Dr Baba is a staff scientist in the laboratory of Dr W. Marston Linehan in the Urologic Oncology Branch of the National Cancer Institute, which is part of the National Institutes of Health in the United States. Prior to this work, Dr Baba trained as a urologist in Japan and had published extensively in the VHL field (Baba et al., 2003; Nakaigawa et al., 2006). In fact, it was Dr Baba’s experience of treating patients with kidney cancer that first motivated him to be involved in basic research.
Moreover, Dr Baba heard about BHD syndrome and the FLCN gene at a VHL meeting. Subsequently, his work has done much to elucidate the function of FLCN, where he was part of the team that identified FNIP1 and FNIP2, which linked FLCN to AMPK and mTOR signalling (Baba et al., 2006; Hasumi et al., 2008). He also played a part in identifying other FLCN-associated pathways (Hong et al., 2010a; Hong et al., 2010b) and mutations (Benhammou et al., 2011), as discussed here and here respectively. For more information regarding these findings, please visit “What is BHD?” in the For Researchers section of BHDSyndrome.org. In particular, the recently updated signalling diagram visually summarises many of these papers.
Dr Baba was also instrumental in the development of two BHD mouse models (Baba et al., 2008; Hasumi et al., 2009) which are discussed in more detail here. In addition to discovering more about the in vivo role of FLCN, such models could be useful for screening novel drugs. Most recently, Dr Baba has helped develop a FNIP1 knockout mouse which will provide clues towards the role of FNIP1 (Baba et al., 2012), and this paper will be discussed in more detail in the following weeks.
To hear more about the challenges and future direction of BHD research, do watch Dr Baba’s video interview (with its associated transcript and audio-only file). Furthermore, the following citations may also be of interest:
- 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. Kidney-targeted Birt-Hogg-Dube gene inactivation in a mouse model: Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys. J Natl Cancer Inst. 2008 Jan 16;100(2):140-54. PMID: 18182616
- Baba M, Hirai S, Yamada-Okabe H, Hamada K, Tabuchi H, Kobayashi K, Kondo K, Yoshida M, Yamashita A, Kishida T, Nakaigawa N, Nagashima Y, Kubota Y, Yao M, Ohno S. Loss of von Hippel-Lindau protein causes cell density dependent deregulation of CyclinD1 expression through hypoxia-inducible factor. Oncogene. 2003 May 8;22(18):2728-38. PMID: 12743597
- 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. Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15552-7. PMID: 17028174
- Baba M, Keller JR, Sun HW, Resch W, Kuchen S, Suh HC, Hasumi H, Hasumi Y, Kieffer-Kwon KR, Gonzalez CG, Hughes RM, Klein ME, Oh HF, Bible P, Southon E, Tessarollo L, Schmidt LS, Linehan WM, Casellas R. The Folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dube syndrome is required for mouse B cell development. Blood. 2012 Jun 18. [Epub ahead of print] PMID: 22709692
- Benhammou JN, Vocke CD, Santani A, Schmidt LS, Baba M, Seyama K, Wu X, Korolevich S, Nathanson KL, Stolle CA, Linehan WM. Identification of intragenic deletions and duplication in the FLCN gene in Birt-Hogg-Dubé syndrome. Genes Chromosomes Cancer. 2011 Jun;50(6):466-77. PMID: 21412933
- Hasumi Y, Baba M, Ajima R, Hasumi H, Valera VA, Klein ME, Haines DC, Merino MJ, Hong SB, Yamaguchi TP, Schmidt LS, Linehan WM. Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18722-7. PMID: 19850877
- Hasumi H, Baba M, Hong SB, Hasumi Y, Huang Y, Yao M, Valera VA, Linehan WM, Schmidt LS. Identification and characterization of a novel folliculin-interacting protein FNIP2. Gene. 2008 May 31;415(1-2):60-7. PMID: 18403135
- Hong SB, Oh H, Valera VA, Baba M, Schmidt LS, Linehan WM. Inactivation of the FLCN tumor suppressor gene induces TFE3 transcriptional activity by increasing its nuclear localization. PLoS One. 2010 Dec 29;5(12):e15793. PMID: 21209915
- Hong SB, Oh H, Valera VA, Stull J, Ngo DT, Baba M, Merino MJ, Linehan WM, Schmidt LS. Tumor suppressor FLCN inhibits tumorigenesis of a FLCN-null renal cancer cell line and regulates expression of key molecules in TGF-beta signaling. Mol Cancer. 2010 Jun 23;9:160. PMID: 20573232
- Nakaigawa N, Yao M, Baba M, Kato S, Kishida T, Hattori K, Nagashima Y, Kubota Y. Inactivation of von Hippel-Lindau gene induces constitutive phosphorylation of MET protein in clear cell renal carcinoma. Cancer Res. 2006 Apr 1;66(7):3699-705. PMID: 16585196
www.bhdsyndrome.org – the primary online resource for anyone interested in BHD Syndrome.