Skip to Content

'
Hui-Kuan Lin, Ph.D.

Present Title & Affiliation

Primary Appointment

Associate Professor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Faculty, Graduate School of Biomedical Sciences (GSBS), The University of Texas Health Science Center, Houston, TX

Research Interests

• Ubiquitination and Cancers
• Cancer invasion and Metastasis
• PTEN/PI3K/Akt signaling in cancers
• Cytoplamic PML in Cancers
• The biology of normal stem cells and cancer stem cells

The research interests in my lab aim to decipher the signal transduction pathways important for tumorigenesis and cancer metastasis. We have combined the biochemical approaches and genetic mouse modeling to address the relevant oncogene and tumor suppressor gene networks in cancer progression and metastasis. Several areas of the research are actively studied in the lab.

1. The PTEN/PI3K/Akt pathway in cancer progression and metastasis. The PTEN/PI3K/Akt pathway is aberrant activated in various human cancers and plays a critical role in cancer initiation and progression, as determined by the genetic mouse models. Our current research goals aim to identify the downstream effectors critical for the tumor phenotypes induced by the activated PI3K/Akt pathway by using the Pten knockdown mouse and conditional Ptenlox/Lox mouse model. In addition, we are also interested to study how the PTEN/PI3K/Akt pathway is regulated and to explore the mechanism by which this pathway regulates the functions of normal stem cells and cancer stem cells.

2. The novel functions of the cytoplasmic PML (cPML) in signal transduction and cancers. PML (promyelocytic leukemia protein) is involved in the development of acute promyolucytic leukemias. We have recently discovered for the first time the biological functions of cPML and identified cPML as a key regulator of TGF- signaling. Our current research goals aim to decipher novel signaling transduction pathways regulated by cPML and to understand how cPML regulates cancer development using the biochemical approaches and genetic mouse models.

3. Ubiquitination and Cancers. The ubiquitination pathway has recently emerged to play an important role in many aspects of biological functions and has linked to cancer development. We are particularly interested in studying the potential role of Skp2 and TRAF6, two key E3 ligases involved in p27-mediated cell cycle regulation and Toll-like receptor signaling, respectively, in many aspects of the biological functions and cancer progression and metastasis. We are also interested to study how their activity and functions are regulated in the cells.

Office Address

The University of Texas MD Anderson Cancer Center
1515 Holcombe Blvd.
Unit Number: 108
Houston, TX 77030
Room Number: Y7.6079
Phone: 713-794-5224
Fax: 713-794-3270

Education & Training

Degree-Granting Education

2002 University of Rochester, Rochester, NY, PHD, Pathology (Cancer Biology)
1995 National Taiwan University, Taipei, Taiwan, Taiwan, MS, Pharmacology
1993 National Taiwan University, Taipei, Taiwan, Taiwan, BS, Pharmacy

Postgraduate Training

2002-2007 Research Fellow, Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY, Dr. Pier Paolo Pandolfi

Experience/Service

Academic Appointments

Assistant Professor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2/2007-8/2011
Faculty, Cancer Biology Program, Graduate School of Biomedical Science, The University of Texas Health Science Center and MD Anderson Cancer Center, Houston, TX, 2007-present

Selected Publications

Peer-Reviewed Original Research Articles

1. Chan CH, Morrow JK, Li CF, Gao Y, Jin G, Moten A, Stagg LJ, Ladbury JE, Cai Z, Xu D, Logothetis CJ, Hung MC, Zhang S, Lin HK. Pharmacological Inactivation of Skp2 SCF Ubiquitin Ligase Restricts Cancer Stem Cell Traits and Cancer Progression. Cell 154(3):556-68, 8/2013.
2. Yang WL, Jin G, Li CF, Jeong YS, Moten A, Xu D, Feng Z, Chen W, Cai Z, Darnay B, Gu W, Lin HK. Cycles of ubiquitination and deubiquitination critically regulate growth factor-mediated activation of Akt signaling. Sci Signal 6(257):ra3, 1/2013. e-Pub 1/2013. PMID: 23300340.
3. Chen D, Sun Y, Wei Y, Zhang P, Rezaeian AH, Teruya-Feldstein J, Gupta S, Liang H, Lin HK, Hung MC, Ma L. LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker. Nat Med 18(10):1511-7, 9/2012. e-Pub 9/2012. PMID: 23001183.
4. Wu J, Zhang X, Zhang L, Wu CY, Rezaeian AH, Chan CH, Li JM, Wang J, Gao Y, Han F, Jeong YS, Yuan X, Khanna KK, Jin J, Zeng YX, Lin HK. Skp2 E3 ligase integrates ATM activation and homologous recombination repair by ubiquitinating NBS1. Mol Cell 46(3):351-61, 5/2012. e-Pub 3/2012. PMID: 22464731.
5. Chan CH, Li CF, Yang WL, Gao Y, Lee SW, Feng Z, Huang HY, Tsai KK, Flores LG, Shao Y, Hazle JD, Yu D, Wei W, Sarbassov D, Hung MC, Nakayama KI, Lin HK. The Skp2-SCF E3 Ligase Regulates Akt Ubiquitination, Glycolysis, Herceptin Sensitivity, and Tumorigenesis. Cell 149(5):1098-111, 5/2012. PMID: 22632973.
6. Wu J, Lee SW, Zhang X, Han F, Kwan SY, Yuan X, Yang WL, Jeong YS, Rezaeian AH, Gao Y, Zeng YX, Lin HK. Foxo3a transcription factor is a negative regulator of Skp2 and Skp2 SCF complex. Oncogene. e-Pub 2/2012. PMID: 22310285.
7. Wang J, Han F, Wu J, Lee SW, Chan CH, Wu CY, Yang WL, Gao Y, Zhang X, Jeong YS, Moten A, Samaniego F, Huang P, Liu Q, Zeng YX, Lin HK. The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal. Blood 118(20):5429-38, 11/2011. e-Pub 9/2011. PMCID: PMC3217347.
8. Wu CY, Kang HY, Yang WL, Wu J, Jeong YS, Wang J, Chan CH, Lee SW, Zhang X, Lamothe B, Campos AD, Darnay BG, Lin HK. Critical Role of Monoubiquitination of Histone H2AX Protein in Histone H2AX Phosphorylation and DNA Damage Response. J Biol Chem 286(35):30806-15, 9/2011. e-Pub 6/2011. PMCID: PMC3162441.
9. Tao RH, Berkova Z, Wise JF, Rezaeian AH, Daniluk U, Ao X, Hawke DH, Karp JE, Lin HK, Molldrem JJ, Samaniego F. PMLRAR{alpha} binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo. Blood 118(11):3107-18, 9/2011. e-Pub 7/2011. PMID: 21803845.
10. Chen CH, Shaikenov T, Peterson TR, Aimbetov R, Bissenbaev AK, Lee SW, Wu J, Lin HK, Sarbassov dos D. ER stress inhibits mTORC2 and Akt signaling through GSK-3ß-mediated phosphorylation of rictor. Sci Signal 4(161):ra10, 2011. e-Pub 2/2011. PMID: 21343617.
11. Giorgi C, Ito K, Lin HK, Santangelo C, Wieckowski MR, Lebiedzinska M, Bononi A, Bonora M, Duszynski J, Bernardi R, Rizzuto R, Tacchetti C, Pinton P, Pandolfi PP. PML Regulates Apoptosis at Endoplasmic Reticulum by Modulating Calcium Release. Science 330(6008):1247-51, 11/2010. e-Pub 10/2010. PMCID: PMC3017677.
12. Chan CH, Lee SW, Li CF, Wang J, Yang WL, Wu CY, Wu J, Nakayama KI, Kang HY, Huang HY, Hung MC, Pandolfi PP, Lin HK. Identification of a transcription network critical for RhoA gene expression and cancer metastasis. Nat Cell Biol 12(12):457-467, 5/2010. e-Pub 4/2010. PMID: 20383141.
13. Lin HK, Chen Z, Wang G, Lee SW, Wang J, Chan CH, Yang WL, Nakayama KI, Cordon-Cardo C, Teruya-Feldstein J, Pandolfi PP. Skp2 targeting suppresses tumorigenesis through induction of cellular senescence independently of p19Arf/p53. Nature 464(7287):374-379, 3/2010. PMCID: PMC2928066.
14. Yang WL, Wang J, Chan CH, Lee SW, Campos AD, Lamothe B, Hur L, Grabiner BC, Lin X, Darnay BG, Lin HK. The E3 ligase TRAF6 regulates Akt ubiquitination and activation. Science 325(5944):1134-1138, 8/2009. PMID: 19713527.
15. Lin HK, Wang G, Chen Z, Teruya-Feldstein J, Liu Y, Chan CH, Yang WL, Erdjument-Bromage H, Nakayama KI, Nimer S, Tempst P, Pandolfi PP. Phosphorylation-dependent regulation of Skp2 cytosolic localization and oncogenic function of Skp2 by Akt/PKB. Nat Cell Biol 11(4):420-432, 4/2009. e-Pub 3/2009. PMCID: PMC2830812.
16. Chen Z, Carracedo A, Lin HK, Koutcher JA, Behrendt N, Egia A, Gerald W, Teruya-Feldstein J, Loda M, Pandolfi PP. Oncosuppressive and tumor-promoting cell specific outcomes of p19Arf loss uncoupled from p53. Sci Signal 2:ra44, 2009. PMID: 19690330.
17. Shen TH, Lin HK, Scaglioni PP, Yung TM, Pandolfi PP. The mechanisms of PML-nulcear body formation. Mol. Cell 24:331-339, 2006.
18. Chen Z, Trotman LC, Dotan ZA, Lin HK, Niki M, Koutcher JA, Ludwig T, Cordon-Cardo, C, Pandolfi PP. Critical role of p53 dependent cellular senescence in suppression of Pten deficient tumourigenesis. Nature 436:725-730, 2005.
19. Lin HK, Bergmann S, Pandolfi PP. Cytoplasmic PML function in TGF-beta signaling. Nature 431:205- 211, 2004.
20. Lin HK, Hu YC, Lee TK, Chang C. Regulation of androgen receptor signaling by PTEN tumor suppressor through distinct mechanisms in prostate Cancer Cells. Mol. Endocrinol. 18:2409-2423, 2004.
21. Wang L, Lin HK, Hu YC, Xie S, Yang L, Chang C. Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 in prostate cells. J. Biol. Chem. 279, 2004.
22. Lin HK, Hu YC, Yang L, Altuwaijri S, Kang HY, Chang C. Suppression vs induction of androgen receptor functions by the phosphatidylinositol 3-Kinase/Akt pathway in prostate cancer LNCaP cells with different passage numbers. J. Biol. Chem. 278:50902-50907, 2003.
23. Lin HK, Wang L, Hu YC, Altuwaijri S, Chang C. Phosphorylation-dependent ubiquitination and degradation of androgen receptor by Akt requires Mdm2 E3 ligase. EMBO J 21(15):4037-48, 2002. PMCID: PMC126152.
24. Lin HK, Altuwaijri S, Kan PY, Chang C. Proteasome activity is required for androgen receptor transcriptional activity via regulation of androgen receptor nuclear translocation and interaction with androgen receptor coregulators in prostate cancer cells. J. Biol. Chem. 277:36570-36576, 2002.
25. Lin HK, Yeh S, Kang HY, Chang C. Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor. Proc. Natl. Acad. Sci. USA 98:7200-7205, 2001.

Invited Articles

1. Wang G, Chan CH, Gao Y, Lin HK. Novel roles of Skp2 E3 ligase in cellular senescence, cancer progression and metastasis. Chin J Cancer 31(4):169-77, 4/2012. e-Pub 12/23/2011. PMID: 22200179.
2. Chan CH, Gao Y, Moten A, Lin HK. Novel senescence pathways in cancer progression. J. Mol. Med. 89:857-867, 2011.
3. Yang WL, Wu CY, Wu J, Lin HK. Regulation of Akt signaling activation by ubiquitination. Cell Cycle 9(3):487-497, 2/2010. PMID: 20081374.
4. Yang WL, Zhang X, Lin HK. Emerging role of ubiquitination in protein kinase and phosphatase activation and cancer development. Oncogene 29:4439-503, 2010.
5. Chan CH, Lin HK. Regulation of Skp2 E3 ligase activitiy and its role in cancer progression and metastasis. Scientific World Journal 10:1001-15, 2010.
6. Lin HK, Bergmann S, Pandolfi PP. Deregulated TGF-beta signaling in leukemogenesis. Oncogene 24(37):5693-700, 8/2005. PMID: 16123802.

Last updated: 1/28/2014