Michael McClelland, Ph.D.
Professor, University of California, Irvine
Dr. McClelland received his doctorate in Molecular and Population Genetics from the University of Georgia in 1983. He was a postdoctoral fellow in the lab of Allan Wilson at the UC Berkeley, and then the lab of Charles Cantor at Columbia University. He was awarded a Markey Fellowship and moved to the University of Chicago as an Assistant Professor in 1986, and on to San Diego in 1989. He has served on the editorial board of Nucleic Acids Research, the National Institutes of Health Genomics Study Section, and regularly serves as an ad hoc member of various study sections. Dr. McClelland has published over 200 peer-reviewed papers, which have been cited over 10,000 times. Dr. McClelland also works with a number of companies developing cancer prognosticators and cancer therapies.
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 currently 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.
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 microarray resources and techniques to over 50 laboratories worldwide for study of Salmonella genomes, transcription, and mutant library screens. In addition, we develop novel techniques for high throughput forward genetic analyses.
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.
1. McClelland M, Ivarie R. 1982. Asymmetrical distribution of CpG in an "average" mammalian gene. Nucleic Acids Research. 10:7865-77. (Discovery of CpG islands).
2. Welsh J, McClelland M. 1990. Fingerprinting genomes using PCR with arbitrary primers. Nucleic Acids Research. 18:7213-7218. (4000 citations).
3. McClelland M, et al., 2001. Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413:852-6. (600 citations).
4. McClelland M, et al., 2004. Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid. Nature Genetics 36:1268-74.
5. Arrach N, Zhao M, Porwollik S, Hoffman RM, McClelland M. 2008. Salmonella promoters preferentially activated inside tumors. Cancer Research. 68:4827-32.