Research
Programs

Cancer Cell Signaling

Program Leaders

To be named

Program Themes | Program Information | Program Members | Focus Groups

Program Themes

Determining how specific inflammatory stimuli induce gene expression and thus generate responses that predispose to malignancy
Identifying molecular mechanisms that underlie the roles of nuclear receptors in cancer, especially hormone-responsive malignancies such as breast and prostate cancer
Investigating the roles of aberrant cell adhesion and migration in carcinogenesis and the pathways that govern these processes, and examining the role of the tumor microenvironment, including functions of stem cells, endothelial cells and angiogenesis in tumor formation
Examining the complex and paradoxical roles of TGFβ in tumorigenesis, noting that this cytokine is a tumor suppressor during early stages, but an oncogene at later stages in the development of solid tumors

Program Information

The major scientific focus of this program is to provide improved understanding of the signaling pathways that contribute to cancer. For example, the important connection between inflammation and cancer; the key role of the tumor microenvironment in progression; the roles of receptor tyrosine kinases, nuclear receptors, transcription factors and chromatin remodeling proteins in specific malignancies (breast cancer, prostate cancer, colorectal cancer, lung cancer, melanoma and glioma); and the multiple roles of the TGFβ in tumorigenesis.

The Cancer Cell Signaling Program is organized around 4 focus areas:

Cytokine Signaling, Inflammation, and Cancer
Leaders: Xiaoxia Li, PhD
The Cytokine Signaling, Inflammation, and Cancer focus group includes investigators with interests in innate immune signaling pathways that lead to inflammatory responses and cancer. Included are studies of cytokines (TGFβ, interferons), Toll-like receptors (TLRs), and key stress-inducible transcription factors (STATs, NFκB).

Nuclear Receptor Signaling and Hormone Responsive Cancers
Leaders: David Danielpour, PhD and Noa Noy, PhD
The Nuclear Receptors focus group includes investigators with interest in nuclear hormone receptors, ligand-activated transcription factors that regulate gene expression in response to small hydrophobic hormones, such as steroid hormones, vitamin D, thyroid hormone, and metabolites of vitamin A, long chain fatty acids, and cholesterol. Nuclear receptors and their ligands control key aspects of cellular metabolism, differentiation, proliferation, and apoptosis, and they play key roles in multiple biological functions during embryonic development and in the adult. The group aims to obtain new insights into molecular mechanisms that underlie the transcriptional activities of nuclear receptors, that govern their cross-talk with other signaling pathways, that integrate into biological functions at the cellular and organismal levels, and that are ultimately involved in human health and disease. Of special interest is the utilization of information derived from these investigations for developing strategies that will target receptors and their associated coregulators for prevention of and therapeutic interventions in cancer.

TGFβ
Leader: William Schiemann, PhD
The TGFβ focus group brings together a group of basic scientists and physician-scientists with a common interest in exploring the basic biology and biochemistry of TGFβ signaling, and a shared goal to define the complex roles of this pathway in disease pathogenesis and carcinogenesis. During the earliest stages of carcinogenesis TGFβ principally functions as a tumor suppressor. However, during the later stages of malignant progression biologically active TGFβ, often produced by cancer cells, can aid tumor growth and metastasis through the ability to suppress immune cells, enhance angiogenesis, promote matrix production and induce cancer cell migration. By this time, most tumors have become refractory to the growth inhibitory effects of the cytokine, often through mechanisms involving the downregulation of expression of TGFβ receptors at the cell surface.

Tumor Microenvironment and Metastasis
Leaders: Danny Manor, PhD
Members of this focus group investigate the role of cell surface and extracellular cues as well as their signaling pathways in tumorigenesis. This focus group will facilitate interactions among the Cancer Center Members that research similar biological processes in different types of cancer.

Tumor cells are influenced by their extracellular environment which can facilitate uncontrolled growth, invasion and metastasis. The cues that regulate tumor cells include growth factors, cell adhesion molecules and extracellular matrix proteins. In most tumor cells, growth factor signaling is constitutively active indicating its importance to tumorigenesis. These types of molecules may be produced by the tumor cells themselves or synthesized by the surrounding stromal cells in their local environment.

These extracellular or cell surface cues converge on various signaling pathways to regulate cell adhesion, growth and migration. The ability of tumor cells not only to recognize these cues but to alter their surrounding environment is key to both migration and invasion which are prerequisites for metastasis. Improved clinical treatment and the creation of novel therapeutics require that we understand the basic signaling pathways that regulate metastatic progression.

Program Members

Derek Abbott, MD, PhD
Assistant Professor, Pathology
Derek.Abbott@case.edu

Fadi W. Abdul-Karim, MD
Professor, Pathology
karimf@ccf.org

Suneel S. Apte, MBBS, DPhil
Associate Professor, Biomedical Engineering
aptes@ccf.org

Susann M. Brady-Kalnay, PhD
Professor, Molecular Biology & Microbiology
smb4@case.edu

Matthias Buck, PhD
Associate Professor, Physiology & Biophysics
mxb150@case.edu

Cathleen R. Carlin, PhD
Professor, Molecular Biology and Microbiology
cxc39@case.edu

Ronald A. Conlon, PhD
Associate Professor, Genetics
ronald.conlon@case.edu

Analisa DiFeo, PhD
Assistant Professor, General Medical Sciences (Oncology)
analisa.difeo@case.edu

Thomas T. Egelhoff, PhD
Professor, Cell Biology
tte@case.edu

Rob Ewing, PhD
Assistant Professor, Center for Proteomics and Bioinformatics
robert.ewing@case.edu

Paul L. Fox, PhD
Professor, Cell Biology
foxp@ccf.org

Thomas A. Gerken, PhD
Professor, Pediatrics
thomas.gerken@case.edu

Candece L. Gladson, MD
Professor, Cancer Biology
gladsoc@ccf.org

Anton V. Gorbachev, PhD
Instructor, Immunology
gorbaca@ccf.org

Edward M. Greenfield, PhD
Professor, Orthopaedics
emg3@case.edu

Dolores Hambardzumyan, PhD
Assistant Professor, Stem Cell Biology and Regenerative Medicine
hambard@ccf.org

Thomas A. Hamilton, PhD
Professor, Immunology
hamiltt@ccf.org

Anita B. Hjelmeland, PhD
Assistant Professor, Stem Cell Biology and Regenerative Medicine
hjelmea@ccf.org

Mukesh K. Jain, MD
Professor, Medicine-Cardiology
mukesh.jain2@case.edu

Hung-Ying Kao, PhD
Professor, Biochemistry
hxk43@case.edu

Ruth A. Keri, PhD
Associate Professor, Pharmacology
rak5@case.edu

Justin D. Lathia, PhD
Assistant Professor, Cell Biology
lathiaj@ccf.org

Jeongwu Lee, PhD
Assistant Professor, Stem Cell Biology and Regenerative Medicine
leej7@ccf.org

Alan D. Levine, PhD
Professor, Medicine-Gastroenterology
adl4@case.edu

Xiaoxia Li, PhD
Professor, Immunology
lix@ccf.org

Danny Manor, PhD
Associate Professor, Nutrition
danny.manor@case.edu

Keith R. McCrae, MD
Professor, Hematologic Oncology and Blood Disorders
mccraek@ccf.org

Christine L. McDonald, PhD
Assistant Professor, Pathobiology
mcdonac2@ccf.org

Robert H. Miller, PhD
Professor, Neurosciences
rhm3@case.edu

Saurav Misra, PhD
Assistant Professor, Molecular Cardiology
misras@ccf.org

Monica M. Montano, PhD
Associate Professor, Pharmacology
mxm126@case.edu

Marvin T. Nieman, PhD
Assistant Professor, Pharmacology
nieman@case.edu

Noa Noy, PhD
Professor, Pharmacology
noa.noy@case.edu

Edward F. Plow, PhD
Professor, Molecular Cardiology
plowe@ccf.org

Jun Qin, PhD
Professor, Molecular Cardiology
qinj@ccf.org

Diana L. Ramirez-Bergeron, PhD
Assistant Professor, Medicine-Cardiology
diana.ramirez@case.edu

Jeremy N. Rich, MD
Professor, Stem Cell Biology and Regenerative Medicine
richj@ccf.org

Steven S. Rosenfeld, MD, PhD
Professor, Cancer Biology
rosenfs@ccf.org

Takao Sakai, MD, PhD
Assistant Professor, Biomedical Engineering
sakait@ccf.org

William P. Schiemann, PhD
Associate Professor, General Medical Sciences-Oncology
william.schiemann@case.edu

Alvin H. Schmaier, MD
Professor, Medicine-Hematology/Oncology
alvin.schmaier@case.edu

Ganes C. Sen, PhD
Professor, Molecular Genetics
seng@ccf.org

Khalid Sossey-Alaoui, PhD
Assistant Professor, Molecular Cardiology
sosseyk@ccf.org

George R. Stark, PhD
Professor, Molecular Genetics
starkg@ccf.org

Duncan Stearns, MD
Assistant Professor, Pediatrics-Hematology/Oncology
duncan.stearns@case.edu

Hoonkyo Suh, PhD
Assistant Professor, Stem Cell Biology and Regenerative Medicine
suhh2@ccf.org