Todd W Miller, Ph.D.
Assistant Professor of Pharmacology & Toxicology
Pharmacology & Toxicology
University of Connecticut, B.S., 1998
State University of New York at Albany, Ph.D., 2004
Program in Experimental and Molecular Medicine
1 Medical Center Drive
Rubin Bldg, HB 7936
Lebanon NH 03756
Office: Rubin 604
Breast cancer, targeted therapeutics, signaling pathways, drug resistance, biomarker development
Rotations and Thesis Projects:
1) Determine the role of PI3K pathway activation on the methylation and expression of genes encoding Rac-activating proteins, which promote cancer cell migration and invasion.
2) Determine the therapeutic utility of targeting a protein-protein interaction domain of a Rac1-activating protein in breast cancer.
3) Determine the mechanism underlying CDK4-inhibitor induced cell cycle arrest, senescence, and/or apoptosis in antiestrogen-sensitive and -resistant ER+ breast cancer.
4) Determine whether pharmacological inhibition of CDK4 synergizes with antiestrogens or PI3K inhibitors in ER+ breast cancer.
5) Determine whether subtypes of ER+ breast cancer can be distinguished based on ER genomic activity, and whether estrogen-independent ER genomic activity confers antiestrogen resistance in breast cancer.
Dr. Miller received his B.S. in Physiology and Neurobiology at the University of Connecticut in 1998, and his Ph.D. in Biomedical Sciences at the State University of New York at Albany in 2004 (thesis: Immunization and single-chain Fv intrabody gene therapies for Huntington’s Disease). He did his postdoctoral training at Vanderbilt University (2004-2009), and served as a Research Faculty member 2009-2012. Dr. Miller joined the Geisel School of Medicine at Dartmouth as an Assistant Professor in 2012.
Balko JM, Cook RS, Miller TW, Bhola NE, Sanders ME, Granja-Ingram NM, Meszoely IM,Salter J, Dowsett M, Stemke-Hale K, González-Angulo AM, Mills GB, Arteaga C. Digital RNA quantification in formalin-fixed, tumor cell-sparse breast cancers following neoadjuvant chemotherapy identifies DUSP4 as a mediator of drug resistance in basal-like breast cancer. Nat. Med. (in press)
Miller TW, Rexer BN, Garrett JT, Arteaga CL. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res. 2011;13(6):224. (view details on MedLine)
Miller TW, Balko JM, Arteaga CL. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J Clin Oncol. 2011 Nov 20;29(33):4452-61. (view details on MedLine)
Fox EM, Miller TW, Balko JM, Kuba MG, Sánchez V, Smith RA, Liu S, González-Angulo AM, Mills GB, Ye F, Shyr Y, Manning HC, Buck E, Arteaga CL. A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer. Cancer Res. 2011 Nov 1; 71: 6773-84. (view details on MedLine)
Miller TW, Balko JM, Fox EM, Ghazoui Z, Dunbier A, Anderson H, Dowsett M, Jiang A, Smith RA, Maira SM, Manning HC, González-Angulo AM, Mills GB, Higham C, Chanthaphaychith S, Kuba MG, Miller WR, Shyr Y, Arteaga CL. ERα-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer. Cancer Discov. 2011 Sep;1(4):338-351. (view details on MedLine)
Miller TW, Balko JM, Ghazoui Z, Dunbier A, Anderson H, Dowsett M, González-Angulo AM, Mills GB, Miller WR, Wu H, Shyr Y, Arteaga CL. A gene expression signature from human breast cancer cells with acquired hormone independence identifies MYC as a mediator of antiestrogen resistance. Clin Cancer Res. 2011 Apr 1;17(7):2024-34. (view details on MedLine)
Miller TW, Hennessy BT, González-Angulo AM, Fox EM, Mills GB, Chen H, Higham C, García-Echeverría C, Shyr Y, Arteaga CL. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest. 2010 Jul;120(7):2406-13 (view details on MedLine)
Miller TW, Forbes JT, Shah C, Wyatt SK, Manning HC, Olivares MG, Sanchez V, Dugger TC, de Matos Granja N, Narasanna A, Cook RS, Kennedy JP, Lindsley CW, Arteaga CL. Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells. Clin Cancer Res. 2009 Dec 1;15(23):7266-76. (view details on MedLine)
Shah C, Miller TW, Wyatt SK, McKinley ET, Olivares MG, Sanchez V, Nolting DD, Buck JR, Zhao P, Ansari MS, Baldwin RM, Gore JC, Schiff R, Arteaga CL, Manning HC. Imaging biomarkers predict response to anti-HER2 (ErbB2) therapy in preclinical models of breast cancer. Clin Cancer Res. 2009 Jul 15;15(14):4712-21. (view details on MedLine)
Miller TW, Pérez-Torres M, Narasanna A, Guix M, Stål O, Pérez-Tenorio G, Gonzalez-Angulo AM, Hennessy BT, Mills GB, Kennedy JP, Lindsley CW, Arteaga CL. Loss of Phosphatase and Tensin homologue deleted on chromosome 10 engages ErbB3 and insulin-like growth factor-I receptor signaling to promote antiestrogen resistance in breast cancer. Cancer Res. 2009 May 15;69(10):4192-201. (view details on MedLine)