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

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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

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

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

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

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

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

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

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

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.

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

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.

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

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

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

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

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

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

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

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

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

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

Explore

Ji-Hye Paik, PhD, Principal Investigator

Active Projects

Active Grants

Selected Publications

Functional regulation of FoxO1 in neural stem cell differentiation

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

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

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

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

Metabolic circuits in neural stem cells.

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

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

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

ZNF365 promotes stalled replication forks recovery to maintain genome stability.

ZNF365 promotes stability of fragile sites and telomeres.

FoxOs in neural stem cell fate decision

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

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

Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice

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

PI3 kinase signals BCR-dependent mature B cell survival

FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis

Codependent activators direct myoblast-specific MyoD transcription

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

FoxOs in the maintenance of vascular homeostasis

Faculty

Explore

Laboratory of Stem Cell Aging and Cancer

Ji-Hye Paik, PhD, Principal Investigator

Active Projects

Active Grants

Selected Publications

Functional regulation of FoxO1 in neural stem cell differentiation

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

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

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

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

Metabolic circuits in neural stem cells.

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

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

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

ZNF365 promotes stalled replication forks recovery to maintain genome stability.

ZNF365 promotes stability of fragile sites and telomeres.

FoxOs in neural stem cell fate decision

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

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

Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice

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

PI3 kinase signals BCR-dependent mature B cell survival

FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis

Codependent activators direct myoblast-specific MyoD transcription

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

FoxOs in the maintenance of vascular homeostasis

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Faculty