Sheila Collins, Ph.D.

Faculty Appointments
Professor of Medicine Professor of Molecular Physiology & Biophysics
Ph.D., Applied Biology/Biology, Massachusetts Institute of Technology, Cambridge, MassachusettsB.S., Zoology, University of Massachusetts, Amherst, Massachusetts
Research Description
We study adipose tissue metabolism from the point of view of how it contributes to whole-body regulation of caloric fuel management. This management is critical for balancing energy needs for daily life but more importantly in our current modern living environment we must figure out how to mitigate the obesity epidemic in our midst. Most important regarding obesity is that it is the main driver of 'cardiometabolic disease', meaning diabetes, atherosclerosis, high blood pressure, fatty liver.
Research Keywords
adipocyte beta-adrenergic receptors cyclic nucleotides brown adipocytes energy expenditure kinases protein phosphorylation mitochondria
Liu D, Ceddia RP, Collins S. Cardiac natriuretic peptides promote adipose 'browning' through mTOR complex-1. Mol Metab [print-electronic]. 2018 Mar; 9: 192-8. PMID: 29396369, PMCID: PMC5870104, PII: S2212-8778(17)31003-7, DOI: 10.1016/j.molmet.2017.12.017, ISSN: 2212-8778.

Shi F, Collins S. Second messenger signaling mechanisms of the brown adipocyte thermogenic program: an integrative perspective. Horm Mol Biol Clin Investig. 2017 Sep 9/26/2017; 31(2): PMID: 28949928, PII: /j/hmbci.ahead-of-print/hmbci-2017-0062/hmbci-2017-0062.xml, DOI: 10.1515/hmbci-2017-0062, ISSN: 1868-1891.

Wu W, Shi F, Liu D, Ceddia RP, Gaffin R, Wei W, Fang H, Lewandowski ED, Collins S. Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle, protects against diet-induced obesity and insulin resistance. Sci Signal. 2017 Jul 7/25/2017; 10(489): PMID: 28743802, PII: 10/489/eaam6870, DOI: 10.1126/scisignal.aam6870, ISSN: 1937-9145.

Liu D, Bordicchia M, Zhang C, Fang H, Wei W, Li JL, Guilherme A, Guntur K, Czech MP, Collins S. Activation of mTORC1 is essential for ß-adrenergic stimulation of adipose browning. J. Clin. Invest [print-electronic]. 2016 May 5/2/2016; 126(5): 1704-16. PMID: 27018708, PMCID: PMC4855937, PII: 83532, DOI: 10.1172/JCI83532, ISSN: 1558-8238.

Kovacova Z, Tharp WG, Liu D, Wei W, Xie H, Collins S, Pratley RE. Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes. Obesity (Silver Spring) [print-electronic]. 2016 Apr; 24(4): 820-8. PMID: 26887289, PMCID: PMC5067565, DOI: 10.1002/oby.21418, ISSN: 1930-739X.

Mazar J, Zhao W, Khalil AM, Lee B, Shelley J, Govindarajan SS, Yamamoto F, Ratnam M, Aftab MN, Collins S, Finck BN, Han X, Mattick JS, Dinger ME, Perera RJ. The functional characterization of long noncoding RNA SPRY4-IT1 in human melanoma cells. Oncotarget. 2014 Oct 10/15/2014; 5(19): 8959-69. PMID: 25344859, PMCID: PMC4253410, PII: 1863, DOI: 10.18632/oncotarget.1863, ISSN: 1949-2553.

Collins S. A heart-adipose tissue connection in the regulation of energy metabolism. Nat Rev Endocrinol [print-electronic]. 2014 Mar; 10(3): 157-63. PMID: 24296515, PII: nrendo.2013.234, DOI: 10.1038/nrendo.2013.234, ISSN: 1759-5037.

Dib L, Bugge A, Collins S. LXRa fuels fatty acid-stimulated oxygen consumption in white adipocytes. J. Lipid Res [print-electronic]. 2014 Feb; 55(2): 247-57. PMID: 24259533, PMCID: PMC3886663, PII: jlr.M043422, DOI: 10.1194/jlr.M043422, ISSN: 1539-7262.

Bugge A, Dib L, Collins S. Measuring respiratory activity of adipocytes and adipose tissues in real time. Meth. Enzymol. 2014; 538: 233-47. PMID: 24529442, PII: B978-0-12-800280-3.00013-X, DOI: 10.1016/B978-0-12-800280-3.00013-X, ISSN: 1557-7988.

Collins S, Bordicchia M. Heart hormones fueling a fire in fat. Adipocyte. 2013 Apr 4/1/2013; 2(2): 104-8. PMID: 23805407, PMCID: PMC3661113, PII: 2012APIDOCYTE043R, DOI: 10.4161/adip.22515, ISSN: 2162-3945.

Müller TD, Lee SJ, Jastroch M, Kabra D, Stemmer K, Aichler M, Abplanalp B, Ananthakrishnan G, Bhardwaj N, Collins S, Divanovic S, Endele M, Finan B, Gao Y, Habegger KM, Hembree J, Heppner KM, Hofmann S, Holland J, Küchler D, Kutschke M, Krishna R, Lehti M, Oelkrug R, Ottaway N, Perez-Tilve D, Raver C, Walch AK, Schriever SC, Speakman J, Tseng YH, Diaz-Meco M, Pfluger PT, Moscat J, Tschöp MH. P62 links ß-adrenergic input to mitochondrial function and thermogenesis. J. Clin. Invest [print-electronic]. 2013 Jan; 123(1): 469-78. PMID: 23257354, PMCID: PMC3533288, PII: 64209, DOI: 10.1172/JCI64209, ISSN: 1558-8238.

Collins S, Pi J, Yehuda-Shnaidman E. Uncoupling and reactive oxygen species (ROS)--a double-edged sword for ß-cell function? "Moderation in all things". Best Pract. Res. Clin. Endocrinol. Metab [print-electronic]. 2012 Dec; 26(6): 753-8. PMID: 23168277, PII: S1521-690X(12)00083-8, DOI: 10.1016/j.beem.2012.08.002, ISSN: 1878-1594.

Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessì-Fulgheri P, Zhang C, Takahashi N, Sarzani R, Collins S. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J. Clin. Invest [print-electronic]. 2012 Mar; 122(3): 1022-36. PMID: 22307324, PMCID: PMC3287224, PII: 59701, DOI: 10.1172/JCI59701, ISSN: 1558-8238.

Rogers C, Moukdar F, McGee MA, Davis B, Buehrer BM, Daniel KW, Collins S, Barakat H, Robidoux J. EGF receptor (ERBB1) abundance in adipose tissue is reduced in insulin-resistant and type 2 diabetic women. J. Clin. Endocrinol. Metab [print-electronic]. 2012 Mar; 97(3): E329-40. PMID: 22238402, PII: jc.2011-1033, DOI: 10.1210/jc.2011-1033, ISSN: 1945-7197.

Hou Y, Xue P, Bai Y, Liu D, Woods CG, Yarborough K, Fu J, Zhang Q, Sun G, Collins S, Chan JY, Yamamoto M, Andersen ME, Pi J. Nuclear factor erythroid-derived factor 2-related factor 2 regulates transcription of CCAAT/enhancer-binding protein ß during adipogenesis. Free Radic. Biol. Med [print-electronic]. 2012 Jan 1/15/2012; 52(2): 462-72. PMID: 22138520, PMCID: PMC3307524, PII: S0891-5849(11)01129-4, DOI: 10.1016/j.freeradbiomed.2011.10.453, ISSN: 1873-4596.

Park D, Han CZ, Elliott MR, Kinchen JM, Trampont PC, Das S, Collins S, Lysiak JJ, Hoehn KL, Ravichandran KS. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature. 2011 Aug 8/21/2011; 477(7363): 220-4. PMID: 21857682, PMCID: PMC3513690, PII: nature10340, DOI: 10.1038/nature10340, ISSN: 1476-4687.

Mailloux RJ, Seifert EL, Bouillaud F, Aguer C, Collins S, Harper ME. Glutathionylation acts as a control switch for uncoupling proteins UCP2 and UCP3. J. Biol. Chem [print-electronic]. 2011 Jun 6/17/2011; 286(24): 21865-75. PMID: 21515686, PMCID: PMC3122241, PII: M111.240242, DOI: 10.1074/jbc.M111.240242, ISSN: 1083-351X.

Collins S. ß-Adrenoceptor Signaling Networks in Adipocytes for Recruiting Stored Fat and Energy Expenditure. Front Endocrinol (Lausanne). 2011; 2: 102. PMID: 22654837, PMCID: PMC3355892, DOI: 10.3389/fendo.2011.00102, ISSN: 1664-2392.

Yehuda-Shnaidman E, Buehrer B, Pi J, Kumar N, Collins S. Acute stimulation of white adipocyte respiration by PKA-induced lipolysis. Diabetes [print-electronic]. 2010 Oct; 59(10): 2474-83. PMID: 20682684, PMCID: PMC3279548, PII: db10-0245, DOI: 10.2337/db10-0245, ISSN: 1939-327X.

Fu J, Woods CG, Yehuda-Shnaidman E, Zhang Q, Wong V, Collins S, Sun G, Andersen ME, Pi J. Low-level arsenic impairs glucose-stimulated insulin secretion in pancreatic beta cells: involvement of cellular adaptive response to oxidative stress. Environ. Health Perspect [print-electronic]. 2010 Jun; 118(6): 864-70. PMID: 20100676, PMCID: PMC2898865, DOI: 10.1289/ehp.0901608, ISSN: 1552-9924.

Hao Q, Hansen JB, Petersen RK, Hallenborg P, Jørgensen C, Cinti S, Larsen PJ, Steffensen KR, Wang H, Collins S, Wang J, Gustafsson JA, Madsen L, Kristiansen K. ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes. Biochim. Biophys. Acta [print-electronic]. 2010 Apr; 1801(4): 421-9. PMID: 19962449, PII: S1388-1981(09)00280-7, DOI: 10.1016/j.bbalip.2009.11.008, ISSN: 0006-3002.

Pi J, Zhang Q, Fu J, Woods CG, Hou Y, Corkey BE, Collins S, Andersen ME. ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function. Toxicol. Appl. Pharmacol [print-electronic]. 2010 Apr 4/1/2010; 244(1): 77-83. PMID: 19501608, PMCID: PMC2837798, PII: S0041-008X(09)00224-5, DOI: 10.1016/j.taap.2009.05.025, ISSN: 1096-0333.

Pi J, Bai Y, Daniel KW, Liu D, Lyght O, Edelstein D, Brownlee M, Corkey BE, Collins S. Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function. Endocrinology [print-electronic]. 2009 Jul; 150(7): 3040-8. PMID: 19246534, PMCID: PMC2703519, PII: en.2008-1642, DOI: 10.1210/en.2008-1642, ISSN: 1945-7170.

Moukdar F, Robidoux J, Lyght O, Pi J, Daniel KW, Collins S. Reduced antioxidant capacity and diet-induced atherosclerosis in uncoupling protein-2-deficient mice. J. Lipid Res [print-electronic]. 2009 Jan; 50(1): 59-70. PMID: 18698091, PII: M800273-JLR200, DOI: 10.1194/jlr.M800273-JLR200, ISSN: 0022-2275.

Elorza A, Hyde B, Mikkola HK, Collins S, Shirihai OS. UCP2 modulates cell proliferation through the MAPK/ERK pathway during erythropoiesis and has no effect on heme biosynthesis. J. Biol. Chem [print-electronic]. 2008 Nov 11/7/2008; 283(45): 30461-70. PMID: 18687678, PMCID: PMC2576537, PII: M805400200, DOI: 10.1074/jbc.M805400200, ISSN: 0021-9258.

Liu HY, Collins QF, Moukdar F, Zhuo D, Han J, Hong T, Collins S, Cao W. Suppression of hepatic glucose production by human neutrophil alpha-defensins through a signaling pathway distinct from insulin. J. Biol. Chem [print-electronic]. 2008 May 5/2/2008; 283(18): 12056-63. PMID: 18347011, PMCID: PMC2335365, PII: M801033200, DOI: 10.1074/jbc.M801033200, ISSN: 0021-9258.

Kumar N, Liu D, Wang H, Robidoux J, Collins S. Orphan nuclear receptor NOR-1 enhances 3',5'-cyclic adenosine 5'-monophosphate-dependent uncoupling protein-1 gene transcription. Mol. Endocrinol [print-electronic]. 2008 May; 22(5): 1057-64. PMID: 18238829, PMCID: PMC2366189, PII: me.2007-0464, DOI: 10.1210/me.2007-0464, ISSN: 0888-8809.

Wang H, Zhang Y, Yehuda-Shnaidman E, Medvedev AV, Kumar N, Daniel KW, Robidoux J, Czech MP, Mangelsdorf DJ, Collins S. Liver X receptor alpha is a transcriptional repressor of the uncoupling protein 1 gene and the brown fat phenotype. Mol. Cell. Biol [print-electronic]. 2008 Apr; 28(7): 2187-200. PMID: 18195045, PMCID: PMC2268430, PII: MCB.01479-07, DOI: 10.1128/MCB.01479-07, ISSN: 1098-5549.

Pi J, Zhang Q, Woods CG, Wong V, Collins S, Andersen ME. Activation of Nrf2-mediated oxidative stress response in macrophages by hypochlorous acid. Toxicol. Appl. Pharmacol [print-electronic]. 2008 Feb 2/1/2008; 226(3): 236-43. PMID: 17980396, PII: S0041-008X(07)00420-6, DOI: 10.1016/j.taap.2007.09.016, ISSN: 0041-008X.

Wikstrom JD, Katzman SM, Mohamed H, Twig G, Graf SA, Heart E, Molina AJ, Corkey BE, de Vargas LM, Danial NN, Collins S, Shirihai OS. Beta-Cell mitochondria exhibit membrane potential heterogeneity that can be altered by stimulatory or toxic fuel levels. Diabetes [print-electronic]. 2007 Oct; 56(10): 2569-78. PMID: 17686943, PII: db06-0757, DOI: 10.2337/db06-0757, ISSN: 1939-327X.

Pi J, Bai Y, Zhang Q, Wong V, Floering LM, Daniel K, Reece JM, Deeney JT, Andersen ME, Corkey BE, Collins S. Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes [print-electronic]. 2007 Jul; 56(7): 1783-91. PMID: 17400930, PII: db06-1601, DOI: 10.2337/db06-1601, ISSN: 1939-327X.

Pi J, Bai Y, Reece JM, Williams J, Liu D, Freeman ML, Fahl WE, Shugar D, Liu J, Qu W, Collins S, Waalkes MP. Molecular mechanism of human Nrf2 activation and degradation: role of sequential phosphorylation by protein kinase CK2. Free Radic. Biol. Med [print-electronic]. 2007 Jun 6/15/2007; 42(12): 1797-806. PMID: 17512459, PMCID: PMC1950666, PII: S0891-5849(07)00176-1, DOI: 10.1016/j.freeradbiomed.2007.03.001, ISSN: 0891-5849.

Kumar N, Robidoux J, Daniel KW, Guzman G, Floering LM, Collins S. Requirement of vimentin filament assembly for beta3-adrenergic receptor activation of ERK MAP kinase and lipolysis. J. Biol. Chem [print-electronic]. 2007 Mar 3/23/2007; 282(12): 9244-50. PMID: 17251187, PII: M605571200, DOI: 10.1074/jbc.M605571200, ISSN: 0021-9258.

Robidoux J, Kumar N, Daniel KW, Moukdar F, Cyr M, Medvedev AV, Collins S. Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal growth factor receptor-dependent ERK1/2 activation. J. Biol. Chem [print-electronic]. 2006 Dec 12/8/2006; 281(49): 37794-802. PMID: 17032647, PII: M605572200, DOI: 10.1074/jbc.M605572200, ISSN: 0021-9258.

Cao W, Collins QF, Becker TC, Robidoux J, Lupo EG, Xiong Y, Daniel KW, Floering L, Collins S. P38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis. J. Biol. Chem [print-electronic]. 2005 Dec 12/30/2005; 280(52): 42731-7. PMID: 16272151, PII: M506223200, DOI: 10.1074/jbc.M506223200, ISSN: 0021-9258.

Robidoux J, Cao W, Quan H, Daniel KW, Moukdar F, Bai X, Floering LM, Collins S. Selective activation of mitogen-activated protein (MAP) kinase kinase 3 and p38alpha MAP kinase is essential for cyclic AMP-dependent UCP1 expression in adipocytes. Mol. Cell. Biol. 2005 Jul; 25(13): 5466-79. PMID: 15964803, PMCID: PMC1157000, PII: 25/13/5466, DOI: 10.1128/MCB.25.13.5466-5479.2005, ISSN: 0270-7306.

Collins S. Overview of clinical perspectives and mechanisms of obesity. Birth Defects Res. Part A Clin. Mol. Teratol. 2005 Jul; 73(7): 470-1. PMID: 15959883, DOI: 10.1002/bdra.20140, ISSN: 1542-0752.

Collins S. An interview with Sheila Collins, Ph.D. Interview by Vicki Glaser. Assay Drug Dev Technol. 2005 Jun; 3(3): 253-60. PMID: 15971987, DOI: 10.1089/adt.2005.3.253, ISSN: 1540-658X.

Bai Y, Onuma H, Bai X, Medvedev AV, Misukonis M, Weinberg JB, Cao W, Robidoux J, Floering LM, Daniel KW, Collins S. Persistent nuclear factor-kappa B activation in Ucp2-/- mice leads to enhanced nitric oxide and inflammatory cytokine production. J. Biol. Chem [print-electronic]. 2005 May 5/13/2005; 280(19): 19062-9. PMID: 15757894, PMCID: PMC1382174, PII: M500566200, DOI: 10.1074/jbc.M500566200, ISSN: 0021-9258.

Collins S, Cao W, Robidoux J. Learning new tricks from old dogs: beta-adrenergic receptors teach new lessons on firing up adipose tissue metabolism. Mol. Endocrinol [print-electronic]. 2004 Sep; 18(9): 2123-31. PMID: 15243132, PII: me.2004-0193, DOI: 10.1210/me.2004-0193, ISSN: 0888-8809.

de Bilbao F, Arsenijevic D, Vallet P, Hjelle OP, Ottersen OP, Bouras C, Raffin Y, Abou K, Langhans W, Collins S, Plamondon J, Alves-Guerra MC, Haguenauer A, Garcia I, Richard D, Ricquier D, Giannakopoulos P. Resistance to cerebral ischemic injury in UCP2 knockout mice: evidence for a role of UCP2 as a regulator of mitochondrial glutathione levels. J. Neurochem. 2004 Jun; 89(5): 1283-92. PMID: 15147521, PII: JNC2432, DOI: 10.1111/j.1471-4159.2004.02432.x, ISSN: 0022-3042.

Collins S, Martin TL, Surwit RS, Robidoux J. Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics. Physiol. Behav. 2004 Apr; 81(2): 243-8. PMID: 15159170, PII: S0031938404000460, DOI: 10.1016/j.physbeh.2004.02.006, ISSN: 0031-9384.

Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, Floering LM, Spiegelman BM, Collins S. P38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol. Cell. Biol. 2004 Apr; 24(7): 3057-67. PMID: 15024092, PMCID: PMC371122, ISSN: 0270-7306.

Robidoux J, Martin TL, Collins S. Beta-adrenergic receptors and regulation of energy expenditure: a family affair. Annu. Rev. Pharmacol. Toxicol. 2004; 44: 297-323. PMID: 14744248, DOI: 10.1146/annurev.pharmtox.44.101802.121659, ISSN: 0362-1642.

Medvedev AV, Robidoux J, Bai X, Cao W, Floering LM, Daniel KW, Collins S. Regulation of the uncoupling protein-2 gene in INS-1 beta-cells by oleic acid. J. Biol. Chem [print-electronic]. 2002 Nov 11/8/2002; 277(45): 42639-44. PMID: 12205102, PII: M208645200, DOI: 10.1074/jbc.M208645200, ISSN: 0021-9258.

Aubriot S, Nicolle E, Lattier M, Morel C, Cao W, Daniel KW, Collins S, Leclerc G, Faure P. New series of aryloxypropanolamines with both human beta(3)-adrenoceptor agonistic activity and free radical scavenging properties. Bioorg. Med. Chem. Lett. 2002 Jan 1/21/2002; 12(2): 209-12. PMID: 11755356, PII: S0960894X01007168, ISSN: 0960-894X.