Visit the Ajit Lab.

Dr. Ajit's research focus is to understand the molecular mechanisms of pain with emphasis on epigenetics. She is interested in pursuing various aspects of epigenetics, such as DNA methylation, histone modifications and small noncoding RNAs called microRNAs (miRNAs).

Aberrant miRNA expression is a common feature in a variety of human diseases, thus providing avenues for the identification of biomarkers and new opportunities for the discovery and validation of novel therapeutic targets. Currently Dr. Ajit's lab is studying miRNA regulation and its utility as biomarkers in patients with complex regional pain syndrome (CRPS), a chronic neuropathic pain condition. The lab has identified several differentially expressed miRNAs, highlighting the potential utility of these miRNAs as biomarkers in grouping patients based on their disease etiology.

One mode of miRNAs transport in body fluids is via exosomes. Exosomes are small vesicles originating from the inward budding of the plasma membrane. They carry mRNAs and miRNAs to recipient cells with functional gene regulatory consequences via blood, indicating a new mechanism of intercellular communication. Intercellular communication was thought to be limited to gap junctions or secreted signals such as hormones and neurotransmitters. Interestingly, a majority of differentially expressed miRNAs identified in CRPS patients are present in exosomes. Dr. Ajit is studying the role of these miRNAs in exosome-mediated signal transduction in pain.

The lab is also extending its studies to rodent models of pain, since the patient population is heterogeneous in terms of genetics and prior treatments received. This will enable them to evaluate and confirm the feasibility of testing miRNA fingerprints after administering therapeutic agents and to develop rigorous translational approaches to predict utility for novel therapeutics and clinical response.

Dr. Ajit's lab is investigating alterations of key epigenetic regulators to understand the molecular changes underlying pain. A multi-pronged approach, combining next generation sequencing to characterize the epigenome with pharmacological and behavioral studies using rodent models of pain, is being pursued to elucidate the role of epigenetics in pain.

"Unlocking the Secrets of Pain"
College of Medicine Alumni Magazine (Fall/Winter 2016)

Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells
Shenoda BB, Ajit SK
Clin Med Insights Pathol; 9(Suppl 1):1-8. doi: 10.4137/CPath.S39925, September 14, 2016

Regulation of proinflammatory genes by the circulating microRNA hsa-miR-939
McDonald MK, Ramanathan S, Touati A, Zhou Y, Thanawala RU, Alexander GM, Sacan A, Ajit SK
Sci Rep; 6:30976. doi: 10.1038/srep30976, PMID: 27498764, Aug 8, 2016

Genome-wide redistribution of MeCP2 in dorsal root ganglia after peripheral nerve injury
Manners MT, Ertel A, Tian Y, Ajit SK
Epigenetics Chromatin; 9:23. doi: 10.1186/s13072-016-0073-5. eCollection 2016, Jun 7, 2016

Hsa-miR-34a mediated repression of corticotrophin releasing hormone receptor 1 regulates pro-opiomelanocortin expression in patients with complex regional pain syndrome
Shenoda BB, Alexander GM, Ajit SK
Journal of Translational Medicine; 14(1):64, 2016

MicroRNA-Based Biomarkers in Pain
Ramanathan S, Ajit SK
Advances in Pharmacology (San Diego, Calif.); 75:35-62, 2016

Book chapter: Epigenetics and personalized pain management
Ajit, SK
In: “Personalized Epigenetics,” Elsevier Press, Editor: Trygve Tollefsbol, Pages 389–427, 2015

MicroRNAs downregulated in neuropathic pain regulate MeCP2 and BDNF related to pain sensitivity
Manners MT, Tian Y, Zhou Z, Ajit SK
FEBS Open Bio; 5:733-40. doi: 10.1016/j.fob.2015.08.010. eCollection 2015, Aug 31, 2015

Circulating microRNA Signatures in Rodent Models of Pain
Qureshi RA, Tian Y, McDonald MK, Capasso KE, Douglas SR, Gao R, Orlova IA, Barrett JE, Ajit SK, Sacan A
Mol Neurobiol. [Epub ahead of print] Jun 18, 2015

Analgesic Response to Intravenous Ketamine Is Linked to a Circulating microRNA Signature in Female Patients With Complex Regional Pain Syndrome
Douglas SR, Shenoda BB, Qureshi RA, Sacan A, Alexander GM, Perreault M, Barrett JE, Aradillas-Lopez E, Schwartzman RJ, Ajit SK
J Pain; 16(9):814-24. doi: 10.1016/j.jpain.2015.05.008. (Epub Jun 11, 2015 ) Sep 2015

MicroRNA biology and pain
McDonald MK, Ajit SK
Prog Mol Biol Transl Sci.; 131:215-49. doi: 10.1016/bs.pmbts.2014.11.015. Review, Epub Feb 15, 2015

Effect of histone deacetylase inhibitor JNJ-26481585 in pain
Capasso KE, Manners MT, Quershi RA, Tian Y, Gao R, Hu H, Barrett JE, Sacan A, Ajit SK
J Mol Neurosci.; 55(3):570-8. doi: 10.1007/s12031-014-0391-7. (Epub Aug 2, 2014) Mar 2015

Functional significance of macrophage-derived exosomes in inflammation and pain
McDonald MK, Tian Y, Qureshi RA, Gormley M, Ertel A, Gao R, Aradillas Lopez E, Alexander GM, Sacan A, Fortina P, Ajit SK
Pain.; 155(8):1527-39. doi: 10.1016/j.pain.2014.04.029. (Epub Apr 30, 2014) Aug 2014

Purification and microRNA profiling of exosomes derived from blood and culture media
McDonald MK, Capasso KE, Ajit SK
J Vis Exp; (76):e50294. doi: 10.3791/50294, Jun 14, 2013

Circulating microRNAs as biomarkers, therapeutic targets, and signaling molecules
Ajit SK
Sensors (Basel).;12(3):3359-69. doi: 10.3390/s120303359. Review (Epub Mar 8, 2012) 2012

MicroRNA modulation in complex regional pain syndrome
Orlova IA, Alexander GM, Qureshi RA, Sacan A, Graziano A, Barrett JE, Schwartzman RJ, Ajit SK
J Transl Med.; 9:195. doi: 10.1186/1479-5876-9-195, Nov 10, 2011

Dynamic changes in the microRNA expression profile reveal multiple regulatory mechanisms in the spinal nerve ligation model of neuropathic pain
von Schack D, Agostino MJ, Murray BS, Li Y, Reddy PS, Chen J, Choe SE, Strassle BW, Li C, Bates B, Zhang L, Hu H, Kotnis S, Bingham B, Liu W, Whiteside GT, Samad TA, Kennedy JD, Ajit SK
PLoS One.;6(3):e17670. doi: 10.1371/journal.pone.0017670, Mar 14, 2011

Development of a FLIPR assay for the simultaneous identification of MrgD agonists and antagonists from a single screen
Ajit SK, Pausch MH, Kennedy JD, Kaftan EJ
J Biomed Biotechnol.; 2010. pii: 326020. doi: 10.1155/2010/326020. Epub Sep 14, 2010

The molecular basis of pain and its clinical implications in rheumatology
Bingham B, Ajit SK, Blake DR, Samad TA
Nat Clin Pract Rheumatol.; 5(1):28-37. doi: 10.1038/ncprheum0972. Review, Jan 2009

MrgD activation inhibits KCNQ/M-currents and contributes to enhanced neuronal excitability
Crozier RA, Ajit SK, Kaftan EJ, Pausch MH
J Neurosci.; 27(16):4492-6, Apr 18, 2007

RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling
Ajit SK, Ramineni S, Edris W, Hunt RA, Hum WT, Hepler JR, Young KH
<Cell Signal.; 19(4):723-30. (Epub Oct 7, 2006) Apr 2007

Use of a murine cell line for identification of human nitric oxide synthase inhibitors
Naureckiene S, Edris W, Ajit SK, Katz AH, Sreekumar K, Rogers KE, Kennedy JD, Jones PG
J Pharmacol Toxicol Methods.; 55(3):303-13. (Epub Aug 2006) May-Jun 2007

Analysis of chimeric RGS proteins in yeast for the functional evaluation of protein domains and their potential use in drug target validation
Ajit SK, Young KH
Cell Signal.; 17(7):817-25. Epub Dec 10, 2004) Jul 2005

Enhancement of pheromone response by RGS9 and Gbeta5 in yeast
Ajit SK, Young KH
Biochem Biophys Res Commun.; 324(2):686-91, Nov 12, 2004

Yeast-based screening for inhibitors of RGS proteins
Young KH, Wang Y, Bender C, Ajit S, Ramirez F, Gilbert A, Nieuwenhuijsen BW
Methods Enzymol.; 389:277-301, 2004