Leaders

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

Summary

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).

This focus group brings together basic and physician scientists with a common interest in 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 later stages of disease, biologically active TGFβ, often produced by cancer cells, can aid tumor growth and metastasis through its ability to suppress immune cells, enhance angiogenesis, promote matrix production and induce cancer cell migration. At late times, most tumors become refractory to the growth inhibitory effects of the cytokine, often through mechanisms involving the down-regulation of expression of TGFβ receptors at the cell surface.

TLRs, key components in generating immune and inflammatory responses, recognize pathogen-associated molecules, leading to the production of pro-inflammatory cytokines, which further up-regulate the expression of inflammatory genes at both transcriptional and posttranscriptional levels. While the TLR- and cytokine-mediated inflammatory responses are critical for innate immunity and host defense against infections, uncontrolled inflammation is detrimental to the host, leading to chronic inflammatory diseases. It is now commonly accepted that chronic inflammation contributes to tumor promotion and progression. New insight about TLR- and cytokine-mediated regulatory mechanisms can lead to strategies to limit the production of harmful toxins, resulting in better resolution of inflammatory diseases. Activation of TLRs leads to activation of NFκB and production of type I interferons, which are additional major topics within the focus group.

Signal transduction is the process through which stimuli in the external milieu of a cell are first detected by a cell surface receptor, and then interpreted within the cell, through a series of biochemical events, resulting most often in changes in gene expression. STATs and NFκB transmit this information, and their dysregulation can contribute to cell transformation and unregulated cell growth. The STATs function as transcription factors in response to a wide range of environmental stimuli, including the interferon family of cytokines. Members of this focus group investigate the function of STATs family tumorigenesis and in the setting of inflammatory stimulation of carcinogenesis.

Program Activities

Members

Jill S. Barnholtz-Sloan, PhD
Associate Professor, General Medical Sciences (Oncology)
jsb42@case.edu

Ernest C. Borden, MD
Professor, Translational Hematology and Oncology Research
bordene@ccf.org

Clemencia Colmenares, PhD
Professor, Cancer Biology
colmenc@ccf.org

David Danielpour, PhD
Professor, General Medical Sciences (Oncology)
dxd49@case.edu

Afshin Dowlati, MD
Associate Professor, Medicine-Hematology/Oncology
axd44@case.edu

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

Saikh Jaharul Haque, PhD
Assistant Professor, Cancer Biology
haquej@ccf.org

Janet A. Houghton, PhD
Professor, Cancer Biology
houghtj@ccf.org

Eckhard Jankowsky, PhD
Professor, Biochemistry
exj13@case.edu

Ge Jin, PhD
Assistant Professor, Biological Sciences
ge.jin@case.edu

Jeffrey A. Kern, MD
Professor, Medicine-Pulmonary & Critical Care
jeffrey.kern@UHhospitals.org

John J. Letterio, MD
Professor, Pediatric Hematology/Oncology
john.letterio@UHhospitals.org

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

Li Li, MD, PhD
Associate Professor, Family Medicine
lxl62@case.edu

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

Sanford D. Markowitz, MD, PhD
Professor, Medicine-Hematology/Oncology
sxm10@case.edu

John J. Pink, PhD
Assistant Professor, General Medical Sciences (Oncology)
john.pink@case.edu

Cheng-Kui Qu, MD, PhD
Associate Professor, Medicine-Hematology/Oncology
cxq6@case.edu

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

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

Andrew E. Sloan, MD
Associate Professor, Neurological Surgery
andrew.sloan@UHhospitals.org

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

Edward Stavnezer, PhD
Professor, Biochemistry
exs44@case.edu

Saba Valadkhan, MD, PhD
Assistant Professor, RNA Molecular Biology
saba.valadkhan@case.edu

Guang Zhou, PhD
Assistant Professor, Orthopaedics
guang.zhou@case.edu

Yu-Chung Yang, PhD
Professor, Biochemistry
yxy36@case.edu

Qing Yin Zheng, MD
Associate Professor, Otolaryngology
qyz@case.edu