Cancer Genomics

Human cancers are largely driven by aberrations – inherited and acquired – at the DNA, RNA, and protein levels. Faculty in the Department of Genetics and Genome Sciences work to discover these aberrations and dissect their impact using a variety of cutting-edge approaches.  

DNA-level variation is the focus of the laboratories led by Charis Eng, Thomas LaFramboise, and Peter Scacheri. Charis Eng is the Director of the Genomic Medicine Institute, and leads a group focusing on inherited cancer syndromes. Among a wide range of projects, her group is examining the PTEN and SDH genes in Cowden syndrome, which has a high risk of breast, thyroid and endometrial cancers, and SDH-related heritable neuroendocrine neoplasias. Thomas LaFramboise's laboratory is primarily computational, and develops algorithmic approaches to mine large DNA sequence data sets for aberrations with roles in cancer and other diseases. His group has interests in both the germline (inherited) and sporadic DNA-level contributions to malignancy. Peter Scacheri and his team study the cancer epigenome, which is comprised of several classes of chemical modifications to DNA that can affect gene expression. His group has shown that signature epigenetic alterations underlie altered gene expression programs in cancer.

Ahmad Khalil studies a class of RNA molecules, termed long intergenic non-coding RNAs (lincRNAs), that do not code for proteins. His group has published several studies demonstrating roles for these molecules in breast and colon cancers, most recently elucidating lincRNAs in epigenetic dysregulation.

Tyrosine kinases are a class of tumorigenic proteins that has received considerable attention. Less well-studied are tyrosine phosphotases, which are a focus of Zhenghe (John) Wang's group. The Wang laboratory has identified six protein tyrosine phosphatase genes mutated in colorectal cancers, and has published evidence that non-mutated versions of these proteins function as tumor suppressors.

Experiments involving model organisms are critical for cancer research, as they yield insights that would not be apparent from empirical human data. Kurt Runge and Guangbin Luo are experts in the use of model organisms, specifically yeast and mouse, respectively. Among other efforts, Professor Luo has made extensive use of a mouse model to study both Bloom and Rothmund-Thomson syndromes in the laboratory. The goal of Professor Runge’s laboratory is to understand what roles telomeres play in chromosome stability and segregation and how this information is communicated to the cell cycle machinery, using yeast genetics and molecular biological and biochemical approaches. Chromosome stability and segregation are central processes in cancer development, as deficiencies in them can lead to duplications and deletions of genes whose dysregulations leads to tumor initiation and promotion.

Anna Mitchell is a board-certified clinical geneticist. In her practice, she sees patients with a variety of genetic conditions. She has a strong interest in identifying the specific inherited mutations that contribute to familial cancers and related syndromes.

In addition to his laboratory’s vibrant and productive research efforts, Drew Adams also serves as Director of the Small-Molecule Drug Development Core, a facility in the CWRU School of Medicine that enables high-throughput screening to accelerate academic drug discovery efforts. Among his many collaborators are researchers searching for drugs that target specific aberrations in human cancer.