University of Wisconsin–Madison

Richard Anderson, PhD

Professor, Dean's Office, Basic Sciences


3750 Medical Sciences Center

Lab Website
Anderson Lab

Richard Anderson

Research Interests

Our major research focus has the objective of understanding phosphoinositide (PI) and inositol phosphate signal transduction pathways that impact cellular regulatory events. All eukaryotic cells are regulated by phosphoinositide signals. In phosphoinositide signaling, PI, a phospholipid, is sequentially phosphorylated on the inositol ring to form essential signaling molecules such phosphatidylinositol-4,5-bisphosphate (PI4,5P2). PI4,5P2 is directly synthesized by phosphatidylinositol-phosphate kinases (PIPKs), and PI4,5P2 occupies an essential position in PI signaling by directly regulating cellular functions that include cell proliferation, secretion, cytoskeletal assembly and cell motility. In addition, PI4,5P2 is a key transducer of cellular signals as a precursor for many second messengers. The PIPKs define an enzyme superfamily responsible for the generation of all PI derived second messengers, demonstrating that these kinases have roles in many cellular functions. The different PIPK family members are targeted to subcellular compartments by specific protein-protein interactions. The interactions between the PIPKs and targeting proteins results in spatial and temporal generation of PI4,5P2 that regulates specific cellular functions.

The laboratory focuses on two broad topics:

  • Signaling mechanisms that control epithelial cancer metastasis. The metastasis of cancers of epithelial origin (~75% of all human cancers) progress through two stages: 1) loss of epithelial polarity and cell-cell contacts, called the epithelial to mesenchymal transition (EMT), and 2) development of a migratory phenotype with the resulting migration of tumor cells to the vasculature or lymph system where they can move to different parts of the body.
    We have shown that a PIPK (PIPKIg) is required for the assembly of E-cadherin based cell-cell contacts. E-cadherin complex assembly is a key event, as the loss of these cell-cell contacts is a hallmark of cancer progression and is required for the metastasis of epithelial cancers. Upon loss of E-cadherin, cells migrate to the vasculature a process driven by cytokines. This migratory process is also dependent upon PIPKIg. We have defined aspects of the molecular basis for PIPKIg regulation of cell-cell contacts and migration, and have evidence that PIPKIg plays a role in the progression of human breast cancers.  Many mechanistic aspects remain to be defined.
  • Nuclear phosphoinositide signaling controls gene expression. Within nuclei, we have discovered a unique phosphoinositide signaling pathway that modulates the expression of a set of genes that play roles in Alzheimer’s disease, cardiovascular disease and cancer. In elucidating the underlying mechanism for this regulation, we have discovered a novel poly(A) polymerase that is activated by phosphoinositide messengers. Poly(A) polymerase regulates the expression of specific messenger RNAs by adding a 3’-end poly(A) tail that is required for nuclear export and efficient translation. The mechanism of how this poly(A) polymerase is regulated, as well as the elucidation of other nuclear pathways regulated by phosphoinositides will be the continuing focus.

The laboratory uses cutting edge techniques including 1) cell culture, 2) videomicroscopy of cells and molecular dynamics of proteins within living cells, 3) 3-D structure-function analysis, 4) expression of genes with functionally targeted mutations, 5) microarray analysis of gene expression, 6) knock out techniques, 7) molecular genetic analysis of gene expression, and 8) molecular biological approaches to analyze for analysis of signal transduction mechanisms.

Honors & Awards

  • 2005 – Kellett Mid-Career Award
  • Sigma Xi Graduate Research Award
  • NIH Postdoctoral Fellowship
  • American Cancer Society Postdoctoral Fellowship
  • Bacaner Basic Science Award

Selected Publications

(Find further publications on PubMed)

  • Schill, N.J., Hedman, A.C., Choi, S. and Anderson, R.A. (2014) Isoform 5 of PIPKIγ regulates the endosomal trafficking and degradation of E-cadherin. J. Cell Science. 127, 2189-2203, PMID: 24610942, PMCID: PMC4021470  Emphasized in the JCS Snapshot
  • Tan, X., Thapa, N., Sun, Y. & Anderson, R.A. (2015) A kinase-independent role for EGF receptor in autophagy initiation. Cell 160, 145-160. PMID: 25594178, PMCID: PMC4297316. News release UW, Emphasized in Science Comments, Oncology-central, Science Daily, Cancer Discovery – News in Brief, “Study Illuminates How Cancers Evade EGFR Inhibitors”
  • Tan X, Sun Y, Thapa N, Liao Y, Hedman AC, Anderson RA. (2015) LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation. The EMBO journal. PMID: 25588945, “PMCID: PMC4331002
  • Choi, S., Thapa, N., Tan, X., Hedman, A.C. & Anderson, R.A. (2015) PIP kinases define PI4,5P signaling specificity by association with effectors. Biochimica et biophysica acta 1851, 711-723. PMID: 25617736,  PMCID: PMC4380618
  • Thapa, N., Choi, S., Tan, X., Wise, T. & Anderson, R.A. (2015) Phosphatidylinositol Phosphate 5-Kinase Igamma and PI3K/Akt Signaling Couple to Promote Oncogenic Growth. In press, J. Biol. Chem.
  • Choi, S., Hedman, A.C., Thapa, N., Sacks, D., and Anderson, R.A. (2015) Agonist-stimulated PI3,4,5P3 generation by scaffolded phosphoinositide kinases. In revision, Nature.