Bruce Blumberg

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.

One major research interest in the Blumberg laboratory concerns gene-environment interactions and the developmental basis of health and disease. 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. Effects of prenatal obesogen exposure can be transmitted transgenerationally through at least 4 subsequent generations by altering large scale chromatin structure to promote a “thrifty phenotype”. Understanding the role of these environmental obesogens in regulating fat cell development will provide important insights into a novel contributing factor for obesity.

The steroid and xenobiotic receptor, 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. Researchers in the Blumberg laboratory are studying the interactions between SXR and the gut microbiome in the development of lymphoma and other cancers.

A 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.

Recent Publications                              

• Trasande, L, Blumberg, B. (2018) Endocrine Disruptors as Obesogens. in Freemark, M.S. ed: Pediatric Obesity: Etiology, Pathogenesis, and Treatment, 2nd Edition, Humana Press, New York, NY 812 pp.
• Vandenberg, LN, Blumberg, B. (2017) Alternative Approaches to Dose–Response Modeling of Toxicological Endpoints for Risk Assessment: Nonmonotonic Dose Responses for Endocrine Disruptors. In: McQueen, C. and Eaton, D.L. eds: Comprehensive Toxicology, 3rd Edition (Elsevier Science, Oxford, UK) 8624 pp.
• Chamorro-Garcia, R, Diaz-Castillo, C, Shoucri, BM, Kach, H, Leavitt, R, Shioda, T, Blumberg, B. (2017) Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice. Nat Commun 8(1): 2012. PMCID: 5722856
• Shoucri, BM, Martinez, ES, Abreo, TJ, Hung, VT, Moosova, Z, Shioda, T, Blumberg, B. (2017) Retinoid X Receptor Activation Alters the Chromatin Landscape To Commit Mesenchymal Stem Cells to the Adipose Lineage. Endocrinology 158(10): 3109-25.
• Bornman, MS, Aneck-Hahn, NH, de Jager, C, Wagenaar, GM, Bouwman, H, Barnhoorn, IEJ, Patrick, SM, Vandenberg, LN, Kortenkamp, A, Blumberg, B, Kimmins, S, Jegou, B, Auger, J, DiGangi, J, Heindel, JJ. (2017) Endocrine Disruptors and Health Effects in Africa: A Call for Action. Environ Health Perspect 125(8): 085005.
• Janesick, A, Tang, W, Nguyen, TTL, Blumberg, B. (2017) RARbeta2 is required for vertebrate somitogenesis. Development (Cambridge, England) 144(11): 1997-2008.
• Janesick, AS, Dimastrogiovanni, G, Chamorro-Garcia, R, Blumberg, B. (2017) Reply to “Comment on ‘On the Utility of ToxCast and ToxPi as Methods for Identifying New Obesogens'”. Environ Health Perspect 125(1): A12-A4. PMCID: 5224935
• Heindel, JJ, Blumberg, B, Cave, M, Machtinger, R, Mantovani, A, Mendez, MA, Nadal, A, Palanza, P, Panzica, G, Sargis, R, Vandenberg, LN, Vom Saal, F. (2017) Metabolism disrupting chemicals and metabolic disorders. Reprod Toxicol 68: 3-33. PMCID: 536535
• Zhu, J, Janesick, A, Wu, L, Hu, L, Tang, W, Blumberg, B, Shi, H. (2017) The unexpected teratogenicity of RXR antagonist UVI3003 via activation of PPARgamma in Xenopus tropicalis. Toxicol Appl Pharmacol 314: 91-7. PMCID: 5183475
• Vandenberg, LN, Blumberg, B, Antoniou, MN, Benbrook, CM, Carroll, L, Colborn, T, Everett, LG, Hansen, M, Landrigan, PJ, Lanphear, BP, Mesnage, R, Vom Saal, FS, Welshons, WV, Myers, JP. (2017) Is it time to reassess current safety standards for glyphosate-based herbicides? J Epidemiol Community Health 71(6): 613-8. PMCID: 5484035
• Chamorro-García, R, Blumberg, B. (2017) Endocrine Disrupting Chemicals, Obesogens, and the Obesity Epidemic. in Bergeron, N., Siri-Tarino, P., Bray, G.A., Krauss, R.M., eds: Nutrition and Cardiometabolic Health (CRC Press, Boca Raton, FL), pp: 603-14.
• Janesick, AS, Blumberg, B. (2016) Obesogens: an emerging threat to public health. Am J Obstet Gynecol 214(5): 559-65. PMCID: 4851574
• Wang, J, Bi, W, Zhao, W, Varghese, M, Koch, RJ, Walker, RH, Chandraratna, RA, Sanders, ME, Janesick, A, Blumberg, B, Ward, L, Ho, L, Pasinetti, GM. (2016) Selective brain penetrable Nurr1 transactivator for treating Parkinson’s disease. Oncotarget 7(7): 7469-79. PMCID: 4884932
• Shoucri, BM, Blumberg, B. (2016) Impact of Environmental Obesogens Focus on Mechanisms Linking to Childhood Obesity. in Goran, M.I editor, Childhood Obesity: Causes, Consequences and Intervention Approaches, (CRC Press, Boca Raton, FL) pp 219-34.
• Pedram, A, Razandi, M, Blumberg, B, Levin, ER. (2016) Membrane and nuclear estrogen receptor alpha collaborate to suppress adipogenesis but not triglyceride content. FASEB J 30(1): 230-40. PMCID: 4684544
• Myers, JP, Antoniou, MN, Blumberg, B, Carroll, L, Colborn, T, Everett, LG, Hansen, M, Landrigan, PJ, Lanphear, BP, Mesnage, R, Vandenberg, LN, Vom Saal, FS, Welshons, WV, Benbrook, CM. (2016) Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement. Environ Health 15: 19. PMCID: 4756530
• Lind, L, Lind, PM, Lejonklou, MH, Dunder, L, Bergman, A, Guerrero-Bosagna, C, Lampa, E, Lee, HK, Legler, J, Nadal, A, Pak, YK, Phipps, RP, Vandenberg, LN, Zalko, D, Agerstrand, M, Oberg, M, Blumberg, B, Heindel, JJ, Birnbaum, LS. (2016) Uppsala Consensus Statement on Environmental Contaminants and the Global Obesity Epidemic. Environ Health Perspect 124(5): A81-3. PMCID: 4858400
• Janesick, AS, Dimastrogiovanni, G, Vanek, L, Boulos, C, Chamorro-Garcia, R, Tang, W, Blumberg, B. (2016) On the Utility of ToxCast and ToxPi as Methods for Identifying New Obesogens. Environ Health Perspect 124(8): 1214-26. PMCID: 4977052
• Lille-Langoy R, Goldstone JV, Rusten M, Milnes MR, Male R, Stegeman JJ, Blumberg B, Goksoyr A. (2015) Environmental contaminants activate human and polar bear (Ursus maritimus) pregnane X receptors (PXR, NR1I2) differently. Toxicol Appl Pharmacol 284(1): 54-64. PMCID: 4387200r PMID:25680588.
• Legler J, Fletcher T, Govarts E, Porta M, Blumberg B, Heindel JJ, Trasande L. (2015) Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European union. J Clin Endocrinol Metab 100(4): 1278-88. PMCID: 4399302r PMID:25742518.
• Janesick A, Wu SC, Blumberg B. (2015) Retinoic acid signaling and neuronal differentiation. Cell Mol Life Sci 72(8): 1559-76. PMID:25558812.
• Heindel JJ, Vom Saal FS, Blumberg B, Bovolin P, Calamandrei G, Ceresini G, Cohn BA, Fabbri E, Gioiosa L, Kassotis C, Legler J, La Merrill M, Rizzir L, Machtinger R, Mantovani A, Mendez MA, Montanini L, Molteni L, Nagel SC, Parmigiani S, Panzica G, Paterlini S, Pomatto V, Ruzzin J, Sartor G, Schug TT, Street ME, Suvorov A, Volpi R, Zoeller RT, Palanza P. (2015) Parma consensus statement on metabolic disruptors. Environ Health 14(1): 54. PMCID: 4473834r PMID:26092037.
• Bavik C, Henry SH, Zhang Y, Mitts K, McGinn T, Budzynski E, Pashko A, Lieu KL, Zhong S, Blumberg B, Kuksa V, Orme M, Scott I, Fawzi A, Kubota R. (2015) Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity. PLoS One 10(5): e0124940. PMCID: 4430241r PMID:25970164.
• Azuma K, Casey SC, Urano T, Horie-Inoue K, Ouchi Y, Blumberg B, Inoue S. (2015) Pregnane X receptor knockout mice display aging-dependent wearing of articular cartilage. PLoS One 10(3): e0119177. PMCID: 4352085r PMID:25749104.
• Ortiz L, Nakamura B, Li X, Blumberg B, Luderer U. (2014) Reprint of “In utero exposure to benzo[a]pyrene increases adiposity and causes hepatic steatosis in female mice, and glutathione deficiency is protective”. Toxicol Lett 230(2): 314-21. PMID:24291350.
• Kamstra JH, Hruba E, Blumberg B, Janesick A, Mandrup S, Hamers T, Legler J. (2014) Transcriptional and epigenetic mechanisms underlying enhanced in vitro adipocyte differentiation by the brominated flame retardant BDE-47. Environ Sci Technol 48(7): 4110-9. PMCID: 3983330r PMID:24559133.
• Janesick AS, Shioda T, Blumberg B. (2014) Transgenerational inheritance of prenatal obesogen exposure. Mol Cell Endocrinol 398(1-2): 31-5. PMCID: 4262625r PMID:25218215.
• Janesick A, Schug TT, Heindel JJ, Blumberg B. (2014) Environmental pollutants and obesity. Handbook of obesity : epidemiology, etiology, and physiopathology, Third Edition 1: 471-88.
• Janesick A, Nguyen TT, Aisaki K, Igarashi K, Kitajima S, Chandraratna RA, Kanno J, Blumberg B. (2014) Active repression by RARgamma signaling is required for vertebrate axial elongation. Development (Cambridge, England) 141(11): 2260-70. PMID:24821986.
• Chamorro-Garcia R, Blumberg B. (2014) Transgenerational effects of obesogens and the obesity epidemic. Curr Opin Pharmacol 19: 153-8. PMCID: 4297575r PMID:25460228.
• Blumberg B. (2014) Andres Carrasco (1946-2014). Dev Biol 393(1): 1-2. PMID:25275141.
• 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 J, Watson CS, Saal FS, Zoeller RT, O’Brien KP, Myers JP. (2013) Designing Endocrine Disruption Out of the Next Generation of Chemicals. Green Chem 15(1): 181-98. PMCID: 4125359r PMID:25110461.
• 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: 3622257r PMID:23585695.
• Ortiz L, Nakamura B, Li X, Blumberg B, Luderer U. (2013) In utero exposure to benzo[a]pyrene increases adiposity and causes hepatic steatosis in female mice, and glutathione deficiency is protective. Toxicol Lett 223(2): 260-7. PMCID: 3856224r PMID:24107266.
• Janesick A, Abbey R, Chung C, Liu S, Taketani M, Blumberg B. (2013) ERF and ETV3L are retinoic acid-inducible repressors required for primary neurogenesis. Development (Cambridge, England) 140(15): 3095-106. PMID:23824578.
• 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.
• Chamorro-Garcia R, Sahu M, Abbey RJ, Laude J, Pham N, Blumberg B. (2013) Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal exposure to the obesogen tributyltin in mice. Environ Health Perspect 121(3): 359-66. PMCID: 3621201r PMID:23322813.
• 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: 69. PMCID: 3765603r PMID:23981490.
• 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.

Faculty Login