Molecular & Human Genetics

2014 Recipient

Winners of the 2001 Michael E. DeBakey, M.D., Excellence in Research Awards. From left: Joseph S. Coselli, M.D., Susan M. Rosenberg, Ph.D., Michael E. DeBakey, M.D., Salih J. Wakil, Ph.D, Lutfi Abu-Elheiga, Ph.D., Dennis R. Roop, Ph.D.

Dr. Rosenberg’s nomination was based on her groundbreaking papers on the mechanisms of genomic instability and the ability of cells and organisms to evolve, on the harnessing of mechanistic understanding of evolution to combat cancer and infectious disease, and on creating new universal tools for genome-instability research in all organisms and potentially for therapy.  This work provided a beacon in the search for new targets for a new kind of anti-pathogen and anti-cancer therapy, which Dr. Rosenberg proposed: the development of drugs that would stop evolution of pathogens, making them susceptible to antibiotics without the evolution of resistance, and that would allow cancers to be treated with chemotherapies without provoking resistance.

Dr. Rosenberg’s nomination was based on the following publications: 

 Al Mamun AALombardo MJShee CLisewski AMGonzalez CLin DNehring RBSaint-Ruf CGibson JLFrisch RLLichtarge OHastings PJRosenberg SMIdentity and function of a large gene network underlying mutagenic repair of DNA breaks. Science. 2012 Dec 7;338(6112):1344-8. 

Shee CCox BDGu FLuengas EMJoshi MCChiu LYMagnan DHalliday JAFrisch RLGibson JLNehring RBDo HGHernandez MLi LHerman CHastings PBates DHarris RSMiller KMRosenberg SMEngineered proteins detect spontaneous DNA breakage in human and bacterial cells. Elife. 2013 Oct 29;2:e01222.

Rosenberg SMQueitsch C. Medicine. Combating evolution to fight diseaseScience. 2014 Mar 7;343 (6175):1088-9.

2001 Recipient

Nurture remodels nature: environmentally-inducible genetic change

Dr. Rosenberg received the award for her research on mutations and genome rearrangement that alter chromosome structure. These changes to a cell’s genome are the underlying causes of many medically important problems. Examples in which the human genome is changed include cancer formation, tumor progression, and evolution of cancer resistance to chemotherapeutic drugs. Mutations and genome rearrangements also fuel the evolution of pathogenic microbes allowing them to escape the immune system, and to develop resistance to antibiotics. For many decades, remodeling of the genome (“nature”) was presumed to occur randomly and independently of environmental conditions (“nurture”). Dr. Rosenberg’s group studies a process that contradicts this view: mutation and genome rearrangement provoked by environmental stress to cells. They have discovered that under stress conditions, a special mistake-prone DNA copying enzyme is produced by cells, and the errors it makes lead to high levels of mutation. Some of the mutations allow the cells to thrive in the previously stressful environment. The cells studied are those of a model organism, the bacterium E. coli. However the error-prone enzyme is a member of a newly discovered superfamily of DNA copying enzymes present in all branches of the tree of life. The action of the four similar enzymes in humans, and similar enzymes in human pathogens, is likely to be important in human cancers, and to microbial pathogenesis. Dr. Rosenberg’s group, in collaboration with Dr. Philip Hastings at Baylor College of Medicine, has also discovered a second kind of environmentally provoked genome remodeling: adaptive gene amplification. Potentially highly relevant to cancer evolution, this is a stress-provoked expansion in the numbers of copies of a gene in cells, the outcome of which is cell growth in the stressful environment.

Dr. Rosenberg’s nomination was based on the following publications:

Hastings PJ, Bull HJ, Klump JR, Rosenberg SM. Adaptive amplification: an inducible chromosomal instability mechanism. Cell. 2000 Nov 22;103(5):723-31.

McKenzie GJ, Lee PL, Lombardo MJ, Hastings PJ, Rosenberg SM. SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification. Mol Cell. 2001 Mar;7(3):571-9.

Rosenberg SM. Evolving responsively: adaptive mutation. Nat Rev Genet. 2001 Jul;2(7):504-15.