FACULTY

Cancer Biology Faculty Research Interests

Steve Anderson, PhD, Professor of Pathology – Breast Cancer. We are interested in the role of Akt in mammary gland development and tumorigenesis. In addition to suppressing apoptosis, Akt may be important in regulating glucose transport, and the physiology of mammary epithelial cells during lactation. Akt accelerates tumor formation my the ErbB2/Neu oncogene in transgenic mouse models, and may be important in altering the physiology of these cells.

Andrew P. Bradford, PhD, Assistant Professor of Obstetrics and Gynecology. –Gynecological Cancers. Our laboratory is studying the role of selective protein kinase C (PKC) isoforms in the modulation of cell growth and death in endometrial cancer. Using endometrial cancer cell lines and specific adenoviral constructs, our results indicate that PKCα promotes proliferation and survival of endometrial cancer cells, whereas PKCα is pro-apoptotic. Further study of PKCs in the endometrium may identify novel diagnostic/ prognostic indicators and provide new potential targets for therapeutic intervention. We are also investigating the role of growth factor signaling and Ets transcription factors in the pathogenesis of uterine fibroids or leiomyomata.

James DeGregori, PhD, Associate Professor of Biochemistry and Molecular Genetics –Leukemia and Lymphoma. Studies to better understand the conditions that foster the initiation of leukemias and lymphomas are currently a major thrust of the lab. In particular, we are investigating how conditions of stress (particularly those that impair DNA replication) promote the competitive expansion of cells expressing particular oncogenes, and the mechanism whereby these oncogenes can improve cell cycle progression and survival under conditions of stress. In addition, our studies of E2F transcription factors range from the organismal level, such as the development of disease in E2F knock-out mice, to the molecular level, such as our mechanistic studies of E2F control of transcription.

Harry Drabkin, MD, Professor of Medicine and Robert Gemmill, PhD, Associate Professor of Medicine –Kidney, Lung Cancer, Leukemia. Bob Gemmill and Harry Drabkin are a long-term collaborative team. In kidney cancer, we are studying the structure and function of TRC8, a polytopic (multi-membrane spanning) E3 ubiquitin ligase that is a potent, sterol-regulated, tumor suppressor. Many kidney cancer genes, including TRC8, regulate aspects of protein translation initiation and this forms a second line of investigation. In lung cancers, we are investigating the Class 3 semaphorin, SEMA3F, to understand its function as a tumor suppressor through Erk phosphorylation, HIF1 regulation and control of the integrin signaling network. We are also studying the epithelial-mesenchymal transition in lung tumors and how E-cadherin and its transcriptional repressor, ZEB1, work to determine sensitivity or resistance to inhibitors of EGF receptor signaling. Homeobox genes control fundamental properties of differentiated cells and we have found that patterns of expression correlate with biological characteristics of leukemia sub-types. We are interested in developing this HOX expression analysis as a diagnostic tool to identify patient subsets that will benefit from different therapies.

Heide Ford, PhD, Assistant Professor of Obstetrics and Gynecology – Breast Cancer. Homeobox genes encode transcription factors that play a crucial role in development. During development, many changes take place that parallel those seen in cancers, including alterations in cell proliferation and differentiation, in cell death, neovascularization, cell motility, and in invasion of surrounding tissue. My laboratory is interested in how homeobox genes can be "hijacked" by cancer cells to promote the processes of proliferation, migration, and invasion out of context and contribute to tumor initiation and progression.

Wilbur A. Franklin, MD, Professor of Pathology – Lung Cancer. Research in my laboratory along with my collaborators is directed toward defining the molecular changes leading to lung cancer. We are seeking correlations between the unique morphological changes that we have identified in the lower airways of smokers with specific mutations and changes in gene methylation and expression. Our work is also defining the biological and molecular features that predict response to new molecularly targeted therapeutic agents.

Robert Gemmill, PhD, Associate Professor of Medicine –Kidney, Lung Cancer, Leukemia. (see Harry Drabkin)

Arthur Gutierrez-Hartmann, MD, Professor of Medicine and of Biochemistry & Molecular Genetics –Breast, Pituitary, GI cancer. The main focus of the Gutierrez-Hartmann laboratory is to determine the role specific POU-homeodomain and ETS transcription factors in mediating the ontogeny, maintenance and tumorigenesis of epithelial cells in the pituitary, mammary and GI systems. The epithelial-specific ETS transcription factor, Ese-1, is particularly relevant to breast cancer, since the Ese-1 chromosomal locus is amplified in 50% of early breast cancers and Ese-1 mRNA is over-expressed in human breast ductal carcinoma in situ (DCIS). Our most exciting recent discovery is that Ese-1 transforms human mammary epithelial cells via a novel cytoplasmic mechanism and a unique 40-amino acid motif. We use biochemical, molecular, transgenic and pre-clinical approaches to elucidate mechanism and to identify cancer markers.

Lynn E. Heasley, PhD, Professor of Medicine – Lung Cancer. My laboratory is interested in signal transduction pathways that negatively and positively control cellular transformation. The primary focus is on mitogen-activated protein kinases, especially the c-Jun N-terminal kinases (JNKs), which appear to function either as tumor suppressors or pro-transforming signals in a context-dependent manner as well as growth factor autocrine loops as key activators of lung cancer growth.

Jeffrey T. Holt, MD, Professor of Pathology. –Breast Cancer. The Holt laboratory studies the function of the hereditary breast cancer genes BRCA1 and BRCA2 and investigates their role in DNA repair and carcinogenesis. BRCA1 mutant proteins have variable stability in different cells and we are studying the mechanism responsible for protein stability and localization. BRCA2 is phosphorylated by a cell-cycle regulated protein kinase which is altered in cancer and appears responsible for BRCA2 binding to Rad51 and other DNA repair proteins.

Kathryn B. Horwitz, PhD, Distinguished Professor of Medicine. – Breast Cancer. Our laboratory focuses on the actions of women’s hormones, estradiol and progesterone, and their role in breast cancer. Active areas of investigation range from the molecular basis of transcriptional regulation by progesterone receptors and expression profiling of genes regulated by estrogens and progesterone, to novel mouse tumor models we have created to study the role of hormones in cancer growth and metastases. The models are used to address questions regarding hormonal regulation of the expansion of breast cancer progenitor cells; the influence of activated stroma on aggressiveness of adenocarcinomas; and hormonal regulation of the extent and organ localization of metastases. Finally, findings from these studies are applied to translational analysis of human tumor samples.

Jim Lambert, PhD, Research Assistant Professor of Pathology –Prostate Cancer.
Dr. Lambert’s research focuses on the role of a novel signaling protein, prostate derived factor (PDF), in prostate cancer tumorigenicity. Specifically, we have shown: i) forced expression of PDF in human prostate cancer cells dramatically inhibits their growth in vitro and prostate cancer tumor growth in animal models and ii) that PDF is a target gene regulated by one of the most important molecules in cancer research, p53. Thus, PDF appears to be an important control point in the development and/or progression of prostate cancer with our studies serving as the foundation for future research on the role of PDF in the etiology of prostate cancer.

Robert L. Low, MD, PhD, Professor of Pathology Mitochondrial function and role in Cancer.

M. Scott Lucia, MD, Associate Professor of Pathology –Prostate Cancer. Dr. Lucia’s research revolves around prostatic diseases, particularly prostate cancer. The scope of research ranges from analysis of tissue and serum biomarkers in clinical trials to computer imaging/ morphometrics of prostatic disease to molecular signaling pathways. Ongoing projects include the development of new biomarkers of aggressive prostate cancer for diagnostic and prognostic clinical application.

James Maller, PhD. Professor of Pharmacology. Dr Maller’s laboratory studies the molecular regulation of checkpoints in the cell cycle that control the activity of various protein kinases necessary for cell cycle progression. Of particular interest are checkpoints that control entry into and exit from mitosis, including ones triggered by DNA damage, abnormal spindles, or incomplete DNA replication. These checkpoints are studied in early embryos and can also be reproduced in egg extracts that carry out cell cycle transitions in vitro.

Jaime Modiano, VMD, PhD, Associate Professor of Immunology – Our lab studies mechanisms that are responsible for the origin and progression of tumors, as well as how we can manipulate these to improve outcomes of cancer patients. Specifically, we use models where cancer occurs naturally along with laboratory systems to identify genes that contribute to risk, susceptibility, and response to treatment. We are also working to develop new targeted strategies for cancer gene therapy and immunotherapy that will have greater efficacy, and at the same time will reduce treatment-related toxicity.

Raphael A. Nemenoff, PhD, Professor of Medicine –Lung Cancer. The focus of my lab is in examining the molecular events mediating initiation and progression of lung cancer. Specifically, we are studying two interacting pathways that contribute to this process: production of eicosanoids, which are bioactive signaling lipids, and nuclear receptors of the peroxisome proliferator-activated receptor family. Our studies examine these pathways in lung cancer cell lines, co-culture of cancer cells with stromal cells, and in mouse models.

Steven K. Nordeen, PhD, Program Director and Professor of Pathology –Prostate and Breast Cancer. Research in our laboratory is highly collaborative, focusing on the role of the sex steroids, testosterone, estrogen, and progesterone in hormone-dependent cancers of the breast and prostate. Investigations into the molecular details of the mechanisms of regulation of gene expression by the hormone-activated steroid receptors reveal potential new targets and strategies for cancer therapy. We are dissecting the fine balance between growth, differentiation, and apoptosis mediated by the signaling mechanisms of steroids in both cell culture and tumor models.

Mary E.Reyland, PhD, Associate Professor of Craniofacial Biology – Head and Neck Cancer. My laboratory is interested in how specific members of the protein kinase C (PKC) family function to modulate apoptosis. Using salivary epithelial cells either in culture, or derived from genetically modified mice that have specific defects in protein kinase C directed signal transduction, our goal is to identify nuclear phosphorylation targets of PKCδ and to understand the mechanism by which PKCδ regulates the apoptotic pathway. Studies are also underway to understand the molecular mechanisms by which PKCδ is activated during apoptosis and to identify “downstream” pathways through which protein kinase C regulates apoptotic-specific gene expression.

Pepper Schedin, PhD, Associate Professor of Medicine –Breast Cancer. My lab focuses on the biochemical identification and characterization of extracellular matrix (ECM) proteins that mediate mammary epithelial cell homeostasis and death. Two major areas of research are the understanding of how dietary intake influences adolescent mammary gland development and subsequent risk for breast cancer and in determining the role of ECM in breast cancer metastasis. Our long term goals are to develop breast cancer prevention strategies that 1) reduce susceptibility of the pubertal gland to carcinogenic insult and 2) reduce metastatic occurrence immediately following pregnancy.

Robert A. Sclafani, PhD, Professor of Biochemistry and Molecular Genetics – Lung and Breast Cancer. The main area of focus of the laboratory is the regulation of the G1 to S phase transition of the cell cycle in yeast and human cells, especially the processes of chromosomal DNA replication and mutagenesis. When these processes are altered, it results in mutations and aneuploidy, which lead to cancer. By studying these processes, we hope to provide important information for cancer patient diagnosis, prognosis and in design of therapies.

Kenneth R. Shroyer, MD, PhD, Professor of Pathology. – Gynecological Cancers. The Shroyer laboratory is focused on the identification and validation of cancer biomarkers as potential diagnostic adjuncts, prognostic indicators, or novel therapeutic targets in surgical pathology and cytopathology specimens. Current areas of investigation are focused on the study of HPV infection, p16INK4a, minichromosome maintenance proteins, topoisomerase II alpha, and B7-H4 in cervical, endometrial, and ovarian cancer.

Alexander Sorkin, PhD, Associate Professor of Pharmacology- The Sorkin laboratory studies the mechanisms of endocytosis and signaling of the epidermal growth factor (EGF) receptor. In particular, the focus of the research is on elucidation of the mechanisms of EGF receptor endocytosis and on the regulatory role of endocytosis in signling processes initiated by EGF.

Ann D. Thor, MD, Professor and Chair of Pathology. – Breast Cancer. The Thor laboratory studies molecular and environmental factors involved in mammary (breast) carcinogenesis and or chemotherapeutic response. Studies include the use of transgenic mouse models, archival and clinical trials associated breast cancer and normal mammary tissues. Signaling pathways of interest include those associated with the receptor tyrosine kinase receptors, type I and nuclear steroid receptors.

Andrew Thorburn, PhD, Professor of Pharmacology –Breast, Prostate, Brain Cancer, and Leukemia. The Thorburn lab studies the mechanisms of cell death regulation during the development and treatment of cancer. Projects in the lab focus on: 1. characterization of a novel apoptotic and autophagic cell death pathway that we think is one of the earliest cell death-related defects that arise during the development of epithelial cancers. 2. Analysis of the tumor cell killing by therapeutic antibodies that target death receptors. 3. Analysis of the mechanism of action of tumor-targeted bacterial toxins that are in clinical development for treating acute myeloid leukemia and brain tumors.