Faculty / Research

Chia-Hsin (Lori) Chan, PhD

Assistant Professor 

 

Ph.D.: National Taiwan University, Taiwan

Postdoctoral Fellowship: University of Texas MD Anderson Cancer Center

Basic Science Tower 8-121
631-444-3085/office  chia-hsin.chan@stonybrook.edu
Cancer Metabolism and Stemness

Tumor heterogeneity is frequently displayed in human cancers and is known as a major contributor for drug resistance, tumor relapse and consequently cancer death. Currently, there are two mechanisms that contribute to tumor heterogeneity. One mechanism is that during tumorigenesis, various normal cell clones acquire genetic/epigenetic alterations, thus give rise to heterogeneous tumor cells.  Another mechanism that accounts for tumor heterogeneity is the existence of cancer stem cells (CSCs). Therefore, my research focus is to decipher regulatory machinery responsible for tumor heterogeneity and hope to develop therapeutic strategies accordingly by pursuing the following directions.

1)      To delineate the network of metabolic reprogramming in tumor initiation and progression. Glucose metabolism reprogramming is a newly engaged cancer hallmark. Recently, ample evidence including my recent finding (Chan et al. Cell 2012) has demonstrated that targeting glycolysis could overcome resistance to current therapies, such as chemotherapy and targeted therapy (Herceptin therapy). Hence, my laboratory is interested in deciphering regulatory network for glucose metabolism, which will reveal novel therapeutic targets beneficial for cancer treatment.

2)      To explore regulatory machinery orchestrating EMT-driven cancer stemness and drug resistance. The CSC population preferably stays in quiescence stage (G0 phase) and thus adversely sensitizes to chemo- or radio-therapies. Epithelial to mesenchymal transition (EMT) program is responsible for cancer progression, drug resistance and recently is engaged in acquiring CSC properties. Thus, my research is to decode regulatory network of EMT, which will identify new strategies to eliminate CSC population and overcome drug resistance.

3)      Development of small molecule inhibitors targeting glycolysis or EMT as new therapeutic interventions. Once novel targets for cancer prevention have been identified as described above, I will use in silico screening to develop novel therapeutic arsenals accordingly. This research program is expected to identify effective inhibitors that are anticipated to overcome drug resistance and prolong tumor remission through targeting glycolysis or EMT. 

For a complete list of current publications please click HERE.

 

1. The DNA Damage Transducer RNF8 Facilitates Cancer Chemoresistance and Progression through Twist Activation.
Lee HJ, Li CF, Ruan D, Powers S, Thompson PA, Frohman MA, Chan CH. Molecular cell. 2016

2. Chan CH, Ko CC, Chang JG, Chen SF, Wu MS, Lin JT, Chow LP. (2006) Subcellular and Functional  Proteomic Analysis of the Cellular Responses Induced by Helicobacter pylori. Molecular & Cellular Proteomics 5:702–713 (No. 1 ranked journal in Proteomics field; 5-year impact factor: 9.4)

3. Lin HK, Wang G, Chen Z, Teruya-Feldstein J, Liu Y, Chan CH, Yang WL, Erdjument-Bromage H, Nimer S, Tempst P, Pandolfi PP (2009) Phosphorylation-dependent regulation of Skp2 cytosolic localization oncogenic function by Akt/PKB. Nat. Cell Biol. 11:420-432

4. Yang WL, Wang J, Chan CH, Lee SW, Campos AD, Hur L, Grabiner B, Lin X, Darnay B, Lin HK (2009). The E3 ligase TRAF6 regulates Akt ubiquitination and activation. Science 325:1134-1138.

5. Lin HK, Chen Z, Wang G, Lee SW, Wang J, Chan CH, Yang WL, Nakayama KI, Cordon-Cardo C, Teruya-Feldstein J, Pandolfi PP (2010). Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature (Article), 464, 374-379.

6. 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 (2010) Deciphering the transcription complex critical for RhoA gene expression and cancer metastasis. Nat. Cell Biol. (Article), 12, 457-467. 

7. Chan CH, Lee SW, Wang J, Lin HK (2010). Regulation of Skp2 Expression and Activity and Its Role In Cancer Progression. The ScientificWorld Journal 10, 1001–1015.  

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 (2011) The critical role of monoubiquitination of Histone H2AX in Histone H2AX phosphorylation and DNA damage response. J. Bio. Chem. 286:30806-30815.

9. 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. (2011) The role of Skp2 in hematopoietic stem cell quiescence, pool size and self-renewal. Blood 118:5429-38.

10. Chan CH, Gao Y, Moten A, Lin HK (2011). Novel ARF/p53-independent senescence pathway in cancer repression. J. Mol. Med. 89:857-867

11. Wang F, Chan CH, Chen K, Guan X, Lin HK, Tong Q (2012) Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation. Oncogene 31: 1546-57

12. Wu J, Zhang X, Zhang L, Wu CY, Rezaelan AH, Chan CH, Li JM, Wang J, Gao Y, Fei H, Jeong YS, Yuan X, Khanna KK, Jin J, Zeng YX, Lin HK (2012) Skp2 E3 ligase integrates ATM activation and homologous recombination repair by ubiquitinating NBS1. Mol. Cell 46: 351-61

13. Chan CH, Li CF, Yang WL, Gao Y, Lee SW, Huang HY, Tsai KT, Flores LG, Shao Y, Hazle JD, Yu D, Wei W, Sarbassov D, Hung, MC, Nakayama KI, Lin HK (2012). The Skp2 E3 ubiquitin ligase regulates Akt ubiquitination, glycolysis, Herceptin sensitivity and tumorigenesis. Cell 149: 1098–1111.  

14. Wang G, Chan CH, Gao Y, Lin HK. (2012) Novel roles of Skp2 E3 ligase in cellular senescence, cancer progression, and metastasis. Chin. J. Cancer 31: 169-177 

15. Song S*, Maru DM, Ajani JA,  Chan CH, Honjo S, Lin HK, Correa A, Hofstetter WL, Davila M, Stroehlein J, Mishra L* (2013). Loss of TGF-β Adaptor β2SP Activates Notch Signaling and SOX9 in Barrett’s Esophageal Adenocarcinoma. Cancer Research 73:2159-2169.

16.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* (2013). Pharmacological Skp2 inactivation restricts cancer stem cell traits and cancer progression. Cell 154:556-68.

 Research highlights by Sarah Seton-Rogers (2013) Nature Review Cancer 13, 609

Research highlights by Charlotte Harrison (2013) Nature Review Drug Discovery 12, 740-741

Research highlights in Cancer Discovery (2013) 3(10),OF30

17. Wagner, KW, Alam H, Dhar, SS, Giri U, Li N, Wei Y, Giri D, Cascone T, Kim JH, Ye Y, Multani A, Chan CH,  Erez B, Saigal B, Chung J,  Lin HK, Wu X, Hung MC, Heymach JV, Lee MG.(2013) KDM2A Activates ERK1/2 via DUSP3’s Epigenetic Repression and promotes NSCLC. J. Clin. Inv. 123: 5261-46

18. Kim JH, Sharma A, Dhar SS, Lee SH, Gu B, Chan CH, Lin HK, Lee MG (2014). UTX and MLL4 Coordinately Regulate Transcriptional Programs for Cell Proliferation and Invasiveness in Breast Cancer Cells. Cancer Research 74:1705-17.

19. Wang J, Han F, Lee SW, Wu J, Chan CH, Zhang X, Gao Y, Su HK, Feng ZZ, Xu DZ, Lin HK (2014).       E3-ligase Skp2 regulates β-catenin expression and maintains hematopoietic stem cell homing. Biochem

Biophys Res Commun. 445:566-71.

20. Chan CH, Morrow JK, Zhang S*, Lin HK* (2014). Skp2 is a dream target for cancer therapy. Cell              Cycle 13: 679-80.

21. Chan CH*, Jo U, Kohrman A, Rezaeian AH, Chou PC, Logothetis C, Lin, HK* (2014). Posttranslational regulation of Akt in human cancer. Cell & Bioscience (In press)

     * Correspondence author

22. Lee SW, Li CF, Jin G, Cai Z, Han F, Chan CH, Yang WL, Li BK, Rezaeian AH, Li HY, Huang HY, Lin HK (2015). Skp2-Dependent Ubiquitination and Activation of LKB1 Is Essential for Cancer Cell Survival under Energy Stress. Mol Cell 57: 1022-33

23. Xu D, Li CF, Zhang X, Gong Z, Chan CH, Lee SW, Jin G, Rezaeian AH, Han F, Wang J, Yang WL,
Feng ZZ, Chen W, Wu CY, Wang YJ, Chow LP, Zhu XF, Zeng YX, Lin HK.(2015) Skp2-MacroH2A1-
CDK8 axis orchestrates G2/M transition and tumorigenesis. Nat Commun (EPub)

24. Jin G, Lee SW, Zhang X, Cai Z, Gao Y, Chou PC, Rezaeian AH, Han F, Wang CY, Yao JC, Gong Z, Chan CH, Huang CY, Tsai FJ, Tsai CH, Tu SH, Wu CH, Sarbassov dos D, Ho YS, Lin HK. (2015) Skp2-Mediated RagA Ubiquitination Elicits a Negative Feedback to Prevent Amino-Acid-Dependent mTORC1 Hyperactivation by Recruiting GATOR1. Mol. Cell 58: 989-1000.
       
Patent
1. Zhang S, Lin HK, Chan CH, Morrow JK. Small Molecule Inhibitors Targeting the SKP2 Pathway for Cancer Treatment. US Provisional Patent application. (PATENT UTSC.P1114US.P1)



Research Group


Hong-Jen (Joshua) Lee
Postdoctoral Associate
Hong-Jen.Lee@stonybrook.edu

Jun Pan
Graduate Student (MCB Ph.D. program)
pjun2014@gmail.com

Diane Ruan
Graduate student (MCP MS Program)
diane.ruan@stonybrook.edu

Jiabei He
Graduate student (MCP MS Program)
jiabei.he.1@stonybrook.edu

Chia-Hsin (Lori) Chan Ph.D.
Assistant Professor
Department of Pharmacological Science
Basic Science Tower 8-121
Stony Brook University 
Stony Brook, NY 11794-8651
Phone: 631-444-3085 (Office); 631-444-9743 (Lab)

E-Mail: chia-hsin.chan@stonybrook.edu