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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
412 BRB II/III
421 Curie Boulevard
Philadelphia, PA 19104-6160
Office: (215) 746-5565
Fax: (215) 746-5525
Lab: (215)746-5566
Education:
M.D.
Hubei Medical College, China, 1983.
M.S.
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:
Remy Thorpe, Administrative Assistant (rthorpe@upenn.edu)
Miriam Doepner, Research Specialist and Lab Manager
Zijie Feng, Postdoctoral Researcher
Rebecca Glynn, Research Specialist
Xin He, Postdoctoral Researcher
Bryson Katona, Gastroenterology Fellow
Sunbin Ling, Visiting Student
Jian Ma, Postdoctoral Researcher
Gengchen Xie, Visiting Student

Selected Publications

Jiang Z, Xing B, Feng Z, Ma J, Ma X, Hua X: Menin Upregulates FOXO1 Protein Stability by Repressing Skp2-Mediated Degradation in β Cells. Pancreas 2019.

Tejashree Redij Rajan Chaudhari, Xianxin Hua, Zhiyu L: Structural Modeling and in Silico Screening of Potential Small-Molecule Allosteric Agonists of a Glucagon-like Peptide 1 Receptor. ACS Omega 2019.

Katona BW, Glynn RA, Paulosky KE, Feng Z, Davis CI, Ma J, Berry CT, Szigety KM, Matkar S, Liu Y, Wang H, Wu Y, He X, Freedman BD, Brady DC, Hua X: Combined Menin and EGFR Inhibitors Synergize to Suppress Colorectal Cancer via EGFR-Independent and Calcium-Mediated Repression of SKP2 Transcription. Cancer Research 2019.

HUIPING GUO, XINLU DU, YING ZHANG ,JIACHENG WU, CHENGHUI WANG ,b MINGYOU LI, XIANXIN HUA, XIN A. ZHANG,JIZHOU YAN: Specific miRNA-G Protein-Coupled Receptor Networks Regulate Sox9a/Sox9b Activities to Promote Gonadal Rejuvenation in Zebrafish. Stem Cell 2019.

Xing B, Ma J, Jiang Z, Feng Z, Ling S, Szigety K, Su W, Zhang L, Jia R, Sun Y, Zhang L, Kong X, Ma X, Hua X: GLP-1 signaling suppresses menin's transcriptional block by phosphorylation in β cells. The Journal of cell biology 2019.

Li JWY, Hua X, Reidy-Lagunes D, Untch BR: MENIN loss as a tissue-specific driver of tumorigenesis. Molecular and cellular endocrinology 2018.

iang Z, Shi D, Tu Y, Tian J, Zhang W, Xing B, Wang J, Liu S, Lou J, Gustafsson JÅ, Hua X, Ma X: Human Proislet Peptide Promotes Pancreatic Progenitor Cells to Ameliorate Diabetes Through FOXO1/Menin-Mediated Epigenetic Regulation. Diabetes 2018.

FOXO family in regulating cancer and metabolism: FOXO family in regulating cancer and metabolism. Seminars in Cancer Biology 2018.

Wang, L., Smita Matkar, Gengchen Xie, Chiying An, Xin He, Xiangchen Kong, Xiuheng Liu, and Xianxin Hua: BRD4 Inhibitor IBET Upregulates p27kip/cip Protein Stability in Neuroendocrine Tumor Cells. Cancer Biology and Therapy 2017.

Zijie Feng, Lei Wang, Yanmei Sun, Zongzhe Jiang, Bowen Xing, John Domsic, Jingjing Tian, David C. Metz, Xiaolu Yang, Ronen Marmostein, Xiaosong Ma and Xianxin Hu: Menin and Daxx Interact to Control Pancreatic Neuroendocrine Tumors via Epigenetic Regulation of Membrane Metallo-Endopeptidase. Cancer Research 2017.

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Last updated: 06/19/2019
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