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Elizabeth S. Yeh

Title
InstitutionMedical University of South Carolina
DepartmentCell and Molecular Pharmacology and Experimental Therapeutics
AddressP.O. Box MSC 509
DDB 408
Drug Discovery Building - 70 President St.
Phone843-876-2301
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    Collapse Overview 
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    The overarching goal of the Yeh Lab is to examine how the deregulation of cellular signaling events results in the physiological changes that lead to human disease. We are particularly interested in elucidating how targeting protein kinase directed signaling impacts cell biological processes to become over-activated or under-activated, thereby resulting in a therapeutic effect. The Yeh Lab currently pursues this avenue of investigation by studying a novel AMPK-related protein kinase called Hormonally Up-regulated Neu-associated Kinase (HUNK) whose function we have determined to be critical in the etiology and progression of human breast cancer. However, the intracellular function of this kinase is still poorly understood.

    Our findings demonstrate that Hunk regulates cellular signaling via activation of two of the Epidermal Growth Factor Receptor family members EGFR and HER2. Downstream signaling of these receptors is mediated by Hunk resulting in changes in cell survival. Our data indicates that through mechanisms that are related to EGFR/HER2 signaling, as well as those that are likely un-related, Hunk regulates cell survival by apoptosis and autophagy. Moreover, Hunk potentially feeds back to EGFR by regulating this receptor’s turnover through endocytosis. Armed with these observations, we strive to elucidate the relationship between these seemingly disparate functions of Hunk—apoptosis, autophagy, and endocytosis– that we have uncovered.

    Our recent finding that Hunk participates in the two important membrane trafficking pathways: endocytosis and autophagy, is critical because these processes have been implicated not only in human cancer but a wide spectrum of human diseases including neurological disorders, pathogenic infection, cystic fibrosis, obesity and inflammation.

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    Protein kinase signaling in cancer

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    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. Rutkovsky AC, Yeh ES, Guest ST, Findlay VJ, Muise-Helmericks RC, Armeson K, Ethier SP. Eukaryotic initiation factor 4E-binding protein as an oncogene in breast cancer. BMC Cancer. 2019 May 23; 19(1):491. PMID: 31122207.
      View in: PubMed
    2. Herrera H, Dilday T, Uber A, Scott D, Zambrano JN, Wang M, Angel PM, Mehta AS, Drake RR, Hill EG, Yeh ES. Core-Fucosylated Tetra-Antennary N-Glycan Containing A Single N-Acetyllactosamine Branch Is Associated with Poor Survival Outcome in Breast Cancer. Int J Mol Sci. 2019 May 23; 20(10). PMID: 31126011.
      View in: PubMed
    3. Zambrano JN, Williams CJ, Williams CB, Hedgepeth L, Burger P, Dilday T, Eblen ST, Armeson K, Hill EG, Yeh ES. Staurosporine, an inhibitor of hormonally up-regulated neu-associated kinase. Oncotarget. 2018 Nov 13; 9(89):35962-35973. PMID: 30542510.
      View in: PubMed
    4. Yeh E. The continuing evolution of strategies for cancer therapeutics. Curr Opin Pharmacol. 2018 08; 41:iv-vi. PMID: 30139513.
      View in: PubMed
    5. Rhett JM, Yeh ES. The Potential for Connexin Hemichannels to Drive Breast Cancer Progression through Regulation of the Inflammatory Response. Int J Mol Sci. 2018 Mar 30; 19(4). PMID: 29601539.
      View in: PubMed
    6. Yeh ES, Williams CJ, Williams CB, Bonilla IV, Klauber-DeMore N, Phillips SL. Dysregulated connexin 43 in HER2-positive drug resistant breast cancer cells enhances proliferation and migration. Oncotarget. 2017 Dec 12; 8(65):109358-109369. PMID: 29312613.
      View in: PubMed
    7. Phillips SL, Williams CB, Zambrano JN, Williams CJ, Yeh ES. Connexin 43 in the development and progression of breast cancer: What's the connection? (Review). Int J Oncol. 2017 Oct; 51(4):1005-1013. PMID: 28902343.
      View in: PubMed
    8. Mesnil M, Aasen T, Boucher J, Chépied A, Cronier L, Defamie N, Kameritsch P, Laird DW, Lampe PD, Lathia JD, Leithe E, Mehta PP, Monvoisin A, Pogoda K, Sin WC, Tabernero A, Yamasaki H, Yeh ES, Dagli MLZ, Naus CC. An update on minding the gap in cancer. Biochim Biophys Acta Biomembr. 2018 Jan; 1860(1):237-243. PMID: 28655619.
      View in: PubMed
    9. Zambrano JN, Neely BA, Yeh ES. Hormonally up-regulated neu-associated kinase: A novel target for breast cancer progression. Pharmacol Res. 2017 05; 119:188-194. PMID: 28189783.
      View in: PubMed
    10. Phelps-Polirer K, Abt MA, Smith D, Yeh ES. Co-Targeting of JNK and HUNK in Resistant HER2-Positive Breast Cancer. PLoS One. 2016; 11(4):e0153025. PMID: 27045589.
      View in: PubMed
    11. Zambrano J, Yeh ES. Autophagy and Apoptotic Crosstalk: Mechanism of Therapeutic Resistance in HER2-Positive Breast Cancer. Breast Cancer (Auckl). 2016; 10:13-23. PMID: 26997868.
      View in: PubMed
    12. Grek CL, Rhett JM, Bruce JS, Ghatnekar GS, Yeh ES. Connexin 43, breast cancer tumor suppressor: Missed connections? Cancer Lett. 2016 Apr 28; 374(1):117-126. PMID: 26884256.
      View in: PubMed
    13. Abt MA, Grek CL, Ghatnekar GS, Yeh ES. Evaluation of Lung Metastasis in Mouse Mammary Tumor Models by Quantitative Real-time PCR. J Vis Exp. 2016 Jan 29; (107):e53329. PMID: 26862835.
      View in: PubMed
    14. Williams CB, Yeh ES, Soloff AC. Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy. NPJ Breast Cancer. 2016; 2. PMID: 26998515.
      View in: PubMed
    15. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, Airoldi EM, Ait-Si-Ali S, Akematsu T, Akporiaye ET, Al-Rubeai M, Albaiceta GM, Albanese C, Albani D, Albert ML, Aldudo J, Algül H, Alirezaei M, Alloza I, Almasan A, Almonte-Beceril M, Alnemri ES, Alonso C, Altan-Bonnet N, Altieri DC, Alvarez S, Alvarez-Erviti L, Alves S, Amadoro G, Amano A, Amantini C, Ambrosio S, Amelio I, Amer AO, Amessou M, Amon A, An Z, Anania FA, Andersen SU, Andley UP, Andreadi CK, Andrieu-Abadie N, Anel A, Ann DK, Anoopkumar-Dukie S, Antonioli M, Aoki H, Apostolova N, Aquila S, Aquilano K, Araki K, Arama E, Aranda A, Araya J, Arcaro A, Arias E, Arimoto H, Ariosa AR, Armstrong JL, Arnould T, Arsov I, Asanuma K, Askanas V, Asselin E, Atarashi R, Atherton SS, Atkin JD, Attardi LD, Auberger P, Auburger G, Aurelian L, Autelli R, Avagliano L, Avantaggiati ML, Avrahami L, Awale S, Azad N, Bachetti T, Backer JM, Bae DH, Bae JS, Bae ON, Bae SH, Baehrecke EH, Baek SH, Baghdiguian S, Bagniewska-Zadworna A, Bai H, Bai J, Bai XY, Bailly Y, Balaji KN, Balduini W, Ballabio A, Balzan R, Banerjee R, Bánhegyi G, Bao H, Barbeau B, Barrachina MD, Barreiro E, Bartel B, Bartolomé A, Bassham DC, Bassi MT, Bast RC, Basu A, Batista MT, Batoko H, Battino M, Bauckman K, Baumgarner BL, Bayer KU, Beale R, Beaulieu JF, Beck GR, Becker C, Beckham JD, Bédard PA, Bednarski PJ, Begley TJ, Behl C, Behrends C, Behrens GM, Behrns KE, Bejarano E, Belaid A, Belleudi F, Bénard G, Berchem G, Bergamaschi D, Bergami M, Berkhout B, Berliocchi L, Bernard A, Bernard M, Bernassola F, Bertolotti A, Bess AS, Besteiro S, Bettuzzi S, Bhalla S, Bhattacharyya S, Bhutia SK, Biagosch C, Bianchi MW, Biard-Piechaczyk M, Billes V, Bincoletto C, Bingol B, Bird SW, Bitoun M, Bjedov I, Blackstone C, Blanc L, Blanco GA, Blomhoff HK, Boada-Romero E, Böckler S, Boes M, Boesze-Battaglia K, Boise LH, Bolino A, Boman A, Bonaldo P, Bordi M, Bosch J, Botana LM, Botti J, Bou G, Bouché M, Bouchecareilh M, Boucher MJ, Boulton ME, Bouret SG, Boya P, Boyer-Guittaut M, Bozhkov PV, Brady N, Braga VM, Brancolini C, Braus GH, Bravo-San Pedro JM, Brennan LA, Bresnick EH, Brest P, Bridges D, Bringer MA, Brini M, Brito GC, Brodin B, Brookes PS, Brown EJ, Brown K, Broxmeyer HE, Bruhat A, Brum PC, Brumell JH, Brunetti-Pierri N, Bryson-Richardson RJ, Buch S, Buchan AM, Budak H, Bulavin DV, Bultman SJ, Bultynck G, Bumbasirevic V, Burelle Y, Burke RE, Burmeister M, Bütikofer P, Caberlotto L, Cadwell K, Cahova M, Cai D, Cai J, Cai Q, Calatayud S, Camougrand N, Campanella M, Campbell GR, Campbell M, Campello S, Candau R, Caniggia I, Cantoni L, Cao L, Caplan AB, Caraglia M, Cardinali C, Cardoso SM, Carew JS, Carleton LA, Carlin CR, Carloni S, Carlsson SR, Carmona-Gutierrez D, Carneiro LA, Carnevali O, Carra S, Carrier A, Carroll B, Casas C, Casas J, Cassinelli G, Castets P, Castro-Obregon S, Cavallini G, Ceccherini I, Cecconi F, Cederbaum AI, Ceña V, Cenci S, Cerella C, Cervia D, Cetrullo S, Chaachouay H, Chae HJ, Chagin AS, Chai CY, Chakrabarti G, Chamilos G, Chan EY, Chan MT, Chandra D, Chandra P, Chang CP, Chang RC, Chang TY, Chatham JC, Chatterjee S, Chauhan S, Che Y, Cheetham ME, Cheluvappa R, Chen CJ, Chen G, Chen GC, Chen G, Chen H, Chen JW, Chen JK, Chen M, Chen M, Chen P, Chen Q, Chen Q, Chen SD, Chen S, Chen SS, Chen W, Chen WJ, Chen WQ, Chen W, Chen X, Chen YH, Chen YG, Chen Y, Chen Y, Chen Y, Chen YJ, Chen YQ, Chen Y, Chen Z, Chen Z, Cheng A, Cheng CH, Cheng H, Cheong H, Cherry S, Chesney J, Cheung CH, Chevet E, Chi HC, Chi SG, Chiacchiera F, Chiang HL, Chiarelli R, Chiariello M, Chieppa M, Chin LS, Chiong M, Chiu GN, Cho DH, Cho SG, Cho WC, Cho YY, Cho YS, Choi AM, Choi EJ, Choi EK, Choi J, Choi ME, Choi SI, Chou TF, Chouaib S, Choubey D, Choubey V, Chow KC, Chowdhury K, Chu CT, Chuang TH, Chun T, Chung H, Chung T, Chung YL, Chwae YJ, Cianfanelli V, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016; 12(1):1-222. PMID: 26799652.
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    16. Williams CB, Soloff AC, Ethier SP, Yeh ES. Perspectives on Epidermal Growth Factor Receptor Regulation in Triple-Negative Breast Cancer: Ligand-Mediated Mechanisms of Receptor Regulation and Potential for Clinical Targeting. Adv Cancer Res. 2015; 127:253-81. PMID: 26093903.
      View in: PubMed
    17. Grek CL, Rhett JM, Bruce JS, Abt MA, Ghatnekar GS, Yeh ES. Targeting connexin 43 with a-connexin carboxyl-terminal (ACT1) peptide enhances the activity of the targeted inhibitors, tamoxifen and lapatinib, in breast cancer: clinical implication for ACT1. BMC Cancer. 2015 Apr 03; 15:296. PMID: 25881004.
      View in: PubMed
    18. Yeh ES, Abt MA, Hill EG. Regulation of cell survival by HUNK mediates breast cancer resistance to HER2 inhibitors. Breast Cancer Res Treat. 2015 Jan; 149(1):91-8. PMID: 25515931.
      View in: PubMed
    19. Yeh ES, Yang TW, Jung JJ, Gardner HP, Cardiff RD, Chodosh LA. Hunk is required for HER2/neu-induced mammary tumorigenesis. J Clin Invest. 2011 Mar; 121(3):866-79. PMID: 21393859.
      View in: PubMed
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