Jennifer W Bradford

Publications (2)18.09 Total impact

• Article: Polyglutamine toxicity in non-neuronal cells.

  Jennifer W Bradford, Shihua Li, Xiao-Jiang Li
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  ABSTRACT: The neurodegenerative polyglutamine diseases are caused by an expansion of unstable polyglutamine repeats in various disease proteins. Although these mutant proteins are expressed ubiquitously in neuronal and non-neuronal cells, they cause selective degeneration of specific neuronal populations. Recently, increasing evidence shows that polyglutamine disease proteins also affect non-neuronal cells. However, it remains unclear how the expression of polyglutamine proteins in non-neuronal cells contributes to the course of the polyglutamine diseases. Here, we discuss recent findings about the expression of mutant polyglutamine proteins in non-neuronal cells and their influence on neurological symptoms. Understanding the contribution of non-neuronal polyglutamine proteins to disease progression will help elucidate disease mechanisms and also help in the development of new treatment options.
  Cell Research 03/2010; 20(4):400-7. · 8.19 Impact Factor
• Article: Functional characterization of natural telomerase mutations found in patients with hematologic disorders.

  Zhong-Tao Xin, Adam D Beauchamp, Rodrigo T Calado, Jennifer W Bradford, Joshua A Regal, Aarthi Shenoy, Yuying Liang, Peter M Lansdorp, Neal S Young, Hinh Ly
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  ABSTRACT: Human telomerase hTERC RNA serves as a template for the catalytic hTERT protein to synthesize telomere repeats at chromosome ends. We have recently shown that some patients with bone marrow failure syndromes are heterozygous carriers for hTERC or hTERT mutations. These sequence variations usually lead to a compromised telomerase function by haploinsufficiency. Here, we provide functional characterization of an additional 8 distinct hTERT sequence variants and 5 hTERC variants that have recently been identified in patients with dyskeratosis congenita (DC) or aplastic anemia (AA). Among the mutations, 2 are novel telomerase variants that were identified in our cohort of patients. Whereas most of the sequence variants modulate telomerase function by haploinsufficiency, 2 hTERC variants with sequence changes located within the template region appear to act in a dominant-negative fashion. Inherited telomerase gene mutations, therefore, operate by various mechanisms to shorten telomere lengths, leading to limited marrow stem cell reserve and renewal capacity in patients with hematologic disorders.
  Blood 02/2007; 109(2):524-32. · 9.90 Impact Factor