Positions
- Ben F. Love Chair in Cancer Research
-
ÌÇÐÄvlogÃÛÌÒ of Medicine
- Professor
-
Molecular and Human Genetics
ÌÇÐÄvlogÃÛÌÒ of Medicine
- Professor
-
Biochemistry & Molecular Biology
ÌÇÐÄvlogÃÛÌÒ of Medicine
- Professor
-
Molecular Virology & Microbiology
ÌÇÐÄvlogÃÛÌÒ of Medicine
- Leader
-
Mechanisms in Cancer Evolution Program
Dan L Duncan Comprehensive Cancer Center
ÌÇÐÄvlogÃÛÌÒ of Medicine
- Professor
-
Graduate Program in Genetics and Genomics
ÌÇÐÄvlogÃÛÌÒ of Medicine
- Professor
-
Graduate Program in Cancer & Cell Biology
ÌÇÐÄvlogÃÛÌÒ of Medicine
- Professor
-
Graduate Program in Development, Disease Models & Therapeutics
ÌÇÐÄvlogÃÛÌÒ of Medicine
- Professor
-
Graduate Program in Chemical, Physical & Structural Biology
ÌÇÐÄvlogÃÛÌÒ of Medicine
- Professor
-
Graduate Program in Systems, Synthetic, and Physical Biology
Rice University
Education
- BA from State University of New York
- Potsdam
- PhD from University of Oregon
- Eugene
- Post-Doctoral Fellowship at University of Paris VII
- Paris, France
- Post-Doctoral Fellowship at University of Utah School of Medicine
- Salt Lake City
- Post-Doctoral Fellowship at National Cancer Institute
- Frederick
Honors & Awards
- The 2026 Lyda Hill Philanthropies Prize in Biological Sciences
- Texas Academy of Medicine, Engineering, Science & Technology (01/2026)
- NIH Director’s Pioneer Awards 2020 & 2009
- Science Magazine, Senior Editorial Board
- WM Keck Foundation Medical Research Award
- American Association for the Advancement of Science, Fellow
- American Academy of Microbiology
- Ben F. Love Chair in Cancer Research
- Biosphere and Humanity Medal, Russian Academies of Medicine and Science
- Cullen Endowed Professor in Molecular Genetics
- The Genetics Society of Canada Young Scientist Award
- The Eli Lilly/National Cancer Institute of Canada William Rawls Prize
- Michael E. DeBakey Excellence in Research Award
- Recipient, 2014, 2001
- ÌÇÐÄvlogÃÛÌÒ of Medicine Student Awards for Graduate Teaching Excellence
- Recipient, 2015, 2008, 2006, 2001, 2000
- Certificate of Honorary Member
- Associazione Internazionale di Sensibilizzazione e Prevenzione delle patologie della Donna (International Association of Awareness and Prevention of Women’s Diseases) (10/2025)
Professional Interests
- Molecular mechanisms of genome instability
- Stress-induced mutagenesis
- Cancer
- Antibiotic resistance
- Spontaneous DNA damage
Professional Statement
Genome Instability in Evolution, Antibiotic Resistance and Cancer
STRESS-INDUCED MUTAGENESIS: For 50 years the world believed that mutations occur at random. The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. The stress-induced mutations occur during growth-limiting stress and can include adaptive mutations that allow growth in the otherwise growth-limiting environment. We are elucidating molecular mechanisms by which these mutations form in E. coli using a variety of genetic, molecular, genomic, and whole-genome-sequencing approaches. We discovered that the normally high-fidelity mechanism of DNA double-strand-break repair is switched to a mutagenic version of that mechanism, using a special error-prone DNA polymerase, specifically when cells are stressed, under the control of two cellular stress responses. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, i.e. are stressed, potentially accelerating evolution. Stress-induced mutation mechanisms may provide important models for genome instability underlying some cancers and genetic diseases, resistance to chemotherapeutic and antibiotic drugs, the pathogenicity of microbes and many other important evolutionary processes. We are interested in molecular mechanisms that drive evolution.
ANTIBIOTIC-RESISTANCE MUTATION: Some mutations that confer antibiotic-resistance form by mechanisms with similarities to recombination-dependent stress-induced mutagenesis described above. We are examining the mechanisms by which these mutations form.
SPONTANEOUS DNA DAMAGE: We created E. coli cells that fluoresce green when their DNA is damaged, and are using flow cytometry to quantify and recover green cells with spontaneous DNA damage. With this direct, sensitive technology we are identifying the amounts, kinds, and sources of spontaneous DNA damage in single living cells. Spontaneous DNA damage is thought to be the main culprit underlying genetic and genomic instability in all living cells. We discovered that spontaneous DNA double-strand breaks are rarer and more dangerous to genomes than predicted and that bacteria with DNA damage undergo a senescence-like state, analogous to that in human cells.
FROM BACTERIA TO HUMAN: GENOMIC CARETAKER PROTEINS AND CANCER. Genomic instability including mutagenesis and chromosome rearrangement is a hallmark of cancer, yet the genomic caretaker proteins that prevent and sometimes cause instability are highly conserved and similar in all organisms. E. coli RecQ is a close relative of five human proteins, mutations in at least three of which cause genome instability underlying cancer-predisposition syndromes: Bloom, Werner, and Rothmund-Thomson. One of the human, the yeast and fly RecQ homologues, appear to play one specific role in genetic recombination in cells. Surprisingly, we found that E. coli RecQ plays the opposite role, and thus exemplifies a second paradigm for the in vivo function of RecQ-family proteins. We are investigating whether any of the human homologues function via the E. coli RecQ paradigm, and the molecular basis of RecQ action in vivo as a model for human oncogenesis. We are pursuing other promising bacterial homologues of human cancer proteins to learn their mechanisms of action first in the simpler, more tractable bacterial system to provide mechanisms and models for the molecular bases of cancer.
STRESS-INDUCED MUTAGENESIS: For 50 years the world believed that mutations occur at random. The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. The stress-induced mutations occur during growth-limiting stress and can include adaptive mutations that allow growth in the otherwise growth-limiting environment. We are elucidating molecular mechanisms by which these mutations form in E. coli using a variety of genetic, molecular, genomic, and whole-genome-sequencing approaches. We discovered that the normally high-fidelity mechanism of DNA double-strand-break repair is switched to a mutagenic version of that mechanism, using a special error-prone DNA polymerase, specifically when cells are stressed, under the control of two cellular stress responses. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, i.e. are stressed, potentially accelerating evolution. Stress-induced mutation mechanisms may provide important models for genome instability underlying some cancers and genetic diseases, resistance to chemotherapeutic and antibiotic drugs, the pathogenicity of microbes and many other important evolutionary processes. We are interested in molecular mechanisms that drive evolution.
ANTIBIOTIC-RESISTANCE MUTATION: Some mutations that confer antibiotic-resistance form by mechanisms with similarities to recombination-dependent stress-induced mutagenesis described above. We are examining the mechanisms by which these mutations form.
SPONTANEOUS DNA DAMAGE: We created E. coli cells that fluoresce green when their DNA is damaged, and are using flow cytometry to quantify and recover green cells with spontaneous DNA damage. With this direct, sensitive technology we are identifying the amounts, kinds, and sources of spontaneous DNA damage in single living cells. Spontaneous DNA damage is thought to be the main culprit underlying genetic and genomic instability in all living cells. We discovered that spontaneous DNA double-strand breaks are rarer and more dangerous to genomes than predicted and that bacteria with DNA damage undergo a senescence-like state, analogous to that in human cells.
FROM BACTERIA TO HUMAN: GENOMIC CARETAKER PROTEINS AND CANCER. Genomic instability including mutagenesis and chromosome rearrangement is a hallmark of cancer, yet the genomic caretaker proteins that prevent and sometimes cause instability are highly conserved and similar in all organisms. E. coli RecQ is a close relative of five human proteins, mutations in at least three of which cause genome instability underlying cancer-predisposition syndromes: Bloom, Werner, and Rothmund-Thomson. One of the human, the yeast and fly RecQ homologues, appear to play one specific role in genetic recombination in cells. Surprisingly, we found that E. coli RecQ plays the opposite role, and thus exemplifies a second paradigm for the in vivo function of RecQ-family proteins. We are investigating whether any of the human homologues function via the E. coli RecQ paradigm, and the molecular basis of RecQ action in vivo as a model for human oncogenesis. We are pursuing other promising bacterial homologues of human cancer proteins to learn their mechanisms of action first in the simpler, more tractable bacterial system to provide mechanisms and models for the molecular bases of cancer.
Selected Publications
-
Liu J, Perren JO, Rogers CM, Wen AX, Nimer S, Halliday J, Fitzgerald DM, Mei Q, Nehring R, Crum M, Kozmin SG, Xia J, Cooke, MB, Zhai Y, Bates D, Lei L, Hastings PJ, Artsimovitch I, Herman C, Sung PM, Miller KM*, Rosenberg SM*. " " Nature. 2025 ; 640 : 240-248.
Pubmed PMID: . -
Russo M, Chen M, Mariella E, Peng H, Rehman SK, Sancho E, Sogari A, Toh TS, Balaban NQ, Battle E, Bernards R, Garnet MJ, Hengaur M, Leucci E, Marine J-C, O’Brian C, Oren Y, Patton E, Robert C, Rosenberg SM, Shen S, Bardelli A. " " Nat Rev Cancer. 2024 ; 24 (10) : 694-717.
Pubmed PMID: . -
Zhai Y, Pribis JP, Dooling SW, Garcia-Villada L, Minnick PJ, Xia J, Liu J, Mei Q, Fitzgerald D, Herman C, Hastings PJ, Costa-Mattioli M, Rosenberg SM. " " Sci Adv. 2023 Jun 23; 9 (25) : eadg0188.
Pubmed PMID: . -
Zhai Y*, Minnick PJ*, Pribis JP, Garcia-Villada L, Hastings PJ, Herman C†, and Rosenberg SM†. " " Mol Cell. 2023 Apr ; 83 : 1298-1310.
Pubmed PMID: .
to edit your profile