Photo of Donald W. Kufe,  MD

Donald W. Kufe, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3141
Fax: (617) 632-2934


donald_kufe@dfci.harvard.edu

Donald W. Kufe, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Identification and characterization of the oncogenic MUC1-C protein. The Kufe laboratory identified DF3/MUC1 in the 1980s as a glycoprotein that is aberrantly overexpressed in ~90% of human breast cancers. Cloning of the DF3/MUC1 gene further identified a unique physical structure comprised of 20 amino acid tandem repeats. Subsequent work showed that MUC1 is a complex consisting of an extracellular N-terminal subunit with glycosylated tandem repeats (MUC1-N; the mucin component) and a C-terminal transmembrane subunit (MUC1-C; the signaling component). In providing protection from the external environment, normal epithelial cells respond to stress with release of MUC1-N into the protective mucous barrier and MUC1-C functions in the transduction of signals to the interior of the cell to promote loss of polarity and induce wound healing and repair. Appropriation of this response by overexpression of MUC1-C, as found in carcinoma cells, was shown to be sufficient for inducing anchorage-independent growth and tumorigenicity, providing the first evidence that MUC1-C functions as an oncoprotein.

MUC1-C activates cell membrane and nuclear signaling pathways. Subsequent work demonstrated that MUC1-C drives loss of polarity, forms complexes with RTKs, such as EGFR, HER2 and others at the cell membrane, and contributes to their activation. These findings were extended by the demonstration that MUC1-C transduces signals from the cell membrane to the nucleus. As one example, MUC1-C was found to directly activate the proinflammatory IKK→NF-κB→p65 pathway, form complexes with p65 on promoters of target genes and contribute to their regulation. Other work showed that MUC1-C promotes the inflammatory response through activation of nuclear STAT1/3 signaling pathways, supporting the notion that MUC1-C contributes to the association between inflammation and cancer.

MUC1-C induces EMT, self-renewal and epigenetic reprogramming. The Kufe laboratory first demonstrated that MUC1-C functions in the regulation of genes that drive EMT and self-renewal of cancer stem-like cells. Further work linked MUC1-C to epigenetic reprogramming by showing that MUC1-C regulates DNA methylation by activating the DNMT1 and DNMT3b genes. Advances also included unrecognized roles for MUC1-C in activating the PRC1/BMI1 and PRC2/EZH2 complexes in driving the repression of tumor suppressor genes, such as such as CHD1, CDKN2A, PTEN, BRCA1 and RASSF1A. Other studies showed that MUC1-C activates the highly conserved NuRD complex, which regulates chromatin assembly and reorganization and is of importance for EMT and invasion. These findings linked MUC1-C to integrating DNA methylation, histone regulation and chromatin remodeling in cancer cells.

MUC1-C promotes genotoxic and targeted drug resistance. The early finding that MUC1-C confers resistance to genotoxic anti-cancer agents was attributed in part to suppression of the DNA damage-induced apoptotic response. Other work in this area extended involvement of MUC1-C in the repair of DNA damage and, more recently, the integration of chromatin remodeling in that response. Other studies showed that MUC1-C confers resistance to targeted agents, such as trastuzumab, tamoxifen, afatinib and others, and that targeting MUC1-C is synergistic with these agents in resistant cells.

MUC1-C inhibits immune recognition and destruction. The Kufe laboratory first demonstrated that MUC1-C activates the PD-L1 gene and represses expression of immune effectors in cancer cells. In concert with these functions, targeting MUC1-C with a novel inhibitor downregulates PD-L1 in mouse tumor models and activates CD8+ T-cells in the immune microenvironment. In addition, MUC1 expression in human cancers correlates negatively with that of the CD8 and IFNγ genes and is associated with poor clinical outcomes. These findings provided the first evidence that MUC1-C plays a role in immune evasion.

MUC1-C drives dedifferentiation and pluripotency cancer cells. Understanding how MUC1-C drives cancer cell plasticity and the multiple above hallmarks of the cancer cell is of critical importance. The Kufe laboratory has found that MUC1-C induces dedifferentiation and pluripotency of breast and prostate cancer cells. In this way, MUC1-C drives stemness in association with induction of Yamanaka pluripotency factors, which have been shown to confer lineage plasticity and dedifferentiation of fibroblasts. These findings have uncovered new lines of ongoing investigation to more precisely define how MUC1-C integrates dedifferentiation, stemness and pluripotency in cancer.

Targeting MUC1-C with agents under development. There are presently no clinically available therapeutic agents against the MUC1-C subunit. To address this unmet need, the Kufe laboratory has developed potential therapeutics that target the MUC1-C extracellular and cytoplasmic domains. The generation of monoclonal antibodies (MAbs) against the MUC1-C extracellular domain provided the basis for development of CAR T-cells, BiTEs and antibody-drug conjugates. A cell-penetrating peptide directed against the MUC1-C cytoplasmic domain CQC motif, which is necessary for MUC1-C homodimerization and oncogenic function, is also under development with NCI Moonshot funding based on its activity in suppressing MUC1-C-induced drug resistance and immune evasion.

Summary of Kufe Lab Contributions. The Kufe laboratory founded and has continued to lead the field of research on the MUC1-C oncoprotein in human cancers. Ongoing work is focused on breaking new ground in MUC1-C research by pursuing novel observations that MUC1-C drives the Yamanaka reprogramming factors and pluripotency in highly aggressive carcinomas.

Publications from Harvard Catalyst Profiles

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  • Yamashita N, Morimoto Y, Fushimi A, Ahmad R, Bhattacharya A, Daimon T, Haratake N, Inoue Y, Ishikawa S, Yamamoto M, Hata T, Akiyoshi S, Hu Q, Liu T, Withers H, Liu S, Shapiro GI, Yoshizumi T, Long MD, Kufe D. MUC1-C Dictates PBRM1-Mediate Chronic Induction of Interferon Signaling, DNA Damage Resistance and Immunosuppression in Triple-Negative Breast Cancer. Mol Cancer Res 2022. PubMed
  • Kufe DW. Emergence of in Mammals for Adaptation of Barrier Epithelia. Cancers (Basel) 2022. PubMed
  • Orr S, Huang L, Moser J, Stroopinsky D, Gandarilla O, DeCicco C, Liegel J, Tacettin C, Ephraim A, Cheloni G, Torres D, Kufe D, Rosenblatt J, Hidalgo M, Muthuswamy SK, Avigan D. Personalized tumor vaccine for pancreatic cancer. Cancer Immunol Immunother 2022. PubMed
  • Morimoto Y, Fushimi A, Yamashita N, Hagiwara M, Bhattacharya A, Cheng J, Frost TC, Ahmad R, Daimon T, Huang L, Hata T, Takahashi H, Yamamoto M, Suzuki Y, DeCaprio JA, Kufe D. Addiction of Merkel cell carcinoma to MUC1-C identifies a potential new target for treatment. Oncogene 2022; 41:3511-3523. PubMed
  • Yamashita N, Fushimi A, Morimoto Y, Bhattacharya A, Hagiwara M, Yamamoto M, Hata T, Shapiro GI, Long MD, Liu S, Kufe D. Targeting MUC1-C Suppresses Chronic Activation of Cytosolic Nucleotide Receptors and STING in Triple-Negative Breast Cancer. Cancers (Basel) 2022. PubMed
  • Bhattacharya A, Fushimi A, Yamashita N, Hagiwara M, Morimoto Y, Rajabi H, Long MD, Abdulla M, Ahmad R, Street K, Liu S, Liu T, Kufe D. MUC1-C Dictates JUN and BAF-Mediated Chromatin Remodeling at Enhancer Signatures in Cancer Stem Cells. Mol Cancer Res 2022; 20:556-567. PubMed
  • Li W, Han Y, Sun C, Li X, Zheng J, Che J, Yao X, Kufe D. Novel insights into the roles and therapeutic implications of MUC1 oncoprotein via regulating proteins and non-coding RNAs in cancer. Theranostics 2022; 12:999-1011. PubMed
  • Hagiwara M, Fushimi A, Bhattacharya A, Yamashita N, Morimoto Y, Oya M, Withers HG, Hu Q, Liu T, Liu S, Wong KK, Long MD, Kufe D. MUC1-C integrates type II interferon and chromatin remodeling pathways in immunosuppression of prostate cancer. Oncoimmunology 2022; 11:2029298. PubMed
  • Kufe DW. Chronic activation of MUC1-C in wound repair promotes progression to cancer stem cells. J Cancer Metastasis Treat 2022. PubMed
  • Luan Z, Morimoto Y, Fushimi A, Yamashita N, Suo W, Bhattacharya A, Hagiwara M, Jin C, Kufe D. MUC1-C Dictates Neuroendocrine Lineage Specification in Pancreatic Ductal Adenocarcinomas. Carcinogenesis 2021. PubMed
  • Hagiwara M, Fushimi A, Yamashita N, Bhattacharya A, Rajabi H, Long MD, Yasumizu Y, Oya M, Liu S, Kufe D. MUC1-C activates the PBAF chromatin remodeling complex in integrating redox balance with progression of human prostate cancer stem cells. Oncogene 2021; 40:4930-4940. PubMed
  • Stroopinsky D, Liegel J, Bhasin M, Cheloni G, Thomas B, Bhasin S, Panchal R, Ghiasuddin H, Rahimian M, Nahas M, Orr S, Capelletti M, Torres D, Tacettin C, Weinstock M, Bisharat L, Morin A, Mahoney KM, Ebert B, Stone R, Kufe D, Freeman GJ, Rosenblatt J, Avigan D. Leukemia vaccine overcomes limitations of checkpoint blockade by evoking clonal T cell responses in a murine acute myeloid leukemia model. Haematologica 2021. PubMed
  • Koşaloğlu-Yalçın Z, Blazeska N, Carter H, Nielsen M, Cohen E, Kufe D, Conejo-Garcia J, Robbins P, Schoenberger SP, Peters B, Sette A. The Cancer Epitope Database and Analysis Resource: A Blueprint for the Establishment of a New Bioinformatics Resource for Use by the Cancer Immunology Community. 2021; 12:735609. PubMed
  • Hagiwara M, Yasumizu Y, Yamashita N, Rajabi H, Fushimi A, Long MD, Li W, Bhattacharya A, Ahmad R, Oya M, Liu S, Kufe D. MUC1-C Activates the BAF (mSWI/SNF) Complex in Prostate Cancer Stem Cells. Cancer Res 2021; 81:1111-1122. PubMed
  • Yamashita N, Long M, Fushimi A, Yamamoto M, Hata T, Hagiwara M, Bhattacharya A, Hu Q, Wong KK, Liu S, Kufe D. MUC1-C integrates activation of the IFN-γ pathway with suppression of the tumor immune microenvironment in triple-negative breast cancer. J Immunother Cancer 2021. PubMed
  • Kufe DW. MUC1-C in chronic inflammation and carcinogenesis; emergence as a target for cancer treatment. Carcinogenesis 2020; 41:1173-1183. PubMed
  • Annapragada A, Sikora A, Bollard C, Conejo-Garcia J, Cruz CR, Demehri S, Demetriou M, Demirdjian L, Fong L, Horowitz M, Hutson A, Kadash-Edmondson K, Kufe D, Lipkin S, Liu S, McCarthy C, Morgan M, Morris Z, Pan Y, Pasquini M, Schoenberger S, Van Allen E, Vilar E, Xing Y, Zha W, , Odunsi A. Cancer Moonshot Immuno-Oncology Translational Network (IOTN): accelerating the clinical translation of basic discoveries for improving immunotherapy and immunoprevention of cancer. J Immunother Cancer 2020. PubMed
  • Yamamoto M, Jin C, Hata T, Yasumizu Y, Zhang Y, Hong D, Maeda T, Miyo M, Hiraki M, Suzuki Y, Hinohara K, Rajabi H, Kufe D. MUC1-C INTEGRATES CHROMATIN REMODELING AND PARP1 ACTIVITY IN THE DNA DAMAGE RESPONSE OF TRIPLE-NEGATIVE BREAST CANCER CELLS. Cancer Res 2019. PubMed
  • Panchamoorthy G, Jin C, Raina D, Bharti A, Yamamoto M, Adeebge D, Zhao Q, Bronson R, Jiang S, Li L, Suzuki Y, Tagde A, Ghoroghchian PP, Wong KK, Kharbanda S, Kufe D. Targeting the human MUC1-C oncoprotein with an antibody-drug conjugate. JCI Insight 2018. PubMed
  • Stroopinsky D, Rajabi H, Nahas M, Rosenblatt J, Rahimian M, Pyzer A, Tagde A, Kharbanda A, Jain S, Kufe T, Leaf RK, Anastasiadou E, Bar-Natan M, Orr S, Coll MD, Palmer K, Ephraim A, Cole L, Washington A, Kufe D, Avigan D. MUC1-C drives myeloid leukaemogenesis and resistance to treatment by a survivin-mediated mechanism. J Cell Mol Med 2018. PubMed
  • Hiraki M, Maeda T, Mehrotra N, Jin C, Alam M, Bouillez A, Hata T, Tagde A, Keating A, Kharbanda S, Singh H, Kufe D. Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer. Signal Transduct Target Ther 2018; 3:13. PubMed
  • Maeda T, Hiraki M, Jin C, Rajabi H, Tagde A, Alam M, Bouillez A, Hu X, Suzuki Y, Miyo M, Hata T, Hinohara K, Kufe D. MUC1-C Induces PD-L1 and Immune Evasion in Triple-Negative Breast Cancer. Cancer Res 2018; 78:205-215. PubMed
  • Sakakibara K, Sato T, Kufe DW, VonHoff DD, Kawabe T. CBP501 induces immunogenic tumor cell death and CD8 T cell infiltration into tumors in combination with platinum, and increases the efficacy of immune checkpoint inhibitors against tumors in mice. 2017; 8:78277-78288. PubMed
  • Jain S, Washington A, Leaf RK, Bhargava P, Clark RA, Kupper TS, Stroopinsky D, Pyzer A, Cole L, Nahas M, Apel A, Rosenblatt J, Arnason J, Kufe D, Avigan D. Decitabine Priming Enhances Mucin 1 Inhibition Mediated Disruption of Redox Homeostasis in Cutaneous T-Cell Lymphoma. Mol Cancer Ther 2017; 16:2304-2314. PubMed
  • Saito N, Mine N, Kufe DW, Von Hoff DD, Kawabe T. CBP501 inhibits EGF-dependent cell migration, invasion and epithelial-to-mesenchymal transition of non-small cell lung cancer cells by blocking KRas to calmodulin binding. 2017; 8:74006-74018. PubMed
  • Mine N, Yamamoto S, Saito N, Sato T, Sakakibara K, Kufe DW, VonHoff DD, Kawabe T. CBP501 suppresses macrophage induced cancer stem cell like features and metastases. 2017; 8:64015-64031. PubMed
  • Yin L, Tagde A, Gali R, Tai YT, Hideshima T, Anderson K, Avigan D, Kufe D. MUC1-C is a target in lenalidomide resistant multiple myeloma. British Journal of Haematology 2017. PubMed
  • Rajabi H, Hiraki M, Tagde A, Alam M, Bouillez A, Christensen CL, Samur M, Wong KK, Kufe D. MUC1-C activates EZH2 expression and function in human cancer cells. Sci Rep 2017; 7:7481. PubMed
  • Pyzer AR, Stroopinsky D, Rajabi H, Washington A, Tagde A, Coll M, Fung J, Bryant MP, Cole L, Palmer K, Somaiya P, Karp Leaf R, Nahas M, Apel A, Jain S, McMasters M, Mendez L, Levine J, Joyce R, Arnason J, Pandolfi PP, Kufe D, Rosenblatt J, Avigan D. MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia. Blood 2017. PubMed
  • Rajabi H, Kufe D. MUC1-C Oncoprotein Integrates a Program of EMT, Epigenetic Reprogramming and Immune Evasion in Human Carcinomas. Biochim Biophys Acta 2017; 1868:117-122. PubMed
  • Ahmad R, Alam M, Hasegawa M, Uchida Y, Al-Obaid O, Kharbanda S, Kufe D. Targeting MUC1-C inhibits the AKT-S6K1-elF4A pathway regulating TIGAR translation in colorectal cancer. Mol Cancer 2017; 16:33. PubMed
  • Bar-Natan M, Stroopinsky D, Luptakova K, Coll MD, Apel A, Rajabi H, Pyzer AR, Palmer K, Reagan MR, Nahas MR, Karp Leaf R, Jain S, Arnason J, Ghobrial IM, Anderson KC, Kufe D, Rosenblatt J, Avigan D. Bone marrow stroma protects myeloma cells from cytotoxic damage via induction of the oncoprotein MUC1. British Journal of Haematology 2017. PubMed
  • Bouillez A, Adeegbe D, Jin C, Hu X, Tagde A, Alam M, Rajabi H, Wong KK, Kufe D. MUC1-C promotes the suppressive immune microenvironment in non-small cell lung cancer. Oncoimmunology 2017; 6:e1338998. PubMed
  • Alam M, Bouillez A, Tagde A, Ahmad R, Rajabi H, Maeda T, Hiraki M, Suzuki Y, Kufe D. MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway. Mol Cancer Res 2016. PubMed
  • Stroopinsky D, Kufe D, Avigan D. MUC1 in hematological malignancies. Leuk Lymphoma 2016. PubMed
  • Tagde A, Rajabi H, Stroopinsky D, Gali R, Alam M, Bouillez A, Kharbanda S, Stone R, Avigan D, Kufe D. MUC1-C induces DNA methyltransferase 1 and represses tumor suppressor genes in acute myeloid leukemia. 2016. PubMed
  • Bouillez A, Rajabi H, Pitroda S, Jin C, Alam M, Kharbanda A, Tagde A, Wong KK, Kufe D. Inhibition of MUC1-C Suppresses MYC Expression and Attenuates Malignant Growth in KRAS Mutant Lung Adenocarcinomas. Cancer Res 2016; 76:1538-48. PubMed
  • Tagde A, Rajabi H, Bouillez A, Alam M, Gali R, Bailey S, Tai YT, Hideshima T, Anderson K, Avigan D, Kufe D. MUC1-C drives MYC in multiple myeloma. Blood 2016. PubMed
  • Hasegawa M, Takahashi H, Rajabi H, Alam M, Suzuki Y, Yin L, Tagde A, Maeda T, Hiraki M, Sukhatme VP, Kufe D. Functional interactions of the cystine/glutamate antiporter, CD44V and MUC1-C oncoprotein in triple-negative breast cancer cells. 2016. PubMed
  • Hiraki M, Suzuki Y, Alam M, Hinohara K, Hasegawa M, Jin C, Kharbanda S, Kufe D. MUC1-C Stabilizes MCL-1 in the Oxidative Stress Response of Triple-Negative Breast Cancer Cells to BCL-2 Inhibitors. Sci Rep 2016; 6:26643. PubMed
  • Jain S, Stroopinsky D, Yin L, Rosenblatt J, Alam M, Bhargava P, Clark RA, Kupper TS, Palmer K, Coll MD, Rajabi H, Pyzer A, Bar-Natan M, Luptakova K, Arnason J, Joyce R, Kufe D, Avigan D. Mucin 1 is a potential therapeutic target in cutaneous T-cell lymphoma. Blood 2015; 126:354-62. PubMed
  • Hasegawa M, Sinha RK, Kumar M, Alam M, Yin L, Raina D, Kharbanda A, Panchamoorthy G, Gupta D, Singh H, Kharbanda S, Kufe D. Intracellular Targeting of the Oncogenic MUC1-C Protein with a Novel GO-203 Nanoparticle Formulation. Clin Cancer Res 2015; 21:2338-47. PubMed
  • Alam M, Ahmad R, Rajabi H, Kufe D. MUC1-C Induces the LIN28B→LET-7→HMGA2 Axis to Regulate Self-Renewal in NSCLC. Mol Cancer Res 2015; 13:449-60. PubMed
  • Raina D, Agarwal P, Lee J, Bharti A, McKnight CJ, Sharma P, Kharbanda S, Kufe D. Characterization of the MUC1-C Cytoplasmic Domain as a Cancer Target. PLoS ONE 2015; 10:e0135156. PubMed
  • Kharbanda A, Rajabi H, Jin C, Tchaicha J, Kikuchi E, Wong KK, Kufe D. Targeting the oncogenic MUC1-C protein inhibits mutant EGFR-mediated signaling and survival in non-small cell lung cancer cells. Clin Cancer Res 2014. PubMed
  • Kharbanda A, Rajabi H, Jin C, Alam M, Wong KK, Kufe D. MUC1-C confers EMT and KRAS independence in mutant KRAS lung cancer cells. 2014. PubMed
  • Raina D, Uchida Y, Kharbanda A, Rajabi H, Panchamoorthy G, Jin C, Kharbanda S, Scaltriti M, Baselga J, Kufe D. Targeting the MUC1-C oncoprotein downregulates HER2 activation and abrogates trastuzumab resistance in breast cancer cells. Oncogene 2014. PubMed
  • Kumar M, Gupta D, Singh G, Sharma S, Bhat M, Prashant CK, Dinda AK, Kharbanda S, Kufe D, Singh H. Novel polymeric nanoparticles for intracellular delivery of peptide Cargos: antitumor efficacy of the BCL-2 conversion peptide NuBCP-9. Cancer Res 2014. PubMed
  • Alam M, Rajabi H, Ahmad R, Jin C, Kufe D. Targeting the MUC1-C oncoprotein inhibits self-renewal capacity of breast cancer cells. 2014. PubMed
  • Yin L, Kufe T, Avigan D, Kufe D. Targeting MUC1-C is synergistic with bortezomib in downregulating TIGAR and inducing ROS-mediated myeloma cell death. Blood 2014. PubMed
  • Rajabi H, Alam M, Takahashi H, Kharbanda A, Guha M, Ahmad R, Kufe D. MUC1-C oncoprotein activates the ZEB1/miR-200c regulatory loop and epithelial-mesenchymal transition. Oncogene 2014; 33:1680-9. PubMed
  • Liu S, Yin L, Stroopinsky D, Rajabi H, Puissant A, Stegmaier K, Avigan D, Kharbanda S, Kufe D, Stone R. MUC1-C oncoprotein promotes FLT3 receptor activation in acute myeloid leukemia cells. Blood 2014; 123:734-42. PubMed
  • Alam M, Ahmad R, Rajabi H, Kharbanda A, Kufe D. MUC1-C oncoprotein activates ERK→C/EBPβ signaling and induction of aldehyde dehydrogenase 1A1 in breast cancer cells. J Biol Chem 2013; 288:30892-903. PubMed
  • Stroopinsky D, Rosenblatt J, Ito K, Mills H, Yin L, Rajabi H, Vasir B, Kufe T, Luptakova K, Arnason J, Nardella C, Levine JD, Joyce RM, Galinsky I, Reiter Y, Stone RM, Pandolfi PP, Kufe D, Avigan D. MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells. Cancer Res 2013; 73:5569-79. PubMed
  • Rosenblatt J, Avivi I, Vasir B, Uhl L, Munshi NC, Katz T, Dey BR, Somaiya P, Mills H, Campigotto F, Weller E, Joyce R, Levine JD, Tzachanis D, Richardson P, Laubach J, Raje N, Boussiotis V, Yuan YE, Bisharat L, Held V, Rowe J, Anderson K, Kufe D, Avigan D. Vaccination with dendritic cell/tumor fusions following autologous stem cell transplant induces immunologic and clinical responses in multiple myeloma patients. Clin Cancer Res 2013; 19:3640-8. PubMed
  • Kharbanda A, Rajabi H, Jin C, Raina D, Kufe D. Oncogenic MUC1-C promotes tamoxifen resistance in human breast cancer. Mol Cancer Res 2013. PubMed
  • Jin C, Rajabi H, Rodrigo CM, Porco JA, Kufe D. Targeting the eIF4A RNA helicase blocks translation of the MUC1-C oncoprotein. Oncogene 2013. PubMed
  • Kufe DW. MUC1-C oncoprotein as a target in breast cancer: activation of signaling pathways and therapeutic approaches. Oncogene 2013. PubMed
  • Uchida Y, Raina D, Kharbanda S, Kufe D. Inhibition of the MUC1-C oncoprotein is synergistic with cytotoxic agents in the treatment of breast cancer cells. Cancer Biol Ther 2013; 14:127-34. PubMed
  • Rajabi H, Ahmad R, Jin C, Joshi MD, Guha M, Alam M, Kharbanda S, Kufe D. MUC1-C oncoprotein confers androgen-independent growth of human prostate cancer cells. Prostate 2012. PubMed
  • Vasir B, Zarwan C, Ahmad R, Crawford KD, Rajabi H, Matsuoka K, Rosenblatt J, Wu Z, Mills H, Kufe D, Avigan D. Induction of antitumor immunity ex vivo using dendritic cells transduced with fowl pox vector expressing MUC1, CEA, and a triad of costimulatory molecules (rF-PANVAC). J Immunother 2012; 35:555-69. PubMed
  • Ahmad R, Alam M, Rajabi H, Kufe D. The MUC1-C oncoprotein binds to the BH3 domain of the pro-apoptotic BAX protein and blocks BAX function. J Biol Chem 2012; 287:20866-75. PubMed
  • Raina D, Ahmad R, Rajabi H, Panchamoorthy G, Kharbanda S, Kufe D. Targeting cysteine-mediated dimerization of the MUC1-C oncoprotein in human cancer cells. Int J Oncol 2012; 40:1643-9. PubMed
  • Rajabi H, Ahmad R, Jin C, Kosugi M, Alam M, Joshi MD, Kufe D. MUC1-C oncoprotein induces TCF7L2 transcription factor activation and promotes cyclin D1 expression in human breast cancer cells. J Biol Chem 2012; 287:10703-13. PubMed
  • Yin L, Kosugi M, Kufe D. Inhibition of the MUC1-C oncoprotein induces multiple myeloma cell death by down-regulating TIGAR expression and depleting NADPH. Blood 2012; 119:810-6. PubMed
  • Jin C, Rajabi H, Pitroda S, Li A, Kharbanda A, Weichselbaum R, Kufe D. Cooperative interaction between the MUC1-C oncoprotein and the Rab31 GTPase in estrogen receptor-positive breast cancer cells. PLoS ONE 2012; 7:e39432. PubMed
  • Panchamoorthy G, Rehan H, Kharbanda A, Ahmad R, Kufe D. A monoclonal antibody against the oncogenic mucin 1 cytoplasmic domain. Hybridoma (Larchmt) 2011; 30:531-5. PubMed
  • Rajabi H, Joshi MD, Jin C, Ahmad R, Kufe D. Androgen receptor regulates expression of the MUC1-C oncoprotein in human prostate cancer cells. Prostate 2011; 71:1299-308. PubMed
  • Yin L, Wu Z, Avigan D, Rosenblatt J, Stone R, Kharbanda S, Kufe D. MUC1-C oncoprotein suppresses reactive oxygen species-induced terminal differentiation of acute myelogenous leukemia cells. Blood 2011. PubMed
  • Zhou Y, Rajabi H, Kufe D. Mucin 1 C-terminal subunit oncoprotein is a target for small-molecule inhibitors. Mol Pharmacol 2011; 79:886-93. PubMed
  • Raina D, Kosugi M, Ahmad R, Panchamoorthy G, Rajabi H, Alam M, Shimamura T, Shapiro GI, Supko J, Kharbanda S, Kufe D. Dependence on the MUC1-C oncoprotein in non-small cell lung cancer cells. Mol Cancer Ther 2011. PubMed
  • Ahmad R, Rajabi H, Kosugi M, Joshi MD, Alam M, Vasir B, Kawano T, Kharbanda S, Kufe D. MUC1-C oncoprotein promotes STAT3 activation in an autoinductive regulatory loop. Sci Signal 2011; 4:ra9. PubMed
  • Yin L, Kufe D. MUC1-C Oncoprotein Blocks Terminal Differentiation of Chronic Myelogenous Leukemia Cells by a ROS-Mediated Mechanism. Genes Cancer 2011; 2:56-64. PubMed
  • Kosugi M, Ahmad R, Alam M, Uchida Y, Kufe D. MUC1-C oncoprotein regulates glycolysis and pyruvate kinase M2 activity in cancer cells. PLoS ONE 2011; 6:e28234. PubMed
  • Yin L, Ahmad R, Kosugi M, Kufe T, Vasir B, Avigan D, Kharbanda S, Kufe D. Survival of human multiple myeloma cells is dependent on MUC1 C-terminal transmembrane subunit oncoprotein function. Mol Pharmacol 2010; 78:166-74. PubMed
  • Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer 2009; 9:874-85. PubMed
  • Joshi MD, Ahmad R, Yin L, Raina D, Rajabi H, Bubley G, Kharbanda S, Kufe D. MUC1 oncoprotein is a druggable target in human prostate cancer cells. Mol Cancer Ther 2009; 8:3056-65. PubMed
  • Ahmad R, Raina D, Joshi MD, Kawano T, Ren J, Kharbanda S, Kufe D. MUC1-C oncoprotein functions as a direct activator of the nuclear factor-kappaB p65 transcription factor. Cancer Res 2009; 69:7013-21. PubMed
  • Kufe DW. Functional targeting of the MUC1 oncogene in human cancers. Cancer Biol Ther 2009; 8:1197-203. PubMed
  • Raina D, Ahmad R, Joshi MD, Yin L, Wu Z, Kawano T, Vasir B, Avigan D, Kharbanda S, Kufe D. Direct targeting of the mucin 1 oncoprotein blocks survival and tumorigenicity of human breast carcinoma cells. Cancer Res 2009; 69:5133-41. PubMed
  • Jin C, Rajabi H, Rodrigo CM, Porco JA, Kufe D. Targeting the eIF4A RNA helicase blocks translation of the MUC1-C oncoprotein Oncogene ; 32:2179-2188.
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