Olivier Lichtarge, M.D., Ph.D.
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Positions
- Cullen Chair and Professor
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Molecular and Human Genetics
Baylor College of Medicine
- Professor
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Biochemistry & Molecular Biology
Baylor College of Medicine
- Professor
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Pharmacology
Baylor College of Medicine
- Cullen Foundation Chair and Director
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Computational and Integrative Biomedical Research Center
Baylor College of Medicine
- Co-Director
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Program in Structural & Computational Biology and Molecular Biophysics
Baylor College of Medicine
- Member
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Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
Education
- BS from McGill University
- 01/1980 - Montreal, Quebec Canada
- PhD from Stanford University
- 01/1987 - Stanford, California United States
- MD from Stanford University School Of Medicine
- 01/1990 - Stanford, California United States
- Residency at University Of California, San Francisco Affiliate Hospitals
- 01/1993 - San Francisco, California United States
- Internal Medicine
- Fellowship at University Of California, San Francisco Affiliate Hospitals
- 01/1996 - San Francisco, CA United States
- Endocrinology
- Post-Doctoral Fellowship at University Of California, San Francisco
- 01/1997 - San Francisco, California United States
Honors & Awards
- Fellow, American Association for the Advancement of Science
- 11/2019
- Michael E. DeBakey Excellence in Research Award
- 07/2015
- Raymond and Beverley Sackler Fellowship, IHES
- France (01/2005)
- Basil O’Connor Award, March of Dimes
- 01/2001
- American Heart Association Faculty Development Award
- 01/1999
- American Heart Association Postdoctoral Fellowship
- 01/1997
- Dorothy Penrose Stout Fellowship Award, American Heart Association
- California Affiliate (01/1995)
Professional Interests
- Cognitive computing towards multi-scale data integration and rational design of multi-drug therapies.
Professional Statement
Our lab marries computation with experiments to understand the molecular evolution of genes and pathways—how their functions may become corrupted by genetic mistakes or how they may be re-engineered to new designs. Technically, we draw upon a wide range of disciplines to address fundamental questions in structural biology, clinical genomics and precision medicine. Over the long-term, we hope to discover new therapeutic paths and improve screening and early detection to preserve health and also to harness the synthetic potential of organisms for biotechnology. In the short-term we seek to interpret the mutational action of human genome variations and pinpoint the genes that drive complex diseases.Starting from structural bioinformatics, our algorithms broadly merge mathematical and evolutionary principles. They enable multi-scale data integration and, in favorable conditions, precise control of molecular functions. This has led to discoveries across diverse systems, including G protein signaling, malaria, cancer and neurological disorders. Newer interests include network theory, text-mining and cognitive computing. Specific examples include a network compression scheme that made tractable the diffusion of information across nearly 400 species. This approach uncovered a possible mechanism for the best drug against malaria. Other network studies, reasoned over the entire PubMed literature to discover new kinases and protein interactions for p53.
A recent promising line of research quantifies the evolutionary action (EA) of mutations on fitness to make a bridge between molecular biology and population genetics. EA correlates with experimental loss of function in proteins; with morbidity and mortality in people; and with purifying gene selection in populations. In head and neck cancer patients, EA stratifies outcomes and suggests alternate therapy for some patients. In autism, the mutational EA burden correlated with the depth of cognitive harm (IQ). In the future, we hope to unite these different approaches into a coherent path to compute precision therapy and personalized risk based on each patient’s unique profile of genome variations.
Websites
Selected Publications
- Koire A, Katsonis P, Kim YW, Buchovecky C, Wilson SJ, Lichtarge O "A method to delineate de novo missense variants across pathways prioritizes genes linked to autism.." Sci Transl Med.. 2021;13:eabc1739.
- Kim YW, Al-Ramahi I, Koire A, Wilson SJ, Konecki DM, Mota S, Soleimani S, Botas J, Lichtarge O "Harnessing the paradoxical phenotypes of APOE ɛ2 and APOE ɛ4 to identify genetic modifiers in Alzheimer’s disease.." Alzheimers Dement.. 2021;17:831-846.
- Choi BK, Dayaram T, Parikh N, Wilkins A, Nagarajan M, Novikov I, (…), Lichtarge O "Literature-Based Automated Discovery of Tumor Suppressor p53 Phosphorylation and Inhibition by NEK2." PNAS. 2021;115:10666-10671.
- Cancer Genome Atlas Research Network "Comprehensive and Integrative Genomics Characterization of Hepatocellular Carcinoma.." Cell. 2017;169:1327-41.
- Marciano DC, Lua RC, Herman C, Lichtarge O "Cooperativity of Negative Autoregulation Confers Increased Mutational Robustness.." Phys Rev Lett.. 2016;116:258104.
- Osman AA, Neskey DM, Katsonis P, Patel AA, Ward AM, Hsu TK, Hicks SC, McDonald TO, Ow TJ, Alves MO, Pickering CR, Skinner HD, Zhao M, Sturgis EM, Kies MS, El-Naggar A, Perrone F, Licitra L, Bossi P, Kimmel M, Frederick MJ, Lichtarge O, Myers JN "Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients." Cancer Res. 2015 Apr 1;75:1205-15. Pubmed PMID: 25691460
- Neskey DM, Osman AA, Ow TJ, Katsonis P, McDonald T, Hicks SC, Hsu TK, Pickering CR, Ward A, Patel A, Yordy JS, Skinner HD, Giri U, Sano D, Story MD, Beadle BM, El-Naggar AK, Kies MS, William WN, Caulin C, Frederick M, Kimmel M, Myers JN, Lichtarge O "Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer." Cancer Res. 2015 Apr 1;75:1527-36. Pubmed PMID: 25634208
- Peterson SM, Pack TF, Wilkins AD, Urs NM, Urban DJ, Bass CE, Lichtarge O, Caron MG "Elucidation of G-protein and β-arrestin functional selectivity at the dopamine D2 receptor." Proc Natl Acad Sci U S A. 2015 Jun 2;122:7097-102. Pubmed PMID: 25964346
- M Nagarajan* , AD Wilkins*, BJ. Bachman*,..., S Spangler*, O Lichtarge "Predicting Future Scientific Discoveries Based on a Networked Analysis of the Past Literature." Proceedings of the 21th ACM SIGKDD internatio. 2015;
- Spangler S, Wilkins AD, Bachman BJ, Nagarajan M, Dayaram T, Haas P, (...), Lichtarge O "Automated hypothesis generation based on mining scientific literature.." Proceedings of the 20th ACM SIGKDD internatio. 2014;
- Katsonis P, Lichtarge O "A formal perturbation between genotype and phenotype determines the evolutionary action of protein coding variations on fitness." Genome Res. 2014 Sep 12; Pubmed PMID: 25217195
- Lisewski AM, Quiros JP, Ng CL, Adikesavan AK, Miura K, Putluri N, Eastman RT, Scanfeld D, Regenbogen SJ, Altenhofen L, Llinás M, Sreekumar A, Long C, Fidock DA, Lichtarge O "Supergenomic network compression and the discovery of EXP1 as a glutathione transferase inhibited by artesunate." Cell. 2014 Aug 14;158(4):916-28. Pubmed PMID: 25126794
- Marciano DC, Lua RC, Katsonis P, Amin SR, Herman C,Lichtarge O "Negative feedback in genetic circuits confers evolutionary resilience and capacitance." Cell Rep. 2014 Jun 26;7(6):1789-95. Pubmed PMID: 24910431
- Kang HJ, Menlove K, Ma J, Wilkins A, Lichtarge O, Wensel TG "Selectivity and evolutionary divergence of metabotropic glutamate receptors for endogenous ligands and G proteins coupled to phospholipase C or TRP channels." J Biol Chem. 2014 Sep 5; Pubmed PMID: 25193666
- Baker SA, Chen L, Wilkins AD, Yu P, Lichtarge O, Zoghbi HY "An AT-Hook Domain in MeCP2 Determines the Clinical Course of Rett Syndrome and Related Disorders." Cell. 2013 Feb 28;152(5):984-96. Pubmed PMID: 23452848
- Shoji-Kawata S, Sumpter R, Leveno M, Lichtarge O, et al. and Levine B "Identification of a candidate therapeutic autophagy-inducing peptide." Nature. 2013 Feb 14;494(7436):201-6. Pubmed PMID: 23364696
- Adikesavan AK, Katsonis P, Marciano DC, Lua R, Herman C, Lichtarge O "Separation of Recombination and SOS Response in Escherichia coli RecA Suggests LexA Interaction Sites." PLoS Genet. 2011 Sep;7(9):e1002244. Pubmed PMID: 21912525
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