Parameswari namasivayam - Academia.edu (original) (raw)

Papers by Parameswari namasivayam

Research paper thumbnail of Repressive LTR nucleosome positioning by the BAF complex is required for HIV latency

PLoS biology, 2011

Persistence of a reservoir of latently infected memory T cells provides a barrier to HIV eradicat... more Persistence of a reservoir of latently infected memory T cells provides a barrier to HIV eradication in treated patients. Several reports have implicated the involvement of SWI/SNF chromatin remodeling complexes in restricting early steps in HIV infection, in coupling the processes of integration and remodeling, and in promoter/LTR transcription activation and repression. However, the mechanism behind the seemingly contradictory involvement of SWI/SNF in the HIV life cycle remains unclear. Here we addressed the role of SWI/SNF in regulation of the latent HIV LTR before and after transcriptional activation. We determined the predicted nucleosome affinity of the LTR sequence and found a striking reverse correlation when compared to the strictly positioned in vivo LTR nucleosomal structure; sequences encompassing the DNase hypersensitive regions displayed the highest nucleosome affinity, while the strictly positioned nucleosomes displayed lower affinity for nucleosome formation. To exa...

Research paper thumbnail of Phase I Study of Atevirdine, a Nonnucleoside Reverse Transcriptase Inhibitor, in Combination with Zidovudine for Human Immunodeficiency Virus Type 1 Infection

Journal of Infectious Diseases, 1995

Twenty patients were enrolled in a phase I clinical trial of atevirdine, a nonnucleoside reverse ... more Twenty patients were enrolled in a phase I clinical trial of atevirdine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), given in combination with zidovudine for treatment of human immunodeficiency virus type 1 (HIV-1) infection. Fifteen patients had received no previous antiretroviral therapy. HIV-1 isolates obtained at 6-week intervals were tested for sensitivity to atevirdine and zidovudine. Two patients developed a rash within 2 weeks of enrollment, and 1 of these developed concomitant fever and hepatitis. No hematopoietic, neurologic, or pancreatic toxicities were observed. Atevirdine had considerable initial interpatient pharmacokinetic variability. Forty-seven percent of patients treated with atevirdine plus zidovudine had increased CD4 lymphocyte counts, and HIV isolates from 62% of patients remained sensitive to atevirdine after 24 weeks of therapy. Atevirdine plus zidovudine was well-tolerated. Additional studies should be done to determine the role of atevirdine in the therapy for HIV infection.

Research paper thumbnail of Myosin phosphatase dephosphorylates HDAC7, controls its nucleocytoplasmic shuttling, and inhibits apoptosis in thymocytes

Genes & Development, 2007

The repressive activity of histone deacetylase 7 (HDAC7), a class IIa HDAC expressed in CD4 + CD8... more The repressive activity of histone deacetylase 7 (HDAC7), a class IIa HDAC expressed in CD4 + CD8 + double-positive thymocytes, is regulated by its nucleocytoplasmic shuttling. In resting thymocytes, HDAC7 is nuclear and functions as a transcriptional repressor. After T-cell receptor (TCR) activation, the serine/threonine kinase PKD1 phosphorylates HDAC7, resulting in its nuclear export and the derepression of its target genes. Here, we identify protein phosphatase 1␤ (PP1␤) and myosin phosphatase targeting subunit 1 (MYPT1), two components of the myosin phosphatase complex, as HDAC7-associated proteins in thymocytes. Myosin phosphatase dephosphorylates HDAC7 and promotes its nuclear localization, leading to the repression of the HDAC7 target, Nur77, and the inhibition of apoptosis in CD4 + CD8 + thymocytes. Supplemental material is available at http://www.genesdev.org. 1 Corresponding author. E-MAIL everdin@gladstone.ucsf.edu; FAX (415) 355-0855. Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1513107.

Research paper thumbnail of Regulatory signal transduction pathways for class IIa histone deacetylases

Current Opinion in Pharmacology, 2010

Research paper thumbnail of Repressive LTR nucleosome positioning by the BAF complex is required for HIV latency

PLoS biology, 2011

Persistence of a reservoir of latently infected memory T cells provides a barrier to HIV eradicat... more Persistence of a reservoir of latently infected memory T cells provides a barrier to HIV eradication in treated patients. Several reports have implicated the involvement of SWI/SNF chromatin remodeling complexes in restricting early steps in HIV infection, in coupling the processes of integration and remodeling, and in promoter/LTR transcription activation and repression. However, the mechanism behind the seemingly contradictory involvement of SWI/SNF in the HIV life cycle remains unclear. Here we addressed the role of SWI/SNF in regulation of the latent HIV LTR before and after transcriptional activation. We determined the predicted nucleosome affinity of the LTR sequence and found a striking reverse correlation when compared to the strictly positioned in vivo LTR nucleosomal structure; sequences encompassing the DNase hypersensitive regions displayed the highest nucleosome affinity, while the strictly positioned nucleosomes displayed lower affinity for nucleosome formation. To exa...

Research paper thumbnail of Phase I Study of Atevirdine, a Nonnucleoside Reverse Transcriptase Inhibitor, in Combination with Zidovudine for Human Immunodeficiency Virus Type 1 Infection

Journal of Infectious Diseases, 1995

Twenty patients were enrolled in a phase I clinical trial of atevirdine, a nonnucleoside reverse ... more Twenty patients were enrolled in a phase I clinical trial of atevirdine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), given in combination with zidovudine for treatment of human immunodeficiency virus type 1 (HIV-1) infection. Fifteen patients had received no previous antiretroviral therapy. HIV-1 isolates obtained at 6-week intervals were tested for sensitivity to atevirdine and zidovudine. Two patients developed a rash within 2 weeks of enrollment, and 1 of these developed concomitant fever and hepatitis. No hematopoietic, neurologic, or pancreatic toxicities were observed. Atevirdine had considerable initial interpatient pharmacokinetic variability. Forty-seven percent of patients treated with atevirdine plus zidovudine had increased CD4 lymphocyte counts, and HIV isolates from 62% of patients remained sensitive to atevirdine after 24 weeks of therapy. Atevirdine plus zidovudine was well-tolerated. Additional studies should be done to determine the role of atevirdine in the therapy for HIV infection.

Research paper thumbnail of Myosin phosphatase dephosphorylates HDAC7, controls its nucleocytoplasmic shuttling, and inhibits apoptosis in thymocytes

Genes & Development, 2007

The repressive activity of histone deacetylase 7 (HDAC7), a class IIa HDAC expressed in CD4 + CD8... more The repressive activity of histone deacetylase 7 (HDAC7), a class IIa HDAC expressed in CD4 + CD8 + double-positive thymocytes, is regulated by its nucleocytoplasmic shuttling. In resting thymocytes, HDAC7 is nuclear and functions as a transcriptional repressor. After T-cell receptor (TCR) activation, the serine/threonine kinase PKD1 phosphorylates HDAC7, resulting in its nuclear export and the derepression of its target genes. Here, we identify protein phosphatase 1␤ (PP1␤) and myosin phosphatase targeting subunit 1 (MYPT1), two components of the myosin phosphatase complex, as HDAC7-associated proteins in thymocytes. Myosin phosphatase dephosphorylates HDAC7 and promotes its nuclear localization, leading to the repression of the HDAC7 target, Nur77, and the inhibition of apoptosis in CD4 + CD8 + thymocytes. Supplemental material is available at http://www.genesdev.org. 1 Corresponding author. E-MAIL everdin@gladstone.ucsf.edu; FAX (415) 355-0855. Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1513107.

Research paper thumbnail of Regulatory signal transduction pathways for class IIa histone deacetylases

Current Opinion in Pharmacology, 2010