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profileTae Ho Lee, Ph.D.

TitleAssistant Professor of Medicine
InstitutionBeth Israel Deaconess Medical Center
DepartmentMedicine
AddressBeth Israel Deaconess Medical Center
Gerontology, DA 519A
330 Brookline Ave
Boston MA 02215
Phone617/667-0091
Fax617/667-0102
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Collapse Overview 
Collapse overview
Our laboratory focuses on understanding the role that post-translational modifications in proteins including phosphorylation play in aging and age-related disease. Significantly, many of these aging modulators in other biological processes are regulated by protein phosphorylation, whose deregulation contributes to age-related disease, notably Alzheimer’s disease (AD). However, the significance and regulation of this signaling pathway in aging is largely unknown

We have recently shown that DAPK1 (death-associated protein kinase 1) is the inhibitory kinase responsible for phosphorylation of Pin1. This is especially exciting because Pin1 is a pivotal role in aging processes and Pin1 knockout mice display widespread premature aging and AD-like phenotypes. Our lab is interested in understanding how DAPK1 mediate the interplay between Pin1 activity and aging.

The main goals of our research are: 1) to determine the molecular mechanisms by which DAPK1 regulates in aging, 2) to understand pathogenic mechanisms in age-related diseases, and 3) to identify novel DAPK1 substrates and determine their function in normal aging and age-related disease. To accomplish these goals, our research integrates molecular biology, biochemistry, proteomics, cell biology and mouse genetics. This study will have a significant impact upon our basic understanding of aging and age-related disease, and might eventually facilitate the development of novel treatments of human diseases.

Please see our website for more information:
http://www.bidmc.org/Research/Departments/Medicine/Divisions/Gerontology/Laboratories/Molecular-and-Cellular-Biology-of-Aging.aspx


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Collapse selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Wei S, Kozono S, Kats L, Nechama M, Li W, Guarnerio J, Luo M, You MH, Yao Y, Kondo A, Hu H, Bozkurt G, Moerke NJ, Cao S, Reschke M, Chen CH, Rego EM, Lo-Coco F, Cantley LC, Lee TH, Wu H, Zhang Y, Pandolfi PP, Zhou XZ, Lu KP. Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer. Nat Med. 2015 May; 21(5):457-66. PMID: 25849135; PMCID: PMC4425616.
  2. Chen CH, Li W, Sultana R, You MH, Kondo A, Shahpasand K, Kim BM, Luo ML, Nechama M, Lin YM, Yao Y, Lee TH, Zhou XZ, Swomley AM, Allan Butterfield D, Zhang Y, Lu KP. Pin1 cysteine-113 oxidation inhibits its catalytic activity and cellular function in Alzheimer's disease. Neurobiol Dis. 2015 Apr; 76:13-23. PMID: 25576397; PMCID: PMC4423621.
  3. Yoon WS, Yoo Y, Lee TH, Park SH, Kim BM. MicroRNAs are potential biomarkers and therapeutic targets of atopic dermatitis. Jacobs J Allergy Immunol. 2015; 2:013.
  4. Kim BM, You MH, Chen CH, Lee S, Hong Y, Hong Y, Kimchi A, Zhou XZ, Lee TH. Death-associated protein kinase 1 has a critical role in aberrant tau protein regulation and function. Cell Death Dis. 2014 May 22; 5:e1237. PMID: 24853415; PMCID: PMC4047864.
  5. Liu P, Begley M, Michowski W, Inuzuka H, Ginzberg M, Gao D, Tsou P, Gan W, Papa A, Kim BM, Wan L, Singh A, Zhai B, Yuan M, Wang Z, Gygi SP, Lee TH, Lu KP, Toker A, Pandolfi PP, Asara JM, Kirschner MW, Sicinski P, Cantley L, Wei W. Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus. Nature. 2014 Apr 24; 508(7497):541-5. PMID: 24670654; PMCID: PMC4076493.
  6. Lee TH, Chang J, Kim BM. Saikosaponin C inhibits lipopolysaccharide-induced apoptosis by suppressing caspase-3 activation and subsequent degradation of focal adhesion kinase in human umbilical vein endothelial cells. Biochem Biophys Res Commun. 2014 Mar 14; 445(3):615-21. PMID: 24565837.
    View in: PubMed
  7. Liu P, Gan W, Inuzuka H, Lazorchak AS, Gao D, Arojo O, Liu D, Wan L, Zhai B, Yu Y, Yuan M, Kim BM, Shaik S, Menon S, Gygi SP, Lee TH, Asara JM, Manning BD, Blenis J, Su B, Wei W. Sin1 phosphorylation impairs mTORC2 complex integrity and inhibits downstream Akt signalling to suppress tumorigenesis. Nat Cell Biol. 2013 Nov; 15(11):1340-50. PMID: 24161930; PMCID: PMC3827117.
  8. Chen CH, Chang CC, Lee TH, Luo M, Huang P, Liao PH, Wei S, Li FA, Chen RH, Zhou XZ, Shih HM, Lu KP. SENP1 deSUMOylates and regulates Pin1 protein activity and cellular function. Cancer Res. 2013 Jul 01; 73(13):3951-62. PMID: 23633483; PMCID: PMC3818121.
  9. Min SH, Lau AW, Lee TH, Inuzuka H, Wei S, Huang P, Shaik S, Lee DY, Finn G, Balastik M, Chen CH, Luo M, Tron AE, Decaprio JA, Zhou XZ, Wei W, Lu KP. Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase. Mol Cell. 2012 Jun 29; 46(6):771-83. PMID: 22608923; PMCID: PMC3389221.
  10. Rangasamy V, Mishra R, Sondarva G, Das S, Lee TH, Bakowska JC, Tzivion G, Malter JS, Rana B, Lu KP, Kanthasamy A, Rana A. Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function. Proc Natl Acad Sci U S A. 2012 May 22; 109(21):8149-54. PMID: 22566623; PMCID: PMC3361382.
  11. Tun-Kyi A, Finn G, Greenwood A, Nowak M, Lee TH, Asara JM, Tsokos GC, Fitzgerald K, Israel E, Li X, Exley M, Nicholson LK, Lu KP. Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and type I interferon-mediated immunity. Nat Immunol. 2011 Jul 10; 12(8):733-41. PMID: 21743479; PMCID: PMC3298750.
  12. Lee TH, Pastorino L, Lu KP. Peptidyl-prolyl cis-trans isomerase Pin1 in ageing, cancer and Alzheimer disease. Expert Rev Mol Med. 2011 Jun 20; 13:e21. PMID: 21682951.
    View in: PubMed
  13. Lee TH, Chen CH, Suizu F, Huang P, Schiene-Fischer C, Daum S, Zhang YJ, Goate A, Chen RH, Zhou XZ, Lu KP. Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function. Mol Cell. 2011 Apr 22; 42(2):147-59. PMID: 21497122; PMCID: PMC3088080.
  14. Zhou XZ, Huang P, Shi R, Lee TH, Lu G, Zhang Z, Bronson R, Lu KP. The telomerase inhibitor PinX1 is a major haploinsufficient tumor suppressor essential for chromosome stability in mice. J Clin Invest. 2011 Apr; 121(4):1266-82. PMID: 21436583; PMCID: PMC3069765.
  15. Choi MS, Min SH, Jung H, Lee JD, Lee TH, Lee HK, Yoo OJ. The essential role of FKBP38 in regulating phosphatase of regenerating liver 3 (PRL-3) protein stability. Biochem Biophys Res Commun. 2011 Mar 11; 406(2):305-9. PMID: 21320469.
    View in: PubMed
  16. Soohoo CY, Shi R, Lee TH, Huang P, Lu KP, Zhou XZ. Telomerase inhibitor PinX1 provides a link between TRF1 and telomerase to prevent telomere elongation. J Biol Chem. 2011 Feb 04; 286(5):3894-906. PMID: 21119197; PMCID: PMC3030390.
  17. Lee TH, Zhou XZ, Lu KP . Pin1. UCSD-Nature Molecule pages. 2010.
  18. Ryo A, Wulf G, Lee TH, Lu KP. Pinning down HER2-ER crosstalk in SMRT regulation. Trends Biochem Sci. 2009 Apr; 34(4):162-5. PMID: 19269830.
    View in: PubMed
  19. Lee TH, Tun-Kyi A, Shi R, Lim J, Soohoo C, Finn G, Balastik M, Pastorino L, Wulf G, Zhou XZ, Lu KP. Essential role of Pin1 in the regulation of TRF1 stability and telomere maintenance. Nat Cell Biol. 2009 Jan; 11(1):97-105. PMID: 19060891; PMCID: PMC2699942.
  20. Balastik M, Ferraguti F, Pires-da Silva A, Lee TH, Alvarez-Bolado G, Lu KP, Gruss P. Deficiency in ubiquitin ligase TRIM2 causes accumulation of neurofilament light chain and neurodegeneration. Proc Natl Acad Sci U S A. 2008 Aug 19; 105(33):12016-21. PMID: 18687884; PMCID: PMC2575299.
  21. Lim J, Balastik M, Lee TH, Nakamura K, Liou YC, Sun A, Finn G, Pastorino L, Lee VM, Lu KP. Pin1 has opposite effects on wild-type and P301L tau stability and tauopathy. J Clin Invest. 2008 May; 118(5):1877-89. PMID: 18431510; PMCID: PMC2323189.
  22. Lu KP, Finn G, Lee TH, Nicholson LK. Prolyl cis-trans isomerization as a molecular timer. Nat Chem Biol. 2007 Oct; 3(10):619-29. PMID: 17876319.
    View in: PubMed
  23. Lee TH, Perrem K, Harper JW, Lu KP, Zhou XZ. The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated degradation and regulates telomere maintenance. J Biol Chem. 2006 Jan 13; 281(2):759-68. PMID: 16275645.
    View in: PubMed
  24. Discenza MT, He S, Lee TH, Chu LL, Bolon B, Goodyer P, Eccles M, Pelletier J. WT1 is a modifier of the Pax2 mutant phenotype: cooperation and interaction between WT1 and Pax2. Oncogene. 2003 Nov 06; 22(50):8145-55. PMID: 14603255.
    View in: PubMed
  25. Lee TH, Lwu S, Kim J, Pelletier J. Inhibition of Wilms tumor 1 transactivation by bone marrow zinc finger 2, a novel transcriptional repressor. J Biol Chem. 2002 Nov 22; 277(47):44826-37. PMID: 12239212.
    View in: PubMed
  26. Lee TH, Pelletier J. Functional characterization of WT1 binding sites within the human vitamin D receptor gene promoter. Physiol Genomics. 2001 Dec 21; 7(2):187-200. PMID: 11773605.
    View in: PubMed
  27. Lee TH, Moffett P, Pelletier J. The Wilms' tumor suppressor gene (wt1) product represses different functional classes of transcriptional activation domains. Nucleic Acids Res. 1999 Jul 15; 27(14):2889-97. PMID: 10390530; PMCID: PMC148503.
  28. Lee JH, Lee TH, Lim YB, Park YK, Kim CK, Min KH, Lee YN. Nucleotide sequence Determination and homology analysis of catechol 2,3-dioxygenase gene isolated from aniline-degrading Pseudmonas acidovorans. Kor. Jour. Microbiol. 1994; 32:480-85.
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