Key words: Transcriptional regulation, oncogenes, cancer biology, chromatin Research interests
Transcriptional deregulation plays a critical role in the development of many cancers. Mechanisms that result in oncogenic transcriptional deregulation include alterations in the expression or structure of proteins that modulate transcription directly or through epigenetic modifications. Hematopoetic cancers and solid tumors (in particular sarcomas) frequently harbor recurrent and specific cytogenetic abnormalities such as chromosomal translocations and amplifications. In many of these cancers, the pathognomonic translocations involve genes that encode transcription factors. Translocations combine features of both native genes to generate unique fused (or chimeric) genes characterized by alterations in expression and structure. Although the importance of these gene fusions to cancer development has been clearly demonstrated, a fundamental understanding of how these changes mediate oncogenesis remains elusive.
Notable examples of translocation-associated transcription factor dysregulation include the MYC or MiT basic helix-loop-helix leucine zipper families which can be amplified or translocated in a wide range of cancers including lymphoma, neuroblastoma, melanoma, pediatric renal carcinoma and clear cell sarcoma. Similarly, ETS winged helix-turn-helix transcription factors and PAX3 or PAX7 paired box/homeodomain transcription factors are translocated in Ewing’s sarcoma and alveolar rhabdomyosarcoma, respectively. In each case, the abnormal transcription factor plays central role in the oncogenic process.
While it is presumed that these deregulated transcription factors mediate oncogenesis by altering target gene expression, we lack a mechanistic understanding of how dysregulation modifies the activity of these transcription factors and their participation in transcriptional networks. Furthermore, in contrast to the success of chimeric kinase inhibition, the molecular attributes of transcription factors make them challenging candidates for therapeutic modulation by small molecules. Focusing on those classes of transcription factors strongly implicated in oncogenesis, our lab employs genomic and proteomic approaches to study transcription factor targeting and gene regulation in cancer and in normal development. Through the identification of oncogenic transcriptional mechanisms and relevant transcriptional targets, we hope to develop novel biologically based therapies for these cancers.
Ian Davis in UNC Genetics News
October 19, 2020
Department of Genetics Publications for October 4-10, 2020
Department of Genetics faculty, postdocs, students and collaborators published seven papers during October 4-10, 2020.
September 8, 2020
Department of Genetics Publications for August 23 – Sept. 5, 2020
Department of Genetics faculty, postdocs, students and collaborators published eight papers during August 23 – Sept. 5, 2020.
August 10, 2020
Department of Genetics Publications for July 26 – August 8, 2020
Department of Genetics faculty, postdocs, students and staff published nine papers during July 26 – August 8, 2020.
June 7, 2019
UNC Bioinformatics and Computational Biology Graduate Student Shelsa Marcel Recipient of the 2019 Gilliam Fellowship
UNC Bioinformatics and Computational Biology Graduate Student Shelsa Marcel in the labs of Ian Davis and Joel Parker has been awarded a 2019 Gilliam Fellowship for Advanced Study by the Howard Hughes Medical Institute.
May 6, 2019
Department of Genetics Publications from April 21-May 4, 2019
Department of Genetics faculty, postdocs, students and collaborators published fourteen papers during April 21-May 4, 2019.
November 7, 2016
Genetics Faculty Publications for Oct 15 – Nov 4, 2016
During the last three weeks, Department of Genetics faculty members, along with their colleagues, have published 21 manuscripts on a wide variety of topics. A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories. O’Daniel JM, McLaughlin HM, Amendola LM, Bale SJ, Berg JS, Bick D, Bowling KM, Chao …