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Ashok Kulkarni, Ph.D.

Ashok Kulkarni, Ph.D.Senior Investigator
Chief, Functional Genomics Section
Manager, Gene Transfer Core

BETHESDA MD 20892-4395

Phone: (301) 435-2887
Fax: (301) 435-2888

Biographical Sketch

Dr. Kulkarni received his Ph.D. from M.S. University in Baroda, India. He served as a postdoctoral fellow at Columbia University, NY, from 1982-1987, and then as a senior staff fellow in NINDS at NIH from 1987-1995. In 1995, he joined NIDCR as a tenure track investigator to head the Functional Genomics Unit and the Gene Transfer Facility, and in 2000 he was tenured as a senior investigator and appointed chief of the Functional Genomics Section in the NIDCR. His laboratory studies the molecular mechanisms involved in cancer and pain affecting the oral and craniofacial areas. He continues to serve as manager of the Gene Transfer Facility, which provides research and technical services to generate and preserve genetically engineered mouse models for the investigators in the Division of Intramural Research of NIDCR. He is a member of the American Association of Dental Research, the International Association of Dental Research, the Society for Neuroscience, and the International Association for the Study of Pain. He currently serves as a reviewer for numerous scientific journals, and as an editorial board member for The Journal of Dental Research and Neurochemical Research.

Honors and Awards (selected):

1993 Henry Christian Award, American Federation for Clinical Research and Merck Foundation, Washington, DC.
1998 NIDR, Outstanding Contributions to the Programs and Objectives of NIDR
2004 NIDCR EEO Diversity Achievement Award

Invited Presentations (selected):

2006 Cdk5: a key player brain development and disease. Univ. of Otago, Dunedin, New Zealand
2007 Cdk5: from brain to pain. Croucher Symposium, The Hong Kong University of Science and Technology, Hong Kong.
2008 Cdk5: Key regulator in pain signaling. Univ. Maryland Dental School, Baltimore, MD.
2009 Cdk5 in pain signaling. Cdk5 Symposium, Tokyo, Japan. Molecular roles of Cdk5 in neuronal functions. XXIII Annual Meeting of Chilean Society of Cell Biology, Pucon, Chile.

Research Interests/Scientific Focus

Our research focuses on characterizing TGF-ß and Cdk5 signaling pathways and their crosstalk. Our research efforts are mainly centered on delineating how these signaling pathways affect disease processes that cause inflammation and fibrosis of salivary glands, promote tumor growth in the head and neck region, and affect neuronal functions that cause inflammatory pain in the body, particularly in the craniofacial region. In order to investigate the mechanisms and crosstalk between these pathways, we have used an array of molecular approaches. These approaches include conventional and conditional gene targeting coupled with genomic and proteomic analysis. Our present studies will not only contribute to a greater understanding of the molecular roles of TGF‑ß and Cdk5 in development and disease, but should also help future efforts to effectively treat many disorders.

We have recently discovered that (a) conditional overexpression of active TGF-ß1 disrupts  mouse salivary gland development and function, (b)  conditional deletion of TGF-ß signaling in murine head and neck epithelia and subsequent DMBA treatment leads to  progressive tumor formation with activation of the PI3K/Akt pathway, (c)  compound deletion of TGF-ß receptor 1 and PTEN genes in oral epithelium results in spontaneous and rapid  HNSCC with complete penetrance, (d) TNF-α is a key regulator of Cdk5 activity during pain signaling through transcriptional activation of p35, (e) resveratrol, a known analgesic, inhibits Cdk5 activity by  modulating p35 expression, and (f) active crosstalk between the TGF- ß and Cdk5 pathways mediates inflammatory pain signaling.  We continue characterizing modulators of Cdk5 activity in inflammatory pain, and newly identified potential Cdk5 substrates for their involvement in pain signaling. We will extend our current studies to analyze the role of Cdk5 in craniofacial pain. Particularly, we will delineate the precise nature of the crosstalk between TGF-ß and Cdk5 and how it affects disease processes.  

Selected Publications

  1. Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S. 1993. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci U S A. 90(2): 770-774.
  2. Ohshima T, Ward JM, Huh CG, Longenecker G, Veeranna, Pant HC, Brady RO, Martin LJ, Kulkarni AB. 1996. Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc Natl Acad Sci U S A. 93(20): 11173-11178.
  3. Ohshima T, Murray GJ, Swaim WD, Longenecker G, Quirk JM, Cardarelli CO, Sugimoto Y, Pastan I, Gottesman MM, Brady RO, Kulkarni AB. 1997. alpha-Galactosidase A deficient mice: a model of Fabry disease. Proc Natl Acad Sci U S A. 94(6): 2540-2544.
  4. Gibson CW, Yuan ZA, Hall B, Longenecker G, Chen E, Thyagarajan T, Sreenath T, Wright JT, Decker S, Piddington R, Harrison G, Kulkarni AB. 2001. Amelogenin-deficient mice display an amelogenesis imperfecta phenotype. J Biol Chem. 276(34): 31871-31875.
  5. Tanaka T, Veeranna, Ohshima T, Rajan P, Amin ND, Cho A, Sreenath T, Pant HC, Brady RO, Kulkarni AB. 2001. Neuronal cyclin-dependent kinase 5 activity is critical for survival.. J Neurosci. 21(2): 550-558.
  6. Sreenath T, Thyagarajan T, Hall B, Longenecker G, D'Souza R, Hong S, Wright JT, MacDougall M, Sauk J, Kulkarni AB. 2003. Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III.J Biol Chem. 278(27): 24874-24880.
  7. Hirasawa M, Ohshima T, Takahashi S, Longenecker G, Honjo Y, Veeranna, Pant HC, Mikoshiba K, Brady RO, Kulkarni AB. 2004. Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects. Proc Natl Acad Sci U S A. 101(16): 6249-6254.
  8. Pareek TK, Keller J, Kesavapany S, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB. 2006. Cyclin-dependent kinase 5 activity regulates pain signaling. Proc Natl Acad Sci U S A. 103(3): 791-796.
  9. 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. 2007. Female mice are more susceptible to developing inflammatory disorders due to impaired transforming growth factor beta signaling in salivary glands. Arthritis Rheum. 56(6): 1798-1805.
  10. 10.  Pareek TK, Keller J, Kesavapany S, Agarwal N, Kuner R, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB. 2007. Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1.Proc Natl Acad Sci U S A. 104(2): 660-665.
  11. Utreras E, Futatsugi A, Rudrabhatla P, Keller J, Iadarola MJ, Pant HC, Kulkarni AB.2009. Tumor necrosis factor-alpha regulates cyclin-dependent kinase 5 activity during pain signaling through transcriptional activation of p35. J Biol Chem. 284(4):2275-84.
  12. Utreras E, Terse A, Keller J, Iadarola M, and Kulkarni AB. 2011.Resveratrol inhibits Cdk5 activity through regulation of p35 expression. Molecular Pain 7 (1): 49 doi:10.1186/1744-8069-7-49
  13. Bian Y, Hall B, Sun ZJ, Molinolo A, Chen WJ,  Gutkind  JS, Van Waes C, Kulkarni AB. 2011. Loss of TGF-β signaling and PTEN promotes head and neck squamous cell carcinoma through cellular senescence evasion and cancer-related inflammation. Oncogene 2011 Oct. 31:10.1038/onc.2011.494 (Epublished ahead of print).
  14. Utreras E, Keller J, Terse A, Prochazkova M, Iadarola MJ, Kulkarni AB. 2012. Transforming Growth Factor-β1 Regulates Cdk5 Activity in Primary Sensory Neurons. J. Biol. Chem. 11 (20): 16917-16927.
  15. Prochazkova M, Terse A, Amin ND, Hall B, Utreras E, Pant HC, Kulkarni AB. 2013. Activation of cyclin-dependent 5 mediates orofacial mechanical hyperalgesia. Mol Pain 9(1): 66.




  • United States Patent US 003495 and 129515. Modulation of the TGF-beta And P13K/AKT Pathways in the diagnosis and treatment of squamous cell carcinoma  


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This page last updated: May 28, 2014