Professor, Department of Molecular and Human Genetics

B.A., University of Cambridge, Cambridge, England, 1962
Ph.D., University of Cambridge, Cambridge, England, 1965
Postdoc, Harvard University, 1967

RESEARCH INTERESTS:

My current work is concentrating on the genetic responses to stress in Escherichia coli. We have shown that gene amplification occurs in response to stress, and is, therefore, an adaptive process comparable to the well-known adaptive mutation response. We are using genetic and molecular techniques to elucidate the mechanism by which adaptive amplification occurs. We predict that amplification will be accompanied by a high rate of chromosomal instability throughout the genome, just as adaptive mutation is a genome wide phenomenon, not targeted to useful mutations. Because this genetic instability would be part of an adaptive response, we expect to be able to induce it, and thus to study the processes by which genetic instability occurs. This might provide a model system in which to study the induction of chromosomal instability in oncogenesis (about 80 percent of cancers show chromosomal instability), and in evolution.

We have discovered that amplification is initiated by a template-switch mechanism during replication. By comparing our data to those derived from yeast and human cancer and genomic disease, we have derived a model for the origin of chromosomal structural changes for all organisms. This then suggests a mechanism for the origin of copy number variation (the major genetic difference between individuals) and for genomic disease. The model involves modification of the mechanism of replication fork repair occurring in cells experiencing a programmed stress-response. We are testing predictions of this model.

SELECTED PUBLICATIONS:

1. Slack A, Thornton PC, Magner DB, Rosenberg SM, Hastings PJ (2006). On the mechanism of gene amplification induced under stress in Escherichia coli. PLoS Genet. 2: e48.

2. Rosenberg SM, Hastings PJ (2004). Genomes: worming into genetic instability. Nature 430: 625-626.

3. Hastings PJ, Rosenberg SM, Slack A (2004). Antibiotic-induced lateral transfer of antibiotic resistance. Trends Microbiol. 12: 401-404.

4. Hastings PJ, Slack A, Petrosino JF, Rosenberg SM (2004). Adaptive amplification and point mutation are independent mechanisms: evidence for various stress-inducible mutation mechanisms. PLoS Biol. 2: e399.

5. Rosenberg SM, Hastings PJ (2003). Modulating mutation rates in the wild. Science 300: 1382-1383.

6. Hastings PJ, Rosenberg SM (2002). In pursuit of a molecular mechanism for adaptive gene amplification. DNA Repair 1: 111-123.

7. McKenzie GJ, Lee PL, Lombardo MJ, Hastings PJ, Rosenberg SM (2001). SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification. Mol. Cell 7: 571-579.

8. Hastings PJ, Bull HJ, Klump J, Rosenberg SM (2000). Adaptive amplification: An inducible chromosomal instability mechanism. Cell 103: 723-731.

9. Bull HJ, McKenzie GJ, Hastings PJ, Rosenberg SM (2000). Evidence that stationary-phase hypermutation in the E. coli chromosome is promoted by recombination. Genetics 154: 1427-1437.

For more publications, see listing on Pub Med.

CONTACT INFORMATION:

Philip J. Hastings, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza
Houston, Texas 77030, U.S.A.
Mail Stop: BCM225

Phone: 713-798-5787
Fax: 713-798-8704
E-mail:

Back to top