Case Western Reserve University

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

Research in the laboratory focuses on drug discovery and drug screening to combat infectious diseases, heart disease and cancer.
Methicillin-Resistant Staphylococcus aureus (MRSA) is a serious pathogen that kills 100,000 per year in the US. It is resistant to most antibiotics and it is widespread in hospitals as well as in the community. Our goal is not to develop new antibiotics but to screen for drugs that will prevent toxin secretion and biofilm formation, thereby rendering the bacteria harmless. The approach is based on inhibiting key elements in the biosynthetic pathway of toxin production. We are using virtual screening of large numbers of small-molecule compounds in order to reduce the number of compounds subjected to activity assays. Another line of research focuses on drug screening against malaria. The idea is to inhibit blood-stage invasion of the parasite Plasmodium vivax.
Yet another project is geared towards drugs against congestive heart failure. Vaptans (vasopressin receptor antagonists) are a new class of drugs currently in clinical trials against congestive heart failure. Our goal is to elucidate the structural determinants responsible for the specificity of these drugs to different subtypes of the vasopressin receptor located in the heart and in the kidneys. In this way drugs could be designed to be active in one or the other tissues or in both. We have recently determined the crystal structure of an adhesin from the major bacterial component in dental plaque that causes periodontal disease.

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)
• Kiran MD, Vijayarangan Adikesavan N, Cirioni O, Giacometti A, Silvestri C, Scalise G, Ghiselli R, Saba V, Orlando F, Shoham M and Balaban N.
  “Discovery of a quorum sensing inhibitor of drug resistant staphylococcal infections by structure-based virtual screening.”
  Mol Pharmacol 73,1578-1586 (2008)
• Macion-Dazard R, Callahan N, Xu Z, Wu N, Thibonnier M and 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)
• Wu N, Hanson SM, Francis DJ, Vishnivetskiy SA, Thibonnier M, Klug CS, Shoham M, and Gurevich VV.
  “Arrestin binding to calmodulin: a direct interaction between two ubiquitous signaling proteins.”
  J. Mol. Biol. 364, 955-963 (2006)