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Ian Macara, Ph.D.

  • Co-Leader, Signal Transduction and Chemical Biology Research Program
  • Louise B. McGavock Professor and Chair of Cell and Developmental Biology

Phone

615-875-5565

Email

ian.g.macara@Vanderbilt.Edu
Dept. of Cell and Developmental Biology
Vanderbilt University Medical Center
465 21st Avenue S., U 3209 MRB III
Nashville, TN 37232-8240

Ian Macara, Ph.D.

  • Co-Leader, Signal Transduction and Chemical Biology Research Program
  • Louise B. McGavock Professor and Chair of Cell and Developmental Biology

615-875-5565

ian.g.macara@Vanderbilt.Edu

Dept. of Cell and Developmental Biology
Vanderbilt University Medical Center
465 21st Avenue S., U 3209 MRB III
Nashville, TN 37232-8240

Profile

Dr. Macara studies the development of the ducts that form breast tissue, and the mechanisms that can result in the initiation and spread of breast cancer. Most types of cancer arise from epithelial cells. These cells form many of the organs in the body, and arrange themselves into either sheets (such as the skin) or branching ducts (such as kidney, or mammary glands). Epithelial cells are polarized - they have a top and bottom, which differ from one another in form and function. Dr. Macara is studying how polarization occurs, how this process might be disrupted in breast cancer, and how defects in polarization contribute to invasive behavior and metastasis.

Education

  • BSc - University of Sheffield, UK
  • PhD - University of Sheffield, UK
  • Postdoctoral training - Harvard University, MA

Research Emphasis

Breast cancer; stem cells; progenitors; morphogenesis; cell polarity; epithelia; DNA repair; tumor promoters; development; mammary gland

Research Description

Our lab is interested in the ways in which cells break symmetry, and initiate and maintain spatial asymmetries. Asymmetries can form as cells polarize, or can occur within cells, for instance during mitosis. Gradients of proteins or other molecules can create asymmetries that the cell uses to specify orientations and subcellular locations. Carcinomas arise from epithelial cells, and tumor progression involves a loss of polarity, so an understanding of cell polarity is important in the identification of novel therapeutic approaches to cancer. Cell polarity is usually lost early during tumor progression, and several polarity proteins have been identified as tumor suppressors.
We have four major research programs on:
(a) understanding the polarization machinery of mammalian epithelial cells
(b) control of epithelial homeostasis in mammary gland morphogenesis, breast cancer initiation and metastasis
(c) the role of stem cells and mechanisms controling stemness in the mammary gland and in breast cancer
(d) the role of a novel exonuclease in DNA repair of inter-strand crosslinks.
We use a range of approaches to study these cell processes, including a mammary gland regeneration model in which mammary stem cells are transduced with lentivirus then transplanted into the cleared fat pads of recipient mice, where the cells regenerate an entire new mammary ductal tree. In vitro studies include single molecule measurements of polarity complexes using TIRF microscopy and CRISPR gene-editing; genome-wide CRISPR screens for genes that regulate homeostais; 3D culture of mammary gland organoids; human breast tissue organotypic cultures; and renal epithelial cysts. We are using these systems to explore the mechanisms that control spindle orientation during mitosis, epithelial homeostasis, and multipotency versus unipotency in mammary stem cells.

Publications

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