Todd W Miller, Ph.D.
Assistant Professor of Pharmacology & Toxicology
Scientific Director, Comprehensive Breast Program, Norris Cotton Cancer Center
Co-Director, Molecular Tumor Board, Norris Cotton Cancer Center
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 mechanism by which pharmacologic inhibition of Rac GTPase blocks cancer growth.
2) Develop novel, organ-specific models of metastatic breast cancer; determine underlying differences in gene/protein expression and therapeutic sensitivity between tumors in different organs.
3) Determine the optimal treatment sequence of anti-estrogens and PI3K inhibitors for ER+ breast cancer.
1K99 CA142899-01A1 (PI: Miller)
09/03/2010 – 07/31/2015
Project: The effects of PTEN on tyrosine kinase signaling in breast cancer.
Clinical Research Pilot Grant (co-PIs: Miller, Chamberlin) Norris Cotton Cancer Center Developmental Funds
01/01/2013 – 12/31/2014
Project: Plasma DNA as a surrogate for tumor biopsy to identify tumor genetic alterations in patients with advanced breast cancer.
Management of Cancer Grant (PI: Miller)
Doctors’ Cancer Foundation
11/17/2012 – 11/16/2015
Project: Circulating tumor DNA as a biomarker of disease burden and response to cytotoxic therapy.
Pilot Project Grant (PI: Miller)
Norris Cotton Cancer Center Phase I Program
05/01/2012 – 08/01/2014
Project: Circulating tumor DNA as a biomarker of tumor burden and response to cytotoxic chemotherapy.
Investigator-initiated Phase I clinical study (PI: Schwartz)
06/01/2014 – 05/31/2015
Project: Phase 1 study of combination of MLN9708 and Fulvestrant in patients with advanced ER+ breast cancer.
Research Grant (co-PIs: Ronan, Miller)
The Hitchcock Foundation
07/01/2014 – 06/30/2015
Project: Pilot study to develop circulating tumor DNA in cerebrospinal fluid as an early biomarker of leptomeningeal carcinomatosis in patients with metastatic solid tumor cancer.
Investigator-initiated Phase I clinical study (PI: Fadul)
08/01/2014 – 07/31/2015
Project: Phase 1b study to assess tumor pharmacokinetics, pharmacodynamics, and efficacy of the CDK4/6 inhibitor LEE011 in patients with recurrent glioblastoma or anaplastic astrocytoma.
Investigator-initiated Phase I clinical study (PI: Schwartz)
02/01/2015 – 03/31/2016
Project: Phase 1b neoadjuvant run-in study with MLN0128 followed by Letrozole/MLN0128 in women with high-risk ER+/HER2- breast cancer.
PEMM 102- Scientific Basis of Disease II
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.
2012-present Lloye Dillon, Ph.D., Postdoctoral Fellow
2012-present Wei Yang, M.S., Graduate Student
2013-present Sarah Hosford, B.S., Graduate Student
Dillon LM, Bean JR, Yang W, Shee K, Symonds LK, Balko JM, McDonald WH, Liu S, Gonzalez-Angulo AM, Mills GB, Arteaga CL, Miller TW. P-REX1 creates a positive feedback loop to activate growth factor receptor, PI3K/AKT and MEK/ERK signaling in breast cancer. Oncogene. 2014 Oct 6 (view details on MedLine)
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;13:224. (view details on MedLine)
Miller TW, Balko JM, Arteaga CL. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J Clin Oncol. 2011;29:4452-61. (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; 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;1:338-351. (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;17:2024-34. (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;120:2406-13 (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;15:7266-76. (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;69:4192-201. (view details on MedLine)