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Xianxin Hua, M.D., Ph.D.

Xianxin Hua, M.D., Ph.D.

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Professor of Cancer Biology
Department: Cancer Biology

Contact information
421 Curie Boulevard
Philadelphia, PA 19104-6160
Office: (215) 746-5565
Fax: (215) 746-5525
Lab: (215)746-5566
Hubei Medical College, China, 1983.
Hubei Medical College, China, 1986.
Ph.D. (Cell Regulation)
Department of Molecular Genetics, The University of Texas Southwestern Medical Center at Dallas, Laboratory of Dr. Joseph Goldstein and Dr. Michael Brown, 1995.
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Description of Research Expertise

Research Interests

1) The critical role of the tumor suppressor, Menin, in epigenetic regulation of gene transcription, cell signaling, cell proliferation, and the underlying mechanisms; suppression of neuroendocrine/carcinoid tumors by targeting menin-regulated pathways
2) The interplay of Menin, MLL methyltransferase, and oncogenic MLL fusion proteins in promoting leukemogenesis
3) Reversal of diabetes by inhibiting menin
4) Signal transduction mediated by transforming growth factor beta (TGF-ß) and menin.

Key words: Menin, Men1, epigenetics, MLL, histone methyltransferase, leukemia, neuroendocrine tumors, diabetes, and TGF-ß signaling.

Description of Research

Our research focuses on elucidating the molecular mechanisms whereby menin, a scaffold protein interacting with multiple epigenetic regulators, regulates endocrine cells, including pancreatic beta cells, endocrine tumors, and MLL fusion protein-induced leukemia. In particular, we are interested in dissecting the function of menin, which is mutated in hereditary human tumor syndrome, Multiple Endocrine Neoplasia Type 1 (MEN1), in repressing beta cells and endocrine tumors and in promoting leukemogenesis.

1. We seek to elucidate how menin suppresses endocrine cells, such as pancreatic beta cells, via regulating histone methylations and expression of pro-proliferative genes. We are also interested in identifying menin-regulated key pathways that can be suppressed to inhibit neuroendocrine tumors.

2. Determining how menin, which acts as a tumor promoter in MLL fusion protein-induced leukemia, cooperates with wild-type MLL protein to promote leukemia and how the menin and wt MLL axis can be suppressed to improve therapy for this aggressive leukemia.

3. Understanding how inhibition of menin leads to reversal of established diabetes in mouse models and determining whether the menin pathway could be explored to ameliorate diabetes.

4. Investigating the interplay between menin, post-transcriptional modifications of menin, and TGF-ß signaling in repressing pancreatic beta cells. As both menin and TGF-ß inhibit cell proliferation, we will test whether menin and TGF-ß cooperate to suppress beta cell proliferation and the underlying mechanisms, using biochemical studies and mouse models.

These comprehensive approaches will provide novel insights into the molecular mechanisms for MEN1 tumorigenesis, regulation of beta cells, and leukemogenesis, shedding light on improving therapy against neuroendocrine tumors, leukemia, and diabetes.

Rotation Projects
1. To identify potentially functional post-translational modifications of menin
2. To investigate how Men1 excision de-represses multiple pro-proliferative genes and upregulates beta cell proliferation
3. To identify functional and epigenetic partners of menin that control leukemogenesis or neuroendocrine tumors.

Lab personnel:
Ashley Banks, Administrative Assistant (asbanks@mail.med.upenn.edu)
Brian Bakke, Research Specialist and Lab Manager
Buddha Gurung, Research Fellow
Xin He, Postdoctoral Researcher
Bryson Katona, Gastroenterology Fellow
Xiangchen Kong, Postdoctoral Researcher
Smita Matkar, Research Associate
Abdul Bari Muhammad, Postdoctoral Fellow
Kate Szigety, MD/PhD Graduate Rotation Student
Haoren Wang, Research Specialist
Lei Wang, Visiting Graduate Student

Selected Publications

Huang J, Gurung B, Wan B, Matkar S, Veniaminova NA, Wan K, Merchant JL, Hua X, *Lei M.: The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature 482(7386): 542-6, February 2012 Notes: *Co-corresponding author.

Thiel AT, Blessington P, Zou T, Feather D, Wu X, Yan J, Zhang H, Liu Z, Ernst P, Koretzky GA, Hua X.: MLL-AF9-Induced Leukemogenesis Requires Coexpression of the Wild-Type Mll Allele. Cancer Cell 17(2): 148-159, Feb 2010 Notes: Highlighted on the cover of journal.

Yang Y, Gurung B, Wu T, Wang H, Stoffers DA, Hua X: Reversal of preexisting hyperglycemia in diabetic mice by acute deletion of the Men1 gene. Proceedings of the National Academy of Sciences USA 107(47): 20358-63, Nov 2010.

Wu T, Zhang X, Huang X, Yang Y, Hua X: Regulation of cyclin B2 expression and cell cycle G2/m transition by menin. The Journal of Biological Chemistry 285(24): 18291-300, Jun 2010.

Aggarwal P, Vaites LP, Kim JK, Mellert H, Gurung B, Nakagawa H, Herlyn M, Hua X, Rustgi AK, McMahon SB, Diehl JA: Nuclear cyclin D1/CDK4 kinase regulates CUL4 expression and triggers neoplastic growth via activation of the PRMT5 methyltransferase. Cancer Cell 18(4): 329-40, Oct 2010.

Yan J, Yang Y, Zhang H, King C, Kan H-M, Cai Y, Yuan C-X, Bloom G S, Hua X: Menin interacts with IQGAP1 to enhance intercellular adhesion of beta-cells. Oncogene 28(7): 973-82, Feb 2009.

Maillard I, Chen Y-X, Friedman A, Yang Y, Tubbs AT, Shestova O, Pear WS, Hua X: Menin regulates the function of hematopoietic stem cells and lymphoid progenitors. Blood 113(8): 1661-9, Feb 2009.

Wu X-J, Hua X: Menin, histone h3 methyltransferases, and regulation of cell proliferation: current knowledge and perspective. Current Molecular Medicine 8(8): 805-15, Dec 2008.

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

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Last updated: 06/22/2015
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