Nickolai Dulin, Ph.D.

APPOINTMENTS

  • Associate Professor, Department of Medicine- Section of Pulmonary and Critical Care Medicine, Cancer Research Center, Committee on Cancer Biology, Committee on Molecular Medicine/MPMM, Committee on Cellular and Molecular Physiology

EDUCATION

Ph.D., Moscow State University, 1991

M.S., Moscow State University, 1987

CONTACT INFORMATION

The University of Chicago
5841 S. Maryland Ave.
AMB M648
Chicago, IL  60637

ndulin@medicine.bsd.uchicago.edu

Phone: (773) 702-5198

Webpage (Cell Phys)

RESEARCH SUMMARY

TGF-beta and G Protein Coupled Receptor (GPCR) Signaling

Myofibroblasts, characterized by expression of smooth muscle (SM)-alpha-actin, extracellular matrix proteins and pro-fibrotic factors, are invariably found in fibrotic and stromal tissues and are believed to play important role in the pathogenesis of fibrosis and cancer progression. Transforming growth factor-beta (TGF-beta) is the most established pro-fibrotic mediator of myofibroblast differentiation.  We and others have described a complex signaling mechanism for TGF-beta-induced myofibroblast differentiation, involving Smad-dependent expression of various G protein coupled receptor (GPCR)-activating signaling molecules, subsequent activation of Rho small GTPases and recruitment of serum response factor (SRF) transcription factor. Our current studies focus on the further understanding this mechanism and on regulation of the above pathway by targeting G protein signaling, actin and microtubule dynamics, and of SRF-dependent gene transcription, with the goal of attenuating myofibroblast differentiation in vitro and in animal models.

Regulators of G protein Signaling (RGS) proteins represent another subject of our studies. The established function of RGS proteins is to inactivate the alpha subunits of heterotrimeric G proteins and to control the signaling mediated by various G protein-coupled receptors. We have found that one of the RGS family members, RGS3, non-canonically interacts with Smad transcription factors and inhibits  TGF-beta signaling. Our current studies using knockdown and knockout approaches suggest a critical role of RGS3 in control of T cell-mediated inflammation and of epithelial-to-mesenchymal transition (EMT) of cancer cells.  Furthermore, we identified novel interactions of RGS3 with signaling molecules controlling cell growth and differentiation, the functional significance of which is under investigation.

Research Papers in PubMed