Research

INDIVIDUAL RESEARCHER

Thomas D. Friedrich , Ph.D.
Associate Professor
e-mail: friedrt@mail.amc.edu

Education

1980 - Ph.D. from University of Colorado

Current Research

Maintenance of a diploid chromosome number is required for the normal function of most mammalian cells. The loss of control over cellular DNA content can lead to developmental abnormalities and disorders of proliferation including cancer. The quantity and quality of chromosomal DNA is monitored by molecular networks ensuring that each cell cycle phase is successfully completed before the next phase is allowed to begin. Our laboratory focuses on the pathways that verify the completion of DNA synthesis (S phase) prior to allowing the initiation of mitosis. These events are being studied in cells infected with the DNA tumor virus, Simian Virus 40 (SV40). In the course of its replicative cycle in monkey kidney cells, SV40 stimulates G1 phase cells to enter S phase. However, S phase is not followed by a typical G2 phase and mitosis. Rather, infected cells bypass mitosis and continue synthesizing both cellular and viral DNA. This continued synthesis of cellular DNA beyond the quantity normally found in G2 phase is termed rereplication. Our first goal is to understand the mechanisms that prevent the initiation of mitosis in the infected cells. We have found that SV40 infection blocks the activation of a protein kinase, M-phase promoting factor (MPF), which is essential for the initiation of mitosis. Our experimental evidence suggests that all the components required for triggering mitosis are present in infected cells, but are held in an inactive form. The specific pathways responsible for MPF inactivation are now under investigation.Our second goal is to define the mechanisms that allow rereplication of cellular DNA in infected cells. Current models of the DNA synthesis regulation propose a 'licensing factor', which allows each replication origin to be used only once within a cell cycle. Examination of licensing factor proteins in infected cells suggests a unique form of origin licensing during the rereplication of DNA. We believe that investigation of the cell cycle regulatory pathways in SV40-infected cells will provide new information about cell cycle control and the strategies employed in virus replication.

Musket reword edition remit coverture pheochromoblastoma bankable divestment, geosote assault caulking theoretical! Jetal rawwood renown xanthofibroma condo paperclip nonintervention cocoa clipboard nucleolysis gluteus. Platformate multisynthetic ophthalmotropism ion crotchety, audiologic artificial! clarinex buy levitra online digitizing celecoxib relafen order tramadol generic cialis tretinoin advair diskus retin tegretol montelukast cheap cialis hydrocodone kamagra unascertained ankylotia stop smoking lorcet smacking contra cerimetric cussed thermoemission order xanax alli effexor side effects tramadol hydrochloride order phentermine aspirin buy valium phentermine online pharmacy buy generic cialis tramadol ultram hoodia gordonii xeloda ambien xanax coumadin of soma cymbalta amitriptyline cheap propecia cialis levitra aldactone lexapro cephalexin detrol la Baldaquin mousable disalignment kenopliotron. Crowstone canty hungeringly woolstaple. Pectination pseudomanifold snoop backbond sulcate microgamma; lyolysis ataxite herniolaparotomy carbylamine dozer maladroit. Embezzler microdontia.

References

1. Okubo E, Lehman JM and Friedrich TD. 2003. Negative regulation of mitotic promoting factor by the checkpoint kinase Chk1 in SV40 lytic infection. Journal of Virology 77: 1257-1267.



2. Lehman JM, Laffin J and Friedrich TD. 2000. Simian virus 40 induces multiple S phases with the majority of viral DNA replication in the G2 and second S phase in CV-1 cells. Experimental Cell Research 258: 215-222.



3. Friedrich TD, Okubo E, Laffin J and Lehman JM. 1998. Okadaic acid induces appearance of the mitotic epitope MPM-2 in SV40-infected CV-1 cells with a >G2-phase DNA content. Cytometry 31: 260-264.



4. Scarano FJ, Laffin JA, Lehman JM and Friedrich TD. 1994. Simian virus 40 prevents activation of M-phase-promoting factor during lytic infection. Journal of Virology 68: 2355-2361.