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Structural and Computational Biology and Molecular Biophysics

Houston, Texas

A BCM research lab.
Structural and Computational Biology & Molecular Biophysics
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Olivier Lichtarge, M.D., Ph.D.

Professor, Molecular and Human Genetics, Biochemistry and Molecular Biology

Co-Director of SCBMB Graduate ProgramOlivier Lichtarge, M.D., Ph.D.

SCBMB Executive Committee Member

Baylor College of Medicine

Education:

B.S. Math. & Physics, McGill University (1980)
Ph.D. Biophysics, Stanford (1987), M.D., Stanford (1990)
Post Doc. Molecular Pharmacology, UCSF (1997)
Internal Medicine, UCSF (1993); Endocrinology, UCSF (1996)

Research Interests:

Our lab in the Department of Molecular and Human Genetics marries computation with experiments to study three areas of protein structure-function: the molecular basis of protein catalysis and interaction, the design of peptides and proteins, and the annotation of protein sequence and structure. In each case, our long-term goals are to engineer proteins or peptides to probe and then rationally disrupt protein pathways.

To guide experiments, we rely on an integrated computational analysis of the evolution of protein sequences, structures, and functions. This phylogenomic strategy is called the Evolutionary Trace (ET) and, most simply, it assigns to each sequence residue a relative score of “functional importance”. From this we can formulate hypotheses on the molecular determinants of activity and specificity, and rationally target experiments to the most relevant sites of a protein.

Current computational projects focus on data integration on a proteomic scale with the ultimate goal to discover the function of novel proteins. Our experimental focus is on the general manipulationg of cellular pathways by engineering specific perturbations of protein-protein interactions. In our own wet lab and through collaborations this is done in the context of G protein signaling, nuclear receptors, and kinases. In these proteins of pharmaceutical interest, our the hope is that computation and design can together lead to novel drug targets and, eventually, to novel approaches for the development of therapeutics.

More details on our website, plus access to the Evolutionary Trace Server for functional site discovery in protein structures.

Selected Publications:

  • Erdin S, Venner E, Lisewski AM and Lichtarge O. Function prediction from networks of local evolutionary similarity in protein structure. BMC Bioinformatics, 14 Suppl 3:S6 (2013). PubMed
  • Baker SA, Chen L, Wilkins AD, Yu P, Lichtarge O and Zoghbi HY. An AT-hook domain in MeCP2 determines the clinical course of Rett syndrome and related disorders. Cell, 152(5):984-96 (2013). PubMed
  • Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ and Rosenberg SM. Identity and function of a large gene network underlying mutagenic repair of DNA breaks. Science, 338(6112):1344-8 (2012). PubMed
  • Bachman BJ, Venner E, Rua C, Erdin S and Lichtarge O. ETAscape: analyzing protein networks to predict enzymatic function and substrates in Cytoscape. Bioinformatics, 28(16):2186-8, (2012). PubMed
  • Wilkins AD, Bachman BJ, Erdin S and Lichtarge O. The use of evolutionary patterns in protein annotation. Curre Opin Struct Biol, 22(3):316-25 (2012). PubMed
  • Wilkins A, Erdin S, Lua R and Lichtarge O. Evolutionary trace for prediction and redesign of protein functional sites. Methods Mol Biol, 819:29-42 (2012). PubMed
  • Adikesavan AK, Katsonis P, Marciano DC, Lua R, Herman C and Lichtarge O. Separation of recombination and SOS response in Escherichia coli RecA suggests LexA interaction sites. PLoS Genet, 7(9):e1002244 (2011). PubMed

For more publications, see listing on PubMed.

Contact Information:

Department: Molecular and Human Genetics, and Biochemistry and Molecular Biology
Address: Baylor College of Medicine
One Baylor Plaza
Room T921
Houston, TX 77030
Phone: 713-798-5646
Fax: 713-798-1116
E-mail: lichtarge@bcm.edu
Additional Links: Lichtarge Computational Biology Lab, Molecular and Human Genetics

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