Breast Cancer Research Program
The Breast Cancer Program (BC) includes 27 members from 12 academic departments from Vanderbilt University School of Medicine (VUSM), Vanderbilt School of Nursing, and Meharry Medical College. Program members have expertise in cellular signaling and molecular biology, breast pathology, medical, surgical, and radiation oncology, clinical trial design, epidemiology and quality of life studies, mass spectrometry, biostatistics, and biomedical informatics.
Program Leader: Carlos Arteaga, M.D.
The program has a strong emphasis on breast epithelial cell and molecular biology, basic science driven translational and clinical research, and molecular epidemiology. Main scientific goals of the BC include:
- To stimulate collaborative, extramurally fundable basic science-based translational and clinical research in breast cancer.
- To enhance communication between program members and dissemination of new data and cutting-edge methodologies.
- To stimulate novel, investigator-initiated pre-surgical and neoadjuvant clinical trials of new therapies and therapeutic combinations with an emphasis on biomarker discovery.
- To mentor and train investigators in translational research in breast cancer.
- To establish research partnerships with biotechnology and industry that will enhance the program’s translational and clinical research.
Program Focus to Meet Scientific Goals
BC focuses on several themes that cover the spectrum from mechanistic science to clinical investigation. Areas of interest include the following:
- Role of oncogene signaling (ErbB2, ErbB3, PI3K, TGFβ) and tumor suppressors (TGFβ) in mammary development, transformation, and tumor progression
- Role of the p53 family of transcription factors on the pathogenesis of triple negative (basal-like) breast cancer and its response to therapy.
- Discovery of pharmacodynamic and non-invasive imaging biomarkers predictive of response to established and novel anti-cancer agents.
- Association of gene variants and gene-environment interactions with progression of premalignant breast disease and risk of breast cancer.
- Cellular and molecular mechanisms of bone metastasis and markers of bone quality in patients with breast cancer disseminated to bone.
- Discovery of mechanisms of de novo and acquired resistance to anti-HER2 and endocrine therapy.
- Advocacy, education, and outreach activities to inform patients and community about breast cancer research and enhance accrual into clinical trials.
About the Program Leader
Carlos L. Arteaga, M.D. directs this program and is responsible for its overall scientific and administrative leadership. He joined the Vanderbilt faculty in 1989 and now holds the Donna S. Hall Chair in Breast Cancer Research. He is also Professor of Medicine and Cancer Biology and a member of the Division of Hematology-Oncology in the Department of Medicine. His research focuses on the role of signaling by growth factor receptors and oncogenes in the progression of breast tumor cells as well as the clinical development of molecular therapeutics in breast cancer. He is certified by the American Board of Internal Medicine in internal medicine and in medical oncology. His laboratory is funded by the NCI, the American Cancer Society (ACS), the DOD Breast Cancer Research Program, the Susan G. Komen and Breast Cancer Research foundations, and partners in biotechnology and industry. In 1998 he was elected into the American Society of Clinical Investigation (ASCI) and in 2005 into the Association of American Physicians (AAP). He serves (or has served) as a member of the NCI Parent Committee for Review of Cancer Centers (Subcommittee A; 2004-2008), the Board of Scientific Counselors (BSC) of NCI (1999-2004), the Breast Cancer Core Committee of the Eastern Cooperative Oncology Group (ECOG), and the Board of Directors of the American Association for Cancer Research (AACR; 2004-2007). He co-chaired the Developmental Therapeutics Committee of ECOG and chaired the Special Conferences Committee of the AACR (2002-2008). He is also the 2003 recipient of the AACR Richard & Hinda Rosenthal Foundation Award and more recently received the 2007-2012 ACS Clinical Research Professorship Award and the 2009 Gianni Bonadonna Award from the American Society of Clinical Oncology (ASCO). He chaired the AACR Special Conferences Advances in Breast Cancer Research in 2003, 2005, 2007, and 2009. He is Deputy Editor of Clinical Cancer Research and Associate Editor or member of the Editorial Board of Cancer Cell, Journal of Mammary Gland Biology & Neoplasia, Breast Cancer Research, Molecular Cancer Therapeutics, Journal of Clinical Oncology, and Cancer Biology & Therapy.
Areas Of Program Expertise
BC members have expertise over a wide range of disciplines from molecular and cell biology to translational and clinical research in breast cancer. These are listed below:
- Vandana Abramson, M.D. A recent recruit from the University of Pennsylvania, Dr. Abramson is a breast cancer clinical investigator with expertise in Phase I development of new agents and the use of pharmacodynamic endpoints to assess drug action. She recently obtained a Bonadonna Fellowship Award from ASCO (2009). Her main role is to generate, implement, and lead IITs based in BC.
- Carlos L. Arteaga, M.D. This laboratory focuses on the role of TGFβ and ErbB receptor signaling in mammary gland development and transformation. There is also emphasis on discovery of biomarkers of drug action and mechanisms of resistance to anti-oncogene (HER2, PI3K, IGF-IR) and endocrine therapies in breast cancer using established human cell lines, transgenic mouse models of mammary development and cancer, and primary tumor tissues from patients enrolled in BC-based pre-surgical and neoadjuvant IITs.
- Anuradha (Bapsi) Chakravarthy, M.D. Dr. Chakravarthy is a radiation oncologist who serves as co-Director of the Tissue Core of the Breast Cancer SPORE. She is co-investigator in several IITs focused on discovery of pharmacodynamic and non-invasive imaging predictors of response to neoadjuvant chemotherapy.
- Gautam Chaudhuri, Ph.D. Dr. Chaudhuri is Professor of Microbiology & Immunology at Meharry Medical College. His research interests include understanding the genetic and epigenetic regulation of the BRCA2 gene with respect to the proliferation and metastatic progression of human breast cancer cells, evaluation of the role of non-coding RNAs in determining the immune functions of myeloid cells, and the identification and validation of targets of nucleic acid-based therapies against breast cancer and myeloid cell malignancies.
- Rebecca S. Cook, Ph.D. Dr. Cook has expertise in using the applications of cell biology and developmental biology to interrogate stages of cancer formation and malignant progression in mouse models. Her expertise with genetically engineered mouse models of breast cancer has led to the generation of physiologically meaningful results that mimic precise genetic events occurring in human breast cancers. There is emphasis on early events in breast development that contribute to future formation of cancers, particularly those events influenced by the ErbB receptor signaling pathway..
- William D. Dupont, Ph.D. Dr. Dupont has collaborated for the past 32 years with David Page, M.D. and more recently with Jeffrey Smith, M.D., Ph.D., both BC members, in the discovery of histopathologic, genetic and molecular risk factors for breast cancer in women with benign breast disease. Their approach to classifying benign breast disease has impacted the clinical management of these lesions and their findings have been extensively replicated by other investigators.
- Ana M. Grau, M.D., is an Associate Professor of Surgical Oncology at Vanderbilt University Medical Center and the Vanderbilt Breast Center at One Hundred Oaks. Dr. Grau's clinical practice encompasses breast disease with a primary focus on breast cancer. Her research interests include both clinical and translational breast cancer-related research.
- John G. Huff, M.D. Dr. Huff joined the Vanderbilt faculty in 2007 as Director of Breast Imaging and Imaging Director of the Breast Center. He has a special interest in the multidisciplinary approach to breast cancer management as well as advanced breast imaging including magnetic resonance mammography.
- Mark C. Kelley, M.D. Dr. Kelley is Director of the Division of Surgical Oncology. He is a key co-investigator in several BC-based investigator-initiated trials. In collaboration with colleagues in the Department of Biomedical Engineering, he is involved in the development of optical spectroscopic methods for the intra-operative demarcation of breast tumors.
- Alecia Malin, Ph.D. Dr. Malin obtained a Ph.D. in health promotion and education and postdoctoral training in molecular epidemiology at Vanderbilt. Her research focuses on lifestyle epidemiology and health services research factors related to breast cancer risk. She is currently the PI of several epidemiologic studies. She is funded by the ACS to examine the role of serial mammography in minority and medically underserved women with breast cancer and by the NCI to study the role of vitamin D, obesity and breast density in breast cancer risk in African-American women.
- Lynn M. Matrisian, Ph.D. Dr. Matrisian was one of the first to report that growth factors and oncogenes induce the expression of extracellular matrix-degrading matrix metalloproteases (MMPs). She is PI of the Vanderbilt Tumor Microenvironment Network U54 Grant, which focuses on studying mechanisms of paracrine TGFβ signaling in mammary tumor initiation and progression. This group uses in vitro and in vivo model systems, including chemical carcinogenesis protocols and genetically altered transgenic or knockout mice, to examine the role of MMPs in specific stages of mammary cancer and the therapeutic effect of small molecule MMP inhibitors.
- Ingrid A. Mayer, M.D. Dr. Mayer is a clinical investigator who completed the Master of Science in Clinical Investigation (MSCI) program at Vanderbilt in May 2006. Her role is to implement and conduct investigator-initiated, mechanism-based clinical and translational trials focusing on HER2, PI3K, and IGF-IR pathways as mechanisms of resistance in HER2-overexpressing, triple-negative, and hormone-sensitive breast cancers. She is a member of the ECOG Breast Committee and has experience as principal investigator in design, conduct, and analysis of several Phase I, II, and III clinical trials based in BC.
- Ingrid M. Meszoely, M.D. Dr. Meszoely serves as Clinical Director of VICC’s Breast Center at One Hundred Oaks, the primary point of tissue/body fluids collection and entry of patient accrual to our IITs. In that capacity, she oversees the clinical trials and tissue collection support personnel at the Breast Center, which is supported by BC members’ extramural funding. In addition, she is PI of one of our SPORE-based IITs and serves as our liaison with the NSABP, a premier national surgical group to which this trial (BRE0776) is being extended.
- Harold L. Moses, M.D. Since co-discovering the tumor suppressor/promoter TGFβ in the early 1980s, this laboratory has continued to be at the forefront of this area of investigation. This group utilizes elegant transgenic mouse models expressing active TGFβ1 or dominant-negative type II TGFβ receptor (TβRII) under the control of conditional tissue-specific promoters, either in epithelium or in stroma. There is a focus on paracrine mechanisms by which loss and/or overexpression of TGFβ signaling contributes to tumor initiation and metastases in the context of oncogene-driven EMT and mammary epithelial cell transformation.
- Gregory R. Mundy, M.D. Dr. Mundy directs the Vanderbilt Center in Bone Biology. He has had long-term funding for studies on the effects and mechanisms by which human breast cancer cells metastasize to bone and disrupt calcium homeostasis, thus causing bone destruction. He has used preclinical in vivo methods to examine the mechanism of action of drugs such as bisphosphonates and 6-thioguanine on osteolysis and calcium homeostasis. There is an emphasis on molecular mechanisms responsible for the vicious cycle that exists between breast cancer cells and host cells of the bone microenvironment with a focus on PTHrP and TGFβ-induced impairment of osteoblast-mediated new bone formation.
- David L. Page, M.D. An internationally recognized breast cancer pathologist, Dr. Page is co-investigator in the Breast Cancer SPORE, where he studies molecular markers in pre-neoplastic lesions of the breast that predict for the subsequent progression to invasive breast cancer. He assists Dr. Sanders in training and oversight of the research fellow of the Breast Cancer SPORE Tissue Core.
- Fritz F. Parl, M.D., Ph.D. This laboratory investigates estrogen-induced carcinogenesis and breast cancer. The research focuses on the role of phase I (CYP1A1, CYP1B1) and phase II enzymes (COMT, GSTs) in estrogen metabolism including production of catechol estrogens, methoxy estrogens, and estrogen quinones. These studies are mechanistic, addressing the formation of estrogen-DNA adducts; or epidemiological, examining the contribution of genetic enzyme variants to inter-individual differences in breast cancer risk.
- Jennifer A. Pietenpol, Ph.D. This laboratory focuses on the role of the p53 family of transcription factors and biochemical pathways that control cell cycle checkpoint response in human breast cancer cells. There is an increasing emphasis by this group on discovery of pathways critical for the progression of basal-like (triple negative) breast cancer and IITs of novel therapies in patients with this type of breast cancer. Dr. Pietenpol also serves as co-director of the Breast Cancer SPORE.
- Sheila H. Ridner, Ph.D., R.N. Dr. Ridner is Associate Professor in the School of Nursing. Her research is directed toward developing a better understanding of the impact of treatment-related lymphatic damage on cancer patients and survivors. That information is then used to design and test physical and psychological interventions geared toward improving symptoms and quality of life in cancer survivors with lymphatic damage. Her work has been funded by NIH, the ACS, and the Oncology Nursing Society Foundation. She is currently PI on three funded intervention studies addressing lymphedema in breast cancer survivors.
- Marylyn D. Ritchie, Ph.D. Dr. Ritchie is Associate Professor in the Department of Molecular Physiology & Biophysics, investigator in the Center for Human Genetics Research at Vanderbilt and the Breast Cancer SPORE, and Director of the Program in Computational Genomics. Dr. Ritchie is a statistical and computational geneticist with a focus on detecting disease-susceptibility genes associated with common, complex human disease. She is also a member of the Pharmacogenetics Research Network (PGRN) and has expertise in developing novel statistical and computational methods for the detection of gene-gene and gene-environment interactions associated with clinical endpoints.
- Melinda E. Sanders, M.D. Dr. Sanders is an expert breast academic pathologist. She is one of three partners in the Vanderbilt Breast Consultation service that provides more than 5,000 consults per year from all over the world. She serves as research pathologist for all VICC-based breast cancer clinical trials, and as co-Director of the Tissue Core of the Breast Cancer SPORE, where she supervises the role of the SPORE-dedicated research fellow and technical personnel. Her translational research program in breast cancer focuses on genomic and proteomic profiling studies in breast cancer.
- Douglas B. Sawyer, M.D., Ph.D. Dr. Sawyer is Director of the Division of Cardiology and a physician-scientist who specializes in heart failure. His laboratory conducts basic and translational work examining mechanisms of treatment-induced heart failure in patients with breast cancer. Major areas of focus are the role of ErbB receptors in heart physiology, the cellular and molecular mechanisms by which new and established breast cancer therapies and combinations targeting this receptor network can cause cardiac dysfunction, and the use of circulating endothelial progenitors as indicators of cardiac repair in these clinical settings.
- Claus Schneider, Ph.D. Dr. Schneider’s research focuses on the biosynthesis of lipid mediators in inflammatory and human breast cancer cells. This laboratory investigates the formation and role of novel lipid mediators that arise from a cross-over of the COX-2 and 5-lipoxygenase pathways. A second research interest in Dr. Schneider’s laboratory is the biochemistry and biology of oxidative transformation of the dietary cancer chemopreventive agent curcumin.
- Jeffrey R. Smith, M.D., Ph.D. The Smith laboratory employs genomics, bioinformatics, statistical genetics, and high-performance computational approaches to determine the role of genes in the onset and course of both breast and prostate cancer. This group is conducting an extensive investigation of genes on polypeptide growth factor signaling networks and estrogen metabolism pathways in the progression of premalignant breast disease to invasive breast cancer.
- Fen Xia, M.D., Ph.D. This laboratory focuses on elucidating the mechanisms that regulate the repair of chromosomal double-strand breaks (DSB) that arise during physiological DNA metabolism and after radiation therapy or chemotherapy. The overall aims of this research are to understand: 1) the impact of deregulated DSB repair on carcinogenesis and the development of tumor resistance to therapy, and 2) to explore novel avenues of cancer treatment targeting the DSB repair pathways.
- Baogang Jonathan Xu, Ph.D. Dr. Xu trained with Richard Caprioli, Ph.D. at the Vanderbilt Mass Spectrometry Research Center, where he gained significant experience on proteomics-based approaches. He is interested in the application of these methods for studying of the breast tumor microenvironment. His research involves the use of quantitative proteomics and in vivo microdialysis for the identification of secretome changes associated with mammary tumors where stromal cells have been modified by genetic means.
- Thomas E. Yankeelov, Ph.D. Dr. Yankeelov is Director of Cancer Imaging Research at the Vanderbilt University Institute of Imaging Science (VUIIS) and serves as Director of the VICC Animal and Human Imaging Shared Resource and as co-Director of the Breast Cancer SPORE Imaging Core. His research involves the development and application of multi-modal, non-invasive, in vivo imaging methods for monitoring treatment response in breast cancer patients. This investigation extends from mathematical modeling to applications in pre-clinical mouse models to implementation in human studies, thereby spanning the gamut of cancer imaging
- Wei Zheng, Ph.D., M.P.H. Dr. Zheng is an internationally recognized epidemiologist with a major research interest in host and environmental factors in breast cancer. Currently he is the PI of multiple NCI-funded studies, including a genome-wide association study of breast cancer. He also directs the Shanghai Women’s Health Study, which includes approximately 75,000 women who have been followed for cancer incidence and cause-specific mortality. Dr. Zheng recently received a MERIT award from NIH for his funded work with this large and unique cohort. His research team is also studying biomarkers, nutritional factors and gene-diet interaction in the etiology of breast cancer.
Breast Cancer Program Members
- Abramson, Vandana G., M.D.
Assistant Professor of Medicine; Medical Oncologist
- Arteaga, Carlos L., M.D.
Donna S. Hall Chair in Breast Cancer; Professor of Medicine and Cancer Biology; Associate Director of Clinical Research; Director, VICC Breast Cancer Program; Medical Oncologist
- Chakravarthy, Anuradha (Bapsi), M.D.
Associate Professor; Radiation Oncologist
- Chaudhuri, Gautam, Ph.D.
- Chekmenev, Eduard Y., Ph.D.
Assistant Professor of Radiology and Radiological Sciences
- Cook, Rebecca S., Ph.D.
Assistant Professor of Cancer Biology; Researcher
- Dupont, William D., Ph.D.
Professor of Biostatistics; Researcher
- Huff, John G., M.D.
Professor of Radiology; Chief, Section of Breast Imaging; Imaging Director, Vanderbilt Breast Clinic; Breast Imaging Specialist
- Kelley, Mark C., M.D., M.M.H.C., F.A.C.S.
Chief, Division of Surgical Oncology and Endocrine Surgery; Associate Professor of Surgery; Surgical Oncologist
- Macara, Ian, Ph.D.
Professor and Chair, Department of Cell & Developmental Biology; Researcher
- Malin, Alecia, Ph.D.
Assistant Professor; Cancer Epidemiologist
- Mayer, Ingrid A., M.D., M.S.C.I.
Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist
- Meszoely, Ingrid M., M.D.
Associate Professor of Surgery (Surgical Oncology); Clinical Director, Vanderbilt Breast Center; Surgical Oncologist
- Miller, Todd W., Ph.D.
Research Associate Professor of Cancer Biology; Researcher
- Moses, Harold L., M.D.
Director Emeritus; Hortense B. Ingram Professor of Cancer Research; Professor of Cancer Biology, Medicine and Pathology; Researcher
- Page, David L., M.D.
Professor of Pathology and Preventive Medicine; Pathologist
- Parl, Fritz F., M.D., Ph.D.
Prof Pathology Dir Clinical Chem; Researcher
- Pietenpol, Jennifer A., Ph.D.
Director, Vanderbilt-Ingram Cancer Center; Benjamin F. Byrd, Jr. Professor of Oncology; Professor of Biochemistry; Administrator and Researcher
- Rexer, Brent, M.D., Ph.D.
Assistant Professor of Medicine; Medical Oncologist
- Ridner, Sheila H., M.S.H.S.A. ,M.S.N., Ph.D., R.N.
Associate Professor; Researcher
- Ritchie, Marylyn DeRiggi, Ph.D.
Associate Professor of Molecular Physiology and Biophysics; Researcher
- Sanders, Melinda, M.D.
Assistant Professor; Researcher
- Sawyer, Douglas B., M.D., Ph.D
Associate Professor, Cardiovascular Medicine; Director, Cardiovascular Fellowship Program; Chief, Div Cardiovascular Medicine; Researcher
- Schneider, Claus, Ph.D.
Assistant Professor; Researcher
- Smith, Jeffrey R., M.D., Ph.D.
Assistant Professor of Medicine (Genetic Medicine) and Cancer Biology; Researcher
- Sterling, Julie Ann, Ph.D.
Assistant Professor ; Researcher
- Xia, Fen, M.D., Ph.D.
- Xu, Baogang Jonathan, Ph.D.
Research Assistant Professor of Cancer Biology; Researcher
- Yankeelov, Thomas E., Ph.D.
Director of Cancer Imaging Research, Vanderbilt University Institute of Imaging Science (VUIIS); Associate Professor of Radiology and Radiological Sciences, Biomedical Engineering, Physics and Astronomy, and Cancer Biology; Researcher
- Zheng, Wei, M.D., Ph.D, M.P.H.
Professor and Chief, Division of Epidemiology; Director, Vanderbilt Epidemiology Center; Ingram Professor of Cancer Research; Cancer Epidemiologist