific muropeptides and is required for PknB Localization. PLoS Pathogens 2011; 7:e1002182. PMID: 21829358.
  5. Schifano JM, Edifor R, Ouyang M, Sharp JD, Konkimalla A, Husson RN, Woychik NA. Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site. Proc Natl Acad Sci USA 2013;110:8501-8506. PMID:23650345.
  6. Singh AK, Carette X, Potluri L-P, Sharp JD, Xu R, Prisic S, Husson RN. Investigating essential gene function in Mycobacterium tuberculosis using an efficient CRISPR interference system. Nucl Acids Res 2016; doi: 10.1093/nar/gkw625. PMID:27407107.
  7. Carette X, Platig J, Young DC, Helmel M, Young A, Wang Z, Potluri L-P, Stuver MoodyC, Zeng J, Prisic S, Paulson J, Muntel J, Madduri AVR, Velarde J, Mayfield JA, Locher C, Wang T, Quackenbush J, Rhee KY, Moody DB, Steen H, Husson RN. Multisystems analysis of Mycobacterium tuberculosis reveals kinase-dependent remodeling of the pathogen-environment interface. mBio 2018; 9:e02333-17.

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis. NPJ Syst Biol Appl. 2021 Jan 29; 7(1):8. View abstract
  2. MRSA septic pulmonary emboli presenting as isolated focal chest pain in an adolescent. Radiol Case Rep. 2020 Nov; 15(11):2406-2409. View abstract
  3. Protein kinases PknA and PknB independently and coordinately regulate essential Mycobacterium tuberculosis physiologies and antimicrobial susceptibility. PLoS Pathog. 2020 04; 16(4):e1008452. View abstract
  4. BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny. Front Microbiol. 2020; 11:332. View abstract
  5. Licensed Bacille Calmette-Guérin (BCG) formulations differ markedly in bacterial viability, RNA content and innate immune activation. Vaccine. 2020 02 24; 38(9):2229-2240. View abstract
  6. Correction for Mir et al., "Mycobacterial Gene cuvA Is Required for Optimal Nutrient Utilization and Virulence". Infect Immun. 2019 Aug; 87(8). View abstract
  7. Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome. Nat Commun. 2019 07 10; 10(1):3035. View abstract
  8. Accurate target identification for Mycobacterium tuberculosis endoribonuclease toxins requires expression in their native host. Sci Rep. 2019 04 11; 9(1):5949. View abstract
  9. Multisystem Analysis of Mycobacterium tuberculosis Reveals Kinase-Dependent Remodeling of the Pathogen-Environment Interface. mBio. 2018 03 06; 9(2). View abstract
  10. A Comprehensive Study of the Interaction between Peptidoglycan Fragments and the Extracellular Domain of Mycobacterium tuberculosis Ser/Thr Kinase PknB. Chembiochem. 2017 11 02; 18(21):2094-2098. View abstract
  11. Investigating essential gene function in Mycobacterium tuberculosis using an efficient CRISPR interference system. Nucleic Acids Res. 2016 Oct 14; 44(18):e143. View abstract
  12. Comprehensive Definition of the SigH Regulon of Mycobacterium tuberculosis Reveals Transcriptional Control of Diverse Stress Responses. PLoS One. 2016; 11(3):e0152145. View abstract
  13. tRNA is a new target for cleavage by a MazF toxin. Nucleic Acids Res. 2016 Feb 18; 44(3):1256-70. View abstract
  14. Growth-regulating Mycobacterium tuberculosis VapC-mt4 toxin is an isoacceptor-specific tRNase. Nat Commun. 2015 Jul 09; 6:7480. View abstract
  15. Zinc regulates a switch between primary and alternative S18 ribosomal proteins in Mycobacterium tuberculosis. Mol Microbiol. 2015 Jul; 97(2):263-80. View abstract
  16. Mycobacterium tuberculosis Serine/Threonine Protein Kinases. Microbiol Spectr. 2014 Oct; 2(5). View abstract
  17. Phosphorylation regulates mycobacterial proteasome. J Microbiol. 2014 Sep; 52(9):743-54. View abstract
  18. Mycobacterial gene cuvA is required for optimal nutrient utilization and virulence. Infect Immun. 2014 Oct; 82(10):4104-17. View abstract
  19. Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site. Proc Natl Acad Sci U S A. 2013 May 21; 110(21):8501-6. View abstract
  20. Using bacteria to determine protein kinase specificity and predict target substrates. PLoS One. 2012; 7(12):e52747. View abstract
  21. Growth and translation inhibition through sequence-specific RNA binding by Mycobacterium tuberculosis VapC toxin. J Biol Chem. 2012 Apr 13; 287(16):12835-47. View abstract
  22. A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity. PLoS One. 2012; 7(2):e31307. View abstract
  23. Good outcome with early empiric treatment of neural larva migrans due to Baylisascaris procyonis. Pediatrics. 2012 Mar; 129(3):e806-11. View abstract
  24. The extracytoplasmic domain of the Mycobacterium tuberculosis Ser/Thr kinase PknB binds specific muropeptides and is required for PknB localization. PLoS Pathog. 2011 Jul; 7(7):e1002182. View abstract
  25. A modified immunoblot method to identify substrates of protein kinases. J Microbiol. 2011 Jun; 49(3):499-501. View abstract
  26. Extensive phosphorylation with overlapping specificity by Mycobacterium tuberculosis serine/threonine protein kinases. Proc Natl Acad Sci U S A. 2010 Apr 20; 107(16):7521-6. View abstract
  27. Nitrile-inducible gene expression in mycobacteria. Tuberculosis (Edinb). 2009 Jan; 89(1):12-6. View abstract
  28. Regulation of the SigH stress response regulon by an essential protein kinase in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2008 Sep 02; 105(35):13105-10. View abstract
  29. The mRNA interferases, MazF-mt3 and MazF-mt7 from Mycobacterium tuberculosis target unique pentad sequences in single-stranded RNA. Mol Microbiol. 2008 Aug; 69(3):559-69. View abstract
  30. Wag31, a homologue of the cell division protein DivIVA, regulates growth, morphology and polar cell wall synthesis in mycobacteria. Microbiology (Reading). 2008 Mar; 154(Pt 3):725-735. View abstract
  31. Critical role of a single position in the -35 element for promoter recognition by Mycobacterium tuberculosis SigE and SigH. J Bacteriol. 2008 Mar; 190(6):2227-30. View abstract
  32. Molecular basis of the defective heat stress response in Mycobacterium leprae. J Bacteriol. 2007 Dec; 189(24):8818-27. View abstract
  33. Leaving on the lights: host-specific derepression of Mycobacterium tuberculosis gene expression by anti-sigma factor gene mutations. Mol Microbiol. 2006 Dec; 62(5):1217-9. View abstract
  34. Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and nonribosomal peptide synthetase genes and down regulates virulence-associated surface lipid synthesis. J Bacteriol. 2006 Dec; 188(24):8460-8. View abstract
  35. The Mycobacterium tuberculosis extracytoplasmic-function sigma factor SigL regulates polyketide synthases and secreted or membrane proteins and is required for virulence. J Bacteriol. 2005 Oct; 187(20):7062-71. View abstract
  36. The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape. Genes Dev. 2005 Jul 15; 19(14):1692-704. View abstract
  37. Pharmacokinetics of didanosine and drug resistance mutations in infants exposed to zidovudine during gestation or postnatally and treated with didanosine or zidovudine in the first three months of life. Pediatr Infect Dis J. 2005 Jun; 24(6):503-9. View abstract
  38. Transcription regulation by the Mycobacterium tuberculosis alternative sigma factor SigD and its role in virulence. J Bacteriol. 2004 Oct; 186(19):6605-16. View abstract
  39. Tuberculosis prevention in college students. J Am Coll Health. 2004 Sep-Oct; 53(2):53-8. View abstract
  40. Development of a model of focal pneumococcal pneumonia in young rats. J Immune Based Ther Vaccines. 2004 Jan 23; 2(1):2. View abstract
  41. RshA, an anti-sigma factor that regulates the activity of the mycobacterial stress response sigma factor SigH. Mol Microbiol. 2003 Nov; 50(3):949-59. View abstract
  42. The alternative sigma factor SigH regulates major components of oxidative and heat stress responses in Mycobacterium tuberculosis. J Bacteriol. 2001 Oct; 183(20):6119-25. View abstract
  43. Novel mycobacterium related to Mycobacterium triplex as a cause of cervical lymphadenitis. J Clin Microbiol. 2001 Apr; 39(4):1227-30. View abstract
  44. Related strains of Mycobacterium avium cause disease in children with AIDS and in children with lymphadenitis. J Infect Dis. 2000 Apr; 181(4):1298-303. View abstract
  45. Nontuberculous mycobacterial infection of the head and neck in immunocompetent children: CT and MR findings. AJNR Am J Neuroradiol. 1999 Nov-Dec; 20(10):1829-35. View abstract
  46. Multidrug-resistant tuberculosis meningitis: clinical problems and concentrations of second-line antituberculous medications. Ann Pharmacother. 1999 Nov; 33(11):1184-8. View abstract
  47. A mycobacterial extracytoplasmic sigma factor involved in survival following heat shock and oxidative stress. J Bacteriol. 1999 Jul; 181(14):4266-74. View abstract
  48. In vivo transposition of mariner-based elements in enteric bacteria and mycobacteria. Proc Natl Acad Sci U S A. 1999 Feb 16; 96(4):1645-50. View abstract
  49. Lymphadenitis due to nontuberculous mycobacteria in children: presentation and response to therapy. Clin Infect Dis. 1999 Jan; 28(1):123-9. View abstract
  50. Lack of acceptance of guidelines for prevention of disseminated Mycobacterium avium complex infection in infants and children infected with human immunodeficiency virus. Pediatr Infect Dis J. 1998 Dec; 17(12):1131-5. View abstract
  51. Homologous recombination in Mycobacterium smegmatis. Screening methods for detection of gene replacement. Methods Mol Biol. 1998; 101:199-206. View abstract
  52. A mycobacterial extracytoplasmic function sigma factor involved in survival following stress. J Bacteriol. 1997 May; 179(9):2922-9. View abstract
  53. Vertical transmission of human immunodeficiency virus type 1: autologous neutralizing antibody, virus load, and virus phenotype. J Pediatr. 1995 Jun; 126(6):865-71. View abstract
  54. Clinical and pharmacokinetic evaluation of long-term therapy with didanosine in children with HIV infection. Pediatrics. 1994 Nov; 94(5):724-31. View abstract
  55. Pharmacokinetic evaluation of the combination of zidovudine and didanosine in children with human immunodeficiency virus infection. J Pediatr. 1994 Jul; 125(1):142-6. View abstract
  56. Orally administered clarithromycin for the treatment of systemic Mycobacterium avium complex infection in children with acquired immunodeficiency syndrome. J Pediatr. 1994 May; 124(5 Pt 1):807-14. View abstract
  57. Zidovudine and didanosine combination therapy in children with human immunodeficiency virus infection. Pediatrics. 1994 Feb; 93(2):316-22. View abstract
  58. The uraA locus and homologous recombination in Mycobacterium bovis BCG. J Bacteriol. 1993 Nov; 175(22):7282-9. View abstract
  59. High-level resistance to zidovudine but not to zalcitabine or didanosine in human immunodeficiency virus from children receiving antiretroviral therapy. J Pediatr. 1993 Jul; 123(1):9-16. View abstract
  60. Pancreatitis in human immunodeficiency virus-infected children receiving dideoxyinosine. Pediatrics. 1993 Apr; 91(4):747-51. View abstract
  61. Human immunodeficiency virus (HIV) type 1 strain MN neutralizing antibody in HIV-infected children: correlation with clinical status and prognostic value. J Infect Dis. 1993 Mar; 167(3):538-46. View abstract
  62. Changes in drug sensitivity of human immunodeficiency virus type 1 during therapy with azidothymidine, dideoxycytidine, and dideoxyinosine: an in vitro comparative study. Proc Natl Acad Sci U S A. 1993 Jan 15; 90(2):562-6. View abstract
  63. Cerebral artery aneurysms in children infected with human immunodeficiency virus. J Pediatr. 1992 Dec; 121(6):927-30. View abstract
  64. Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection. J Pediatr. 1992 Nov; 121(5 Pt 1):797-802. View abstract
  65. Defining the population of human immunodeficiency virus-infected children at risk for Mycobacterium avium-intracellulare infection. J Pediatr. 1992 Nov; 121(5 Pt 1):677-83. View abstract
  66. Phase I study of continuous-infusion soluble CD4 as a single agent and in combination with oral dideoxyinosine therapy in children with symptomatic human immunodeficiency virus infection. J Pediatr. 1992 Oct; 121(4):627-33. View abstract
  67. Smooth muscle tumors in children with human immunodeficiency virus infection. Pediatrics. 1992 Sep; 90(3):460-3. View abstract
  68. CD4 status and P24 antigenemia. Are they useful predictors of survival in HIV-infected children receiving antiretroviral therapy? Am J Dis Child. 1992 Aug; 146(8):932-6. View abstract
  69. Pseudomonas infections in children with human immunodeficiency virus infection. Pediatr Infect Dis J. 1992 Jul; 11(7):547-53. View abstract
  70. The use of nucleoside analogues in the treatment of HIV-infected children. AIDS Res Hum Retroviruses. 1992 Jun; 8(6):1059-64. View abstract
  71. Treatment of aggressive cytomegalovirus retinitis with ganciclovir in combination with foscarnet in a child infected with human immunodeficiency virus. J Pediatr. 1992 Mar; 120(3):483-6. View abstract
  72. Retinal toxicity in human immunodeficiency virus-infected children treated with 2',3'-dideoxyinosine. Am J Ophthalmol. 1992 Jan 15; 113(1):1-7. View abstract
  73. Clinical pharmacology of 2',3'-dideoxyinosine in human immunodeficiency virus-infected children. J Infect Dis. 1992 Jan; 165(1):99-104. View abstract
  74. Pneumocystis carinii pneumonia despite prophylaxis in children with human immunodeficiency virus infection. J Pediatr. 1991 Dec; 119(6):992-4. View abstract
  75. Bacterial infections in human immunodeficiency virus type 1-infected children: the impact of central venous catheters and antiretroviral agents. Pediatr Infect Dis J. 1991 Nov; 10(11):813-9. View abstract
  76. Dideoxyinosine in children with symptomatic human immunodeficiency virus infection. N Engl J Med. 1991 Jan 17; 324(3):137-44. View abstract
  77. Drug trial benefited HIV children. Nurs Times. 1991 Jan 30-Feb 5; 87(5):10. View abstract
  78. Dideoxycytidine alone and in an alternating schedule with zidovudine in children with symptomatic human immunodeficiency virus infection. J Pediatr. 1990 Nov; 117(5):799-808. View abstract
  79. Diagnosis of human immunodeficiency virus infection in infants and children. Pediatrics. 1990 Jul; 86(1):1-10. View abstract
  80. Gene replacement and expression of foreign DNA in mycobacteria. J Bacteriol. 1990 Feb; 172(2):519-24. View abstract
  81. In vivo and in vitro characterization of murine T-cell clones reactive to Mycobacterium tuberculosis. Infect Immun. 1987 Sep; 55(9):2223-9. View abstract
  82. Genes for the major protein antigens of Mycobacterium tuberculosis: the etiologic agents of tuberculosis and leprosy share an immunodominant antigen. Proc Natl Acad Sci U S A. 1987 Mar; 84(6):1679-83. View abstract
  83. Human T cell clones recognize two abundant Mycobacterium tuberculosis protein antigens expressed in Escherichia coli. J Immunol. 1987 Feb 01; 138(3):927-31. View abstract
  84. Cloning and direct examination of a structurally abnormal human beta 0-thalassemia globin gene. Proc Natl Acad Sci U S A. 1980 Jun; 77(6):3558-62. View abstract