Functional Genomics Section
Director, Gene Transfer Facility
Building 30, Room 130
30 Convent Dr MSC 4395
Bethesda, MD 20892-4395
Dr. Ashok Kulkarni’s research focuses on characterizing the molecular role of Cdk5 in orofacial pain. His laboratory has shown that the activity of Cdk5 is upregulated due to inflammation that, in turn, modulates peripheral pain signaling. Current research efforts are centered on delineating how Cdk5 and its two activators, p35 and p39, affect pain signaling specifically in the orofacial region. Orofacial pain differs from peripheral pain because the dense innervation of facial structures leads to increased sensitivity to pain, which makes orofacial pain difficult to diagnose and treat. His group uses an array of approaches to investigate the molecular mechanisms involved in how Cdk5 activity modulates orofacial pain signaling. Their research approaches include using genetically engineered mouse models for behavioral, genomic and proteomic analyses. Their current studies will contribute to a greater understanding of the molecular roles of Cdk5 in pain signaling, and also help future efforts to effectively treat pain.
- Rozas P, Lazcano P, Pina R, Cho A, Terse A, Pertusa M, Madrid R, Gonzales-Billault C, Kulkarni AB, Utreras, E. Targeted overexpression of Tumor Necrosis Factor-α increases Cdk5 activity and TRPV1-dependent Ca+ influx in trigeminal neurons. Pain. 2016 Jun;157(6):1346-62.
- Jendryke T, Prochazkova M, Hall BE, Nordmann GC, Schladt M, Milenkovic VM, Kulkarni AB, Wetzel, CH. TRPV1 function is modulated by Cdk5-mediated phosphorylation: insights into the molecular mechanism of nociception. Sci. Rep. 2016 Feb 23;6:22007.
- Hall BE, Zhang L, Sun ZJ, Utreras E, Prochazkova M, Cho, A, Terse A, Dolan JC, Schmidt BL, Kulkarni AB. Conditional TNF-a overexpression in the tooth and alveolar bone results in painful pulpitis and osteitis. J. Dent Res. 2016 Feb;95(2):188-95.
- Prochazkova M, Terse A, Amin ND, Hall B, Utreras E, Pant HC, Kulkarni AB. Activation of cyclin-dependent 5 mediates orofacial mechanical hyperalgesia. Mol Pain. 2013 Dec 21;9: 66.
- Utreras E, Keller J, Terse A, Prochazkova M, Iadarola MJ, Kulkarni AB. Transforming Growth Factor-β1 Regulates Cdk5 Activity in Primary Sensory Neurons. J. Biol. Chem. 2012 May 11;287(20): 16917-29.
- Utreras E, Terse A, Keller J, Iadarola M, and Kulkarni AB. Resveratrol inhibits Cdk5 activity through regulation of p35 expression. Mol Pain. 2011 Jul 7;7:49
- Utreras E, Futatsugi A, Rudrabhatla P, Keller J, Iadarola MJ, Pant HC, Kulkarni AB. Tumor necrosis factor-alpha regulates cyclin-dependent kinase 5 activity during pain signaling through transcriptional activation of p35. J Biol Chem. 2009 Jan 23;284(4):2275-84.
- Pareek TK, Keller J, Kesavapany S, Agarwal N, Kuner R, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB. Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2): 660-665.
- Nandula SR, Amarnath S, Molinolo A, Bandyopadhyay BC, Hall B, Goldsmith CM, Zheng C, Larsson J, Sreenath T, Chen W, Ambudkar IS, Karlsson S, Baum BJ, Kulkarni AB. Female mice are more susceptible to developing inflammatory disorders due to impaired transforming growth factor beta signaling in salivary glands. Arthritis Rheum. 2007 June;56(6): 1798-1805.
- Pareek TK, Keller J, Kesavapany S, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB. Cyclin-dependent kinase 5 activity regulates pain signaling. Proc Natl Acad Sci U S A. 2006 Jan 17;103(3): 791-796.