Visit the Ajit Lab.

Dr. Ajit's research focus is to understand the molecular mechanisms of pain with emphasis on epigenetics.

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 their utility as biomarkers in patients with complex regional pain syndrome (CRPS), a chronic neuropathic pain condition. The lab has identified several differentially expressed miRNAs in CRPS patients, highlighting the potential utility of these miRNAs as biomarkers to group patients based on their disease etiology. We are evaluating the feasibility of testing miRNA fingerprints after administering therapeutic agents, with the goal of developing rigorous translational approaches to predict utility for novel therapeutics and clinical response.

One mode of miRNA transport in body fluids is via exosomes. Exosomes are small extracellular vesicles originating from the inward budding of the plasma membrane. They carry mRNAs and miRNAs to recipient cells via circulation, with functional gene regulatory consequences. However, exosomes do not incorporate everything that is present in the parent cell, suggesting that this well-regulated process is dynamically altered by signaling cues. Thus, the composition of these vesicles varies depending on the source, the physiological conditions of cells releasing them and disease states. Exosome uptake results in modulation of gene expression in recipient cells and represents a novel mechanism of cellular communication. We are investigating alterations in composition, function and signaling mechanisms of small extracellular vesicles using in vitro approaches and rodent models of pain.

Therapeutic and prophylactic effects of macrophage-derived small extracellular vesicles in the attenuation of inflammatory pain
Jean-Toussaint R, Lin Z, Tian Y, Gupta R, Pande R, Luo Z, Hu H, Sacan A, Ajit SK
Brain Behav Immun. :S0889-1591(21)00047-7. doi: 10.1016/j.bbi.2021.02.005. Online ahead of print. 2021 Feb 16

Xist attenuates acute inflammatory response by female cells
Shenoda BB, Ramanathan S, Gupta R, Tian Y, Jean-Toussaint R, Alexander GM, Addya S, Somarowthu S, Sacan A, Ajit SK
Cell Mol Life Sci., doi: 10.1007/s00018-020-03500-3. [Epub ahead of print], Mar 19, 2020, PMID: 32193609

Proteome characterization of small extracellular vesicles from spared nerve injury model of neuropathic pain
Jean-Toussaint R, Tian Y, Chaudhuri AD, Haughey NJ, Sacan A, Ajit SK
J Proteomics.; 211:103540. doi: 10.1016/j.jprot.2019.103540 [Epub 2019 Oct 24]. Jan 16, 2020, PMID: 31669360

Inflammation potentiates miR-939 expression and packaging into small extracellular vesicles
Ramanathan S, Shenoda BB, Lin Z, Alexander GM, Huppert A, Sacan A, Ajit SK
J Extracell Vesicles.; 8(1):1650595. doi: 10.1080/20013078.2019.1650595. eCollection 2019, Aug 6, 2019, PMID: 31489147

Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchange
Ramanathan S, Douglas SR, Alexander GM, Shenoda BB, Barrett JE, Aradillas E, Sacan A, Ajit SK
J Transl Med.; 17(1):81. doi: 10.1186/s12967-019-1833-3, Mar 14, 2019, PMID: 30871575

miR-34a-mediated regulation of XIST in female cells under inflammation
Shenoda BB, Tian Y, Alexander GM, Aradillas-Lopez E, Schwartzman RJ, Ajit SK
J Pain Res.; 11:935-945. doi: 10.2147/JPR.S159458. eCollection 2018, May 8, 2018, PMID: 29773953

Complex regional pain syndrome - phenotypic characteristics and potential biomarkers
Birklein F, Ajit SK, Goebel A, Perez RSGM, Sommer C
Nat Rev Neurol.; 14(5):272-284. doi: 10.1038/nrneurol.2018.20. Epub 2018 Mar 16. Review, May 2018, PMID: 29545626

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, PMID: 27498764

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, PMID: 27279901

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, PMID: 26940669

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, PMID: 26448907

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, PMID: 26081151

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, PMID: 26072390

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, PMID: 25085711

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, PMID: 24792623

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, PMID: 22074333