Gang Huang, PhD

Member, Division of Experimental Hematology & Cancer Biology

Academic Affiliations

Associate Professor, UC Department of Pathology & Laboratory Medicine

Phone 513-636-3214

Fax 513-636-3768

Email gang.huang@cchmc.org

Research in Dr. Huang’s laboratory focuses on genetic and epigenetic regulations of blood cell normal development and leukemia. The lab 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).

The lab 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: Peking 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.

View PubMed Publications

Zhang YW1, Bae SC, Huang G, Fu YX, Lu J, Ahn MY, Kanno Y, Kanno T, Ito Y. A novel transcript encoding an N-terminally truncated AML1/PEBP2 alphaB protein interferes with transactivation and blocks granulocytic differentiation of 32Dcl3 myeloid cells. Mol Cell Biol. 1997 Jul;17(7):4133-45.

Ahn MY1, Huang G, Bae SC, Wee HJ, Kim WY, Ito Y. Negative regulation of granulocytic differentiation in the myeloid precursor cell line 32Dcl3 by ear-2, a mammalian homolog of Drosophila seven-up, and a chimeric leukemogenic gene, AML1/ETO. Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1812-7.

Kohzaki H1, Ito K, Huang G, Wee HJ, Murakami Y, Ito Y. Block of granulocytic differentiation of 32Dcl3 cells by AML1/ETO(MTG8) but not by highly expressed Bcl-2. Oncogene. 1999 Jul 15;18(28):4055-62.

Zhang YW1, Yasui N, Ito K, Huang G, Fujii M, Hanai J, Nogami H, Ochi T, Miyazono K, Ito Y. A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia. Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10549-54.

Huang G1, Shigesada K, Ito K, Wee HJ, Yokomizo T, Ito Y. Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation. EMBO J. 2001 Feb 15;20(4):723-33.

Wee HJ1, Huang G, Shigesada K, Ito Y. Serine phosphorylation of RUNX2 with novel potential functions as negative regulatory mechanisms. EMBO Rep. 2002 Oct;3(10):967-74.

Huang G1, Shigesada K, Wee HJ, Liu PP, Osato M, Ito Y. Molecular basis for a dominant inactivation of RUNX1/AML1 by the leukemogenic inversion 16 chimera. Blood. 2004 Apr 15;103(8):3200-7.

Okuno Y1, Huang G, Rosenbauer F, Evans EK, Radomska HS, Iwasaki H, Akashi K, Moreau-Gachelin F, Li Y, Zhang P, Göttgens B, Tenen DG. Potential autoregulation of transcription factor PU.1 by an upstream regulatory element. Mol Cell Biol. 2005 Apr;25(7):2832-45.

Hoogenkamp M1, Krysinska H, Ingram R, Huang G, Barlow R, Clarke D, Ebralidze A, Zhang P, Tagoh H, Cockerill PN, Tenen DG, Bonifer C. The Pu.1 locus is differentially regulated at the level of chromatin structure and noncoding transcription by alternate mechanisms at distinct developmental stages of hematopoiesis. Mol Cell Biol. 2007 Nov;27(21):7425-38.

Huang G1, Zhang P, Hirai H, Elf S, Yan X, 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 mouse hematopoiesis. Nat Genet. 2008 Jan;40(1):51-60.

Role of the Hypoxia-Inducible Factor-1alpha in Myelodysplastic Syndromes. Principle investigator. National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). March 2015-Feb 2020.

 

A Novel Epigenetic Circuit In Acute Leukemia. Principle investigator. National Institutes of Health (NIH), National Cancer Institute (NCI). July 2014-June 2017.