Charles R. Farber

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.

Associate Professor
Public Health Sciences
P.O. Box 800717
Charlottesville, VA 22908
Telephone: 434-243-8584
Fax: 434-924-1312
Email: crf2s@virginia.edu
Website: http://farberlab.com/

Education

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

Research Interests

Systems Genetics of Skeletal Development and Maintenance

Selected Publications

  • Sabik OL, Medrano JF, Farber CR, Genetic Dissection of a QTL Affecting Bone Geometry., 2017; G3 (Bethesda, Md.). 7(3) 865-870. PMID: 28082324 | PMCID: PMC5345717
  • Ganta VC, Choi MH, Kutateladze A, Fox TE, Farber CR, Annex BH, A MicroRNA93-Interferon Regulatory Factor-9-Immunoresponsive Gene-1-Itaconic Acid Pathway Modulates M2-Like Macrophage Polarization to Revascularize Ischemic Muscle., 2017; Circulation. 135(24) 2403-2425. PMID: 28356443 | PMCID: PMC5503157
  • Sabik OL, Farber CR, Using GWAS to identify novel therapeutic targets for osteoporosis., 2016; Translational research : the journal of laboratory and clinical medicine. 181() 15-26. PMID: 27837649 | PMCID: PMC5357198
  • Calabrese G, Mesner LD, Foley PL, Rosen CJ, Farber CR, Network Analysis Implicates Alpha-Synuclein (Snca) in the Regulation of Ovariectomy-Induced Bone Loss., 2016; Scientific reports. 6() 29475. PMID: 27378017 | PMCID: PMC4932518
  • Calabrese GM, Mesner LD, Stains JP, Tommasini SM, Horowitz MC, Rosen CJ, Farber CR, Integrating GWAS and Co-expression Network Data Identifies Bone Mineral Density Genes SPTBN1 and MARK3 and an Osteoblast Functional Module., 2016; Cell systems. 4(1) 46-59.e4. PMID: 27866947 | PMCID: PMC5269473
  • Pisarska MD, Akhlaghpour M, Lee B, Barlow GM, Xu N, Wang ET, Mackey AJ, Farber CR, Rich SS, Rotter JI, Chen YI, Goodarzi MO, Guller S, Williams J, Optimization of techniques for multiple platform testing in small, precious samples such as human chorionic villus sampling., 2016; Prenatal diagnosis. 36(11) 1061-1070. PMID: 27718505 | PMCID: PMC5142835
  • Gillespie AL, Teoh J, Lee H, Prince J, Stadnisky MD, Anderson M, Nash W, Rival C, Wei H, Gamache A, Farber CR, Tung K, Brown MG, Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection., 2016; PLoS pathogens. 12(2) e1005419. PMID: 26845690 | PMCID: PMC4742223
  • Lusis AJ, Seldin MM, Allayee H, Bennett BJ, Civelek M, Davis RC, Eskin E, Farber CR, Hui S, Mehrabian M, Norheim F, Pan C, Parks B, Rau CD, Smith DJ, Vallim T, Wang Y, Wang J, The Hybrid Mouse Diversity Panel: a resource for systems genetics analyses of metabolic and cardiovascular traits., 2016; Journal of lipid research. 57(6) 925-42. PMID: 27099397 | PMCID: PMC4878195
  • Li C, Zhen G, Chai Y, Xie L, Crane JL, Farber E, Farber CR, Luo X, Gao P, Cao X, Wan M, RhoA determines lineage fate of mesenchymal stem cells by modulating CTGF-VEGF complex in extracellular matrix., 2016; Nature communications. 7() 11455. PMID: 27126736 | PMCID: PMC4855537
  • Frey JL, Li Z, Ellis JM, Zhang Q, Farber CR, Aja S, Wolfgang MJ, Clemens TL, Riddle RC, Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast., 2015; Molecular and cellular biology. 35(11) 1979-91. PMID: 25802278 | PMCID: PMC4420919
  • Orozco LD, Morselli M, Rubbi L, Guo W, Go J, Shi H, Lopez D, Furlotte NA, Bennett BJ, Farber CR, Ghazalpour A, Zhang MQ, Bahous R, Rozen R, Lusis AJ, Pellegrini M, Epigenome-wide association of liver methylation patterns and complex metabolic traits in mice., 2015; Cell metabolism. 21(6) 905-17. PMID: 26039453 | PMCID: PMC4454894
  • Zheng HF, Forgetta V, Hsu YH, Estrada K, Rosello-Diez A, Leo PJ, Dahia CL, Park-Min KH, Tobias JH, Kooperberg C, Kleinman A, Styrkarsdottir U, Liu CT, Uggla C, Evans DS, Nielson CM, Walter K, Pettersson-Kymmer U, McCarthy S, Eriksson J, Kwan T, Jhamai M, Trajanoska K, Memari Y, Min J, Huang J, Danecek P, Wilmot B, Li R, Chou WC, Mokry LE, Moayyeri A, Claussnitzer M, Cheng CH, Cheung W, Medina-Gómez C, Ge B, Chen SH, Choi K, Oei L, Fraser J, Kraaij R, Hibbs MA, Gregson CL, Paquette D, Hofman A, Wibom C, Tranah GJ, Marshall M, Gardiner BB, Cremin K, Auer P, Hsu L, Ring S, Tung JY, Thorleifsson G, Enneman AW, van Schoor NM, de Groot LC, van der Velde N, Melin B, Kemp JP, Christiansen C, Sayers A, Zhou Y, Calderari S, van Rooij J, Carlson C, Peters U, Berlivet S, Dostie J, Uitterlinden AG, Williams SR, Farber C, Grinberg D, LaCroix AZ, Haessler J, Chasman DI, Giulianini F, Rose LM, Ridker PM, Eisman JA, Nguyen TV, Center JR, Nogues X, Garcia-Giralt N, Launer LL, Gudnason V, Mellström D, Vandenput L, Amin N, van Duijn CM, Karlsson MK, Ljunggren Ö, Svensson O, Hallmans G, Rousseau F, Giroux S, Bussière J, Arp PP, Koromani F, Prince RL, Lewis JR, Langdahl BL, Hermann AP, Jensen JE, Kaptoge S, Khaw KT, Reeve J, Formosa MM, Xuereb-Anastasi A, Åkesson K, McGuigan FE, Garg G, Olmos JM, Zarrabeitia MT, Riancho JA, Ralston SH, Alonso N, Jiang X, Goltzman D, Pastinen T, Grundberg E, Gauguier D, Orwoll ES, Karasik D, Davey-Smith G, Smith AV, Siggeirsdottir K, Harris TB, Zillikens MC, van Meurs JB, Thorsteinsdottir U, Maurano MT, Timpson NJ, Soranzo N, Durbin R, Wilson SG, Ntzani EE, Brown MA, Stefansson K, Hinds DA, Spector T, Cupples LA, Ohlsson C, Greenwood CM, Jackson RD, Rowe DW, Loomis CA, Evans DM, Ackert-Bicknell CL, Joyner AL, Duncan EL, Kiel DP, Rivadeneira F, Richards JB, Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture., 2015; Nature. 526(7571) 112-7. PMID: 26367794 | PMCID: PMC4755714
  • Dokun AO, Chen L, Okutsu M, Farber CR, Hazarika S, Jones WS, Craig D, Marchuk DA, Lye RJ, Shah SH, Annex BH, ADAM12: a genetic modifier of preclinical peripheral arterial disease., 2015; American journal of physiology. Heart and circulatory physiology. 309(5) H790-803. PMID: 26163448 | PMCID: PMC4591412
  • Mesner LD, Ray B, Hsu YH, Manichaikul A, Lum E, Bryda EC, Rich SS, Rosen CJ, Criqui MH, Allison M, Budoff MJ, Clemens TL, Farber CR, Bicc1 is a genetic determinant of osteoblastogenesis and bone mineral density., 2014; The Journal of clinical investigation. () . PMID: 24789909 | PMCID: PMC4038574
  • Farber CR, Reich A, Barnes AM, Becerra P, Rauch F, Cabral WA, Bae A, Quinlan A, Glorieux FH, Clemens TL, Marini JC, A Novel IFITM5 Mutation in Severe Atypical Osteogenesis Imperfecta Type VI Impairs Osteoblast Production of Pigment Epithelium-Derived Factor., 2014; Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. () . PMID: 24519609
  • Calabrese G, Bennett BJ, Orozco L, Kang HM, Eskin E, Dombret C, De Backer O, Lusis AJ, Farber CR, Systems genetic analysis of osteoblast-lineage cells., 2013; PLoS genetics. 8(12) e1003150. PMID: 23300464 | PMCID: PMC3531492
  • Orozco LD, Bennett BJ, Farber CR, Ghazalpour A, Pan C, Che N, Wen P, Qi HX, Mutukulu A, Siemers N, Neuhaus I, Yordanova R, Gargalovic P, Pellegrini M, Kirchgessner T, Lusis AJ, Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages., 2012; Cell. 151(3) 658-70. PMID: 23101632 | PMCID: PMC3513387
  • Farber CR, Bennett BJ, Orozco L, Zou W, Lira A, Kostem E, Kang HM, Furlotte N, Berberyan A, Ghazalpour A, Suwanwela J, Drake TA, Eskin E, Wang QT, Teitelbaum SL, Lusis AJ, Mouse genome-wide association and systems genetics identify Asxl2 as a regulator of bone mineral density and osteoclastogenesis., 2011; PLoS genetics. 7(4) e1002038. PMID: 21490954 | PMCID: PMC3072371
  • Bennett BJ, Farber CR, Orozco L, Kang HM, Ghazalpour A, Siemers N, Neubauer M, Neuhaus I, Yordanova R, Guan B, Truong A, Yang WP, He A, Kayne P, Gargalovic P, Kirchgessner T, Pan C, Castellani LW, Kostem E, Furlotte N, Drake TA, Eskin E, Lusis AJ, A high-resolution association mapping panel for the dissection of complex traits in mice., 2010; Genome research. 20(2) 281-90. PMID: 20054062 | PMCID: PMC2813484
  • Hsu YH, Zillikens MC, Wilson SG, Farber CR, Demissie S, Soranzo N, Bianchi EN, Grundberg E, Liang L, Richards JB, Estrada K, Zhou Y, van Nas A, Moffatt MF, Zhai G, Hofman A, van Meurs JB, Pols HA, Price RI, Nilsson O, Pastinen T, Cupples LA, Lusis AJ, Schadt EE, Ferrari S, Uitterlinden AG, Rivadeneira F, Spector TD, Karasik D, Kiel DP, An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits., 2010; PLoS genetics. 6(6) e1000977. PMID: 20548944 | PMCID: PMC2883588