VICC toll-free number
1-877-936-8422

The VICC.ORG Directory of Doctors, Healthcare Providers & Researchers

Pran K. Datta, Ph.D.

Assistant Professor
VICC Member
Researcher

Contact Information:

Vanderbilt University Medical Center
D-2300 Medical Center North
Nashville, TN 37232-2733
615-343-8401

Research Specialty

Role of TGF-ß/Smad7/STRAP signaling in tumor suppression and promotion.

Research Description

Members of the TGF-ß family regulate a wide range of biological processes including cellular proliferation, cell migration, differentiation, apoptosis, and extracellular matrix deposition. The research in my laboratory focuses on the transforming growth factor-ß (TGF-ß) signal transduction pathways and the role of signaling molecules involved in these pathways in tumor suppression and promotion. Recently, we have cloned a novel WD-40 domain containing protein, called STRAP (Serine Threonine Kinase Receptor Associated Protein), that associates with both TGF-ß type I receptor (TßRI) and type II receptor (TßRII). STRAP is involved in the negative regulation of TGF-ß signaling. STRAP synergizes with Smad7, an inhibitory Smad, in the inhibition of TGF-ß-induced tumor suppressor functions. STRAP activates MAPK/ERK pathway, downregulats p21 Cip1, and C-terminus of STRAP is required for its phosphorylation and binding with two phospho-proteins. We have identified STRAP binding proteins by using Proteomics/Mass spectroscopy, and it will be interesting to determine the functional outcome of these interactions. Our long-term objective of this line of investigation is (1) to understand the role of STRAP in TGF-ß signaling, (2) to determine how this protein is involved in the crosstalk between TGF-ß and other signaling cascades and (3) to study the function of STRAP in vivo by Cre-lox targeted deletion of the STRAP gene .

We have observed that STRAP is upregulated in 45% of breast cancers, 70% of colorectal cancers and 75% of lung cancers. STRAP induces anchorage-independent growth and enhances tumorigenicity in nude mice. Overexpression of Smad7 in cell culture model blocks TGF-ß signaling and promotes cell proliferation. The expression of Smad7 is increased in human pancreatic cancer. The current studies address the following issues: (1) to determine the role of STRAP and Smad7 in cellular proliferation and tumorigenicity, (2) to study the contribution of functional synergy between STRAP and Smad7 in the progression of colorectal cancer and lung cancer, and (3) to study the effect of blocking TGF-ß signals in the intestine by conditionally knocking out TßRII. For this study we are using transgenic mice that carry a floxed TGF-ß RII gene.

Another focus of the lab is to understand the mechanism of downregulation of TßRII in human lung cancers that can be targeted by the inhibitors (that are in clinical trial) of epigenetic changes. We are also investigating in vivo the role of TGF-ß signaling in metastasis.

. . .

Publications


You do not have JavaScript enabled. This site works better with JavaScript turned on.