Xianxin Hua
Associate Professor, Dept of Cancer Biology

Cancer Biology Program

Address

412 Biomedical Rsch Bldg II/III (Office)
420 Biomedical Rsch Bldg II/III (Lab)
421 Curie Blvd
Philadelphia, PA19096-6160

Office tel.: 215 746-5565
Lab tel.: 215 746-5567
Fax: 215 746-5525
E-mail: huax@mail.med.upenn.edu

Link(s)

Dr. Hua's Abramson faculty page

Education

Hubei Medical College: MD (Medicine), 1986.

University of Texas Southwestern Medical Center: PhD (Cell and Molceular Biology, Genetics), 1995.

Research Interests

• Elucidating the critical role of the tumor suppressor Menin in regulation of cell proliferation, leukemia and diabetes; investigating signal transduction and epigenetics co-regulated by transforming growth factor beta (TGF-β) and Menin.

Key words: Menin, Men1, cell cycle, epigenetics, leukemia, diabetes, and TGF-β

Search PubMed for articles

Description of Research

Our research interests focus on deciphering the molecular mechanisms that control cell proliferation and tumorigenesis. In particular, we have been interested in elucidating the biochemical functions of tumor suppressor gene MEN1, which encodes protein menin and is mutated in patients with an inherited tumor syndrome, Multiple Endocrine Neoplasia type 1 (MEN1). We have found that menin plays a crucial role in regulating cell cycle by regulating transcription of various cell cycle regulators. Menin specifically represses proliferation of endocrine cells including insulin-secreting beta cells, yet potently promotes proliferation of a subset of leukemia cells, such as mixed lineage leukemia (MLL) cells. Menin inhibits beta cell proliferation at least in part by repressing the activity of cyclin-dependent kinase 2, but promotes proliferation of MLL in part by activating the transcription of Hoxa9 through modulating histone H3K4 methylation. In addition, we are also actively investigating how TGF-ß suppresses proliferation of MLL cells and determining how menin and the TGF-ß pathway interact to regulate proliferation of endocrine and hematopoietic cells. To achieve these goals, we use a variety of approaches, including cellular, molecular, biochemical, and genetic approaches, to investigate the molecular mechanisms underlying the functions of menin. For instance, we have been working to determine how menin specifically represses proliferation of beta cells but promotes proliferation of MLL cells. Second, we will investigate the potential role of modulating menin in altering the progression of diabetes mellitus and also mixed lineage leukemia. Third, we will evaluate the effect of modulating the menin pathway in treating MEN1 tumors. Fourth, we will also test the cooperation or antagonism between menin and the TGF-ß signaling pathways in regulating cell proliferation in a tissue specific manner. The knowledge from these studies will likely provide novel insights into developing new strategies to treat endocrine tumors, leukemia, and diabetes mellitus.

Recent Publications

Chen Y, Yan J, Keeshan, K., Wang H., Silva A.C., Hess J, Pear, W.S., and Hua X. The tumor suppressor menin regulates hematopoiesis and myeloid transformation by influencing Hox gene expression. Proc Natl Acad Sci U S A. 2006 Jan 24;103 (4):1018- 23. Epub 2006 Jan 13.

Schnepp RW, Chen Y, Wang H, Cash T, Silva AC, Diehl JA, Brown E, Hua X. Mutation of Tumor Suppressor Men1 Acutely Enhances Proliferation of Pancreatic Islet Cells. Cancer Research. 2006, Jun 1;66 (11):5707-15.

Yan J, Chen YX, Desmond A, Silva A, Yang Y, Wang H, Hua X. Cdx4 and menin co-regulate hoxa9 expression in hematopoietic cells. PLoS ONE. Dec. 20, 1: e47. 2006.

Yang Y and Hua X. In search of tumor suppressing functions of menin. Molecular and Cellular Endocrinology. 2007 Feb;265-266:34-41. Epub: Jan 11. 2007.

Ping La, Yuqing Yang, Satyajit K. Karnik, Albert C. Silva, Robert W. Schnepp, Seung K. Kim and Hua X. Menin-mediated caspase 8 expression in suppressing multiple endocrine neoplasia type 1. J. Biol. Chem. 2007. Aug. 31. Epub ahead of print.

Lab

Rotation Projects

1. Determine the potential role of menin/histone H3 methylation in regulating beta cell proliferation
2. Detect the potential mutations of oncogenes such as Ras or tumor suppressors such as p53 and pRB in insulinomas from MEN1 tumors
3. Investigate how menin regulates endocrine and hematopoietic cells in a tissue-specific manner
4. Test whether menin and TGF-ß collaboratively regulate cell proliferaton
5. Does menin regulate the chromatin domains in a tissue-specific manner?
6. Does menin regulate cells in a transcription-independent manner?
7. Elucidate how menin regulates cell cycle regulators specifically in insulin-secreting beta cells
8. Create a fluorescent resonance energy transfer (FRET) system to evaluate menin and menin-binding protein interaction
9. Search for menin-binding peptides using phage display system

Lab personnel:

Yaxiong Chen-Postdoctoral Researcher
Peter Blessington-Research Specialist
Yuqing Yang-Postdoctoral Researcher
Catrina King, VMD/Ph.D.-Graduate Student
Austin Thiel-Graduate Student
Xinjiang Wu-Postdoctoral Researcher
Jizhou Yan-Research Associate
Danielle Feather-Research Specialist
Reesa Child-Undergraduate Student
Helen Zhang-Graduate Student
Alicia Nelson-Undergraduate Student