Gary W. Reuther, PhD

Where You Are:
Gary W. Reuther, PhD

Associate Member

"My lab focuses on understanding aberrant cytokine signaling pathways in myeloid neoplasms, with a particular focus on the JAK2 tyrosine kinase and identifying novel targets for therapeutic intervention."

Office  (813) 745-6608

Education And Training
  • Postdoctoral Fellow, University of North Carolina, Chapel Hill, NC, 2004 - Pharmacology
  • PhD, Duke University Medical Center, Durham, NC, 1997 - Pharmacology
  • BS, Pennsylvania State University, University Park, PA, 1992 - Microbiology

My research is focused on characterizing aberrant signaling pathways in hematological cancer in order to identify potential targets for much need therapeutic strategies.  While past focus in the lab has been on acute myeloid leukemia, currently we are interested in understanding the significance of the JAK2-V617F mutation in a family of blood diseases termed myeloproliferative neoplasms (MPNs).  While patients with MPNs have an increased risk of potentially deadly coronary and blood clotting complications, MPNs also transform into acute myeloid leukemia, which is generally incurable.  JAK2 is a tyrosine kinase and the V617F mutation leads to constitutive kinase activity.  This mutation is prevalent in MPNs and its expression in mouse models induces an MPN-like phenotype.  JAK2 inhibitors are under development, with one recently being approved for clinical use.  However, to date these inhibitors have not had a significant effect at eliminating diseased cells from patients and thus do not induce remission.  Therefore, there remains a need for alternative strategies to target MPN cells.  It is possible that combination treatments of JAK2 inhibitors with other small molecule targeted therapies or chemotherapies will provide benefit to MPN patients.  Our research is focused on understanding JAK2-V617F activation and signaling in MPNs, and identifying possible alternative therapeutic targets in MPN cells.  To this end, we utilize molecular biological, cell biological, biochemical, and proteomic approaches to further our understanding of aberrant JAK2 signaling in MPNs.

  • Griner LN, McGraw KL, Johnson JO, List AF, Reuther GW. JAK2-V617F-mediated signalling is dependent on lipid rafts and statins inhibit JAK2-V617F-dependent cell growth. Br J Haematol. 2013 Jan;160(2):177-187. Pubmedid: 23157224.
  • Roll JD, Reuther GW. ALK-activating homologous mutations in LTK induce cellular transformation. PLoS One. 2012 Jul;7(2):e31733. Pubmedid: 22347506. Pmcid: PMC3276580.
  • Reuther GW. Recurring mutations in myeloproliferative neoplasms alter epigenetic regulation of gene expression. Am J Cancer Res. 2011 Nov;1(6):752-762. Pubmedid: 22016825. Pmcid: PMC3195930.
  • Lambert QT, Pradhan A, Roll JD, Reuther GW. Mutations in the transmembrane and juxtamembrane domains enhance IL27R transforming activity. Biochem J. 2011 Aug;438(1):155-164. Pubmedid: 21631431. Pmcid: PMC3145822.
  • Gordon GM, Lambert QT, Daniel KG, Reuther GW. Transforming JAK1 mutations exhibit differential signalling, FERM domain requirements and growth responses to interferon-?. Biochem J. 2010 Dec;432(2):255-265. Pubmedid: 20868368.
  • Griner LN, Reuther GW. Aggressive myeloid leukemia formation is directed by the Musashi 2/Numb pathway. Cancer Biol Ther. 2010 Nov;10(10):979-982. Pubmedid: 21084860.
  • Majumder A, Govindasamy L, Magis A, Kiss R, Polgár T, Baskin R, Allan RW, Agbandje-McKenna M, Reuther GW, Keseru GM, Bisht KS, Sayeski PP. Structure-function correlation of G6, a novel small molecule inhibitor of Jak2: indispensability of the stilbenoid core. J Biol Chem. 2010 Oct;285(41):31399-31407. Pubmedid: 20667821. Pmcid: PMC2951214.
  • Roll JD, Reuther GW. CRLF2 and JAK2 in B-progenitor acute lymphoblastic leukemia: a novel association in oncogenesis. Cancer Res. 2010 Oct;70(19):7347-7352. Pubmedid: 20807819. Pmcid: PMC2948596.
  • Rao R, Nalluri S, Fiskus W, Balusu R, Joshi A, Mudunuru U, Buckley KM, Robbins K, Ustun C, Reuther GW, Bhalla KN. Heat shock protein 90 inhibition depletes TrkA levels and signaling in human acute leukemia cells. Mol Cancer Ther. 2010 Aug;9(8):2232-2242. Pubmedid: 20663926. Pmcid: PMC3008427.
  • Pradhan A, Lambert QT, Griner LN, Reuther GW. Activation of JAK2-V617F by components of heterodimeric cytokine receptors. J Biol Chem. 2010 May;285(22):16651-16663. Pubmedid: 20363735. Pmcid: PMC2878064.
  • Reuther GW. JAK2 activation in myeloproliferative neoplasms: a potential role for heterodimeric receptors. Cell Cycle. 2008 Mar;7(6):714-719. Pubmedid: 18245948.
  • Cha JY, Lambert QT, Reuther GW, Der CJ. Involvement of fibroblast growth factor receptor 2 isoform switching in mammary oncogenesis. Mol Cancer Res. 2008 Mar;6(3):435-445. Pubmedid: 18337450.
  • Gilkes DM, Pan Y, Coppola D, Yeatman T, Reuther GW, Chen J. Regulation of MDMX expression by mitogenic signaling. Mol Cell Biol. 2008 Mar;28(6):1999-2010. Pubmedid: 18172009. Pmcid: PMC2268405.
  • Ren Y, Chen Z, Chen L, Woods NT, Reuther GW, Cheng JQ, Wang HG, Wu J. Shp2E76K mutant confers cytokine-independent survival of TF-1 myeloid cells by up-regulating Bcl-XL. J Biol Chem. 2007 Dec;282(50):36463-36473. Pubmedid: 17942397. Pmcid: PMC3000740.
  • Pradhan A, Lambert QT, Reuther GW. Transformation of hematopoietic cells and activation of JAK2-V617F by IL-27R, a component of a heterodimeric type I cytokine receptor. Proc Natl Acad Sci U S A. 2007 Nov;104(47):18502-18507. Pubmedid: 18003935. Pmcid: PMC2141806.
  • Meyer J, Rhein M, Schiedlmeier B, Kustikova O, Rudolph C, Kamino K, Neumann T, Yang M, Wahlers A, Fehse B, Reuther GW, Schlegelberger B, Ganser A, Baum C, Li Z. Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, deltaTrkA. Leukemia. 2007 Oct;21(10):2171-2180. Pubmedid: 17673903.
  • Lambert Q, Reuther G. Activation of ras proteins by ras Guanine nucleotide releasing protein family members. Methods Enzymol. 2005;407:82-98. Pubmedid: 16757316.
  • Lambert JM, Lambert QT, Reuther GW, Malliri A, Siderovski DP, Sondek J, Collard JG, Der CJ. Tiam1 mediates Ras activation of Rac by a PI(3)K-independent mechanism. Nat Cell Biol. 2002 Aug;4(8):621-625. Pubmedid: 12134164.
  • Reuther G, Lambert Q, Rebhun J, Caligiuri M, Quilliam L, Der C. RasGRP4 is a novel Ras activator isolated from acute myeloid leukemia. J Biol Chem. 2002 Aug;277(34):30508-30514. Pubmedid: 11880369.
  • Reuther G, Lambert Q, Booden M, Wennerberg K, Becknell B, Marcucci G, Sondek J, Caligiuri M, Der C. Leukemia-associated Rho guanine nucleotide exchange factor, a Dbl family protein found mutated in leukemia, causes transformation by activation of RhoA. J Biol Chem. 2001 Jul;276(29):27145-27151. Pubmedid: 11373293.
  • Reuther G, Lambert Q, Caligiuri M, Der C. Identification and characterization of an activating TrkA deletion mutation in acute myeloid leukemia. Mol Cell Biol. 2000 Dec;20(23):8655-8666. Pubmedid: 11073967.
  • Farwell D, Shera K, Koop J, Bonnet G, Matthews C, Reuther G, ColtreraMD, McDougall J, Klingelhutz A. Genetic and epigenetic changes in human epithelial cells immortalized by telomerase. Am J Pathol. 2000 May;156(5):1537-1547. Pubmedid: 10793065.
  • Quackenbush R, Reuther G, Miller J, Courtney K, Pear W, Pendergast A. Analysis of the biologic properties of p230 Bcr-Abl reveals unique and overlapping properties with the oncogenic p185 and p210 Bcr-Abl tyrosine kinases. Blood. 2000 May;95(9):2913-2921. Pubmedid: 10779439.
  • Reuther G, Der C. The Ras branch of small GTPases: Ras family members don't fall far from the tree. Curr Opin Cell Biol. 2000 Apr;12(2):157-165. Pubmedid: 10712923.
  • Reuther G, Buss J, Quilliam L, Clark G, Der C. Analysis of function and regulation of proteins that mediate signal transduction by use of lipid-modified plasma membrane-targeting sequences. Methods Enzymol. 2000;327:331-350. Pubmedid: 11044995.
  • Dai Z, Quackenbush R, Courtney K, Grove M, Cortez D, Reuther G, PendergastAM. Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway. Genes Dev. 1998 May;12(10):1415-1424. Pubmedid: 9585502 .
  • Dai Z, Quackenbush RC, Courtney KD, Grove M, Cortez D, Reuther GW, Pendergast AM. Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway. Gene Dev. 1998 May;12(10):1415-1424. Pubmedid: 9585502. Pmcid: PMC316832.
  • Reuther J, Reuther G, Cortez D, Pendergast A, Baldwin AS J. A requirement for NF-kappaB activation in Bcr-Abl-mediated transformation. Genes Dev. 1998 Apr;12(7):968-981. Pubmedid: 9531535 .
  • Reuther JY, Reuther GW, Cortez D, Pendergast AM, Baldwin AS. A requirement for NF-kappaB activation in Bcr-Abl-mediated transformation. Gene Dev. 1998 Apr;12(7):968-981. Pubmedid: 9531535. Pmcid: PMC316671.
  • Cortez D, Reuther G, Pendergast A. The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells. Oncogene. 1997 Nov;15(19):2333-2342. Pubmedid: 9393877 .
  • Reuther GW, Fu H, Cripe LD, Collier RJ, Pendergast AM. Association of the protein kinases c-Bcr and Bcr-Abl with proteins of the 14-3-3 family. Science. 1994 Oct;266(5182):129-133. Pubmedid: 7939633.
  • Reuther G, Fu H, Cripe L, Collier R, Pendergast A. Association of the protein kinases c-Bcr and Bcr-Abl with proteins of the 14-3-3 family. Science. 1994 Oct;266(5182):129-133. Pubmedid: 7939633 .
  • Reuther G, Pendergast A. The roles of 14-3-3 proteins in signal transduction. Vitam Horm. 1996 52:;52:149-175. Pubmedid: 8909160 .
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