Minerva

Gen*NY*Sis Center for Excellence in Cancer Genomics

University at Albany, State University of New York

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Research Overview


Nuclear Receptors and Disease

Dr. Welsh’s lab investigates the role of nuclear receptors in normal development, aging and cancer.  Nuclear receptors are intracellular proteins that sense and respond to small, lipid-soluble compounds (ligands) including hormones, nutrients, xenobiotics and phytochemicals. Many of these ligands are present in the environment, thus nuclear receptors represent one mechanism for cells to respond to environmental changes. Once activated by their ligands, nuclear receptors participate in complex networks to regulate the expression of target genes that control normal development, cell proliferation and survival, tissue metabolism, drug disposition and homeostasis. Nuclear receptors are known to influence the aging process, and deregulation of these networks has been linked to common diseases such as cancer, diabetes and obesity. Because of their critical roles in normal development, aging and disease processes, nuclear receptors represent attractive targets for drug discovery. Examples of nuclear receptor interacting compounds currently in clinical use include drugs for hormone replacement and breast cancer,  anti-diabetic drugs, cholesterol-lowering drugs and anti-inflammatory agents. 

The overall goals of the Welsh lab’s experiments are to provide insight into the molecular mechanisms by which nuclear receptors work, and to clarify their role in specific tissues and disease processes. Our emphasis is on nuclear receptor ligands derived from diet (vitamin D, retinoids, fatty acids) and from the environment (phytochemicals, xenobiotics, oxysterols).  We believe that more detailed understanding of the molecular mechanisms of nuclear receptor action will lead to more rationale drug design and more appropriate dietary recommendations for prevention of chronic diseases.

Major areas of research:

  • Nuclear receptor regulatory networks in differentiation, development,  metabolism and aging
  • Nutrition and prevention of breast, prostate and colon cancer
  • Stem cell renewal and lineage determination in the bone marrow mesenchymal compartment
  • Genomic patterns of nuclear receptor action

Current projects:

  • Characterizing cancer risk in genetic models of vitamin D deficiency
  • Analyzing the role of nuclear receptors in cellular responses to environmental stress, inflammation and DNA damaging agents 
  • Defining the roles of nuclear receptors (VDR, PPAR, RXR) in stem cell renewal and differentiation of bone marrow mesenchymal stem cells
  • Studying interactions between adipocytes and epithelial cells in mammary gland


Last updated on 02/18/2009

 

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