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Your Environment. Your Health.

Molecular Carcinogenesis Laboratory

Research Summary

Carcinogenesis is a complex process. In any individual, the interplay between genetics, environmental exposure and age combine to create conditions more or less favorable for the development and dissemination of cancer. For cancer cells to develop and thrive, they must acquire a variety of specific capabilities: growing inappropriately, avoiding elimination by defense mechanisms, stimulating their microenvironment, providing needed support and spreading to new locations within the body. The processes that regulate these acquired abilities include gene expression as controlled by chromatin structure, signal transduction events in response to cell-cell interactions, hormone exposure and fatty acid metabolism and DNA damage and repair responses. The Laboratory of Molecular Carcinogenesis (LMC) — headed by Laboratory Chief Trevor K. Archer, Ph.D. ("/Rhythmyx/assembler/render?sys_contentid=36346&sys_revision=1&sys_variantid=1173&sys_context=0&sys_authtype=0&sys_siteid=&sys_folderid=" sys_dependentvariantid="1173" sys_dependentid="36346" inlinetype="rxhyperlink" rxinlineslot="103" sys_dependentid="36346" sys_siteid="" sys_folderid="") — is dedicated to elucidating the molecular mechanisms that facilitate these processes in the hope that understanding will lead to improved cancer prevention and therapy.

 

The goal of the LMC is to define the fundamental molecular mechanisms by which environmental exposures lead to cancer. The pursuit of molecular and environmental causes of cancer represents a synergistic approach to cancer prevention and treatment. Knowing the target genes for environmental agents will permit the development of improved methods for the identification of environmental carcinogens in both laboratory and epidemiological studies.

 

The kinky path: RNA polymerase II goes backwards during gene transcription.
The kinky path: RNA polymerase II goes backwards during gene transcription. Instead of transcribing smoothly, RNA polymerase II (Pol II) stalls at promoter-proximal regions of many genes in vivo (top panel). The early trancribed DNA of these genes contains a signal that causes Pol II to stop and backtrack along the gene, dislodging the growing RNA from the enzyme's catalytic center (second from top). The transcription factor IIS induces cleavage of this RNA (second from bottom), which may release Pol II  from the stalled state and enable productive transcription of the gene (bottom panel).Promoter-proximal Pol II stalling is a newly appreciated yet critical step for the expression of many genes, and might be central for the regulation of organism development as well as response to environmental stimuli. Nechaev, S, Fargo, DC, dos Santos, G, Liu, L, Gao, Y, Adelman, K (2010) Global analysis of short RNAs reveals widespread promoter-proximal stalling and arrest of Pol II in Drosophila. Science, 327: 335-338

The LMC is comprised of nine independent research groups forming a multidisciplinary team of cancer researchers with expertise in biochemistry, cell biology, epidemiology, molecular biology and oncology. LMC scientists bring diverse perspectives to their work, which provides an ideal opportunity for the study of cancer from the molecular level to the clinical. The LMC is actively involved in the following basic research:

 

  • Impact of chromatin and epigenetics on gene transcription
  • Signal transduction events in response to cell-cell interactions
  • Hormone exposure and fatty acid metabolism
  • DNA damage and repair responses
  • Molecular characterization of stem cell models
  • Mechanisms of action of specific genes in cell signaling, cell proliferation and cell death

 

Environmental agents influence cancer development by causing mutation in critical target genes, epigenetic modifications and by altering signal transduction pathways in and between cells, all active areas of research in LMC.

 

Strong ties with the Environmental Toxicological Program (ETP) and the Epidemiology Branch of the NIEHS allows LMC to be very active in the understanding of the etiology of cancer. The LMC is dedicated to elucidating the molecular mechanisms that facilitate these processes in the hope that understanding will lead to improved cancer prevention and therapy.

 

A Message from the Lab Chief

I hope that you will find the site both informative and interesting, with overviews of LMC scientific endeavors. As with all laboratories or departments within the Division of Intramural Research (DIR), LMC is committed to the mission of the NIEHS and its goal to improve human health. Our focus is on cancer and the research ranges from the very basic or fundamental, such as the role of chromatin and epigenetics, to investigating molecular therapeutics and translational and clinical studies of gene-environment interactions in cancer. The scientists within LMC use a broad range of approaches and techniques to understand the molecular mechanisms that underlie the carcinogenic process. As you navigate this Web site you will have an opportunity to read some of this original research as well as gain an appreciation of additional activities such as the LMC Seminar Series ("/Rhythmyx/assembler/render?sys_contentid=39211&sys_revision=3&sys_variantid=1169&sys_context=0&sys_authtype=0&sys_siteid=&sys_folderid=" sys_dependentvariantid="1169" sys_dependentid="39211" inlinetype="rxhyperlink" rxinlineslot="103" sys_dependentid="39211" sys_siteid="" sys_folderid=""), LMC Calendar of Events and links to other NIEHS and NIH Web sites.
 

 

--Trevor K Archer, Ph.D.

 

Scientific Support Staff

Katie Ochoa
Administrative Specialist
Tel (919) 541-0350
Fax (919) 541-0146
ochoak@niehs.nih.gov
Vivian Young
Administrative Technician
Tel (919) 541-2227
Fax (919) 541-0146
vchiu@niehs.nih.gov
Timothy Hinton
Administrative Technician
Tel (919) 541-7797
Fax (919) 541-0146
hintont2@niehs.nih.gov

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