This week we would like to introduce Dr Seung-Beom Hong, a post-doctoral researcher in the lab of Professor Vera Krymskaya at the University of Pennsylvania.

Dr Hong was part of the group at the NIH that helped to identify and characterise FNIP1 and FNIP2, which directly links FLCN with the key cellular energy sensor AMPK (Baba et al., 2006; Hasumi et al., 2008). This work also showed that FLCN is associated with mTOR signalling, which is also a major regulator of growth, proliferation and metabolism in cells.

In addition to this, Dr Hong’s extensive experience with mouse models of VHL (Ma et al., 2003; Hong et al., 2006) and BHD (Baba et al., 2008; Hasumi et al., 2009) places him in an ideal position to further decipher the downstream targets of FLCN. Accordingly, his current research has shown that FLCN plays an essential role in the regulation of TGF-β signalling (Hong et al., 2010a), as well as the nucleo-cytoplasmic transcription factor TFE3 (Hong et al., 2010b). These findings have been discussed further in our blog posts from June 2010 and January 2011 respectively, and are of particular interest as they implicate yet more factors and signalling pathways in the pathogenesis of BHD syndrome. Ultimately, it is hoped that such work can not only identify novel therapeutic targets, but may also lead to the elucidation of effective biomarkers for the varied symptoms of BHD.

To hear more about Dr Hong’s work, watch his video interview from the Third BHD Symposium (with its accompanying transcript and audio only file). Alternatively, the following publications may also be of interest:

• Hong SB, Oh H, Valera VA, Baba M, Schmidt LS, & Linehan WM (2010). Inactivation of the FLCN tumor suppressor gene induces TFE3 transcriptional activity by increasing its nuclear localization. PloS one, 5 (12) PMID: 21209915
• Hong SB, Oh H, Valera VA, Stull J, Ngo DT, Baba M, Merino MJ, Linehan WM, & Schmidt LS (2010). Tumor suppressor FLCN inhibits tumorigenesis of a FLCN-null renal cancer cell line and regulates expression of key molecules in TGF-beta signaling. Molecular cancer, 9 PMID: 20573232
• Hasumi Y, Baba M, Ajima R, Hasumi H, Valera VA, Klein ME, Haines DC, Merino MJ, Hong SB, Yamaguchi TP, Schmidt LS, & Linehan WM (2009). Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2. Proceedings of the National Academy of Sciences of the United States of America, 106 (44), 18722-7 PMID: 19850877
• Hasumi H, Baba M, Hong SB, Hasumi Y, Huang Y, Yao M, Valera VA, Linehan WM, & Schmidt LS (2008). Identification and characterization of a novel folliculin-interacting protein FNIP2. Gene, 415 (1-2), 60-7 PMID: 18403135
• Baba M, Furihata M, Hong SB, Tessarollo L, Haines DC, Southon E, Patel V, Igarashi P, Alvord WG, Leighty R, Yao M, Bernardo M, Ileva L, Choyke P, Warren MB, Zbar B, Linehan WM, & Schmidt LS (2008). Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model: Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys. Journal of the National Cancer Institute, 100 (2), 140-54 PMID: 18182616
• Baba M, Hong SB, Sharma N, Warren MB, Nickerson ML, Iwamatsu A, Esposito D, Gillette WK, Hopkins RF 3rd, Hartley JL, Furihata M, Oishi S, Zhen W, Burke TR Jr, Linehan WM, Schmidt LS, & Zbar B (2006). Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proceedings of the National Academy of Sciences of the United States of America, 103 (42), 15552-7 PMID: 17028174
• Hong SB, Furihata M, Baba M, Zbar B, & Schmidt LS (2006). Vascular defects and liver damage by the acute inactivation of the VHL gene during mouse embryogenesis. Laboratory investigation; a journal of technical methods and pathology, 86 (7), 664-75 PMID: 16652107
• Ma W, Tessarollo L, Hong SB, Baba M, Southon E, Back TC, Spence S, Lobe CG, Sharma N, Maher GW, Pack S, Vortmeyer AO, Guo C, Zbar B, & Schmidt LS (2003). Hepatic vascular tumors, angiectasis in multiple organs, and impaired spermatogenesis in mice with conditional inactivation of the VHL gene. Cancer research, 63 (17), 5320-8 PMID: 14500363