Leona D. Samson, PhD

Email: 

Office: 

56-235

Phone: 

(617) 258-7813
Professor of Biological Engineering
Professor of Biology
Uncas (1924) and Helen Whitaker Professor
American Cancer Society Research Professor

Research-at-a-glance: 

Repair of DNA Alkylation Damage
Animal Models of DNA Repair
Gene-Environment Interactions
Toxigenomics
Spontaneous Mutagenesis
Genomic Phenotyping

Affiliations: 

Member, Center for Environmental Health Sciences

Biography: 

Professor Samson began her education at the University of Aberdeen where she studied Biochemistry. Upon graduation with a Bachelor of Science degree, she moved on to complete her PhD in Molecular Biology at the University College London. Subsequently, she performed postdoctoral research at the University California, San Francisco and the University of California, Berkley. Before joining MIT, Samson was a Professor of Toxicology and Cancer Cell Biology at the Harvard School of Public Health. Samson has also previously served as the Director of the MIT Center for Environmental Health Sciences.

Research: 

Alkylating agents represent an abundant class of chemical DNA damaging agent in our environment. They are toxic, mutagenic, teratogenic and carcinogenic. Since we are continuously exposed to alkylating agents, and since certain alkylating agents are used for cancer chemotherapy, it is important to understand exactly how cells respond when exposed to these agents. The repair of DNA alkylation damage provides tremendous protection against the toxic effects of these agents and the Samson group’s aim is to understand the biology, the biochemistry, and the genetics of numerous DNA repair pathways that act upon DNA alkylation damage.

Organisms separated by enormous evolutionary distances employ similar proteins to protect against DNA damage. Bacteria, yeast, and human cells induce the expression of specific sets of genes in response to such damage. The Samson Lab’s studies on the response of Escherichia coli, Saccharomyces cerevisiae and human cells to alkylating agents have become intimately intertwined. Much of their previous work was based on the findings that bacterial DNA repair functions can operate in eukaryotic cells, and vice versa, i.e., eukaryotic DNA repair functions can operate in bacterial cells. They exploited this phenomenon to clone a large number of yeast, mouse, and human DNA alkylation repair genes, and are using these cloned genes to gain a thorough understanding of how eukaryotic cells respond to alkylating agents. Moreover, the Samson group has extended the alkylation toxicity studies from the cellular level to the whole animal level. Specifically, they have: (i) produced transgenic and knock-out mice with altered DNA repair capabilities and are now measuring their susceptibility to alkylation toxicity; and (ii) transferred DNA alkylation repair genes to bone marrow cells to determine whether such gene therapy could confer a useful level of extra resistance in the bone marrow of chemotherapy patients.

When cells are exposed to DNA damaging agents a signal is generated such that the transcription of various genes is altered. They have used Affymetrix oligonucleotide DNA chip analysis to monitor the transcriptional response of the entire S. cerevisiae genome, i.e., all 6,200 genes in response to a number of different alkylating agents. To the Samson group’s surprise, they identified hundreds of responsive genes and have uncovered a hitherto unknown response that links ubiquitin-mediated protein degradation and DNA repair. They are currently exploring the biological roles that the large number of responsive genes plays in protecting cells against alkylation toxicity. Signals can also be generated, in cells exposed to alkylating agents, which trigger cell cycle checkpoint arrest or apoptosis. The Samson group is also dissecting the molecular mechanisms by which alkylating agents signal these very important downstream events.

Research Areas: 

Honors & Awards: 

Burroughs Wellcome Toxicology Scholar Award (1993)
AACR Women in Cancer Research Award (2000)
Environmental Mutagen Society Annual Award for Research Excellence (2001)
American Cancer Society Research Professor (2001-2011)
Elected to the Institute of Medicine (2003)
Elected President of the Environmental Mutagen Society (2004)
Elected Fellow of the American Association for the Advancement of Science (2007)
NIH Director’s Pioneer Award (2009)
Senior Scholar Award from the Ellison Medical Foundation (2012)
Radcliffe Fellow (2013-2014)