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Karen Reddy Portrait

Karen Reddy
Assistant Professor of Biological Chemistry
Johns Hopkins University School of Medicine

855 N. Wolfe St
Rangos 574
Baltimore, MD21205
Office Phone: 443-287-7216
Lab Phone:
Fax:
Email: kreddy4@jhmi.edu
Lab Web Site

Understanding how the nuclear periphery and other subcompartments contribute to general nuclear architecture and to specific gene regulation

Understanding the cell biology of genomes and how nuclear architecture controls gene expression is necessary to truly understand biological processes such as development and disease. Although sequencing of the genome and comparative genome analysis have yielded insights into the regulation and dis-regulation of genetic information, these efforts shed little light into how genomes actually work in vivo. The impact of architectural and cellular organization of genomes on gene activity is a next step to unlocking genetic and epigenetic mechanisms in development and disease. Recent evidence is emerging that the non-random organization in the nucleus is a contributing factor in regulating genes important to multiple developmental processes. Moreover, some studies suggest that the non-random organization in the nucleus is a contributing factor in initiating translocations. In mammalian nuclei, chromatin is organized into structural domains by association with distinct nuclear compartments. Such interactions are likely to bring together coordinately regulated genes and to focus proteins and enzymes that regulate DNA based activities such as transcription, recombination, replication and repression. While evidence mounts that genes are regulated by association with distinct nuclear compartments, relatively little is known about how specific loci are directed to different domains. I hypothesize that such “nuclear addressing” requires specific cis elements that interact with a set of sequestered proteins (trans factors) to establish and maintain nuclear architecture and functionality. Such self-reinforcing interactions likely lie at the heart of nuclear structure and function. My recent work has demonstrated that one such compartment that is important for both nuclear structure and gene regulation is the nuclear periphery. In addition to regulation of Immunoglobulin Heavy Chain loci, the nuclear envelope (NE) is also implicated in regulating, among other things, muscle specific genes. The focus of the research in my lab is to begin to understand how the nuclear periphery and other subcompartments contribute to general nuclear architecture and to specific gene regulation. These questions comprise three complementary areas of research: understanding how genes are regulated at the nuclear periphery, deciphering how genes are localized (or “addressed”) to specific nuclear compartments and, finally, how these processes are utilized in development and corrupted in disease.

Recent Publications

Reddy KL and Singh HS. (2008) “Using molecular tethering to analyze the role of nuclear compartmentalization in the regulation of mammalian gene activity”, Methods “Visualization of molecular processes in cells using fluorescence imaging”.
PubMed Reference

Reddy KL*, Johnson KJ*, and Singh HS. (2008) Signaling and transcriptional control coordinating V(D)J recombination and B cell development” "V(D)J Recombination", edited by Dr. Ferrier, Landes Bioscience

Reddy KL
*, Schlimgen,R*, Singh HS and Krangel M. (2008) “The Role of Nuclear Localization in Regulating Tcrb Recombination and Allelic Exclusion” Submitted and out for review Nature Immunology (*co-first authors)

Reddy KL, Zullo JM,  Bertolino E and Singh HS. (2008) “Mammalian gene repression mediated by inducible repositioning to the nuclear membrane”, Nature, 452(7184):243-7.
PubMed Reference

Reynaud D, DeMarco I , Reddy,KL, Schjerven H, Bertolino E, Smale ST, Winandy S. and Singh HS. (2008) “Key features of pro-B cells are specifically regulated by Ikaros”, Nature Immunology.
PubMed Reference​

Bertolino E, Reddy KL, Medina KL, Parganas E, Ihle J, and Singh H. (2005). “Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5” Nature Immunology 6, 836-843. PubMed Reference

Medina KL, Pongubala JMR, Reddy KL, Lancki DW, DeKoter R, Kieslinger M, Grosschedl R, and Singh H. (2004). “Assembling a Gene Regulatory Network for Specification of the B Cell Fate” Developmental Cell 7, 607-617. PubMed Reference


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