HomeFacultyBruce Blumberg

Bruce Blumberg

Bruce Blumberg, Ph.D.
Professor

4351 Natural Science II
University of California Irvine
Irvine, CA 92697

Tel: (949) 824-8573
Fax: (949) 824-4709
Email:
blumberg@uci.edu
Website:
Lab Homepage

Hormonal signaling; Functional genomics – Researchers in the Blumberg laboratory study a family of ligand-modulated transcription factors, the nuclear hormone receptors, and their role in development, physiology and disease. Two receptors are particularly relevant to cancer – the retinoic acid receptors, RARs, and the steroid and xenobiotic receptor, SXR.

One long-standing interest in the laboratory concerns the interactions between nuclear receptor and growth factor signaling in important developmental patterning processes. Retinoic acid (RA) and fibroblast growth factors (FGFs) are critical factors that interact to mediate a variety of developmental processes. RA and FGF pathways are mutually inhibitory and this inhibition is important for key developmental processes such as sensory placode formation, neuronal differentiation, somite differentiation, anteroposterior and dorsoventral patterning and the proliferation of stem cells and cancer cells. The Blumberg lab seeks to understand the genetic program and molecular interactions underlying the mutual antagonism between RA and FGF signals in embryonic development and in stem cell differentiation.

A second major interest in the Blumberg laboratory concerns gene-environment interactions and the developmental basis of health and disease. Two receptors are of particular interest in this research, the steroid and xenobiotic receptor, SXR, and the peroxisome proliferator activated receptor gamma (PPARγ). SXR is the key mediator of the body’s response to endobiotics, dietary and xenobiotic chemicals. Differences in SXR underlie some of the known differences between humans and animals and among individuals in their ability to metabolize drugs and chemicals. SXR is also an important mediator of immune function and loss of SXR function leads to widespread inflammation and cancer. Activation of SXR leads to apoptosis of breast cancer cells and may have anti-cancer effects in other tissues.

Obesity and obesity-related disorders such as type 2 diabetes and coronary artery disease have become an epidemic of global proportions. Excessive consumption of calorie-dense food and diminished physical activity (the “Couch Potato model”) are the generally accepted causal factors for obesity. But can environmental factors play a role in exposing preexisting genetic differences or amplifying the effects of diet and excerise? Our “obesogen hypothesis” proposes the existence of environmental chemicals that can perturb lipid homeostasis, adipocyte development and adipose tissue function. We identified organotins as bona fide obesogens that cause adipocyte differentiation in vitro and fat accumulation in vivo. Moreover, prenatal exposure to organotins reprograms metabolism such that affected animals are predisposed to weight gain later in life, despite a normal diet. Understanding the role of these environmental obesogens in regulating fat cell development will provide important insights into a novel contributing factor for obesity.

Recent Publications                              

  • Janesick, A., Schug, T.T., Heindel, J.J., and Blumberg, B. (201x) Environmental pollutants and obesity. in Bray, G., and Bouchard, C. editors. Handbook of Obesity, 3rd Edition, Vol 1, in press.
  • Bergman A, Andersson AM, Becher G, van den Berg M, Blumberg B, Bjerregaard P, Bornehag CG, Bornman R, Brandt I, Brian JV, Casey SC, Fowler PA, Frouin H, Giudice LC, Iguchi T, Hass U, Jobling S, Juul A, Kidd KA, Kortenkamp A, Lind M, Martin OV, Muir D, Ochieng R, Olea N, Norrgren L, Ropstad E, Ross PS, Ruden C, Scheringer M, Skakkebaek NE, Soder O, Sonnenschein C, Soto A, Swan S, Toppari J, Tyler CR, Vandenberg LN, Vinggaard AM, Wiberg K, Zoeller RT. (2013) Science and policy on endocrine disrupters must not be mixed: a reply to a “common sense” intervention by toxicology journal editors. Environ Health 12(1): 69. PMCID: 3765603r  PMID:23981490
  • Goran MI, Dumke K, Bouret SG, Kayser B, Walker RW, Blumberg B. (2013) The obesogenic effect of high fructose exposure during early development. Nat Rev Endocrinol 9(8): 494-500.  PMID:23732284
  • Janesick, A., Abbey, R., Liu, S., Taketani, M., and Blumberg, B. (2013). ERF is a Retinoic Acid-Inducible Repressor Required for Primary Neurogenesis. Development, 140, 3095-3106.
  • Pueyo NC, Raub AG, Jackson S, Metz MM, Mount AC, Naughton KL, Eaton AL, Thomas NM, Hastings P, Greaves J, Blumberg B, Collins TJ, Sogo SG. (2013) Oxidation of Ethidium using TAML Activators: A Model for High School Research Performed in Partnership with University Scientists. J Chem Educ 90(3): 326-31. PMCID: 3622257  PMID:23585695
  • Chamorro-García R, Sahu M, Abbey RJ, Laude J, Pham N, Blumberg B. (2013) Transgenerational inheritance of prenatal obesogen exposure  Environ Health Perspect., 121, 349-366. PMCID:3621201, PMID:23322813.
  • Schug TT, Abagyan R, Blumberg B, Collins TJ, Crews D, DeFur PL, Dickerson SM, Edwards TM, Gore AC, Guillette LJ, Hayes T, Heindel JJ, Moores A, Patisaul HB, Tal TL, Thayer KA, Vandenberg LN, Warner JC, Watson CS, vom Saal FS, Zoeller RT, O’Brien KP, Myers JP. (2013) Designing endocrine disruption out of the next generation of chemicals. Green Chemistry 15, 181-198.
  • Li, X., Pham, H., Janesick, A., and Blumberg, B. (2012) Triflumizole is an environmental obesogen that acts through peroxisome proliferator activated receptor gamma (PPARγ). Environmental Health Perspectives, 120, 1720-1726. PMID:23086663.
  • Boekelheide, K., Blumberg, B., Chapin, R.E., Cote, I., Graziano, J.H., Janesick, A., Lane, R., Lillycrop, K., Myatt, L., States, J.C., Thayer, K., Waalkes., M.P., Rogers, J. (2012) Predicting later life outcomes of early-life exposures. Environmental Health Perspectives, 120, 1353-1361. PMID:22672778. PMCID: 3491941.
  • Chamorro-Garcia, R., Kirchner, S., Li, X., Janesick, A.S., Casey, S.C., Chow, C., and Blumberg, B. (2012). Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator activated receptor gamma-independent mechanism, Environmental Health Perspectives, 120, 984-989. PMID: 22763116
  • Henning, B., Ormsbee, L., McClain, C., Watkins, B.A., Blumberg, B., Bachas, L., Sanderson, W., Gatchett, A.M., Lambert, J.C., Thompson, C., Suk, W.A. (2012). Nutrition can modulate the toxicity of environmental pollutants: Implications in risk assessment and human health. Environmental Health Perspectives, 120, 771-4. PMID:22357258.
  • Janesick, A., and Blumberg, B. (2012) Obesogens, Stem Cells and the Developmental Programming of Obesity. Int. J. Andrology, 35, 437-48. PMCID: 3358413. PMID:22372658.
  • Casey, S.C. and Blumberg, B., (2012) The Steroid and Xenobiotic Receptor Negatively Regulates B-1 Cell Progenitors in the Fetal Liver. Molec. Endocrinol., 26, 916-25. PMCID: 3355537. PMID:22496360.
  • Igarashi K, Kitajima S, Aisaki K, Tanemura K, Taquahashi Y, Moriyama N, Ikeno E, Matsuda N, Saga Y, Blumberg B, Kanno J. (2012) Development of humanized steroid and xenobiotic receptor mouse by homologous knock-in of the human steroid and xenobiotic receptor ligand binding domain sequence. J Toxicol Sci. 37, :373-80. PMID:22467028.
  • Janesick, A., Shiotsugu, J., Taketani, M., and Blumberg, B. (2012) Ripply3 is a Retinoic Acid-Inducible Repressor Required for Setting the Borders of the Pre-placodal Ectoderm. Development, 139, 1213-1224 PMCID: 3283127. PMID:22354841.
  • Janesick A.S., Blumberg B. (2012) Adipocytes as Target Cells for Endocrine Disruption. In: Diamanti-Kandarakis E, Gore AC, editors. Endocrine Disrupters and Puberty. New York, NY: Humana Press/Springer; 2012. pp.255-271.
  • Schug, T.T., Janesick, A., Blumberg, B., and Heindel, J.J. (2011) Endocrine disrupting chemicals and disease susceptibility. J. Steroid Biochem.  Molec. Biol., 127, 204-215. PMCID:3220783, PMID:21899826.
  • Casey, S.C., Nelson, E.L., Turco, G.M., Janes, M.R., Fruman, D.A., and Blumberg, B. (2011) B-1 cell lymphoma in mice lacking the steroid and xenobiotic receptor, SXR. Molec Endocrinol, 25, 933-943.
  • Janesick A.S., Blumberg B. (2011) Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth Defects Research (Part C) Embryo Today. 93, 34-50. PMID:21425440
  • Li, X., Ycaza, J. and Blumberg, B. (2011). The environmental obesogen tributyltin chloride acts via peroxisome proliferator activated receptor gamma to induce adipogenesis in 3T3-L1 preadipocytes. J. Steroid Biochem. Molec. Biol., 127, 9-15 PMCID: 3281769. PMID: 21397693.
  • Janesick A.S., Blumberg B. (2011) PPARγ as the target of obesogens. Journal of Steroid Biochemistry and Molecular Biology.  127, 4-8. PMCID: 3116997. PMID: 21251979.
  • Blumberg, B., Iguchi, T., and Odermatt, A. (2011). Endocrine disrupting chemicals. J. Steroid Biochem. Molec. Biol., 127, 1-2, 1-3. PMID: 21839836.
  • Janesick A.S., Blumberg B. The Role of Environmental Obesogens in the Obesity Epidemic. In: Lustig RH, editor. Obesity Before Birth: Springer US; 2011. p. 383-399.
  • Blumberg B. (2011) Obesogens, stem cells and the maternal programming of obesity. Journal of Developmental Origins of Health and Disease. 2, 3-8. .
  • Azuma K, Casey SC, Ito M, Urano T, Horie K, Ouchi Y, Kirchner S, Blumberg B, Inoue S. (2010) Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption. J Endocrinol. 207(3):257-63. PMID: 20876238.
  • Ellis, W.C., Tran, C.T., Roy, R., Rusten, M., Fischer, A., Ryabov, A.D., Blumberg, B., and Collins, T.J. (2010). Designing green oxidation catalysts for purifying environmental waters. J. Am. Chem. Soc, 132(28):9774-81.
  • Hellsten U., Harland R. M., Gilchrist M. J., Hendrix D., Jurka J., Kapitonov V., Ovcharenko I., Putnam N. H., Shu S., Taher L., Blitz I. L., Blumberg B., Dichmann D. S., Dubchak I., Amaya E., Detter J. C., Fletcher R., Gerhard D. S., Goodstein D., Graves T., Grigoriev I. V., Grimwood J., Kawashima T., Lindquist E., Lucas S. M., Mead P. E., Mitros T., Ogino H., Ohta Y., Poliakov A. V., Pollet N., Robert J., Salamov A., Sater A. K., Schmutz J., Terry A., Vize P. D., Warren W. C., Wells D., Wills A., Wilson R. K., Zimmerman L. B., Zorn A. M., Grainger R., Grammer T., Khokha M. K., Richardson P. M., Rokhsar D. S. (2010) The genome of the Western clawed frog Xenopus tropicalis. Science. 328, 633-636. Faculty of 1000 – 4*
  • Chapman, J. A., Kirkness, E. F., Simakov, O., Hampson, S. E., Mitros, T., Weinmaier, T., Rattei, T., Balasubramanian, P. G., Borman, J., Busam, D., Disbennett, K., Pfannkoch, C., Sumin, N., Sutton, G. G., Viswanathan, L. D., Walenz, B., Goodstein, D. M., Hellsten, U., Kawashima, T., Prochnik, S. E., Putnam, N. H., Shu, S., Blumberg, B., Dana, C. E., Gee, L., Kibler, D. F., Law, L., Lindgens, D., Martinez, D. E., Peng, J., Wigge, P. A., Bertulat, B., Guder, C., Nakamura, Y., Ozbek, S., Watanabe, H., Khalturin, K., Hemmrich, G., Franke, A., Augustin, R., Fraune, S., Hayakawa, E., Hayakawa, S., Hirose, M., Hwang, J. S., Ikeo, K., Nishimiya-Fujisawa, C., Ogura, A., Takahashi, T., Steinmetz, P. R., Zhang, X., Aufschnaiter, R., Eder, M. K., Gorny, A. K., Salvenmoser, W., Heimberg, A. M., Wheeler, B. M., Peterson, K. J., Bottger, A., Tischler, P., Wolf, A., Gojobori, T., Remington, K. A., Strausberg, R. L., Venter, J. C., Technau, U., Hobmayer, B., Bosch, T. C., Holstein, T. W., Fujisawa, T., Bode, H. R., David, C. N., Rokhsar, D. S. and Steele, R. E. (2010). The dynamic genome of Hydra. Nature, 464, 592-6. PMID:20228792.
  • Kirchner, S., Kieu, T., Chow, C. Casey, S.C. and Blumberg, B. (2010). Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Molec. Endocrinol., 24, 526-539.
  • Ellis WC, Tran CT, Roy R, Rusten M, Fischer A, Ryabov AD, Blumberg B, Collins TJ. (2010) Designing green oxidation catalysts for purifying environmental waters. J Am Chem Soc. 132(28):9774-81. PMCID: 2925145. PMID: 20565079.
  • Azuma K, Casey SC, Ito M, Urano T, Horie K, Ouchi Y, Kirchner S, Blumberg B, Inoue S. (2010). Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption. J Endocrinol. PMID: 20876238.
  • Blumberg, B. (2010) Obesogens, Stem Cells, and the Maternal Programming of Obesity, Journal of Developmental Origins of Health and Disease, in press. doi:10.1017/S2040174410000589. Published online by Cambridge University Press 04 Nov 2010.
  • Ellis, W.C., Tran, C.T., Roy, R., Rusten, M., Fischer, A., Ryabov, A.D., Blumberg, B., and Collins, T.J. (2010). Designing green oxidation catalysts for purifying environmental waters. J. Am. Chem. Soc, 132(28):9774-81.

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