Molecular Oncology Program, Molecular Signaling Research interests: Functions of cGMP-dependent protein kinase (PKG, cGK) in inflammation and cancer 1120 15th Street CB 2605 Augusta, GA 30912 Office: (706) 721-9526 E-mail:

Browning, Darren, Ph.D.

Dr. Darren Browning

Browning, Darren, Ph.D.
Department Director, Graduate Program in Biochemistry and Cancer Biology

Member, Tumor Signaling & Angiogenesis Program
Professor, Graduate Studies
Professor, Biochemistry and Molecular Biology
GRU Cancer Center


1120 15th Street, CN 1164
Phone: (706) 721-9526

IFL Link | PubMed Link


Professional Overview

Darren Douglas Browning, Ph.D. is an Associate Professor in the Department of Biochemistry and Molecular Biology in the Medical College of Georgia at GRU and is Director of the Graduate Program in Biochemistry and Cancer Biology. Dr. Browning earned his Ph.D. (1995) from the University of Toronto (Canada), and did his post-doctoral work at The Scripps Research Institute (La Jolla, CA).


Current Research

Dr. Browning studies processes regulated by the cGMP signaling axis using classical biochemical, cell and molecular approaches. His research focus is on ulcerative colitis and colorectal cancer.

Dr. Browning has been characterizing signaling by the cGMP-dependent protein kinases (PKG) in colon cancer cells using in vitro and xenograft systems. His work has demonstrated that type 1 PKG expression blocks colon tumor growth and angiogenesis by inhibiting adaptation to hypoxia. The b-catenin/TCF pathway is a central driver of tumorigenesis in the colon, and PKG1 inhibits this at two stages: (1) by suppressing the CTNNb1 gene (b-catenin); and (2) by activating FoxO, which competes with TCF for the pivotal coactivator b-catenin. PKG1 inhibits adaptation to hypoxia by blocking hypoxia inducible factor (HIF) transcription activity. HIF plays and essential role in angiogenesis and metastasis of colon cancer cells, and understanding how PKG1 blocks this pathway is an important focus. The ability to block key cancer pathways forces cancer cells to suppress PKG1 expression, and efforts are underway to understand the mechanism of PKG1 silencing. Type 2 PKG is well established as a regulator of solute balance in the intestinal epithelium. The Browning team has been characterizing Prkg2 knockout mice, which exhibit increased epithelial apoptosis, crypt hyperplasia, and reduced secretory cell differentiation. To better understand how cGMP/PKG2 signaling regulates homeostasis in the colon, gene-array studies were used to identify cJun N-terminal kinase (JNK) as a key target. Activation of PKG2 suppresses this stress pathway by upregulating the JNK-inhibitory dual specificity phosphatase DUSP10.

The Browning laboratory has also been exploring the use of phosphodiesterase-5 (PDE-5) inhibitors to activate cGMP/PKG signaling in the colon for the prevention and treatment of colitis and colon cancer. Treatment of mice with the FDA-approved PDE-5 inhibitor Vardenafil (Levitra®) was shown to increase cGMP accumulation in the colon mucosa. Activation of cGMP signaling using this approach reduced basal apoptosis in the luminal epithelium, suppressed proliferation in the crypts, and increased the density of protective goblet cells. These homeostatic effects of cGMP are mediated by PKG2 since Vardenafil was ineffective in Prkg2 knockout mice. Treatment of mice with Vardenafil makes them more resistant to experimental colitis, and it is predicted that PDE-5 inhibitors will be effective agents for colon cancer chemoprevention.