Dr. Ian Davis, MD, PhD, is a UNC Lineberger Comprehensive Cancer Center member and an associate professor in the Departments of Genetics and Pediatrics at UNC-Chapel Hill. Davis is specifically involved with Cancer Genetics, Pediatric Hematology Oncology Program and the Bone and Soft Tissue Oncology Program.
His clinical Interests include: pediatric hematology/oncology, pediatric solid tumors, and sarcoma.
His research Interests include: transcriptional regulation, chromatin organization, and developmental therapeutics.
Industry Expertise (5)
Areas of Expertise (11)
Martin D. Abeloff V Scholar Award (professional)
Each year, V Scholars are selected from a group of young cancer scientists that includes the most outstanding candidate from each of the National Cancer Institute designated cancer centers.
Rita Allen Foundation Scholar (professional)
The Rita Allen Foundation Scholars program supports basic biomedical research in the fields of cancer, immunology and neuroscience.
- UNC Lineberger Comprehensive Cancer Center : Member
- The Davis Lab : Principal Investigator
- UNC Chromatin and Epigenetics Program
Media Appearances (2)
UNC RESEARCH AIMS TO FIND TREATMENT FOR RARE CHILDHOOD CANCER
11 ABC (WTVD) online
This article features Dr. Davis.
UNC doctor receives thousands to aid his cancer research
"A Chapel Hill doctor received $250,000 to help his research into a rare childhood cancer."
This article features the achievements of Dr. Davis.
Event Appearances (4)
High throughput small molecule screen to identifies inhibitors of aberrant chromatin accessibility in Ewing sarcoma
Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship Fort Lauderdale, FL
Chromatin dysregulation in renal cell carcinoma
12th International Kidney Cancer Symposium Chicago, IL
Beyond Genetics: the identification of epigenetic therapies in cancer
Pediatric Grand Rounds Chapel Hill, NC
Variation in chromatin accessibility in human kidney cancer links H3K36 methyltransferase loss with widespread RNA processing defects
Chromatin and Epigenetics in Cancer Atlanta, GA
Clear cell sarcoma (CCS), a childhood tumor of the tendons and aponeuroses, is uniformly fatal once it has metastasized because of its profound therapeutic resistance. CCS is characterized by production of a chimeric transcription factor, EWS-ATF1, which is formed as the result of a disease-specific chromosomal translocation. EWS-ATF1 activates the melanocyte transcription factor MITF, which in turn activates transcription of c-Met, an oncogenic receptor tyrosine kinase recently shown to be activated in CCS. Based on this connection, we hypothesized that c-Met inhibition may offer a strategy to treat CCS, as an indirect tactic to defeat a transforming pathway downstream of EWS-ATF1. Here, we show that primary CCS and CCS-derived cell lines express c-Met, which is activated in an autocrine fashion by its ligand hepatocyte growth factor (HGF)/scatter factor in some CCS cell lines. c-Met expression is critical for CCS invasion, chemotaxis, and survival. Blocking c-Met activity with a small-molecule inhibitor (SU11274) or a neutralizing antibody to its ligand HGF (AMG 102) significantly reduced CCS cell growth in culture. Similarly, AMG 102 significantly suppressed in vivo tumor growth in an autocrine xenograft model of CCS. Collectively, these findings suggest the HGF:c-Met signaling axis as a candidate therapeutic target to improve clinical management of CCS.
Clear cell sarcoma (CCS) harbors a pathognomonic chromosomal translocation fusing the Ewing's sarcoma gene (EWS) to the CREB family transcription factor ATF1 and exhibits melanocytic features. We show that EWS-ATF1 occupies the MITF promoter, mimicking melanocyte-stimulating hormone (MSH) signaling to induce expression of MITF, the melanocytic master transcription factor and an amplified oncogene in melanoma. Knockdown/rescue studies revealed that MITF mediates the requirement of EWS-ATF1 for CCS survival in vitro and in vivo as well as for melanocytic differentiation. Moreover, MITF and TFE3 reciprocally rescue one another in lines derived from CCS or pediatric renal carcinoma. Seemingly unrelated tumors thus employ distinct strategies to oncogenically dysregulate the MiT family, collectively broadening the definition of MiT-associated human cancers.
The discovery of recurrent genetic abnormalities in cancer cells has often led to the identification of novel oncogenic genes and gene families. The nature of these alterations may also offer insights into the mechanisms by which these genes mediate their oncogenic role. Amplification, translocation, deletion and point mutation are common mechanisms that result in gain- or loss-of-function of cancer associated genes. Several studies have recently demonstrated multiple genetic strategies that ultimately converge to dysregulate members of the MiT transcription factor family in cancer. The shared dependence on aberrant MiT activity thus defines an expanding family of human solid tumors.