Research in Dr. Huang’s laboratory focuses on genetic and epigenetic regulations of blood cell normal development and leukemia. We first demonstrated that AML1/CBFβ (a hetero-dimer transcription factor) and Mixed-Lineage Leukemia (MLL) protein (an enzyme which methylates lysine 4 of histone H3 tails), form a regulatory complex, which is important for normal blood development and acts as a tumor suppressor in leukemia. Mutations in either one of these three genes account for majority of acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndromes (MDS).

We also found that the AML1/CBFβ/MLL complex regulates another transcription factor, PU.1, through the upstream regulatory region of the PU.1 gene and that the epigenetic changes of the histone tails occurring in the PU.1 regulatory region correlate with the PU.1 expression level. PU.1 expression level changes are critical for blood cell differentiation and dysregulation of PU.1 dosages leading to leukemia.

This research will provide new insight into the interplay between genetics and epigenetics in normal blood development and leukemia. It will also help to develop generic drugs for most of the AML, ALL and MDS, which will benefit the future clinical treatments.

BS: Beijing University, College of Science, Beijing, P.R. China, 1991.

MS: Inner Mongolia University, Graduate School of Science, Huhhort, P.R. China, 1994.

PhD: Kyoto University, Graduate School of Medicine, Kyoto, Japan, 2001.

Liu Y, Elf S, Miyata Y, Sashida G, Liu YH, Huang G, Giandomenico S, Lee J, Deblasio A, Menendez S, Antipin J, Reva B, Koff A, Nimer SD.  Regulates Hematopoietic Stem Cell Quiescence. Cell Stem Cells. 2009 4(1):37-48.

Yokomizo T, Yanagida M, Huang G, Osato M, Honda C, Ema M, Takahashi S, Yamamoto M, Ito Y. Genetic evidence of PEBP2beta-independent activation of Runx1 in the murine embryo. Int J Hematol. 2008 88(2):134-8.

Ebralidze AK, Guibal FC, Steidl U, Zhang P, Lee SH, Bartholdy B, Jorda MA, Petkova V, Rosenbauer F, Huang G, Dayaram T, Klupp J, O’Brien K, Will B, Hoogenkamp M, Borden K, Bonifer C, Tenen DG. PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element. Genes & Dev. 2008 22(15):2085-92.

Zhao XY, Jankovic V, Gural A, Huang G, Pardanani A, Menendez S, Zhang J, Dunne R, Xiao A, Erdjument-Bromage H, Allis CD, Tempst P, Nimer SD. Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity. Genes & Dev. 2008 22(5):640-53.

Huang G, Zhang P, Hirai H, Elf S, Yan XM, Chen Z, Koschmieder S, Okuno Y, Dayaram T, Growney JD, Shivdasani RA, Gilliland DG, Speck NA, Nimer SD, Tenen DG. PU.1 is a major downstream target of AML1/RUNX1 in adult hematopoiesis. Nat Genet. 2008 40(1):51-60.

Hoogenkamp M, Krysinska H, Ingram R, Huang G, Barlow R, Clarke D, Ebralidze A, Pu Zhang, Tagoh H, Cockerill PN,1 Tenen DG, and Bonifer C. The Pu.1 locus is differentially regulated at the level of chromatin structure and non-coding transcription by alternate mechanisms at distinct developmental stages of hematopoiesis. Mol. Cell. Biol. 2007 27(21):7425-38.