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Biochemistry Department - Primary Faculty

Menachem Shoham, Ph.D.

Associate Professor

Education

  • Ph.D.: The Weizmann Institute of Science, Rehovot, Israel
  • Postdoc:Yale University, Department of Molecular Biophysics and Biochemistry

Research Interests

Current research in the laboratory focuses on drug discovery and drug screening to combat infectious diseases.
Methicillin-Resistant Staphylococcus Aureus (MRSA) is the most prevalent bacterial pathogen in the developed world causing an annual mortality rate of 20,000 in the US alone.  MRSA is resistant to most antibiotics and it is widespread in hospitals as well as in the community where it infects even healthy people such as athletes.
Multi-drug resistant Acinetobacter baumannii (MDR-Ab) poses a serious public health threat. The only effective antibiotic against this pathogen has severe side effects. The discovery of new treatment options against MDR-Ab represents an unmet medical need.
Our goal is not to develop new antibiotics but to screen for drugs that will prevent the formation of virulence factors, such as toxins and biofilm, thus disarming the pathogen of its deadly weapons. Since such antivirulence agents will not endanger the survival of the bacteria, resistance is not anticipated to be as severe a problem as with antibiotics.
The approach is based on inhibiting key elements in the biosynthetic pathway of toxin and biofilm production. We are using virtual screening of large numbers of small-molecule compounds in order to select the most promising candidates for activity assays in vitro.
More potent compounds are developed from a series of initial hits by synthetic chemistry and structure-activity relationship studies. The efficacy of these lead compounds is subsequently tested in insect and rodent infection model.

Selected References

  • Nithianatham S, Xu M, Yamada M, Ikegami A, Shoham M and Han YW.
    “Crystal structure of FadA adhesin from fusobacterium nucleatum reveals a novel oligomerization motif: The leucine chain.”
    J Biol Chem 284, 3865-3872 (2009)
  • Témoin S, Wu KL, Wu V, Shoham M, Han YW.
    “Signal peptide of FadA adhesin from Fusobacterium nucleatum plays a novel structural role by modulating the filament's length and width.”
    FEBS Lett 586, 1-6 (2012)

    Siddiqui A, Xainli J, Schloegel J, Carias L, Ntumngia F, Shoham M, Casey J, Foley M, Adams J, King C.
    “Fine Specificity of Plasmodium vivax Duffy Binding Protein Binding Engagement of the Duffy Antigen on Human Erythrocytes.”
    Infect Immun 80, 2920-8 (2012)

    Shoham M.
    “Anti-virulence agents against MRSA.”
    Future Med Chem 3, 775-777 (2011)

    Fardini Y, Wang X, Témoin S, Nithianantham S, Lee D, Shoham M, Han YW. “Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity.”
    Mol Microbi 82, 1468-80 (2011)

    Saks JT, Truitt B, Shoham M.
    “Specificity of Three Vasopressin Receptor Antagonists.”
    Letters in Drug Design & Discovery 8,529-535 (2011)

    Stone MJ, Chuang S, Hou X, Shoham M, Zhu JZ.
    “Tyrosine sulfation: an increasingly recognised post-translational modification of secreted proteins.”
    N Bioctechnol 25, 299-317 (2009)

    Nithianatham S, Xu M, Yamada M, Ikegami A, Shoham M, Han YW.
    “Crystal structure of FadA adhesin from Fusobacterium nucleatum reveals a novel oligomerization motif: The leucine chain.”
    J Biol Chem 284, 3865-3872 (2009)

    Kiran MD, Vijayarangan  Adikesavan N, Cirioni O, Giacometti A, Silvestri AC,  Scalise G, Ghiselli R, Saba V, Orlando F, Shoham M, Balaban N.
    “Discovery of a quorum sensing inhibitor of drug resistant staphylococcal infections by structure-based virtual screening.”
    Mol Pharmacol 73, 1578-1586 (2008)

    Wu N, Hanson SM, Francis DJ, Vishnivetskiy SA, Thibonnier M, Klug CS, Shoham M, Gurevich VV.
    “Arrestin binding to calmodulin: a direct interaction between two ubiquitous signaling proteins.”
    J Mol Biol 364, 955-963 (2006)

    Macion-Dazard R, Callahan N, Xu Z, Wu N, Thibonnier M, Shoham M.
    “Mapping the binding site of six nonpeptide antagonists to the human V2-renal vasopressin receptor.”
    J Pharmacol Exp Ther 316, 564-571 (2006)

    Wu N, Macion-Dazard R, Nithianantham S, Xu Z, Hanson SM, Vishnivetskiy SA, Gurevich VV, Thibonnier M and Shoham M.
    Soluble mimics of the cytoplasmic face of the human V1-vascular vasopressin receptor bind arrestin2 and calmodulin.
    Mol Pharmacol 70:249-258 (2006)

    M. Thibonnier, P. Coles, A. Thibonnier, and M. Shoham.
    “Molecular pharmacology and modeling of vasopressin receptors.”
    Prog Brain Res 139, 179-96 (2002)

    He Y, Lin F, Chipman PR, Bator CM, Baker TS, Shoham M, Kuhn RJ, Medof ME, Rossmann MG.
    Structure of decay-accelerating factor bound to echovirus 7: a virus-receptor complex.
    Proc Natl Acad Sci U S A 99, 10325-9 (2002)

    Soelaiman S, Jakes K, Wu N, Li C, Shoham M.
    “Crystal structure of colicin E3: Implications for cell entry and ribosome inactivation.”
    Mol Cell 8, 1053-1062 (2001)

Menachem Shoham Faculty's publications at pubmed