Our laboratory focuses on developing and applying genetic approaches for identifying new cancer genes and studying their functions.

1. Study mechanisms underlying epigenetic dysregulation-driven tumorigenesis, using brain tumor and prostate cancer models. Specifically, we focus on histone modification pathways recently identified as being common drivers for many types of human cancers. Several genes, including MLL2 (also named KMT2D), MLL3 and UTX, encode proteins with histone methylation modifying activity; however, their tumorigenic roles and the underlying mechanism are unknown. We aim to understand the role of the MLL2/MLL3 pathway with an ultimate goal of applying our findings to the clinical setting. The gigantic sizes of MLL2 and MLL3 pose a challenge for studying them. We have established somatic gene modification-based human cell models, knockout mouse models, and novel genetic assays to overcome this challenge. Using these new tools, we aim to identify downstream cellular signaling pathway and events that mediate the tumorigenic roles of MLL2/MLL3 deficiency, and illuminate the roles of MLL2 in different cellular contexts.
2. Exploiting genetic alterations for cancer treatments. Specifically, we focus on MTAP deletion in glioblastoma.  We have collaborated with colleagues in the Duke Cancer Institute, primarily by applying Nest Generation Sequencing to exome sequencing, in projects aiming to discover novel cancer genes in glioblastoma, and applying them to glioblastoma classification and therapeutics. In one ongoing projects, we focus on exploiting methylthioadenosine phosphorylase (MTAP) deletion (occurs in ~half of all glioblastoma patients) for glioblastoma treatment. We have established patient-derived primary tumor cultures and sequenced their exomes to identify somatic alterations, including MTAP status. We are studying the metabolic and functional effects of MTAP deletion on glioblastoma biology, and devising novel therapeutic approaches to target glioblastoma with MTAP deletion.

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Book Sections

• Chandramohan, V, Sanchez-Perez, L, He, Y, Pirozzi, CJ, Congdon, KL, and Bigner, DD. "Preclinical Immunotherapeutic Animal Models for Brain Tumors." In Translational Immunotherapy of Brain Tumors, 111-147. March 2, 2017

Conference Papers

• Guo, C, Chen, LH, Huang, Y, Chang, C-C, Wang, P, Pirozzi, CJ, Qin, X, Bao, X, Greer, PK, McLendon, RE, Yan, H, Keir, ST, Bigner, DD, and He, Y. "Abstract LB-82: MLL2 maintains neoplastic cell growth and global histone H3 lysine 4 monomethylation." October 1, 2014
• Guo, C, Chang, C-C, Wortham, M, Chen, L, Kernagis, D, Qin, X, Cho, Y-W, Chi, J-T, Grant, G, McLendon, R, Yan, H, Ge, K, Papadopoulos, N, Bigner, D, and He, Y. "GLOBAL IDENTIFICATION OF MLL2-TARGETED LOCI REVEALS MLL2'S ROLE IN DIVERSE SIGNALING PATHWAYS." April 2013
• Wortham, M, Reitman, Z, He, Y, Bigner, D, and Yan, H. "ABERRANT Otx2 EXPRESSION ENHANCES MIGRATION AND INDUCES ECTOPIC PROLIFERATION OF HINDBRAIN NEURONAL PROGENITOR CELLS." April 2013

Journal Articles

• Waitkus, MS, Pirozzi, CJ, Moure, CJ, Diplas, BH, Hansen, LJ, Carpenter, AB, Yang, R, Wang, Z, Ingram, BO, Karoly, ED, Mohney, RP, Spasojevic, I, McLendon, RE, Friedman, HS, He, Y, Bigner, DD, and Yan, H. "Adaptive Evolution of the GDH2 Allosteric Domain Promotes Gliomagenesis by Resolving IDH1R132H-Induced Metabolic Liabilities." Cancer research 78, no. 1 (January 2018): 36-50
• Yang, R, Chen, LH, Hansen, LJ, Carpenter, AB, Moure, CJ, Liu, H, Pirozzi, CJ, Diplas, BH, Waitkus, MS, Greer, PK, Zhu, H, McLendon, RE, Bigner, DD, He, Y, and Yan, H. "Cic Loss Promotes Gliomagenesis via Aberrant Neural Stem Cell Proliferation and Differentiation." Cancer research 77, no. 22 (November 2017): 6097-6108
• Xu, C, Liu, X, Geng, Y, Bai, Q, Pan, C, Sun, Y, Chen, X, Yu, H, Wu, Y, Zhang, P, Wu, W, Wang, Y, Wu, Z, Zhang, J, Wang, Z, Yang, R, Lewis, J, Bigner, D, Zhao, F, He, Y, Yan, H, Shen, Q, and Zhang, L. "Patient-derived DIPG cells preserve stem-like characteristics and generate orthotopic tumors." Oncotarget (July 28, 2017)
• Pirozzi, CJ, Carpenter, AB, Waitkus, MS, Wang, CY, Zhu, H, Hansen, LJ, Chen, LH, Greer, PK, Feng, J, Wang, Y, Bock, CB, Fan, P, Spasojevic, I, McLendon, RE, Bigner, DD, He, Y, and Yan, H. "Mutant IDH1 Disrupts the Mouse Subventricular Zone and Alters Brain Tumor Progression." Molecular cancer research : MCR 15, no. 5 (May 2017): 507-520
• Feng, N, Yin, Y, He, Y, and Huang, J. "Alternative Splicing Provides a Novel Molecular Mechanism for Prostatic Small-cell Neuroendocrine Carcinoma." European urology 71, no. 1 (January 2017): 79-80
• Yin, Y, Zhang, Q, Zhang, H, He, Y, and Huang, J. "Molecular Signature to Risk-Stratify Prostate Cancer of Intermediate Risk." Clinical cancer research : an official journal of the American Association for Cancer Research 23, no. 1 (January 2017): 6-8
• Huang, D-S, Tao, H-Q, He, X-J, Long, M, Yu, S, Xia, Y-J, Wei, Z, Xiong, Z, Jones, S, He, Y, Yan, H, and Wang, X. "Prevalence of deleterious ATM germline mutations in gastric cancer patients." Oncotarget 6, no. 38 (December 2015): 40953-40958
• Zhang, L, Chen, LH, Wan, H, Yang, R, Wang, Z, Feng, J, Yang, S, Jones, S, Wang, S, Zhou, W, Zhu, H, Killela, PJ, Zhang, J, Wu, Z, Li, G, Hao, S, Wang, Y, Webb, JB, Friedman, HS, Friedman, AH, McLendon, RE, He, Y, Reitman, ZJ, Bigner, DD, and Yan, H. "Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas." Nature genetics 46, no. 7 (July 2014): 726-730
• Zhang, L, Chen, LH, Wan, H, Yang, R, Wang, Z, Feng, J, Yang, S, Jones, S, Wang, S, Zhou, W, Zhu, H, Killela, PJ, Zhang, J, Wu, Z, Li, G, Hao, S, Wang, Y, Webb, JB, Friedman, HS, Friedman, AH, McLendon, RE, He, Y, Reitman, ZJ, Bigner, DD, and Yan, H. "Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas." Nature Genetics 46, no. 7 (June 1, 2014): 726-730