Laboratory of Stem Cell Aging and Cancer

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Laboratory of Stem Cell Aging and Cancer

Ji-Hye Paik, PhD, Principal Investigator

We aim to understand the homeostatic mechanism of adult stem cells that is intimately linked to aging and cancer, with a hope to apply these principles for regenerative and cancer therapeutics. We employ multi-disciplinary approaches including mouse models, cell and molecular biology, metabolomics and genomics. We currently pursue PI3K-Akt-FoxO-mediated homeostatic pathway and ZNF365-dependent genomic stability.

Active Projects

  • Mechanism of Oxidative Brain Aging
  • Functional role of ZNF365 in breast cancer pathogenesis

Active Grants

  • The Mechanisms Underlying How Oxidative Stress Influences Neural Stem Cell Fate.
    The goal is to determine the key mechanisms and cellular consequences of oxidative stress in NPCs.
    PI: Jihye Paik, PhD
    NIH/NIA
  • Targeting Methylation Potential of Therapy Resistant Gliomas
    PI: Jihye Paik, PhD
    Irma T. Hirschl Trust - Irma T. Hirschl Career Scientist Award
  • Molecular Mechanism of FOXO-dependent NSC fate decision in aging brain
    PI: Jihye Paik, PhD
    Ellison Medical Foundation
  • Function of FoxO in EGFR-targeted gliomas
    PI: Jihye Paik, PhD
    Sidney Kimmel Cancer Foundation
  • Neural mechanism of sympathoexcitation driven aging
    PI: Jihye Paik, PhD
    Anna-Maria and Stephen Kellen Foundation Junior Faculty Fellowship
  • Transdifferentiation is the molecular underpinning of targeted therapy resistance in gliomas
    PI: Jihye Paik, PhD
    Feldstein Medical Foundation Research Grant

Laboratory of Stem Cell Aging and Cancer

Ji-Hye Paik, PhD, Principal Investigator

We aim to understand the homeostatic mechanism of adult stem cells that is intimately linked to aging and cancer, with a hope to apply these principles for regenerative and cancer therapeutics. We employ multi-disciplinary approaches including mouse models, cell and molecular biology, metabolomics and genomics. We currently pursue PI3K-Akt-FoxO-mediated homeostatic pathway and ZNF365-dependent genomic stability.

Active Projects

  • Mechanism of Oxidative Brain Aging
  • Functional role of ZNF365 in breast cancer pathogenesis

Active Grants

  • The Mechanisms Underlying How Oxidative Stress Influences Neural Stem Cell Fate.
    The goal is to determine the key mechanisms and cellular consequences of oxidative stress in NPCs.
    PI: Jihye Paik, PhD
    NIH/NIA
  • Targeting Methylation Potential of Therapy Resistant Gliomas
    PI: Jihye Paik, PhD
    Irma T. Hirschl Trust - Irma T. Hirschl Career Scientist Award
  • Molecular Mechanism of FOXO-dependent NSC fate decision in aging brain
    PI: Jihye Paik, PhD
    Ellison Medical Foundation
  • Function of FoxO in EGFR-targeted gliomas
    PI: Jihye Paik, PhD
    Sidney Kimmel Cancer Foundation
  • Neural mechanism of sympathoexcitation driven aging
    PI: Jihye Paik, PhD
    Anna-Maria and Stephen Kellen Foundation Junior Faculty Fellowship
  • Transdifferentiation is the molecular underpinning of targeted therapy resistance in gliomas
    PI: Jihye Paik, PhD
    Feldstein Medical Foundation Research Grant

Selected Publications EXPAND ALL ON THIS PAGE

Functional regulation of FoxO1 in neural stem cell differentiation

October 16, 2015
Kim DY, Hwang I, Muller FL, Paik JH.

Functional regulation of FoxO1 in neural stem cell differentiation

Cell Death Differ. 2015 Oct 16. [Epub ahead of print] 

Kim DY, Hwang I, Muller FL, Paik JH.

PMID: 26470727

Forkhead box O transcription factors in chondrocytes regulate endochondral bone formation.

July 29, 2015
Eelen G, Verlinden L, Maes C, Beullens I, Gysemans C, Paik JH, DePinho RA, Bouillon R, Carmeliet G, Verstuyf A.

Forkhead box O transcription factors in chondrocytes regulate endochondral bone formation.

J Steroid Biochem Mol Biol. 2015 Jul 29. [Epub ahead of print]

Eelen G, Verlinden L, Maes C, Beullens I, Gysemans C, Paik JH, DePinho RA, Bouillon R, Carmeliet G, Verstuyf A.

PMID: 26232637

Development of Resistance to EGFR-Targeted Therapy in Malignant Glioma Can Occur through EGFR-Dependent and -Independent Mechanisms

May 15, 2015
Klingler S, Guo B, Yao J, Yan H, Zhang L, Vaseva AV, Chen S, Canoll P, Horner JW, Wang YA, Paik JH, Ying H, Zheng H.

Development of Resistance to EGFR-Targeted Therapy in Malignant Glioma Can Occur through EGFR-Dependent and -Independent Mechanisms

Cancer Res. 2015 May 15;75(10):2109-19.

Klingler S, Guo B, Yao J, Yan H, Zhang L, Vaseva AV, Chen S, Canoll P, Horner JW, Wang YA, Paik JH, Ying H, Zheng H.

PMID: 25808866; PMCID: PMC4433602

FoxO1 integrates direct and indirect effects of insulin on hepatic glucose production and glucose utilization

May 12, 2015
O-Sullivan I, Zhang W, Wasserman DH, Liew CW, Liu J, Paik J, DePinho RA, Stolz DB, Kahn CR, Schwartz MW, Unterman TG.

FoxO1 integrates direct and indirect effects of insulin on hepatic glucose production and glucose utilization

Nat Commun. 2015 May 12;6:7079.

O-Sullivan I, Zhang W, Wasserman DH, Liew CW, Liu J, Paik J, DePinho RA, Stolz DB, Kahn CR, Schwartz MW, Unterman TG.

PMID: 25963540

Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy

April 10, 2015
Milan G, Romanello V, Pescatore F, Armani A, Paik JH, Frasson L, Seydel A, Zhao J, Abraham R, Goldberg AL, Blaauw B, DePinho RA, Sandri M.

Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy

Nat Commun. 2015 Apr 10;6:6670.

Milan G, Romanello V, Pescatore F, Armani A, Paik JH, Frasson L, Seydel A, Zhao J, Abraham R, Goldberg AL, Blaauw B, DePinho RA, Sandri M.

PMID: 25858807; PMCID: PMC4403316

Metabolic circuits in neural stem cells.

November 1, 2014
Kim DY, Rhee I, Paik J.

Metabolic circuits in neural stem cells.

Cell Mol Life Sci. 2014 Nov;71(21):4221-41.

Kim DY, Rhee I, Paik J.

PMID: 25037158

Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase.

July 1, 2014
Zheng X, Zhai B, Koivunen P, Shin SJ, Lu G, Liu J, Geisen C, Chakraborty AA, Moslehi JJ, Smalley DM, Wei X, Chen X, Chen Z, Beres JM, Zhang J, Tsao JL, Brenner MC, Zhang Y, Fan C, DePinho RA, Paik J, Gygi SP, Kaelin WG Jr, Zhang Q.

Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase.

Genes Dev. 2014 Jul 1;28(13):1429-44.

Zheng X, Zhai B, Koivunen P, Shin SJ, Lu G, Liu J, Geisen C, Chakraborty AA, Moslehi JJ, Smalley DM, Wei X, Chen X, Chen Z, Beres JM, Zhang J, Tsao JL, Brenner MC, Zhang Y, Fan C, DePinho RA, Paik J, Gygi SP, Kaelin WG Jr, Zhang Q.

PMID: 24990963; PMCID: PMC4083087

mTORC1 promotes denervation-induced muscle atrophy through a mechanism involving the activation of FoxO and E3 ubiquitin ligases.

February 1, 2014
Tang H, Inoki K, Lee M, Wright E, Khuong A, Khuong A, Sugiarto S, Garner M, Paik J, DePinho RA, Goldman D, Guan KL, Shrager JB.

mTORC1 promotes denervation-induced muscle atrophy through a mechanism involving the activation of FoxO and E3 ubiquitin ligases.

Sci Signal. 2014 Feb 25;7(314):ra18.

Tang H, Inoki K, Lee M, Wright E, Khuong A, Khuong A, Sugiarto S, Garner M, Paik J, DePinho RA, Goldman D, Guan KL, Shrager JB.

PMID: 24570486

FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells.

October 2, 2013
Yeo H, Lyssiotis CA, Zhang Y, Ying H, Asara JM, Cantley LC, Paik JH.

FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells.

EMBO J. 2013 Oct 2;32(19):2589-602. 

Yeo H, Lyssiotis CA, Zhang Y, Ying H, Asara JM, Cantley LC, Paik JH.

PMID: 24013118; PMCID: PMC3791369.

ZNF365 promotes stalled replication forks recovery to maintain genome stability.

September 1, 2013
Zhang Y, Park E, Kim CS, Paik JH.

ZNF365 promotes stalled replication forks recovery to maintain genome stability.

Cell Cycle. 2013 Sep 1;12(17):2817-28. 

Zhang Y, Park E, Kim CS, Paik JH.

PMID: 23966166

ZNF365 promotes stability of fragile sites and telomeres.

July 1, 2013
Zhang Y, Shin SJ, Liu D, Ivanova E, Foerster F, Ying H, Zheng H, Xiao Y, Chen Z, Protopopov A, Depinho RA, Paik JH.

ZNF365 promotes stability of fragile sites and telomeres.

Cancer Discov. 2013 Jul;3(7):798-811.

Zhang Y, Shin SJ, Liu D, Ivanova E, Foerster F, Ying H, Zheng H, Xiao Y, Chen Z, Protopopov A, Depinho RA, Paik JH.

PMID: 23776040; PMCID: PMC3710545.

FoxOs in neural stem cell fate decision

June 1, 2013
Ro SH, Liu D, Yeo H, Paik, JH

FoxOs in neural stem cell fate decision

Arch Biochem Biophys. 2013 Jun;534(1-2):55-63.

Ro SH, Liu D, Yeo H, Paik JH.

PMID: 22902436

Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism.

April 27, 2012
Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik JH, Lim C, Guimaraes AR, Martin ES, Chang J, Hezel AF, Perry SR, Hu J, Gan B, Xiao Y, Asara JM,

Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism.

Cell. 2012 Apr 27;149(3):656-70.

Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik JH, Lim C, Guimaraes AR, Martin ES, Chang J, Hezel AF, Perry SR, Hu J, Gan B, Xiao Y, Asara JM, Weissleder R, Wang YA, Chin L, Cantley LC, DePinho RA.

PMID: 22541435; PMCID: PMC3472002

STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA

January 1, 2012
Chen AJ, Paik JH, Zhang H, Shukla SA, Mortensen R, Hu J, Ying H, Hu B, Hurt J,Farny N, Dong C, Xiao Y, Wang YA, Silver PA, Chin L, Vasudevan S, Depinho RA

STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA

Genes Dev. 2012 Jul 1;26(13):1459-72.

Chen AJ, Paik JH, Zhang H, Shukla SA, Mortensen R, Hu J, Ying H, Hu B, Hurt J, Farny N, Dong C, Xiao Y, Wang YA, Silver PA, Chin L, Vasudevan S, Depinho RA.

PMID: 22751500; PMCID: PMC3403014

Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice

January 1, 2011
Jaskelioff M, Muller FL, Paik JH, Thomas E, Jiang S, Adams AC, Sahin E, Kost-Alimova M, Protopopov A, Cadiñanos J, Horner JW, Maratos-Flier E, Depinho RA

Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice

Nature. 2011 Jan 6;469(7328):102-6.

Jaskelioff M, Muller FL, Paik JH, Thomas E, Jiang S, Adams AC, Sahin E, Kost-Alimova M, Protopopov A, Cadiñanos J, Horner JW, Maratos-Flier E, Depinho RA.

PMID: 21113150; PMCID: PMC3057569

PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas

January 1, 2010
Zheng H, Ying H, Wiedemeyer R, Yan H, Quayle SN, Ivanova EV, Paik JH, Zhang H, Xiao Y, Perry SR, Hu J, Vinjamoori A, Gan B, Sahin E, Chheda MG, Brennan C, Wang YA, Hahn WC, Chin L, Depinho RA

PLAGL2 Regulates Wnt Signaling to Impede Differentiation in Neural Stem Cells and Gliomas

Cancer Cell. 2010 May 18;17(5):497-509.

Zheng H, Ying H, Wiedemeyer R, Yan H, Quayle SN, Ivanova EV, Paik JH, Zhang H, Xiao Y, Perry SR, Hu J, Vinjamoori A, Gan B, Sahin E, Chheda MG, Brennan C, Wang YA, Hahn WC, Chin L, DePinho RA.

PMID: 20478531; PMCID: PMC2900858

FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis

January 1, 2009
Paik JH, Ding Z,, Narurkar R.,Ramkissoon S., Muller F., Kamoun W. S., Chae S., Zheng H., Ying H., Mahoney J., Hiller D., Jiang S., Protppopov A.,Wong W.H., Chin L., Ligon K.L., DePinho RA

FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis

Cell Stem Cell. 2009 Nov 6;5(5):540-53.

Paik JH, Ding Z, Narurkar R, Ramkissoon S, Muller F, Kamoun WS, Chae SS, Zheng H, Ying H, Mahoney J, Hiller D, Jiang S, Protopopov A, Wong WH, Chin L, Ligon KL, DePinho RA.

PMID: 19896444; PMCID: PMC3285492

PI3 kinase signals BCR-dependent mature B cell survival

January 1, 2009
Srinivasan L, Sasaki Y, Calado DP, Zhang B, Paik JH, DePinho RA, Kutok JL,Kearney JF, Otipoby KL, Rajewsky K

PI3 kinase signals BCR-dependent mature B cell survival

Cell. 2009 Oct 30;139(3):573-86.

Srinivasan L, Sasaki Y, Calado DP, Zhang B, Paik JH, DePinho RA, Kutok JL, Kearney JF, Otipoby KL, Rajewsky K.

PMID: 19879843; PMCID: PMC2787092

Codependent activators direct myoblast-specific MyoD transcription

January 1, 2008
Hu P, Geles KG, Paik JH, DePinho RA, Tjian R

Codependent activators direct myoblast-specific MyoD transcription

Dev Cell. 2008 Oct;15(4):534-46.

Hu P, Geles KG, Paik JH, DePinho RA, Tjian R.

PMID: 18854138; PMCID: PMC2614327

FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis

January 1, 2007
Paik, JH*. Kollipara, R*, Chu, G., Ji, H., Thhotova, Z., Miao L, Carrasco DR., Gilliland, DG, Wong WH, Chin L., Castrillon, DH ., DePinho, RA

FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis

Cell. 2007 Jan 26;128(2):309-23.

Paik JH, Kollipara R, Chu G, Ji H, Xiao Y, Ding Z, Miao L, Tothova Z, Horner JW, Carrasco DR, Jiang S, Gilliland DG, Chin L, Wong WH, Castrillon DH, DePinho RA.

PMID: 17254969; PMCID: PMC1855089

FoxOs in the maintenance of vascular homeostasis

October 1, 2006
Paik, JH

FoxOs in the maintenance of vascular homeostasis

Biochem Soc Trans. 2006 Nov;34(Pt 5):731-4.

Paik JH.

PubMed PMID: 17052184

Research faculty

Director

General Contact

Ji-Hye Paik, Ph.D.
Assistant Professor of Pathology and Laboratory Medicine
Weill Cornell Medical College
1300 York Avenue, C-320
New York, NY 10065
Tel: 212-746-6151
Fax: 212-746-8302
jep2025@med.cornell.edu

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