Pathology & Laboratory Medicine

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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

Selected Publications

Functional regulation of FoxO1 in neural stem cell differentiation

Ji-Hye Paik, PhD

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

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

Ji-Hye Paik, PhD

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

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

Ji-Hye Paik, PhD

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

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

Ji-Hye Paik, PhD

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

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

Ji-Hye Paik, PhD

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

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Metabolic circuits in neural stem cells.

Ji-Hye Paik, PhD

Metabolic circuits in neural stem cells.

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

Kim DY, Rhee I, Paik J.

PMID: 25037158

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

Ji-Hye Paik, PhD

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

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

Ji-Hye Paik, PhD

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

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

Ji-Hye Paik, PhD

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.

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ZNF365 promotes stalled replication forks recovery to maintain genome stability.

Ji-Hye Paik, PhD

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

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ZNF365 promotes stability of fragile sites and telomeres.

Ji-Hye Paik, PhD

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.

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FoxOs in neural stem cell fate decision

Ji-Hye Paik, PhD

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

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

Ji-Hye Paik, PhD

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

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

Ji-Hye Paik, PhD

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

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Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice

Ji-Hye Paik, PhD

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

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

Ji-Hye Paik, PhD

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

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PI3 kinase signals BCR-dependent mature B cell survival

Ji-Hye Paik, PhD

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

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FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis

Ji-Hye Paik, PhD

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

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Codependent activators direct myoblast-specific MyoD transcription

Ji-Hye Paik, PhD

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

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

Ji-Hye Paik, PhD

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

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FoxOs in the maintenance of vascular homeostasis

Ji-Hye Paik, PhD

FoxOs in the maintenance of vascular homeostasis

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

Paik JH.

PubMed PMID: 17052184

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Weill Cornell Medicine Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464 Fax: (212) 746-8192