Laboratory of Molecular Biology & Immunology
Ranjan Sen, PhD, Chief
The goal of the Laboratory of Molecular Biology and Immunology (LMBI) is to elucidate molecular mechanisms of processes that contribute to age-associated changes in physiology, including diseases whose prevalence increases with age. Our research has three interconnected themes: 1) molecular mechanisms of basic cellular processes, 2) immune cell function, and 3) translating basic mechanisms to clinical research.
Major areas of emphasis include:
- Elucidation of molecular mechanisms that govern tissue-specific gene expression;
- Molecular mechanisms of antibody diversity
- Mechanisms controlling T cell memory, and
- Contribution of regulatory immune cells to cancer.
As described below for the individual programs, a wide variety of in vitro and in vivo models are employed to approach these issues. These processes have direct relevance to our understanding of critical events associated with various age-related deficits and/or development of age-related diseases including cancer. LMBI investigators also study several aspects of human immunology. These areas of research include: 1) functional changes in immune cell types that occur with age and their contribution to chronic inflammation; 2) properties of age-associated immune subsets and 3) the emergence of autoimmunity in the elderly. The TSDBU led by a Stadtman Investigator Mia Sung developed fluorescent knock-in mice that track one or both of the canonical subunits of NF-κB. The power of these reporters is illustrated in Rahman et al. (Cell Reports, 2022) with several approaches that gain deeper insights to NF-κB biology. The mice enable diverse applications from single-molecule analyses to in situ identification of active inflammatory cells.
- Molecular Biology/Biochemistry
- Chromosome Biology/Epigenetics
- Cell Biology/Cell Signaling
Findings and Publications
Maul, R.W., Cao, Z., Venkataraman, L., Giorgetti, C.A., Press, J.L., Denizot, Y., Du, H., Sen, R. and Gearhart, P.J. Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo-activated cells. J. Exp. Med. 211:2297-2306, 2014.
Bektas, A., Zhang, Y., Lehrmann, E., Wood, W.H. 3rd, Becker, K.G., Madara, K., Ferrucci, L., Sen, R. Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase. Aging (Albany NY) 6(11):957-74, 2014.
Cheng, NL., Chen, X. Nguyen, Q., Wersto, R., and Weng, N-P. MicroRNA-125b modulates inflammatory chemokine CCL4 expression in immune cells and its reduction causes CCL4 increase with age. Aging Cell 14:200-208, 2015. PMID: 25620312.
Najarro, KM, Nguyen, H., Chen, G., Xu, M., Sorokina, A., Alcorta, S., Zukley, L., Lin, Y., Li, H., Oelke, M., Metter, J. Xu., X., Link, S., Schneck, J., Longo, DL., Leng, S., Ferrucci, L., and Weng, N-P.: Telomere length as an indicator of the robustness of B- and T-cell response to influenza in older adults. J. Infect. Disease (in press) 2015. PMID: 25828247.
Lee-Chang C, Bodogai M, Moritoh K, Olkhanud PB, Chan AC, Croft M, Mattison JA, Holst PJ, Gress RE, Ferrucci L, Hakim F, Biragyn, A.: Accumulation of 4-1BBL+ B cells in the elderly induces the generation of granzyme-B+ CD8+ T cells with potential antitumor activity. Blood. 2014 Jul 18. pii: blood-2014-03-563940. [Epub ahead of print] PMID: 25037628.
Lymphocyte Differentiation Section
Antibody Diversity Section
Gene Regulation Section
Section on Replication Stress and Aging
Transcription Systems Dynamics and Biology Unit
Flow Cytometry Unit