Charles R. Farber

Education

  • BS, Western Kentucky University
  • MS, Michigan State University
  • PhD, University of California, Davis
  • Postdoc, University of California, Los Angeles

Primary Appointment

  • Assistant Professor, Public Health Sciences

Contact

Research Interest(s)

Genetics of complex disease, with an emphasis on osteoporosis; Genetics of gene expression; Systems biology of complex disease; Mouse models of complex disease

Research Description

Genetics of complex disease Common diseases, such as osteoporosis, impart significant societal health burdens.  These diseases are, in part, regulated by genetic determinants and understanding their genetic basis is critical to the development of effective therapeutics.  In recent years, technological advances, such as sequencing the genomes of multiple species and the ability to perform bioassays in a massively parallel fashion, have made it possible to begin to understand disease in a systems context.  Systems-biology attempts to determine the direct and interactive roles of all cellular and physiological components (transcripts, proteins, metabolites, etc.) in diseased and normal states using data from high-throughput genomic studies.   Our lab is using systems approaches to investigate the molecular basis of bone strength.  The goal of this work is to combine genetics and global gene expression profiling in the mouse to identify genes and pathways which influence bone strength related traits using techniques such as causality modeling between expression and physiological traits and generating disease focused gene co-expression networks.  An additional component of this work is testing hypotheses generated by systems-analyses using in vitro cell based assays and transgenic mouse models.

Selected Publications

  • Farber C, Reich A, Barnes A, Becerra P, Rauch F, Cabral W, Bae A, Quinlan A, Glorieux F, Clemens T, Marini J. A Novel IFITM5 Mutation in Severe Atypical Osteogenesis Imperfecta Type VI Impairs Osteoblast Production of Pigment Epithelium-Derived Factor. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014. PMID: 24519609
  • Guntur A, Le P, Farber C, Rosen C. Bioenergetics during calvarial osteoblast differentiation reflect strain differences in bone mass. Endocrinology. 2014; en20131974. PMID: 24437492
  • Wang L, Lu W, Zhang L, Huang Y, Scheib R, Liu X, Myers L, Lu L, Farber C, Liu G, Wang C, Deng H, Williams R, Wang Y, Gu W, Jiao Y. Trps1 Differentially Modulates the Bone Mineral Density between Male and Female Mice and Its Polymorphism Associates with BMD Differently between Women and Men. PloS one. 2014;9(1): e84485. PMID: 24416236
  • Systems-level analysis of genome-wide association data. G3 (Bethesda, Md.). 2013;3(1): 119-29. PMID: 23316444
  • Calabrese G, Bennett B, Orozco L, Kang H, Eskin E, Dombret C, De Backer O, Lusis A, Farber C. Systems genetic analysis of osteoblast-lineage cells. PLoS genetics. 2013;8(12): e1003150. PMID: 23300464
  • Hazarika S, Farber C, Dokun A, Pitsillides A, Wang T, Lye R, Annex B. MicroRNA-93 controls perfusion recovery after hindlimb ischemia by modulating expression of multiple genes in the cell cycle pathway. Circulation. 2013;127(17): 1818-28. PMID: 23559675
  • Leamy L, Kelly S, Hua K, Farber C, Pomp D. Quantitative trait loci for bone mineral density and femoral morphology in an advanced intercross population of mice. Bone. 2013;55(1): 222-9. PMID: 23486184
  • Systems genetics: a novel approach to dissect the genetic basis of osteoporosis. Current osteoporosis reports. 2012;10(3): 228-35. PMID: 22802146 | PMCID: PMC3422742
  • Casellas J, Gularte R, Farber C, Varona L, Mehrabian M, Schadt E, Lusis A, Attie A, Yandell B, Medrano J. Genome scans for transmission ratio distortion regions in mice. Genetics. 2012;191(1): 247-59. PMID: 22367040 | PMCID: PMC3338264
  • Furlotte N, Kang E, Van Nas A, Farber C, Lusis A, Eskin E. Increasing association mapping power and resolution in mouse genetic studies through the use of meta-analysis for structured populations. Genetics. 2012;191(3): 959-67. PMID: 22505625 | PMCID: PMC3389987
  • Ghazalpour A, Rau C, Farber C, Bennett B, Orozco L, van Nas A, Pan C, Allayee H, Beaven S, Civelek M, Davis R, Drake T, Friedman R, Furlotte N, Hui S, Jentsch J, Kostem E, Kang H, Kang E, Joo J, Korshunov V, Laughlin R, Martin L, Ohmen J, Parks B, Pellegrini M, Reue K, Smith D, Tetradis S, Wang J, Wang Y, Weiss J, Kirchgessner T, Gargalovic P, Eskin E, Lusis A, LeBoeuf R. Hybrid mouse diversity panel: a panel of inbred mouse strains suitable for analysis of complex genetic traits. Mammalian genome : official journal of the International Mammalian Genome Society. 2012;23(9): 680-92. PMID: 22892838 | PMCID: NIHMS416512
  • Orozco L, Bennett B, Farber C, Ghazalpour A, Pan C, Che N, Wen P, Qi H, Mutukulu A, Siemers N, Neuhaus I, Yordanova R, Gargalovic P, Pellegrini M, Kirchgessner T, Lusis A. Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages. Cell. 2012;151(3): 658-70. PMID: 23101632 | PMCID: PMC3513387
  • DeAtley K, Rincon G, Farber C, Medrano J, Luna-Nevarez P, Enns R, VanLeeuwen D, Silver G, Thomas M. Genetic analyses involving microsatellite ETH10 genotypes on bovine chromosome 5 and performance trait measures in Angus- and Brahman-influenced cattle. Journal of animal science. 2011;89(7): 2031-41. PMID: 21357449
  • Farber C, Bennett B, Orozco L, Zou W, Lira A, Kostem E, Kang H, Furlotte N, Berberyan A, Ghazalpour A, Suwanwela J, Drake T, Eskin E, Wang Q, Teitelbaum S, Lusis A. Mouse genome-wide association and systems genetics identify Asxl2 as a regulator of bone mineral density and osteoclastogenesis. PLoS genetics. 2011;7(4): e1002038. PMID: 21490954 | PMCID: PMC3072371
  • Farber C, Kelly S, Baruch E, Yu D, Hua K, Nehrenberg D, de Villena F, Buus R, Garland T, Pomp D. Identification of quantitative trait loci influencing skeletal architecture in mice: emergence of Cdh11 as a primary candidate gene regulating femoral morphology. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2011;26(9): 2174-83. PMID: 21638317 | PMCID: PMC3304441
  • Ghazalpour A, Bennett B, Petyuk V, Orozco L, Hagopian R, Mungrue I, Farber C, Sinsheimer J, Kang H, Furlotte N, Park C, Wen P, Brewer H, Weitz K, Camp D, Pan C, Yordanova R, Neuhaus I, Tilford C, Siemers N, Gargalovic P, Eskin E, Kirchgessner T, Smith D, Smith R, Lusis A. Comparative analysis of proteome and transcriptome variation in mouse. PLoS genetics. 2011;7(6): e1001393. PMID: 21695224 | PMCID: PMC3111477
  • Park C, Gale G, de Jong S, Ghazalpour A, Bennett B, Farber C, Langfelder P, Lin A, Khan A, Eskin E, Horvath S, Lusis A, Ophoff R, Smith D. Gene networks associated with conditional fear in mice identified using a systems genetics approach. BMC systems biology. 2011;5 43. PMID: 21410935 | PMCID: PMC3070648
  • de Jong S, Kas M, Kiernan J, de Mooij-van Malsen A, Oppelaar H, Janson E, Vukobradovic I, Farber C, Stanford W, Ophoff R. Hippocampal gene expression analysis highlights Ly6a/Sca-1 as candidate gene for previously mapped novelty induced behaviors in mice. PloS one. 2011;6(6): e20716. PMID: 21673958 | PMCID: PMC3108967
  • Identification of a gene module associated with BMD through the integration of network analysis and genome-wide association data. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2010;25(11): 2359-67. PMID: 20499364
  • Bennett B, Farber C, Orozco L, Kang H, Ghazalpour A, Siemers N, Neubauer M, Neuhaus I, Yordanova R, Guan B, Truong A, Yang W, He A, Kayne P, Gargalovic P, Kirchgessner T, Pan C, Castellani L, Kostem E, Furlotte N, Drake T, Eskin E, Lusis A. A high-resolution association mapping panel for the dissection of complex traits in mice. Genome research. 2010;20(2): 281-90. PMID: 20054062
  • Hsu Y, Zillikens M, Wilson S, Farber C, Demissie S, Soranzo N, Bianchi E, Grundberg E, Liang L, Richards J, Estrada K, Zhou Y, van Nas A, Moffatt M, Zhai G, Hofman A, van Meurs J, Pols H, Price R, Nilsson O, Pastinen T, Cupples L, Lusis A, Schadt E, Ferrari S, Uitterlinden A, Rivadeneira F, Spector T, Karasik D, Kiel D. An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits. PLoS genetics. 2010;6(6): e1000977. PMID: 20548944 | PMCID: PMC2883588
  • Suwanwela J, Farber C, Haung B, Song B, Pan C, Lyons K, Lusis A. Systems genetics analysis of mouse chondrocyte differentiation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2010;26(4): 747-60. PMID: 20954177 | PMCID: PMC3179327
  • Verdugo R, Farber C, Warden C, Medrano J. Serious limitations of the QTL/microarray approach for QTL gene discovery. BMC biology. 2010;8 96. PMID: 20624276 | PMCID: PMC2919467
  • Casellas J, Farber C, Gularte R, Haus K, Warden C, Medrano J. Evidence of maternal QTL affecting growth and obesity in adult mice. Mammalian genome : official journal of the International Mammalian Genome Society. 2009;20(5): 269-80. PMID: 19399551
  • Casellas J, Farber C, Verdugo R, Medrano J. Segregation analysis of a sex ratio distortion locus in congenic mice. The Journal of heredity. 2009;101(3): 351-9. PMID: 20032064
  • Farber C, Aten J, Farber E, de Vera V, Gularte R, Islas-Trejo A, Wen P, Horvath S, Lucero M, Lusis A, Medrano J. Genetic dissection of a major mouse obesity QTL (Carfhg2): integration of gene expression and causality modeling. Physiological genomics. 2009;37(3): 294-302. PMID: 19336533
  • Farber C, Lusis A. Future of osteoporosis genetics: enhancing genome-wide association studies. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2009;24(12): 1937-42. PMID: 19888896
  • Rincon G, Farber E, Farber C, Nkrumah J, Medrano J. Polymorphisms in the STAT6 gene and their association with carcass traits in feedlot cattle. Animal genetics. 2009;40(6): 878-82. PMID: 19519791
  • Yang X, Deignan J, Qi H, Zhu J, Qian S, Zhong J, Torosyan G, Majid S, Falkard B, Kleinhanz R, Karlsson J, Castellani L, Mumick S, Wang K, Xie T, Coon M, Zhang C, Estrada-Smith D, Farber C, Wang S, van Nas A, Ghazalpour A, Zhang B, Macneil D, Lamb J, Dipple K, Reitman M, Mehrabian M, Lum P, Schadt E, Lusis A, Drake T. Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks. Nature genetics. 2009;41(4): 415-23. PMID: 19270708
  • Farber C, Chitwood J, Lee S, Verdugo R, Islas-Trejo A, Rincon G, Lindberg I, Medrano J. Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice. BMC genetics. 2008;9 34. PMID: 18439298
  • Farber C, Lusis A. Integrating global gene expression analysis and genetics. Advances in genetics. 2008;60 571-601. PMID: 18358333
  • Farber C, van Nas A, Ghazalpour A, Aten J, Doss S, Sos B, Schadt E, Ingram-Drake L, Davis R, Horvath S, Smith D, Drake T, Lusis A. An integrative genetics approach to identify candidate genes regulating BMD: combining linkage, gene expression, and association. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2008;24(1): 105-16. PMID: 18767929
  • Farber C, Medrano J. Dissection of a genetically complex cluster of growth and obesity QTLs on mouse chromosome 2 using subcongenic intercrosses. Mammalian genome : official journal of the International Mammalian Genome Society. 2007;18(9): 635-45. PMID: 17694346
  • Farber C, Corva P, Medrano J. Genome-wide isolation of growth and obesity QTL using mouse speed congenic strains. BMC genomics. 2006;7 102. PMID: 16670015
  • Farber C, Medrano J. Fine mapping reveals sex bias in quantitative trait loci affecting growth, skeletal size and obesity-related traits on mouse chromosomes 2 and 11. Genetics. 2006;175(1): 349-60. PMID: 17110492
  • Churchill G, Airey D, Allayee H, Angel J, Attie A, Beatty J, Beavis W, Belknap J, Bennett B, Berrettini W, Bleich A, Bogue M, Broman K, Buck K, Buckler E, Burmeister M, Chesler E, Cheverud J, Clapcote S, Cook M, Cox R, Crabbe J, Crusio W, Darvasi A, Deschepper C, Doerge R, Farber C, Forejt J, Gaile D, Garlow S, Geiger H, Gershenfeld H, Gordon T, Gu J, Gu W, de Haan G, Hayes N, Heller C, Himmelbauer H, Hitzemann R, Hunter K, Hsu H, Iraqi F, Ivandic B, Jacob H, Jansen R, Jepsen K, Johnson D, Johnson T, Kempermann G, Kendziorski C, Kotb M, Kooy R, Llamas B, Lammert F, Lassalle J, Lowenstein P, Lu L, Lusis A, Manly K, Marcucio R, Matthews D, Medrano J, Miller D, Mittleman G, Mock B, Mogil J, Montagutelli X, Morahan G, Morris D, Mott R, Nadeau J, Nagase H, Nowakowski R, O'Hara B, Osadchuk A, Page G, Paigen B, Paigen K, Palmer A, Pan H, Peltonen-Palotie L, Peirce J, Pomp D, Pravenec M, Prows D, Qi Z, Reeves R, Roder J, Rosen G, Schadt E, Schalkwyk L, Seltzer Z, Shimomura K, Shou S, Sillanp√§√§ M, Siracusa L, Snoeck H, Spearow J, Svenson K, Tarantino L, Threadgill D, Toth L, Valdar W, de Villena F, Warden C, Whatley S, Williams R, Wiltshire T, Yi N, Zhang D, Zhang M, Zou F. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nature genetics. 2004;36(11): 1133-7. PMID: 15514660
  • Farber C, Medrano J. Identification of putative homology between horse microsatellite flanking sequences and cross-species ESTs, mRNAs and genomic sequences. Animal genetics. 2004;35(1): 28-33. PMID: 14731226
  • Farber C, Raney N, Rilington V, Venta P, Ernst C. Comparative mapping of genes flanking the human chromosome 12 evolutionary breakpoint in the pig. Cytogenetic and genome research. 2004;102(1): 139-44. PMID: 14970693
  • Abiola O, Angel J, Avner P, Bachmanov A, Belknap J, Bennett B, Blankenhorn E, Blizard D, Bolivar V, Brockmann G, Buck K, Bureau J, Casley W, Chesler E, Cheverud J, Churchill G, Cook M, Crabbe J, Crusio W, Darvasi A, de Haan G, Dermant P, Doerge R, Elliot R, Farber C, Flaherty L, Flint J, Gershenfeld H, Gibson J, Gu J, Gu W, Himmelbauer H, Hitzemann R, Hsu H, Hunter K, Iraqi F, Jansen R, Johnson T, Jones B, Kempermann G, Lammert F, Lu L, Manly K, Matthews D, Medrano J, Mehrabian M, Mittlemann G, Mock B, Mogil J, Montagutelli X, Morahan G, Mountz J, Nagase H, Nowakowski R, O'Hara B, Osadchuk A, Paigen B, Palmer A, Peirce J, Pomp D, Rosemann M, Rosen G, Schalkwyk L, Seltzer Z, Settle S, Shimomura K, Shou S, Sikela J, Siracusa L, Spearow J, Teuscher C, Threadgill D, Toth L, Toye A, Vadasz C, Van Zant G, Wakeland E, Williams R, Zhang H, Zou F. The nature and identification of quantitative trait loci: a community's view. Nature reviews. Genetics. 2003;4(11): 911-6. PMID: 14634638
  • Farber C, Medrano J. Putative in silico mapping of DNA sequences to livestock genome maps using SSLP flanking sequences. Animal genetics. 2003;34(1): 11-8. PMID: 12580781
  • Farber C, Raney N, Kuhlers D, Nadarajah K, Ernst C. Mapping of porcine genetic markers generated by representational difference analysis. Animal biotechnology. 2003;14(1): 87-102. PMID: 12887183