Cell Metabolism

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Laboratory of Cell Metabolism

Ann-Hwee Lee, PhD, Principal Investigator

Dr. Lee’s laboratory focuses on metabolic functions of unfolded protein response, a signaling pathway that governs protein folding homeostasis in the endoplasmic reticulum. He also studies the physiological functions and action mechanisms of a group of transcription factors that are anchored in the ER membrane and activated by proteolytic cleavage.

Active Projects

  • Regulation of Triglyceride Metabolism by the transcription factor CREB-H
  • Metabolic functions of the Unfolded Protein Response
  • Role of Unfolded Protein Response in insulin secretory function of beta cells

Active Grants

  • IRE1a and XBP1 dependent microRNAs and their role in hepatic lipid metabolism
    PI: Ann-Hwee Lee, PhD
    Qatar National Research Fund (QNRF) Research Grant
  • Regulation of Triglyceride Metabolism by the transcription factor CREB-H
    PI: Ann-Hwee Lee, PhD
    NIDDK

Laboratory of Cell Metabolism

Ann-Hwee Lee, PhD, Principal Investigator

Dr. Lee’s laboratory focuses on metabolic functions of unfolded protein response, a signaling pathway that governs protein folding homeostasis in the endoplasmic reticulum. He also studies the physiological functions and action mechanisms of a group of transcription factors that are anchored in the ER membrane and activated by proteolytic cleavage.

Active Projects

  • Regulation of Triglyceride Metabolism by the transcription factor CREB-H
  • Metabolic functions of the Unfolded Protein Response
  • Role of Unfolded Protein Response in insulin secretory function of beta cells

Active Grants

  • IRE1a and XBP1 dependent microRNAs and their role in hepatic lipid metabolism
    PI: Ann-Hwee Lee, PhD
    Qatar National Research Fund (QNRF) Research Grant
  • Regulation of Triglyceride Metabolism by the transcription factor CREB-H
    PI: Ann-Hwee Lee, PhD
    NIDDK

Selected Publications EXPAND ALL ON THIS PAGE

Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes

August 24, 2015
Hassan H, Tian X, Inoue K, Chai N, Liu C, Soda K, Moeckel G, Tufro A, Lee AH, Somlo S, Fedeles S, Ishibe S.

Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes

J Am Soc Nephrol. 2015 Aug 24.

Hassan H, Tian X, Inoue K, Chai N, Liu C, Soda K, Moeckel G, Tufro A, Lee AH, Somlo S, Fedeles S, Ishibe S.

PMID: 26303067

The transcription factor XBP1 is selectively required for eosinophil differentiation

August 1, 2015
Bettigole SE, Lis R, Adoro S, Lee AH, Spencer LA, Weller PF, Glimcher LH.

The transcription factor XBP1 is selectively required for eosinophil differentiation

Nat Immunol. 2015 Aug;16(8):829-37.

Bettigole SE, Lis R, Adoro S, Lee AH, Spencer LA, Weller PF, Glimcher LH.

PMID: 26147683; PMCID: PMC4577297

IRE1α-Dependent Decay of CReP/Ppp1r15b mRNA Increases Eukaryotic Initiation Factor 2α Phosphorylation and Suppresses Protein Synthesis

August 1, 2015
So JS, Cho S, Min SH, Kimball SR, Lee AH.

IRE1α-Dependent Decay of CReP/Ppp1r15b mRNA Increases Eukaryotic Initiation Factor 2α Phosphorylation and Suppresses Protein Synthesis

Mol Cell Biol. 2015 Aug;35(16):2761-70.

So JS, Cho S, Min SH, Kimball SR, Lee AH.

PMID: 26031337; PMCID: PMC4508316

ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis

June 18, 2015
Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, Zhang S, Bettigole SE, Gupta D, Holcomb K, Ellenson LH, Caputo T, Lee AH, Conejo-Garcia JR, Glimcher LH.

ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis

Cell. 2015 Jun 18;161(7):1527-38.

Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, Zhang S, Bettigole SE, Gupta D, Holcomb K, Ellenson LH, Caputo T, Lee AH, Conejo-Garcia JR, Glimcher LH.

PMID: 26073941; PMCID: PMC4580135

Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity

May 1, 2015
Fedeles SV, So JS, Shrikhande A, Lee SH, Gallagher AR, Barkauskas CE, Somlo S, Lee AH.

Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity

J Clin Invest. 2015 May;125(5):1955-67.

Fedeles SV, So JS, Shrikhande A, Lee SH, Gallagher AR, Barkauskas CE, Somlo S, Lee AH.

PMID: 25844898; PMCID: PMC4463201.

Transcriptional activation of Fsp27 by the liver-enriched transcription factor CREBH promotes lipid droplet growth and hepatic steatosis

March 1, 2015
Xu X, Park JG, So JS, Lee AH.

Transcriptional activation of Fsp27 by the liver-enriched transcription factor CREBH promotes lipid droplet growth and hepatic steatosis

Hepatology. 2015 Mar;61(3):857-69.

Xu X, Park JG, So JS, Lee AH.

PMID: 25125366; PMCID: PMC4329115

Heteroclitic XBP1 peptides evoke tumor-specific memory cytotoxic T lymphocytes against breast cancer, colon cancer, and pancreatic cancer cells

December 2, 2014
Bae J, Samur M, Munshi A, Hideshima T, Keskin D, Kimmelman A, Lee AH, Dranoff G, Anderson KC, Munshi NC.

Heteroclitic XBP1 peptides evoke tumor-specific memory cytotoxic T lymphocytes against breast cancer, colon cancer, and pancreatic cancer cells

Oncoimmunology. 2014 Dec 2;3(12):e970914.

Bae J, Samur M, Munshi A, Hideshima T, Keskin D, Kimmelman A, Lee AH, Dranoff G, Anderson KC, Munshi NC.

PMID: 25941601; PMCID: PMC4356023

Altered trafficking and stability of polycystins underlie polycystic kidney disease

December 1, 2014
Cai Y, Fedeles SV, Dong K, Anyatonwu G, Onoe T, Mitobe M, Gao JD, Okuhara D, Tian X, Gallagher AR, Tang Z, Xie X, Lalioti MD, Lee AH, Ehrlich BE, Somlo S.

Altered trafficking and stability of polycystins underlie polycystic kidney disease

J Clin Invest. 2014 Dec;124(12):5129-44.

Cai Y, Fedeles SV, Dong K, Anyatonwu G, Onoe T, Mitobe M, Gao JD, Okuhara D, Tian X, Gallagher AR, Tang Z, Xie X, Lalioti MD, Lee AH, Ehrlich BE, Somlo S.

PMID: 25365220; PMCID: PMC4348948

X-box binding protein 1 is a novel key regulator of peroxisome proliferator-activated receptor γ2

November 1, 2014
Cho YM, Kwak SN, Joo NS, Kim DH, Lee AH, Kim KS, Seo JB, Jeong SW, Kwon OJ.

X-box binding protein 1 is a novel key regulator of peroxisome proliferator-activated receptor γ2

FEBS J. 2014 Nov;281(22):5132-46.

Cho YM, Kwak SN, Joo NS, Kim DH, Lee AH, Kim KS, Seo JB, Jeong SW, Kwon OJ.

PMID: 25223794

Transcriptional regulation of apolipoprotein A-IV by the transcription factor CREBH

May 1, 2014
Xu X, Park JG, So JS, Hur KY, Lee AH.

Transcriptional regulation of apolipoprotein A-IV by the transcription factor CREBH

J Lipid Res. 2014 May;55(5):850-9.

Xu X, Park JG, So JS, Hur KY, Lee AH.

PMID: 24598141; PMCID: PMC3995463.

Spliced X-box binding protein 1 couples the unfolded protein response to hexosamine biosynthetic pathway

March 13, 2014
Wang ZV, Deng Y, Gao N, Pedrozo Z, Li DL, Morales CR, Criollo A, Luo X, Tan W, Jiang N, Lehrman MA, Rothermel BA, Lee AH, Lavandero S, Mammen PP, Ferdous A, Gillette TG, Scherer PE, Hill JA.

Spliced X-box binding protein 1 couples the unfolded protein response to hexosamine biosynthetic pathway

Cell. 2014 Mar 13;156(6):1179-92.

Wang ZV, Deng Y, Gao N, Pedrozo Z, Li DL, Morales CR, Criollo A, Luo X, Tan W, Jiang N, Lehrman MA, Rothermel BA, Lee AH, Lavandero S, Mammen PP, Ferdous A, Gillette TG, Scherer PE, Hill JA.

PMID: 24630721; PMCID: PMC3959665.

Regulated IRE1-dependent decay participates in curtailing immunoglobulin secretion from plasma cells

March 1, 2014
Benhamron S, Hadar R, Iwawaky T, So JS, Lee AH, Tirosh B.

Regulated IRE1-dependent decay participates in curtailing immunoglobulin secretion from plasma cells

Eur J Immunol. 2014 Mar;44(3):867-76.

Benhamron S, Hadar R, Iwawaky T, So JS, Lee AH, Tirosh B.

PMID: 24242955

Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP

November 1, 2013
Xu X, So JS, Park JG, Lee AH.

Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP

Semin Liver Dis. 2013 Nov;33(4):301-11.

Xu X, So JS, Park JG, Lee AH.

PMID: 24222088; PMCID: PMC4035704

The role of adipocyte XBP1 in metabolic regulation during lactation.

May 30, 2013
Ann-Hwee Lee, PhD

The role of adipocyte XBP1 in metabolic regulation during lactation.

Cell Rep. 2013 May 30;3(5):1430-9.

Gregor MF, Misch ES, Yang L, Hummasti S, Inouye KE, Lee AH, Bierie B, Hotamisligil GS.

PMID: 23623498

The unfolded protein response element IRE1α senses bacterial proteins invading the ER to activate RIG-I and innate immune signaling.

May 15, 2013
Ann-Hwee Lee, PhD

The unfolded protein response element IRE1α senses bacterial proteins invading the ER to activate RIG-I and innate immune signaling.

Cell Host Microbe. 2013 May 15;13(5):558-69. 

Cho JA, Lee AH, Platzer B, Cross BC, Gardner BM, De Luca H, Luong P, Harding HP, Glimcher LH, Walter P, Fiebiger E, Ron D, Kagan JC, Lencer WI.

PMID: 23684307

Silencing of lipid metabolism genes through IRE1α-mediated mRNA decay lowers plasma lipids in mice.

October 3, 2012
So JS, Hur KY, Tarrio M, Ruda V, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Lichtman AH, Iwawaki T, Glimcher LH, Lee AH

Silencing of lipid metabolism genes through IRE1α-mediated mRNA decay lowers plasma lipids in mice.

Cell Metab. 2012 Oct 3;16(4):487-99. 

So JS, Hur KY, Tarrio M, Ruda V, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Lichtman AH, Iwawaki T, Glimcher LH, Lee AH.

PMID: 23040070

The role of CREB-H transcription factor in triglyceride metabolism.

April 1, 2012
Ann-Hwee Lee, PhD

The role of CREB-H transcription factor in triglyceride metabolism.

Curr Opin Lipidol. 2012 Apr;23(2):141-6. 

Lee AH.

PMID: 22262056

IRE1α activation protects mice against acetaminophen-induced hepatotoxicity.

February 13, 2012
Hur KY, So JS, Ruda V, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Iwawaki T, Glimcher LH, Lee AH

IRE1α activation protects mice against acetaminophen-induced hepatotoxicity.

J Exp Med. 2012 Feb 13;209(2):307-18. 

Hur KY, So JS, Ruda V, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Iwawaki T, Glimcher LH, Lee AH.

PMID: 22291093

Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells.

February 9, 2012
Hu Y, Park KK, Yang L, Wei X, Yang Q, Cho KS, Thielen P, Lee AH, Cartoni R, Glimcher LH, Chen DF, He Z

Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells.

Neuron. 2012 Feb 9;73(3):445-52.

Hu Y, Park KK, Yang L, Wei X, Yang Q, Cho KS, Thielen P, Lee AH, Cartoni R, Glimcher LH, Chen DF, He Z.

PMID: 22325198

Excess of rare variants in non-genome-wide association study candidate genes in patients with hypertriglyceridemia.

February 1, 2012
Johansen CT, Wang J, McIntyre AD, Martins RA, Ban MR, Lanktree MB, Huff MW, Peterfy M, Mehrabian M, Lusis AJ, Kathiresan S, Anand SS, Yusuf S, Lee AH, Glimcher LH, Cao H, Hegele RA

Excess of rare variants in non-genome-wide association study candidate genes in patients with hypertriglyceridemia.

Circ Cardiovasc Genet. 2012 Feb 1;5(1):66-72.

Johansen CT, Wang J, McIntyre AD, Martins RA, Ban MR, Lanktree MB, Huff MW, Péterfy M, Mehrabian M, Lusis AJ, Kathiresan S, Anand SS, Yusuf S, Lee AH, Glimcher LH, Cao H, Hegele RA.

PMID: 22135386

Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade.

February 1, 2012
Kwon J, Han E, Bui CB, Shin W, Lee J, Lee S, Choi YB, Lee AH, Lee KH, Park C, Obin MS, Park SK, Seo YJ, Oh GT, Lee HW, Shin J

Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade.

EMBO Rep. 2012 Feb 1;13(2):150-6.

Kwon J, Han E, Bui CB, Shin W, Lee J, Lee S, Choi YB, Lee AH, Lee KH, Park C, Obin MS, Park SK, Seo YJ, Oh GT, Lee HW, Shin J.

PMID: 22222206

Dissociation of inositol-requiring enzyme (IRE1α)-mediated c-Jun N-terminal kinase activation from hepatic insulin resistance in conditional X-box-binding protein-1 (XBP1) knock-out mice.

January 20, 2012
Jurczak MJ, Lee AH, Jornayvaz FR, Lee HY, Birkenfeld AL, Guigni BA, Kahn M, Samuel VT, Glimcher LH, Shulman GI

Dissociation of inositol-requiring enzyme (IRE1α)-mediated c-Jun N-terminal kinase activation from hepatic insulin resistance in conditional X-box-binding protein-1 (XBP1) knock-out mice.

J Biol Chem. 2012 Jan 20;287(4):2558-67. 

Jurczak MJ, Lee AH, Jornayvaz FR, Lee HY, Birkenfeld AL, Guigni BA, Kahn M, Samuel VT, Glimcher LH, Shulman GI.

PMID: 22128176

Identification of novel myeloma-specific XBP1 peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma.

October 1, 2011
Bae J, Carrasco R, Lee AH, Prabhala R, Tai YT, Anderson KC, Munshi NC

Identification of novel myeloma-specific XBP1 peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma.

Leukemia. 2011 Oct;25(10):1610-9.

Bae J, Carrasco R, Lee AH, Prabhala R, Tai YT, Anderson KC, Munshi NC.

PMID: 21660045; PMCID: PMC3483794

Extensive pancreas regeneration following acinar-specific disruption of Xbp1 in mice.

October 1, 2011
Hess DA, Humphrey SE, Ishibashi J, Damsz B, Lee AH, Glimcher LH, Konieczny SF

Extensive pancreas regeneration following acinar-specific disruption of Xbp1 in mice.

Gastroenterology. 2011 Oct;141(4):1463-72.

Hess DA, Humphrey SE, Ishibashi J, Damsz B, Lee AH, Glimcher LH, Konieczny SF.

PMID: 21704586

The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism.

June 12, 2011
Ann-Hwee Lee, PhD

The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism.

Nat Med. 2011 Jun 12;17(7):812-5.

Lee JH, Giannikopoulos P, Duncan SA, Wang J, Johansen CT, Brown JD, Plutzky J, Hegele RA, Glimcher LH, Lee AH.

PMID: 21666694

Dual and opposing roles of the unfolded protein response regulated by IRE1alpha and XBP1 in proinsulin processing and insulin secretion.

May 24, 2011
Lee AH, Heidtman K, Hotamisligil GS, Glimcher LH

Dual and opposing roles of the unfolded protein response regulated by IRE1alpha and XBP1 in proinsulin processing and insulin secretion.

Proc Natl Acad Sci U S A. 2011 May 24;108(21):8885-90.

Lee AH, Heidtman K, Hotamisligil GS, Glimcher LH.

PMID: 21555585

XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum

December 1, 2010
Huh WJ, Esen E, Geahlen JH, Bredemeyer AJ, Lee AH, Shi G, Konieczny SF, Glimcher LH, Mills JC

XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum

Gastroenterology. 2010 Dec;139(6):2038-49.

Huh WJ, Esen E, Geahlen JH, Bredemeyer AJ, Lee AH, Shi G, Konieczny SF, Glimcher LH, Mills JC.

PMID: 20816838; PMCID: PMC2997137

TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages.

May 1, 2010
Martinon F, Chen X, Lee AH, Glimcher LH

TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages.

Nat Immunol. 2010 May;11(5):411-8.

Martinon F, Chen X, Lee AH, Glimcher LH.

PMID: 20351694; PMCID: PMC3113706

XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development

September 28, 2009
Todd DJ, McHeyzer-Williams LJ, Kowal C, Lee AH, Volpe BT, Diamond B, McHeyzer-Williams MG, Glimcher LH

XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development

J Exp Med. 2009 Sep 28;206(10):2151-9.

Todd DJ, McHeyzer-Williams LJ, Kowal C, Lee AH, Volpe BT, Diamond B, McHeyzer-Williams MG, Glimcher LH.

PMID: 19752183; PMCID: PMC2757870

Intersection of the unfolded protein response and hepatic lipid metabolism

September 1, 2009
Lee AH, Glimcher LH

Intersection of the unfolded protein response and hepatic lipid metabolism

Cell Mol Life Sci. 2009 Sep;66(17):2835-50.

Lee AH, Glimcher LH.

PMID: 19468685; PMCID: PMC3096022

From sugar to fat: How the transcription factor XBP1 regulates hepatic lipogenesis

September 1, 2009
Glimcher LH, Lee AH

From sugar to fat: How the transcription factor XBP1 regulates hepatic lipogenesis

Ann N Y Acad Sci. 2009 Sep;1173 Suppl 1:E2-9.

Glimcher LH, Lee AH.

PMID: 19751410; PMCID: PMC3096021

XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease

September 5, 2008
Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EE, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS

XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease

Cell. 2008 Sep 5;134(5):743-56.

Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EE, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS.

PMID: 18775308; PMCID: PMC2586148

Regulation of hepatic lipogenesis by the transcription factor XBP1

June 13, 2008
Lee AH, Scapa EF, Cohen DE, Glimcher LH

Regulation of hepatic lipogenesis by the transcription factor XBP1

Science. 2008 Jun 13;320(5882):1492-6.

Lee AH, Scapa EF, Cohen DE, Glimcher LH.

PMID: 18556558; PMCID: PMC3620093

Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis.

January 15, 2008
Hetz C, Lee AH, Gonzalez-Romero D, Thielen P, Castilla J, Soto C, Glimcher LH

Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis.

Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):757-62.

Hetz C, Lee AH, Gonzalez-Romero D, Thielen P, Castilla J, Soto C, Glimcher LH.

PMID: 18178615; PMCID: PMC2206609

The endoplasmic reticulum stress response in immunity and autoimmunity

January 1, 2008
Todd DJ, Lee AH, Glimcher LH

The endoplasmic reticulum stress response in immunity and autoimmunity

Nat Rev Immunol. 2008 Sep;8(9):663-74.

Todd DJ, Lee AH, Glimcher LH.

PMID: 18670423

Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha.

April 28, 2006
Hetz C, Bernasconi P, Fisher J, Lee AH, Bassik MC, Antonsson B, Brandt GS, Iwakoshi NN, Schinzel A, Glimcher LH, Korsmeyer SJ

Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha.

Science. 2006 Apr 28;312(5773):572-6.

Hetz C, Bernasconi P, Fisher J, Lee AH, Bassik MC, Antonsson B, Brandt GS, Iwakoshi NN, Schinzel A, Glimcher LH, Korsmeyer SJ.

PMID: 16645094

Human cytomegalovirus protein US11 provokes an unfolded protein response that may facilitate the degradation of class I major histocompatibility complex products

March 1, 2005
Tirosh B, Iwakoshi NN, Lilley BN, Lee AH, Glimcher LH, Ploegh HL

Human cytomegalovirus protein US11 provokes an unfolded protein response that may facilitate the degradation of class I major histocompatibility complex products

J Virol. 2005 Mar;79(5):2768-79.

Tirosh B, Iwakoshi NN, Lilley BN, Lee AH, Glimcher LH, Ploegh HL.

PMID: 15708995; PMCID: PMC548438

XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands

January 1, 2005
Lee AH, Chu GC, Iwakoshi NN, Glimcher LH

XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands

EMBO J. 2005 Dec 21;24(24):4368-80.

Lee AH, Chu GC, Iwakoshi NN, Glimcher LH.

PMID: 16362047; PMCID: PMC1356340

Research Faculty

General Contact

Ann-Hwee Lee, PhD
Pathology and Laboratory Medicine
Assistant Professor of Pathology and Laboratory Medicine
Weill Cornell Medical College
1300 York Avenue, E-012
New York, NY 10065
Tel: 212-746-9087
Fax: 212-746-9226
shb2032@med.cornell.edu

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