Photo of David A. Frank,  MD, PhD

David A. Frank, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4714
Fax: (617) 394-2782


david_frank@dfci.harvard.edu

David A. Frank, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School
  • Associate Physician, Medicine, Oncology, Brigham And Women's Hospital
  • Associate Professor of Medicine, Medical Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our group focuses on the intracellular signaling events that control the growth and differentiation of normal and malignant cells. Extracellular stimuli lead to a cascade of events that culminates in the regulation of gene expression. It is the activation or repression of specific genes that then determines cellular function. We study how these signaling events occur normally by examining the activation of kinase cascades, transcriptional networks, and key target genes. Among the mediators we have focused on are STAT transcription factors, which can be modulated by both tyrosine and serine phosphorylation, and thus may serve as a convergence point for multiple signaling pathways. Thus, one of the areas of focus in our group is how STATs, alone and in conjunction with other transcription factors, modulate gene expression throughout the genome.

One of the hallmarks of malignancy is the ability of cells to grow independent of external signals. Given this, we have extended our work to analyze the activation of intracellular signaling pathways in primary tumor cells and in models of human malignancies. We have found that STATs and other signaling pathways are activated inappropriately in many forms of cancer. Furthermore, we are identifying the specific target genes that mediate the ability of STATs to lead to malignant transformation of cells. This work has shed light both on the pathogenesis of these diseases and on critical regulators of the biology of normal cells.

Finally, we are developing targeted molecular inhibitors of STATs and other transcription factors using both rational design and chemical-biology approaches. These reagents are useful tools for dissecting the roles of signaling pathways in the growth and differentiation of normal cells. Furthermore, given the inappropriate activation of signaling pathways in malignant cells, these approaches may be useful in developing novel therapeutic strategies for the treatment of cancer. We have initiated a clinical trial of a STAT3 inhibitor identified in our lab for patients with cancer, and we are analyzing the effects of this approach on the gene expression and biology of cancer cells obtained from patients on study. We are in the process of initiating clinical trials with additional transcriptional modulators identified by our group.

In summary, our laboratory pursues the study of signal transduction in normal and neoplastic cells, from molecular systems to human cancer patients.

Publications

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  • Toniolo PA, Liu S, Yeh JE, Moraes-Vieira PM, Walker SR, Vafaizadeh V, Barbuto JA, Frank DA. Inhibiting STAT5 by the BET Bromodomain Inhibitor JQ1 Disrupts Human Dendritic Cell Maturation. J Immunol 2015; 194:3180-90. PubMed
  • Liu S, Walker SR, Nelson EA, Cerulli R, Xiang M, Toniolo PA, Qi J, Stone RM, Wadleigh M, Bradner JE, Frank DA. Targeting STAT5 in hematologic malignancies through inhibition of the bromodomain and extra-terminal (BET) bromodomain protein BRD2. Mol Cancer Ther 2014. PubMed
  • Lee RE, Walker SR, Savery K, Frank DA, Gaudet S. Fold Change of Nuclear NF-虜B Determines TNF-Induced Transcription in Single Cells. Mol Cell 2014; 53:867-79. PubMed
  • Walker SR, Xiang M, Frank DA. STAT3 Activity and Function in Cancer: Modulation by STAT5 and miR-146b. Cancers (Basel) 2014; 6:958-68. PubMed
  • Ajay AK, Kim TM, Ramirez-Gonzalez V, Park PJ, Frank DA, Vaidya VS. A bioinformatics approach identifies signal transducer and activator of transcription-3 and checkpoint kinase 1 as upstream regulators of kidney injury molecule-1 after kidney injury. J Am Soc Nephrol 2014; 25:105-18. PubMed
  • Xiang M, Birkbak NJ, Vafaizadeh V, Walker SR, Yeh JE, Liu S, Kroll Y, Boldin M, Taganov K, Groner B, Richardson AL, Frank DA. STAT3 induction of miR-146b forms a feedback loop to inhibit the NF-虜B to IL-6 signaling axis and STAT3-driven cancer phenotypes. Sci Signal 2014; 7:ra11. PubMed
  • Frank DA. Transcription factor STAT3 as a prognostic marker and therapeutic target in cancer. J Clin Oncol 2013; 31:4560-1. PubMed
  • Lathan C, Frank DA. ACP Journal Club. Review: low-dose CT screening reduces lung cancer and mortality in current or former smokers. Ann Intern Med 2013; 159:JC3. PubMed
  • Yeh JE, Toniolo PA, Frank DA. Targeting transcription factors: promising new strategies for cancer therapy. Curr Opin Oncol 2013; 25:652-8. PubMed
  • Yeh JE, Toniolo PA, Frank DA. JAK2-STAT5 signaling: A novel mechanism of resistance to targeted PI3K/mTOR inhibition. JAKSTAT 2014; 2:e24635. PubMed
  • Klitgaard JL, Koefoed K, Geisler C, Gadeberg OV, Frank DA, Petersen J, Jurlander J, Pedersen MW. Combination of two anti-CD5 monoclonal antibodies synergistically induces complement-dependent cytotoxicity of chronic lymphocytic leukaemia cells. British Journal of Haematology 2013; 163:182-93. PubMed
  • Walker SR, Nelson EA, Yeh JE, Pinello L, Yuan GC, Frank DA. STAT5 outcompetes STAT3 to regulate the expression of the oncogenic transcriptional modulator BCL6. Mol Cell Biol 2013; 33:2879-90. PubMed
  • Walker SR, Xiang M, Frank DA. Distinct roles of STAT3 and STAT5 in the pathogenesis and targeted therapy of breast cancer. Mol Cell Endocrinol 2013. PubMed
  • Chmielecki J, Crago AM, Rosenberg M, O'Connor R, Walker SR, Ambrogio L, Auclair D, McKenna A, Heinrich MC, Frank DA, Meyerson M. Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors. Nat Genet 2013; 45:131-2. PubMed
  • Walker SR, Frank DA. Screening approaches to generating STAT inhibitors: Allowing the hits to identify the targets. JAKSTAT 2013; 1:292-299. PubMed
  • Frank DA. Targeting STATs for cancer therapy: "Undruggable" no more. JAKSTAT 2013; 1:261-2. PubMed
  • Greulich H, Kaplan B, Mertins P, Chen TH, Tanaka KE, Yun CH, Zhang X, Lee SH, Cho J, Ambrogio L, Liao R, Imielinski M, Banerji S, Berger AH, Lawrence MS, Zhang J, Pho NH, Walker SR, Winckler W, Getz G, Frank D, Hahn WC, Eck MJ, Mani DR, Jaffe JD, Carr SA, Wong KK, Meyerson M. Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2. Proc Natl Acad Sci U S A 2012; 109:14476-81. PubMed
  • Nelson EA, Walker SR, Xiang M, Weisberg E, Bar-Natan M, Barrett R, Liu S, Kharbanda S, Christie AL, Nicolais M, Griffin JD, Stone RM, Kung AL, Frank DA. The STAT5 Inhibitor Pimozide Displays Efficacy in Models of Acute Myelogenous Leukemia Driven by FLT3 Mutations. Genes Cancer 2012; 3:503-11. PubMed
  • Bar-Natan M, Nelson EA, Xiang M, Frank DA. STAT signaling in the pathogenesis and treatment of myeloid malignancies. JAKSTAT 2013; 1:55-64. PubMed
  • Takakura A, Nelson EA, Haque N, Humphreys BD, Zandi-Nejad K, Frank DA, Zhou J. Pyrimethamine inhibits adult polycystic kidney disease by modulating STAT signaling pathways. Hum Mol Genet 2011; 20:4143-54. PubMed
  • Catenacci DV, Cervantes G, Yala S, Nelson EA, El-Hashani E, Kanteti R, El Dinali M, Hasina R, Brägelmann J, Seiwert T, Sanicola M, Henderson L, Grushko TA, Olopade O, Karrison T, Bang YJ, Kim WH, Tretiakova M, Vokes E, Frank DA, Kindler HL, Huet H, Salgia R. RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma. Cancer Biol Ther 2011; 12:9-46. PubMed
  • Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, Bloushtain-Qimron N, Kim JJ, Choudhury SA, Maruyama R, Wu Z, Gönen M, Mulvey LA, Bessarabova MO, Huh SJ, Silver SJ, Kim SY, Park SY, Lee HE, Anderson KS, Richardson AL, Nikolskaya T, Nikolsky Y, Liu XS, Root DE, Hahn WC, Frank DA, Polyak K. The JAK2/STAT3 signaling pathway is required for growth of CD44竅コCD24竅サ stem cell-like breast cancer cells in human tumors. J Clin Invest 2011; 121:2723-35. PubMed
  • Nelson EA, Sharma SV, Settleman J, Frank DA. A chemical biology approach to developing STAT inhibitors: molecular strategies for accelerating clinical translation. 2011; 2:518-24. PubMed
  • Nelson EA, Walker SR, Weisberg E, Bar-Natan M, Barrett R, Gashin LB, Terrell S, Klitgaard JL, Santo L, Addorio MR, Ebert BL, Griffin JD, Frank DA. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood 2011; 117:3421-9. PubMed
  • Morikawa T, Baba Y, Yamauchi M, Kuchiba A, Nosho K, Shima K, Tanaka N, Huttenhower C, Frank DA, Fuchs CS, Ogino S. STAT3 Expression, Molecular Features, Inflammation Patterns, and Prognosis in a Database of 724 Colorectal Cancers. Clin Cancer Res 2011; 17:1452-62. PubMed
  • Walker SR, Chaudhury M, Frank DA. STAT3 Inhibition by Microtubule-Targeted Drugs: Dual Molecular Effects of Chemotherapeutic Agents. Mol Cell Pharmacol 2011; 3:13-19. PubMed
  • Walker SR, Chaudhury M, Nelson EA, Frank DA. Microtubule-targeted chemotherapeutic agents inhibit signal transducer and activator of transcription 3 (STAT3) signaling. Mol Pharmacol 2010; 78:903-8. PubMed
  • Yoda A, Yoda Y, Chiaretti S, Bar-Natan M, Mani K, Rodig SJ, West N, Xiao Y, Brown JR, Mitsiades C, Sattler M, Kutok JL, DeAngelo DJ, Wadleigh M, Piciocchi A, Dal Cin P, Bradner JE, Griffin JD, Anderson KC, Stone RM, Ritz J, Foà R, Aster JC, Frank DA, Weinstock DM. Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 2010; 107:252-7. PubMed
  • Frank DA. STAT6 in PMBL: pathogenic or passenger? Blood 2009; 114:1133-4. PubMed
  • Walker SR, Nelson EA, Zou L, Chaudhury M, Signoretti S, Richardson A, Frank DA. Reciprocal effects of STAT5 and STAT3 in breast cancer. Mol Cancer Res 2009; 7:966-76. PubMed
  • Sakamoto KM,Frank DA. CREB in the pathophysiology of cancer: implications for targeting transcription factors for cancer therapy. Clin Cancer Res 2009; 15:2583-7. PubMed
  • Ikeuchi Y,Stegmuller J,Netherton S,Huynh MA,Masu M,Frank D,Bonni S,Bonni A. A SnoN-Ccd1 pathway promotes axonal morphogenesis in the mammalian brain. J Neurosci 2009; 29:4312-21. PubMed
  • Frank DA. Targeting transcription factors for cancer therapy. IDrugs 2009; 12:29-33. PubMed
  • Nelson EA,Walker SR,Kepich A,Gashin LB,Hideshima T,Ikeda H,Chauhan D,Anderson KC,Frank DA. Nifuroxazide inhibits survival of multiple myeloma cells by directly inhibiting STAT3. Blood 2008; 112:5095-102. PubMed
  • de la Iglesia N,Konopka G,Lim KL,Nutt CL,Bromberg JF,Frank DA,Mischel PS,Louis DN,Bonni A. Deregulation of a STAT3-interleukin 8 signaling pathway promotes human glioblastoma cell proliferation and invasiveness. J Neurosci 2008; 28:5870-8. PubMed
  • Liddle FJ, Frank DA. STAT1 expression is not required for polyp formation in Min mice. Mol Carcinog 2007; 47:75-9. PubMed
  • Frank DA. Review: Prophylactic use of granulocyte colony-stimulating factor reduces febrile neutropenia and short-term mortality in cancer. ACP J Club 2008; 148:7. PubMed
  • Germain D, Frank DA. Targeting the cytoplasmic and nuclear functions of signal transducers and activators of transcription 3 for cancer therapy. Clin Cancer Res 2007; 13:5665-9. PubMed
  • Frank DA. STAT3 as a central mediator of neoplastic cellular transformation. Cancer Lett 2006; 251:199-210. PubMed
  • Lynch RA, Etchin J, Battle TE, Frank DA. A small-molecule enhancer of signal transducer and activator of transcription 1 transcriptional activity accentuates the antiproliferative effects of IFN-gamma in human cancer cells. Cancer Res 2007; 67:1254-61. PubMed
  • Walker SR, Nelson EA, Frank DA. STAT5 represses BCL6 expression by binding to a regulatory region frequently mutated in lymphomas. Oncogene 2007; 26:224-33. PubMed
  • Bhattacharjee A, Xu B, Frank DA, Feldman GM, Cathcart MK. Monocyte 15-lipoxygenase expression is regulated by a novel cytosolic signaling complex with protein kinase C delta and tyrosine-phosphorylated Stat3. J Immunol 2006; 177:3771-81. PubMed
  • Ishii Y, Pirkmaier A, Alvarez JV, Frank DA, Keselman I, Logothetis D, Mandeli J, O'Connell MJ, Waxman S, Germain D. Cyclin D1 overexpression and response to bortezomib treatment in a breast cancer model. J Natl Cancer Inst 2006; 98:1238-47. PubMed
  • Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D, Bellucci R, Raderschall E, Canning C, Soiffer RJ, Frank DA, Ritz J. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT dependent mechanism and induces the expansion of these cells in vivo. Blood 2006; 108:1571-9. PubMed
  • Arbiser JL, Govindarajan B, Battle TE, Lynch R, Frank DA, Ushio-Fukai M, Perry BN, Stern DF, Bowden GT, Liu A, Klein E, Kolodziejski PJ, Eissa NT, Hossain CF, Nagle DG. Carbazole is a naturally occurring inhibitor of angiogenesis and inflammation isolated from antipsoriatic coal tar. J Invest Dermatol 2006; 126:1396-402. PubMed
  • Liddle FJ, Alvarez JV, Poli V, Frank DA. Tyrosine phosphorylation is required for functional activation of disulfide-containing constitutively active STAT mutants. Biochemistry 2006; 45:5599-605. PubMed
  • Battle TE, Lynch RA, Frank DA. Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis. Cancer Res 2006; 66:3649-57. PubMed
  • Alvarez JV, Greulich H, Sellers WR, Meyerson M, Frank DA. Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor. Cancer Res 2006; 66:3162-8. PubMed
  • Isomoto H, Kobayashi S, Werneburg NW, Bronk SF, Guicciardi ME, Frank DA, Gores GJ. Interleukin 6 upregulates myeloid cell leukemia-1 expression through a STAT3 pathway in cholangiocarcinoma cells. Hepatology 2005; 42:1329-38. PubMed
  • Greulich H, Chen TH, Feng W, J. Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants. PLoS Med 2005; 2:e313. PubMed
  • Kay NE, Bone ND, Lee YK, Jelinek DF, Leland P, Battle TE, Frank DA, Puri RK. A recombinant IL-4-Pseudomonas exotoxin inhibits protein synthesis and overcomes apoptosis resistance in human CLL B cells. Leuk Res 2005; 29:1009-18. PubMed
  • Battle TE, Arbiser J, Frank DA. The natural product Honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Blood 2005; 106:690-7. PubMed
  • Alvarez JV, Febbo PG, Ramaswamy S, Loda M, Richardson A, Frank DA. Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors. Cancer Res 2005; 65:5054-62. PubMed
  • Cerimele F, Battle T, Lynch R, Frank DA, Murad E, Cohen C, Macaron N, Sixbey J, Smith K, Watnick RS, Eliopoulos A, Shehata B, Arbiser JL. Reactive oxygen signaling and MAPK activation distinguish Epstein-Barr Virus (EBV)-positive versus EBV-negative Burkitt's lymphoma. Proc Natl Acad Sci U S A 2004; 102:175-9. PubMed
  • Nelson EA, Walker SR, Alvarez JV, Frank DA. Isolation of unique STAT5 targets by chromatin immunoprecipitation-based gene identification. J Biol Chem 2004; 279:54724-30. PubMed
  • Nelson EA, Walker SR, Alvarez JA, Frank DA. Identification of unique STAT5 targets by chromatin immunoprecipitation-based gene identification J Biol Chem 2004; In press:In press.
  • Yuan H, Liddle FJ, Mahajan S, Frank DA. IL-6-induced survival of colorectal carcinoma cells is inhibited by butyrate through down-regulation of the IL-6 receptor. Carcinogenesis 2004; 25:2247-55. PubMed
  • Yuan H, Liddle F, Mahajan S, Frank DA. IL-6 induced survival of colorectal carcinoma cells is inhibited by butyrate through downregulation of the IL-6 receptor Carcinogenesis 2004; In press:In press.
  • Friedberg JW, Dong DA, Li S, Kim H, Stephans K, Noonan K, Neuberg D, Gribben JG, Fisher DC, Freedman AS, Takvorian T, Jurgens R, Battle TE, Frank DA. Oral fludarabine has significant activity in patients with previously untreated chronic lymphocytic leukemia, and leads to increased STAT1 levels in vivo. Leuk Res 2003; 28:139-47. PubMed
  • Battle TE, Frank DA. STAT1 mediates differentiation of chronic lymphocytic leukemia cells in response to Bryostatin 1. Blood 2003; 102:3016-24. PubMed
  • Battle TE, Castro-Malaspina H, Gribben JG, Frank DA. Sustained complete remission of CLL associated with the use of a Chinese herbal extract: case report and mechanistic analysis. Leuk Res 2003; 27:859-63. PubMed
  • Xu B, Bhattacharjee A, Roy B, Xu HM, Anthony D, Frank DA, Feldman GM, Cathcart MK. Interleukin-13 induction of 15-lipoxygenase gene expression requires p38 mitogen-activated protein kinase-mediated serine 727 phosphorylation of Stat1 and Stat3. Mol Cell Biol 2003; 23:3918-28. PubMed
  • Battle TE, Wierda WG, Rassenti LZ, Zahrieh D, Neuberg D, Kipps TJ, Frank DA. In vivo activation of signal transducer and activator of transcription 1 after CD154 gene therapy for chronic lymphocytic leukemia is associated with clinical and immunologic response. Clin Cancer Res 2003; 9:2166-72. PubMed
  • Frank DA. StAT signaling in cancer: insights into pathogenesis and treatment strategies. Cancer Treat Res 2003; 115:267-91. PubMed
  • Battle TE, Frank DA. The role of STATs in apoptosis. Curr Mol Med 2002; 2:381-92. PubMed
  • Vonderheide RH, Butler MO, Liu JF, Battle TE, Hirano N, Gribben JG, Frank DA, Schultze JL, Nadler LM. CD40 activation of carcinoma cells increases expression of adhesion and major histocompatibility molecules but fails to induce either CD80/CD86 expression or T cell alloreactivity. Int J Oncol 2001; 19:791-8. PubMed
  • Arbiser JL, Yeung R, Weiss SW, Arbiser ZK, Amin MB, Cohen C, Frank D, Mahajan S, Herron GS, Yang J, Onda H, Zhang HB, Bai X, Uhlmann E, Loehr A, Northrup H, Au P, Davis I, Fisher DE, Gutmann DH. The generation and characterization of a cell line derived from a sporadic renal angiomyolipoma: use of telomerase to obtain stable populations of cells from benign neoplasms. Am J Pathol 2001; 159:483-91. PubMed
  • Barber DL, Beattie BK, Mason JM, Nguyen MH, Yoakim M, Neel BG, D'Andrea AD, Frank DA. A common epitope is shared by activated signal transducer and activator of transcription-5 (STAT5) and the phosphorylated erythropoietin receptor: implications for the docking model of STAT activation. Blood 2001; 97:2230-7. PubMed
  • Mahajan S, Gollob JA, Ritz J, Frank DA. CD2 stimulation leads to the delayed and prolonged activation of STAT1 in T cells but not NK cells. Exp Hematol 2001; 29:209-20. PubMed
  • Frank DA, Meuse J, Hirsch D, Ibrahim JG, van den Abbeele AD. The treatment and outcome of cancer patients with thromboses on central venous catheters. J Thromb Thrombolysis 2000; 10:271-5. PubMed
  • Duarte RF, Frank DA. SCF and G-CSF lead to the synergistic induction of proliferation and gene expression through complementary signaling pathways. Blood 2000; 96:3422-30. PubMed
  • Gollob JA, Veenstra KG, Jyonouchi H, Kelly AM, Ferrieri P, Panka DJ, Altare F, Fieschi C, Casanova JL, Frank DA, Mier JW. Impairment of STAT activation by IL-12 in a patient with atypical mycobacterial and staphylococcal infections. J Immunol 2000; 165:4120-6. PubMed
  • Karras JG, McKay RA, Lu T, Pych J, Frank DA, Rothstein TL, Monia BP. STAT3 regulates the growth and immunoglobulin production of BCL(1) B cell lymphoma through control of cell cycle progression. Cell Immunol 2000; 202:124-35. PubMed
  • Wang KS, Frank DA, Ritz J. Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4. Blood 2000; 95:3183-90. PubMed
  • Lin TS, Mahajan S, Frank DA. STAT signaling in the pathogenesis and treatment of leukemias. Oncogene 2000; 19:2496-504. PubMed
  • Wilbanks AM, Mahajan S, Frank DA, Druker BJ, Gilliland DG, Carroll M. TEL/PDGFbetaR fusion protein activates STAT1 and STAT5: a common mechanism for transformation by tyrosine kinase fusion proteins. Exp Hematol 2000; 28:584-93. PubMed
  • Sillaber C, Gesbert F, Frank DA, Sattler M, Griffin JD. STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cells. Blood 2000; 95:2118-25. PubMed
  • Turkson J, Bowman T, Adnane J, Zhang Y, Djeu JY, Sekharam M, Frank DA, Holzman LB, Wu J, Sebti S, Jove R. Requirement for Ras/Rac1-mediated p38 and c-Jun N-terminal kinase signaling in Stat3 transcriptional activity induced by the Src oncoprotein. Mol Cell Biol 1999; 19:7519-28. PubMed
  • Frank DA. STAT signaling in the pathogenesis and treatment of cancer. Mol Med 1999; 5:432-56. PubMed
  • Ho JM, Beattie BK, Squire JA, Frank DA, Barber DL. Fusion of the ets transcription factor TEL to Jak2 results in constitutive Jak-Stat signaling. Blood 1999; 93:4354-64. PubMed
  • Smith D, Buckle GJ, Hafler DA, Frank DA, H. HTLV-I-infected T cells evade the antiproliferative action of IFN-beta. Virology 1999; 257:314-21. PubMed
  • Gollob JA, Schnipper CP, Murphy EA, Ritz J, Frank DA. The functional synergy between IL-12 and IL-2 involves p38 mitogen-activated protein kinase and is associated with the augmentation of STAT serine phosphorylation. J Immunol 1999; 162:4472-81. PubMed
  • Frank DA, Mahajan S, Ritz J. Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling. Nat Med 1999; 5:444-7. PubMed
  • Wang KS, Ritz J, Frank DA. IL-2 induces STAT4 activation in primary NK cells and NK cell lines, but not in T cells. J Immunol 1999; 162:299-304. PubMed
  • Gollob JA, Schnipper CP, Orsini E, Murphy E, Daley JF, Lazo SB, Frank DA, Neuberg D, Ritz J. Characterization of a novel subset of CD8(+) T cells that expands in patients receiving interleukin-12. J Clin Invest 1998; 102:561-75. PubMed
  • Gollob JA, Murphy EA, Mahajan S, Schnipper CP, Ritz J, Frank DA. Altered interleukin-12 responsiveness in Th1 and Th2 cells is associated with the differential activation of STAT5 and STAT1. Blood 1998; 91:1341-54. PubMed
  • Frank DA, Mahajan S, Ritz J. B lymphocytes from patients with chronic lymphocytic leukemia contain signal transducer and activator of transcription (STAT) 1 and STAT3 constitutively phosphorylated on serine residues. J Clin Invest 1998; 100:3140-8. PubMed
  • Karras JG, Wang Z, Huo L, Frank DA, Rothstein TL. Induction of STAT protein signaling through the CD40 receptor in B lymphocytes: distinct STAT activation following surface Ig and CD40 receptor engagement. J Immunol 1997; 159:4350-5. PubMed
  • Bonni A, Sun Y, Nadal-Vicens M, Bhatt A, Frank DA, Rozovsky I, Stahl N, Yancopoulos GD, Greenberg ME. Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway. Science 1997; 278:477-83. PubMed
  • Karras JG, Wang Z, Huo L, Howard RG, Frank DA, Rothstein TL. Signal transducer and activator of transcription-3 (STAT3) is constitutively activated in normal, self-renewing B-1 cells but only inducibly expressed in conventional B lymphocytes. J Exp Med 1997; 185:1035-42. PubMed
  • Arbiser JL, Moses MA, Fernandez CA, Ghiso N, Cao Y, Klauber N, Frank D, Brownlee M, Flynn E, Parangi S, Byers HR, Folkman J. Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci U S A 1997; 94:861-6. PubMed
  • Karras JG, Huo L, Wang Z, Frank DA, Zimmet JM, Rothstein TL. Delayed tyrosine phosphorylation and nuclear expression of STAT1 following antigen receptor stimulation of B lymphocytes. J Immunol 1996; 157:2299-309. PubMed
  • Carlesso N, Frank DA, Griffin JD. Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. J Exp Med 1996; 183:811-20. PubMed
  • Inhorn RC, Carlesso N, Durstin M, Frank DA, Griffin JD. Identification of a viability domain in the granulocyte/macrophage colony-stimulating factor receptor beta-chain involving tyrosine-750. Proc Natl Acad Sci U S A 1995; 92:8665-9. PubMed
  • Sattler M, Durstin MA, Frank DA, Okuda K, Kaushansky K, Salgia R, Griffin JD. The thrombopoietin receptor c-MPL activates JAK2 and TYK2 tyrosine kinases. Exp Hematol 1995; 23:1040-8. PubMed
  • Bonni A, Frank DA, Schindler C, Greenberg ME. Characterization of a pathway for ciliary neurotrophic factor signaling to the nucleus. Science 1993; 262:1575-9. PubMed
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