Keith C. Cheng, M.D., Ph.D.
Chief, Division of Experimental Pathology
Distinguished Professor of Pathology, Biochemistry & Molecular Biology, and Pharmacology
Director, Zebrafish Functional Genomics and Imaging Core
Curator, Zebrafish Atlas and Bio-atlas
Office: Room C7866A
Core Lab: Room C7804
- Office (717) 531-5635
- Lab (717) 531-4704
- Lab (717) 531-5301
- Fax: (717) 531-5634
For scheduling, please contact Joan Clancy-Flynn at (717) 531-6184 or by email at email@example.com
Areas of interest: Phenomics, web-based resources, image Informatics, genomics,cancer genetics and pigmentation genetics
About the Cheng Lab:
|The Cheng lab is interested in fundamental genetic and molecular mechanisms that cause cancer, basic mechanisms underlying the relationship between human skin pigmentation and cancer, and contributing to web-based infrastructures for science, education, and public service. Our laboratory was among the first to pioneer genetic screens in zebrafish to find new genes related to cancer. We are producing an on-line, high-resolution, full-lifespan atlas of the zebrafish that will be integrated with other anatomical web sites of zebrafish, other model organisms, and other disciplines. Collaboratively, we are developing 2D and 3D image informatics tools for systems biology and medicine, and new methods for X-ray based high resolution 3D imaging at cellular and subcellular resolutions. In 2005, we discovered that the putative cation exchanger SLC24A5 played a key role in the evolution of light skin in Europeans and modulates vertebrate pigmentation by its effect on melanosome morphogenesis. We are trying to understand why people of East Asian ancestry are not as susceptible to skin cancer as those of European ancestry, by exploring both the molecular mechanisms of melanosome morphogenesis and the genetics underlying the light skin of East Asians and Amerindians. This work has been sponsored by the Jake Gittlen Memorial Golf Tournament, American Cancer Society, the National Science Foundation, the National institutes of Health, and the Staebler Foundation. |
Answers to the basic question of how and why gene function is lost in somatic tissues will contribute to our understanding of aging and some forms of human disease, including cancer. Those mutations play a key role in the evolution of killer cancer cells from the originally normal ones of cancer victims, and also the evolution of resistant cancer cells after treatment. The tendency to mutate one's DNA can be called genetic instability or genomic instability, and the phenotype of elevated mutation rate is called mutator phenotype. In order to discover new vertebrate genes that control mutation, we have used the zebrafish (Danio rerio) to generate mutants that show elevated rates of somatic (body cell) mutation. In this screen, we scored for increased somatic loss of heterozygosity at a marker locus, golden. We expect genetic instability to be caused by deficiencies in any of a number of functions, including chromosome segregation, recombination, and DNA repair. We are studying the characteristics of mutants, including the ability of the mutations to significantly increase cancer susceptibility, and are engaged in the positional cloning of these mutations. Insights gained from these studies will increase our understanding of the molecular forces that drive evolution and may suggest new ways to fight cancer. Since these genomic instability ("gin") mutants tend to develop cancer, they represent an animal model for human genetic syndromes that predispose to cancer, and may promote the detection of environmental mutagens. This novel approach to the study of genetic instability was sponsored originally by the Jake Gittlen Memorial Golf Tournament, American Cancer Society, and the National Science Foundation.
We performed the first histological genetic screen for mutants in a vertebrate. These mutants are expected to be affected in any of a variety of functions that may affect cell differentiation, cell cycle regulation, or cell communication (Mohideen et al. 2003). Since these and other experiments require knowledge of the normal gross and microscopic anatomy of the zebrafish, we are now generating a web-based histology and 3D anatomic atlas, currently being executed in collaboration with physicists at University of Chicago and Argonne National Laboratory. This life-span atlas (see zfatlas.psu.edu) will provide a scaffold for gene expression and morphological phenotypic data generated globally. In recognition of important work being done by our colleagues across the globe, we welcome contributions from reach laboratories with slide or high-resolution image collections. Images from this resource may be used as long as permissions are requested and approved by email, and appropriate citations made.
Our most recent atlas efforts, designed to advance the development of phenomics, a collaboration with physicists, engineers, and computer scientists, involves the building of high-resolution, high- throughput synchrotron x-ray tomographic imaging (microCT) soft tissue imaging for mm-scale specimens, including whole zebrafish.
We have just created a new Penn State Zebrafish Functional Genomics Core facility, whose activities will include support for work dedicated to a greater understanding of biology and human disease.
Support for our work has been provided by the Jake Gittlen Laboratories for Cancer Research, the National Center for Research Resources, and now the Office of the Director at NIH. The project is planned to include genetic, reverse genetic, and disease abnormalities related to issues in personalized medicine. We work with engineers and computer scientists, and believe that integration with data from the web sites of other model systems and disciplines will make these resources most useful.
We encourage other laboratories to use the power of zebrafish functional genomics to study the functions of genes in the context of the whole organism, and in development.
We are exploring the idea of Systems Morphogenetics, which will yield high-throughput phenotypic profiling as a tool to understand biology and disease. This work, which is currently focused on creating X-ray based micron-scale computed tomographic 3D imaging tools and analysis for whole-animal phenotyping for the zebrafish phenome project, requires a highly collaborative environment that applies cutting edge technologies from computer science, engineering, materials science, bioinformatics, and genetics to the placing of each of these genes in the spatial, temporal, and physiological context of the whole organism. We are building of a team of partners from a broad range of disciplines to create a complete digital map of zebrafish anatomy, microanatomy, and gene expression, in order to create a bioinformatics focused on biological function.
Training Opportunities: Our laboratory pursues independent and collaborative projects utilizing model system approaches to human disease, including Mendelian and population genetics, genomics, molecular and cell biology. Our interests include high-throughput phenotypic profiling for systems biology, cancer genetics, genetic markers of human migration, the molecular genetics of human pigmentation, the primary genetic determinants of genomic instability and abnormal differentiation in cancer, and development of image recognition tools for model systems and pathology. We are exploring second generation screens for genomic instability mutants in zebrafish, and building interfaces between model system and human atlases.
Graduate candidates should apply through one of the following Penn State programs: MD/PhD program of the College of Medicine, Molecular Medicine option of the Integrative Biosciences Graduate Program in the Life Sciences Consortium, Cell and Molecular Biology, Biochemistry & Molecular Biology, and Intercollege Graduate Degree Program in Genetics.
Links: ZFIN at Univ. of Oregon
Education and Certification:
|Publications by Dr. Cheng |
Browse the interactive
Skin Color Audiovisuals
View Job Opportunities
in the Lab
Dr. Keith Cheng was the recipient of the 2008 Penn State Faculty Scholar Medal for Outstanding Achievement in Life and Health Sciences on March 24, 2008.
The Sun, January 13, 2011
Art and Science:
Penn State Mini-Medical School Genetics Lecture
Presented by Dr. Keith Cheng
"The Genetic Basis of Skin Color"
SHIRAZ is a collaborative project at Penn State University between the laboratories of James Z. Wang and Keith Cheng.
More about the SHIRAZ Project
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and his Lab's work