Internal Medicine

Frederick W. Quelle, PhD


Director of Graduate Studies
Associate Professor of Pharmacology
Associate Professor of Internal Medicine

Contact Information

Primary Office: 2-340F Bowen Science Building
Iowa City, IA 52242
Phone: 319-335-8539

Lab: 2-340 Bowen Science Building
Iowa City, IA 52242
Phone: 319-335-7769



BA, Chemistry, Middlebury College
MS, Biochemistry, The Pennsylvania State University
PhD, Genetics, The Pennsylvania State University

Fellowship, Biochemistry, St. Jude's Children's Research Hospital, Department of Biochemistry

Education/Training Program Affiliations

Interdisciplinary Graduate Program in Immunology

Research Summary

Cytokine Receptor Signal Transduction and Regulation of Cell Growth The growth of myeloid and lymphoid blood cells is governed by cytokine growth factors acting through Type I cytokine receptors. This receptor family functions through activation of Jak tyrosine kinases, which phosphorylate components of signaling pathways that control cell survival and proliferation. Blood cell development fails in the absence of Jak kinase activation resulting in anemias, whereas enhanced Jak kinase activity contributes to myeloid and lymphoid leukemias. Work in our laboratory is directed at defining mechanism by which cytokines regulated blood cell growth. Proper regulation of Jak kinase activity requires mechanisms controlling activation of the kinase that are balanced against mechanisms controlling its inactivation. Mechanisms inhibiting Jak kinase activity include its degradation, which is governed by ubiquitination mediated by SOCS proteins. We have shown that Jak kinases and cytokine receptors can also be ubiquitinated by a receptor-associated ubiquitin ligase, RUL. Inhibition of RUL activity limits the ability of cytokines to induce Jak-dependent phosphorylation of signaling proteins and inhibits cell growth, suggesting that Jak activity is enhanced by RUL-mediated ubiquitin ligation. The finding that RUL-mediated ubiquitination enhances Jak signaling is novel, and forms the basis for our hypothesis that different mediators of Jak ubiquitination exert distinct influences on its kinase activity. Thus, a major focus of work in our laboratory is to define the role of RUL in regulating Jak kinase activity, and test the concept that competing ubiquitination between a promoter (e.g., RUL) and inhibitor (e.g., SOCS1) regulates the activity of Jak kinases in vivo. The lack of proliferation by hematopoietic cells deprived of cytokine is associated with their accumulation in G1 phase of the cell cycle. This implies a direct link between the activities of cytokine receptors and regulators of cell cycle progression. However the specific roles of signaling pathways activated by cytokine receptors in promoting G1 phase progression has not been clearly defined. We have shown that cytokine-treatment overrides G1 and G2/M phase growth arrest in hematopoietic cells exposed to DNA damaging agents. Blockade of these growth arrest checkpoints is dependent on activation of phosphoinositide 3-kinase (PI3K) signaling pathways, and correlates with the appearance of a Cdk2 activating kinase (CAK) activity in lysates of irradiated cells. These observations define a signaling pathway connecting cytokine-induced PI3K and regulated Cdk2 activity in hematopoietic cells. Thus a second focus of work in our laboratory is to define the molecular mechanisms that govern this PI3K-mediated signaling pathway, and ultimately to determine the general parameters required for cytokine-dependent blockade of DNA damage checkpoints. These studies will advance our fundamental understanding of cytokine signaling pathways, and will help to establish important paradigms of cell cycle regulation, DNA damage checkpoints, and their regulation by extracellular signals.

Selected Publications

Show All

Lei H, Quelle F.  FOXO transcription factors enforce cell cycle checkpoints and promote survival of hematopoietic cells after DNA damage..  Molecular cancer research : MCR.  2009 August. 7(8):1294-303.

Nimbalkar D, Quelle F.  Phosphoinositide 3-kinase signaling overrides a G2 phase arrest checkpoint and promotes aberrant cell cycling and death of hematopoietic cells after DNA damage..  Cell cycle (Georgetown, Tex.).  2008 September. 7(18):2877-85.

Quelle F.  Cytokine signaling to the cell cycle.  Immunologic Research.  2007. 39(1-3):173-84.

Korgaonkar C, Hagen J, Tompkins V, Frazier A, Allamargot C, Quelle F, Quelle D.  Nucleophosmin (B23) targets ARF to nucleoli and inhibits its function..  Molecular and cellular biology.  2005 February. 25(4):1258-71.

Chakravarti P, Henry M, Quelle F.  Prolactin and heregulin override DNA damage-induced growth arrest and promote phosphatidylinositol-3 kinase-dependent proliferation in breast cancer cells..  International journal of oncology.  2005 February. 26(2):509-14.

Henry M, Nimbalkar D, Hohl R, Quelle F.  Cytokine-induced phosphoinositide 3-kinase activity promotes Cdk2 activation in factor-dependent hematopoietic cells..  Experimental cell research.  2004 September. 299(1):257-66.

Friedman A, Nimbalkar D, Quelle F.  Erythropoietin receptors associate with a ubiquitin ligase, p33RUL, and require its activity for erythropoietin-induced proliferation..  The Journal of biological chemistry.  2003 July. 278(29):26851-61.

Nimbalkar D, Henry M, Quelle F.  Cytokine activation of phosphoinositide 3-kinase sensitizes hematopoietic cells to cisplatin-induced death..  Cancer research.  2003 March. 63(5):1034-9.

Eapen A, Henry M, Quelle D, Quelle F.  DNA damage-induced G(1) arrest in hematopoietic cells is overridden following phosphatidylinositol 3-kinase-dependent activation of cyclin-dependent kinase 2..  Molecular and cellular biology.  2001 September. 21(18):6113-21.

Henry M, Lynch J, Eapen A, Quelle F.  DNA damage-induced cell-cycle arrest of hematopoietic cells is overridden by activation of the PI-3 kinase/Akt signaling pathway..  Blood.  2001 August. 98(3):834-41.

Date Last Modified: 06/06/2016 - 13:17:48