Kolupaeva Lab - Microbiology

Victoria Kolupaeva, Ph.D.
Assistant Professor, Department of Microbiology

Medical Science Building, Office Rm. 228A, Lab Rm. 252
550 First Avenue
, New York, NY 10016
Lab: (212) 263-5331
Email: Victoria.Kolupaeva@nyumc.org

 

 

 

KEY INTERESTS:

Regulation of protein synthesis, cartilage, mesenchymal stem cells, cell lineage fate, chondrogenesis, osteoarthritis, skeletal development, fibroblast growth factors, tyrosine kinase receptors, growth factors/cytokines, Ser/Thr phosphatases.

BIOGRAPHIC DETAILS:

Graduate Education:

Ph.D. in Biochemistry in 1998, Moscow State University, Russia

Postdoctoral Training:

1998-2005 SUNY Downstate Medical Center, Brooklyn, NY
2005-2010 NYU School of Medicine

Academic Responsibilities:

2010 Research Assistant Professor of Microbiology
2014 Assistant Professor (Research) of Microbiology

RESEARCH INTERESTS:

My lab is studying cartilage tissue from a unique perspective – the regulation of protein synthesis. This approach allows investigation of the expression of specific proteins both independent of and dependent on changes at the transcriptional level and provides opportunity for rapid and selective interfering with protein expression at different pathological conditions. We have several ongoing projects in the laboratory.

Regulation of protein synthesis during chondrogenesis. Our group investigates how commitment of mesenchymal stem cells to specific differentiation programs is controlled by translational machinery. We have demonstrated that 4E-BP (the inhibitor of cap-dependent translation that binds eIF-4E cap binding proteins) governs the switch between bone and cartilage cells and we are currently investigating which specific of mRNAs are affected by 4E-BP expression during chondrogenesis. The understanding of molecular mechanisms responsible for chondrogenesis is indispensable for the stem cell-based tissue engineering in cartilage repair.

Translation control in the progression of osteoarthritis (OA). Using samples from the patients with OA we found that translation machinery in the OA cartilage is dysregelated when compared to normal cartilage. The activity of many signaling molecules important for protein synthesis (AKT, p70S6K kinase, eIF4E) was increased in OA cartilage. We are trying to understand how well known markers of OA (MMP13, ADAMTS5 etc.) utilize those changes during progression of OA. We are using an animal model and patient samples in our research. The translational potential of this project is immense and aims to bridge the gap between basic and clinical research.

Regulation of chondrocyte homeostatic by Fibroblast Growth Factors (FGFs.). While in most cell types FGFs induce proliferation and protect from apoptosis, chondrocytes are distinct in their response to FGF. We and others have shown that the major effect of FGF signaling in chondrocytes is growth-inhibition. We demonstrated that FGF inhibits protein synthesis, and this inhibition requires function of the translation repressor 4E-BP. Activation of 4E-BP is mediated by Protein Phosphates 2A (PP2A). Present work in the lab is directed to understand the mechanism of FGF-induced PP2A activation which allows PP2A to dominate over many active kinases including CDK4/Cyclin D1 and mTOR kinases. To characterize this unique aspect of chondrocyte biology we are applying a variety of novel approaches including SILAC (Stable Isotope Labeling by Amino acids in Cell culture) and ribosomal profiling.

 

PUBLICATIONS

 

LAB MEMBERS:


Rachel Ruoff
(research scientists; Rachel.Ruoff@nyumc.org)
 


Olga Katsara, PhD
(post-doc; Olga.Katsara@nyumc.org)
 

LAB NEWS:

April 17th, 2015: Rachel won the Best Poster Award at the CSCB 2015 Annual Retreat.
January 15th 2015: We welcome Olga, our new post-doc from Greece!