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Nan-ping Weng, M.D., Ph.D.

LYMPHOCYTE DIFFERENTIATION SECTION

Nan-Ping Weng, M.D., Ph.D., Senior Investigator
Phone: 410-558-8341
Fax: 410-558-8284
E-mail: wengn@mail.nih.gov

Biography:Dr. Nan-ping Weng received his M.D. from Fudan University Shanghai Medical College (former Shanghai First Medical College), China in 1984 and Ph.D. in Immunology from Baylor College of Medicine in 1993. He obtained his postdoctoral training (1994-1997) at National Cancer Institute, NIH. He joined NIA as a tenure-track investigator in 1997 and was tenured in 2006. 

Epigenetic regulation of transcription, function, and aging of memory CD8 T cells: Immunological memory is a fundamental basis for the adaptive immune response and for the modern practice of vaccination.  However, the mechanism underlying immunological memory is still not fully understood.  We have identified genes that are differentially expressed in naïve (TN) and memory (central, TCM, and effector, TEM) CD8 T cells in the resting and activated states, providing a starting point for elucidating the contribution of these differentially expressed genes in memory T cell formation, maintenance, function and possibly aging.  Currently, we focus our studies on two areas: 1) Epigenetic regulation of differential gene expression in memory T cells by histone methylation (H3K4me3 and H3K27me3) and non-coding RNA and 2) role of histone methyltransferase in memory T cell formation and maintenance.  We are using genome-wide approaches to study histone methylation (H3K4me3 and H3K27me3) in resting and activated TN, TCM and TEM (ChIP-Seq) and gene expression (microarray and RNA-seq), as well as genetically modified mouse models.  Our study will provide insight into the changes of histone methylation and gene expression after activation and the role of histone methylation in regulation and function of memory CD8 T cells.

TCR repertoire diversity, distribution, and age-associated change:  The T cell receptor plays an essential role in T cell mediated response.  However, the critical information regarding the size of TCR diversity, the distribution of specific TCR-bearing T cells in the total T cells, and the degree of age-associated changes of TCR repertoire are not well determined. To address these issues, we have developed a RACE-PCR-next generation sequencing (RAP-Seq) method to directly assess the TCRβ CDR3 repertoire of peripheral blood from healthy adults.  We found that the size of the TCRβ CDR3 diversity of CD4 T cells ranges from 2.6-3.7 x105, which was twice larger than that of CD8 T cells. With age, an expansion of highly abundant TCRβ CDR3 clones was observed in all old adults whereas reduction in TCRβ CDR3 diversity size was observed in most of the old adults. Remarkably, a significant number of TCRβ CDR3s were retained over a decade and some of these retained TCRβ CDR3s were against known viral antigens. To have a better understanding of TCR repertoire change, we are analyzing the specificity of TCR using a single cell approach.  In combination with massive sequencing and individual cell sequencing, we will be able to provide meaningful data to address these outstanding questions. The information could serve as a measure of immune competency and a guide for clinical intervention in elderly.

Roles of telomere and telomerase in human immune function:Telomeres, special structures at chromosomal ends, play a key role in the regulation of cellular replicative lifespan. Telomere attrition occurs in lymphocytes with age but the rates of telomere loss in different individuals may be different.  Also the critically shortened telomeres can cause cessation of cell division in vitro but whether telomere attrition plays a role in age-associated decline of immune function in vivo in humans has not been adequately addressed. We are studying the in vivo telomere/telomerase changes with longitudinal aging in BLSA participants and also comparing the immune response against influenza vaccine in healthy elderly participants who had relatively short or long telomere lengths in peripheral blood mononuclear cells (PBMC). Our study will provide information on the age-associated changes of telomere/telomerase in lymphocytes in vivo and their contribution to the decline of immune response with age.

PubMed: Search for listing of Dr. Nan-ping Weng's publications.
Lymphocyte Differentiation Section
Lymphocyte Differentiation Section

Left to right: Ana Lustig; Kalpana Subedi; Jie Wan Kim; Goubing Chen; Nan-ping Weng; Christina Slota; Thai Truong; Nai-Lin Cheng

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Updated: Thursday April 04, 2013