Dept. of Microbiology and Molecular Genetics
B240 Med Sci Bldg.
Irvine, CA 92697-4025
Phone: (secretary) 949-824-5261
Dept. of Pathology and Laboratory Medicine
D440 Medical Sciences I
Irvine, CA 92697-4800
Phone: (secretary) 949-824-6574
Key Research Area
Dr. McClelland and members of his laboratory use genomics to approach two general research areas.
First, we study dys-regulation of genes that occurs in cancer. We were the first to describe that the regulatory regions of mammalian genes, called promoters, contain sequences called CpG islands. Methylation of these features is important in marking genes for regulation. We constructed the first “promoter microarrays” of DNA fragments from 10,000 promoters and collaborated on the first Chromatin immunoprecipitation-array (ChIP-chip) experiments, which identify proteins bound to promoters in living cells. The McClelland lab is particularly interested in alterations of gene expression in adjacent normal tissue during cancer progression. As part of this work, we are involved in a large multi-center grant to identify changes in gene expression in prostate cancer that are associated with increased risk of recurrence of the disease after prostatectomy.
We invented arbitrarily primed PCR that generates fingerprints from any genome and that has been used in over 6000 publications. We collaborated using the method to discover the mutator phenotype of cancer.
Secondly, we are interested in the evolutionary biology of enteric bacteria. We have organized the sequencing and annotation of the complete genome sequences of major pathogens, including Salmonella enterica serotype Typhimurium, a common cause of bacterial food borne illness. Our laboratory provides genetics resources and techniques to over 50 laboratories worldwide for study of Salmonella genomes, transcription, and mutant library screens. In addition, we develop techniques for high throughput forward genetic analyses. We also created a resource of libraries of random transposon insertion mutants in multiple Salmonella enterica serovars and a collection of defined single-gene and multi-gene deletion mutants in Salmonella enterica sv Typhimurium 14028. These are used in various investigations of gene requirements and fitness in a large variety of different environments.
A further goal of our study of Salmonella overlaps with our cancer studies. Serendipitously, harmless variants of Salmonella prefer to reside in tumors over any other location in the human body, by a factor of 1000 or more. This poorly understood phenomenon can result in tumor regression and cancer cures. We are working to engineer Salmonella so that it can be used as a therapeutic and novel delivery agent for exogenous therapeutics in cancer. We use newly developed high-throughput tools to identify Salmonella promoters that are activated exclusively in tumors. We are using these tumor-specific promoters to express cloned foreign therapeutic proteins only when bacteria reach tumors. In addition, we have developed tools to track thousands of bacterial mutants simultaneously, allowing us to identify mutants with favorable characteristics, such as those that accumulate most highly in tumors.
A list of publications at Google Scholar can be accessed here.
- 1986-1989 L.P. Markey Assistant Professor, Dept. Biochemistry Molecular Biology, U. Chicago, IL
- 1989-1995 Research Program Director, California Institute Bio. Res., CA
- 1995-2009 Professor, Sidney Kimmel Cancer Center, San Diego, CA. Director, Genomics and Bioinformatics Cores.
- 2000-2013 U. California, San Diego, Cancer Center, Member
- 2009-2013 Scientific Director, Vaccine Research Institute of San Diego
- 2011-present U. California, Irvine, Cancer Center, Member
- 1981,82,83 University-wide Predoctoral Research Fellowships, U. Georgia,Athens,GA
- 1983-1985 N.A.T.O. Postdoctoral Fellowship
- 1985-1989 Lucille P. Markey Biomedical Scholarship
- 1986-1989 Goldblatt Cancer Research Fund, Young Investigator
- 1992-2007 Editorial Board, Nucleic Acids Research
- 1995-1998 Member, NIH Genome Study section
- 2005 ASM Divisional lecture and award
- Ongoing Five NIH P01 site visits; NCI Directors Challenge panel; Chair, Novel Technologies RFA Study Section; two Bioterrorism Center Grant reviews; twelve NCI RFA and ad hoc panels; three USDA and NSF panels; external reviewer for DOE, UK; Editorial Board: Prostate, International Journal of Microbiology
Dr. McClelland has published over 250 peer-reviewed papers, which have been cited over 20,000 times. Dr. McClelland also works with a number of companies developing cancer prognosticators and cancer therapies.
|University of Bristol, UK||
|University of Georgia, Athens, GA||
|Mol & Pop Genetics|
|University of California, Berkeley, CA||
|Columbia University, NY, NY||