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Reyland Lab



Phone: (303) 724-4572


Research Interests:


Regulation of Cell Death by the Protein Kinase C Family: Implications for Tissue Damage and Tumorigenesis  


Apoptosis, or programmed cell death, is critical for vertebrate development, the clearance of damaged or genetically altered cells and is induced by a variety of exogenous agents including irradiation, chemotherapeutic drugs and cell toxins. The ability to evade apoptosis is considered a "hallmark" of cancer, and genetic disruption of the apoptotic pathway is a common feature of neoplasia.  Phosphorylation of cellular proteins by protein kinases is a widely used mechanism to relay information within the cell, a process known as "signal transduction".  My laboratory is interested in how specific members of the protein kinase C (PKC) family of lipid-regulated serine/threonine protein kinases function to modulate apoptosis. To explore the role of PKC in these processes, we have use cultured epithelial cells or genetically modified mice that have specific defects in protein kinase C directed signal transduction. Our studies have demonstrated that PKC is an early and essential regulator of apoptosis in salivary epithelial cells, and that disruption of the PKC gene in mice results in resistance to irradiation-induced apoptosis in multiple tissues in vivo. Based on these studies we hypothesize that PKC functions upstream of the mitochondria as an integrator of diverse death signals.  As disruption of apoptosis contributes to cancer promotion/ progression, we have recently initiated studies to understand the role of protein kinase C in these processes.  Surprisingly, our studies indicate that the loss of PKC suppresses tumor formation in both the lung and the mammary gland through mechanisms that are independent of apoptosis.  This exciting data suggests that PKC can regulate signal transduction pathways that promote cell transformation and cancer cell growth.

Current projects in the lab:

1. Exploring the mechanism by which PKC regulates apoptosis.  Using techniques to localize PKC in cells undergoing apoptosis, we have shown that PKC translocates to the nucleus in apoptotic cells, and we have identified a nuclear localization sequence in PKC that is required for nuclear translocation.  Our model suggests that retention of PKC in the cytoplasm is consistent with cell survival and proliferation, while nuclear import signals cell death. 

  • We are currently deciphering the mechanisms by which PKC is activated during apoptosis using a structure/function approach to identify binding sites for PKC interacting proteins.  We hypothesize that such interactions may retain PKC in the cytoplasm in the absence of an apoptotic signal. 
  • Previous studies in the lab have shown that tyrosine phosphorylation of PKC also regulates its sub-cellular localization; we are currently exploring the affect of tyrosine phosphorylation at specific sites on the localization and function of PKC.
  • A long term goal of this project is to identify nuclear phosphorylation targets of PKC in apoptotic cells using substrate tagging strategies.


2. Exploring the role of PKC in tumor promotion and progression.  Our data from lung and mammary gland models of cancer suggests that PKC can regulate signal transduction pathways that promote cell transformation and cancer cell growth, particularly the Ras/Raf/MEK1/ERK pathway.

  • We would like to understand mechanistically how PKC regulates ERK and other proliferative signaling in lung and breast cancer cells.
  • The ability of tumors cells to grow in a three-dimensional matrix requires PKC; this likely requires extracellular matrix interactions involving integrins, fibronectins, etc.
  •  Does PKC regulate the interaction of cancer cells with the extracellular   environment?
  • Can we translate our mouse studies to the human disease?  Is PKC expression/activation/localization altered in human tumors?


Current Traniees:


Brittany Allen-Petersen (CDSV graduate program)

Tariq Adwan  (CDSV graduate program)

Jennifer Symonds (CANB graduate program)

Gregg Banninger (Postdoctoral Associate)


Reyland Photo.JPG

Selected Publications:

Allen-Peterson, B*. Miller, M.R.*, Anderson, S.M., Neville, M.C. and Reyland, M.E.  2010.  Loss of protein kinase C delta alters mammary gland development and apoptosis.  Cell Death Disease 1(1):e17.  PMCID: PMC3032509

Symonds, J.M., Ohm, A.M., Carter, C.J., Heasley, L.E., Aly, T.A., Franklin, W.A. and Reyland, M.E.  2011.  Protein kinase C is a downstream effector of oncogenic KRAS in K-Ras-dependent lung tumors.  Cancer Res 71(6):2087-2097. PMID: 21335545

Adwan, T.S, Ohm, A.A., Jones, D.N.M., Humphries, M.J. and Reyland, M.E. 2011. Regulated binding of importin- to protein kinase C delta (PKC) in response to apoptotic signals facilitates nuclear import. J Biol Chem 286:35716-24. PMCID: PMC3195609

Nguyen, H. M., Reyland, M.E., Barlow, L.A. 2012. Mechanisms of taste bud cell loss  after head and neck irradiation. J Neuroscience 32:3474-3484.

Allen-Petersen, B.L., Carter, C.J., and Reyland, M.E. Protein Kinase C is required for ErbB2-driven mammary gland tumorigenesis and negatively correlates with prognosis in human breast cancer, in press

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