Cancer Pathology

Gang Huang, PhD

Title

Assistant Professor, Cancer Pathology Program of the Division of Experimental Hematology and the Division of Pathology

Appointment

Assistant Professor,University of Cincinnati College of Medicine, University of Cincinnati College of Medicine

Email

gang.huang@cchmc.org

Phone

513-636-3214

Fax

513-636-3768

Credentials

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.

Position History

Research Associate, Memorial Sloan-Kettering Cancer Center, New York, NY, 2005-2009

Research Associate, Harvard University, Beth Israel Deaconess Medical Center, Boston, MA, 2002-2005

Instructor, Kyoto University, Institute for Virus Research, Kyoto, Japan, 2001-2002

Teaching Assistant, Virology and Oncology, Developmental Biology, 1998-1999

Awards and Honors

American Society of Hematology Travel Award (2008)
American Society of Hematology Travel Award (2004)
Toyobo Biotechnology Foundation Travel Award (2002)
The Cell Science Research Foundation Travel Award (2001)
Kyoto Shimbun Research Scholarship for Overseas Student (1999)
Japan International Education Scholarship (1996-1999)
IWADARE Scholarship (1995)

Research

Cancer develops through a series of genetic and epigenetic changes that progressively drive normal cells into highly malignant derivatives and the distinct mutations can cause the same cancer via their effects on the same regulatory network. The key regulators for blood cell development are DNA binding transcription factors and chromatin modification enzymes, which are often targeted by mutations or chromosomal translocations in human leukemia.

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.

Publications, Most Recent

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. p53 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.

Presentations, Most Recent

Huang, Gang: Physical and functional interaction between AML1 and MLL, genetic and epigenetic regulators, in normal hematopoiesis and in leukemia. Presented at the 7th Middle West Blood Club’ April 30-May 1, 2009; Cincinnati, OH.

Huang, Gang: Previously unknown interactions between AML1 and MLL provide epigenetic regulation of gene expression in normal hematopoiesis and in leukemia. Presented at the 50th American Society of Hematology; December 6-9, 2008; San Francisco, CA.

Huang, Gang: Previously unknown interactions between AML1 and MLL provide epigenetic regulation of gene expression in normal hematopoiesis and in leukemia. Presented at the 15th International RUNX Workshop; September 17-19, 2008; Provincetown, MA.