Profiles

W. Keith Jones, PhD

Research Interests

Dr. Jones' laboratory studies the molecular basis of cardiovascular disease and molecular interventions designed as therapeutic measures. Cardiovascular disease remains the number one cause of death in developed countries despite decades of research into the environmental and molecular causation.

Previous work in the lab has elucidated a gene network comprised of 238 genes activated or repressed by the transcription factor NF-?B. Interestingly, most of these genes are regulated by a set of only nine microRNAs (mRNAs). miRNAs are small non-coding RNA molecules that regulate gene products primarily at the post-transcriptional. This suggests that these nine miRNAs are important regulatory nodes and play important roles in this gene network. Interestingly, mRNAs can be manipulated by transfection with mimics (gain of function), and antagomirs (loss of function) and such an approach can be used to dissect the role of each miRNA in gene regulation, cardioprotection, and post-myocardial infarction ventricular function and remodeling. Some of the miRNAs may be, or may point towards key players in the genetic pathway that underlie cardioprotection and beneficial ventricular remodeling, and thus development of new therapeutic targets. We are also investigating the possibility that manipulation of these miRNA pathways can be used to extend the life, or modify the reparative properties of stem cells used in the heart after heart attack. RNA therapeutics are also under development, and being investigated as biomarkers. Lately we have shown that miRNAs carried in exosomes and released from stem cells are taken up and affect gene regulation in cardiac recipient cells, with potent effects upon myocardial infarction. We are currently investigating ways to engineer these exosomes as tools for discovery and as therapeutics..

1. Molecular basis of NF-?B-dependent genes and microRNAs in cardioprotection and in stem cell based tissue repair. Aims,
   1. Elucidate the role of microRNAs in regulating the levels and activity of gene products involved in cardioprotection and stem cell repair;
   2. Determine the role of microRNAs from stem cells in mediating cardiac repair after stem cell injection.
2. Novel diet-induced cardioprotection and connection to GI microflora and adipokine signaling. Aims
   1. Elucidate the role of GI tract microflora in regulating adipokines as initiators of cardioprotecion,
   2. Determine the mechanism of adipokine signaling in the heart that results in activation of the NF-?B transcription factor and downstream effects upon autophagy and apoptosis.
3. microRNAs as paracrine signaling factors and biomarkers. Aims,
   1. Elucidate the microRNAs that are secreted from the heart during cardioprotective maneuvers and where they end up in other tissues and organs,
   2. Determine whether these microRNAs confer remote organ protection.

Selected Publications

• Thao Doan, Fabio Lievano, Linda Scarazzini, Kate Liebelt, Mark Jaradeh, Bulent Kantarcioglu, Jawed Fareed and W. Keith Jones. Development and Implementation of an Online Global Pharmacovigilance Certificate During the COVID-19 Pandemic Clinical and Applied Thrombosis/Hemostasis 28 (2022): 10760296221115112 https://journals.sagepub.com/doi/full/10.1177/10760296221115112
• Lenz MR, Tsai SY, Roessler AE, Wang Y, Sethupathi P, Jones WK, Kartje GL, Simmons WH A Potent Inhibitor of Aminopepitdase P2 Reduces Reperfusion Injury in Model of Myocardial Infarction and Stroke. J Pharmacol Exp Ther. 2022 Jan 3:JPET-AR-2021-000875. Doi:10.11124/jpet.121.000875.Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/34980660/ 
• Perez-Neut,M.; Haar,L.; Rao,V.; Santha,S.; Lansu,K.; Rana,B.; Jones,W. K.; Gentile, S. Activation of hERG3 channel stimulates autophagy and promotes cellular senescence in melanoma Oncotarget 2016 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008339/
• Russo,S.; Blackstock,A. W.; Herman,J. M.; Abdel-Wahab,M.; Azad,N.; Das,P.; Goodman,K. A.; Hong,T. S.; Jabbour, S. K.; Jones,W. E., 3rd; Konski, A. A.; Koong, A. C.; Kumar, R.; Rodriguez-Bigas, M.; Small, W., Jr; Thomas, C. R.,Jr; Suh, W. W.ACR Appropriateness Criteria(R) Local Excision in Early Stage Rectal Cancer American Journal of Clinical Oncology 2015 ;38(5):520-525
• Thomas,C. M.; Yong,Q. C.; Rosa,R. M.; Seqqat,R.; Gopal,S.; Casarini,D. E.; Jones,W. K.; Gupta,S.; Baker,K. M.; Kumar,R.Cardiac-specific suppression of NF-kappaB signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system American journal of physiology.Heart and circulatory physiology 2014 ;307(7):H1036-45
• Haar,L.; Ren,X.; Liu,Y.; Koch,S. E.; Goines,J.; Tranter,M.; Engevik, M. A.; Nieman, M. L.; Rubinstein,J.; Jones, W. K.Consumption of high fat diet acutely prior to ischemia/reperfusion results in cardioprotection through NF-kappaB dependent regulation of autophagic pathways American journal of physiology.Heart and circulatory physiology 2014 ;307(12):H1705-H1713
• Haar,L.; Ren,X.; Liu,Y.; Koch,S. E.; Goines,J.; Tranter,M.; Engevik,M. A.; Nieman,M.; Rubinstein,J.; Jones,W. K.Acute consumption of a high-fat diet prior to ischemia-reperfusion results in cardioprotection through NF-kappaB-dependent regulation of autophagic pathways American journal of physiology.Heart and circulatory physiology 2014 ;307(12):H1705-13
• Singh,U.; Bernstein,J. A.; Haar,L.; Luther,K.; Jones,W. K.Azelastine desensitization of transient receptor potential vanilloid 1: A potential mechanism explaining its therapeutic effect in nonallergic rhinitis American Journal of Rhinology & Allergy 2014 ;28(3):215-224
• Smiley,D.; Smith,M. A.; Carreira,V.; Jiang,M.; Koch,S. E.; Kelley,M.; Rubinstein,J.; Jones,W. K.; Tranter,M.Increased fibrosis and progression to heart failure in MRL mice following ischemia/reperfusion injury Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 2014 ;23(6):327-334
• Koh,H. K.; Kobau,R.; Whittemore,V. H.; Mann,M. Y.; Johnson,J. G.; Hutter,J. D.; Jones,W. K.Toward an integrated public health approach for epilepsy in the 21st century Preventing Chronic Disease 2014 ;11:E146
• Rubinstein,J.; Lasko,V. M.; Koch,S. E.; Singh,V. P.; Carreira,V.; Robbins,N.; Patel,A. R.; Jiang,M.; Bidwell,P.; Kranias,E. G.; Jones,W. K.; Lorenz,J. N.Novel role of transient receptor potential vanilloid 2 in the regulation of cardiac performance American journal of physiology.Heart and circulatory physiology 2014 ;306(4):H574-84
• Lam,C. K.; Zhao,W.; Cai,W.; Vafiadaki,E.; Florea,S. M.; Ren,X.; Liu,Y.; Robbins,N.; Zhang,Z.; Zhou,X.; Jiang,M.; Rubinstein,J.; Jones,W. K.; Kranias,E. G.Novel role of HAX-1 in ischemic injury protection involvement of heat shock protein 90 Circulation research 2013 ;112(1):79-89
• Koch,S. E.; Haworth,K. J.; Robbins,N.; Smith,M. A.; Lather,N.; Anjak,A.; Jiang,M.; Varma,P.; Jones,W. K.; Rubinstein,J.Age- and gender-related changes in ventricular performance in wild-type FVB/N mice as evaluated by conventional and vector velocity echocardiography imaging: a retrospective study Ultrasound in medicine & biology 2013 ;39(11):2034-2043
• Koch,S. E.; Tranter,M.; Robbins,N.; Luther,K.; Singh,U.; Jiang,M.; Ren,X.; Tee,T.; Smith,L.; Varma,P.; Jones,W. K.; Rubinstein,J.Probenecid as a noninjurious positive inotrope in an ischemic heart disease murine model JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS 2013 ;18(3):280-289
• Wei,C.; Kim,I. K.; Kumar,S.; Jayasinghe,S.; Hong,N.; Castoldi,G.; Catalucci,D.; Jones,W. K.; Gupta,S.NF-kappaB mediated miR-26a regulation in cardiac fibrosis Journal of cellular physiology 2013 ;228(7):1433-1442
• Kumar,S.; Wei,C.; Thomas,C. M.; Kim,I. K.; Seqqat,R.; Kumar,R.; Baker,K. M.; Jones,W. K.; Gupta,S.Cardiac-specific genetic inhibition of nuclear factor-kappaB prevents right ventricular hypertrophy induced by monocrotaline American journal of physiology.Heart and circulatory physiology 2012 ;302(8):H1655-66
• Koch,S. E.; Gao,X.; Haar,L.; Jiang,M.; Lasko,V. M.; Robbins,N.; Cai,W.; Brokamp,C.; Varma,P.; Tranter,M.; Liu,Y.; Ren,X.; Lorenz,J. N.; Wang,H. S.; Jones,W. K.; Rubinstein,J.Probenecid: novel use as a non-injurious positive inotrope acting via cardiac TRPV2 stimulation Journal of Molecular and Cellular Cardiology 2012 ;53(1):134-144
• Zuo,S.; Jones,W. K.; Li,H.; He,Z.; Pasha,Z.; Yang,Y.; Wang,Y.; Fan,G. C.; Ashraf,M.; Xu,M.Paracrine effect of Wnt11-overexpressing mesenchymal stem cells on ischemic injury STEM CELLS AND DEVELOPMENT 2012 ;21(4):598-608
• Tranter,M.; Liu,Y.; He,S.; Gulick,J.; Ren,X.; Robbins,J.; Jones,W. K.; Reineke,T. M.In vivo delivery of nucleic acids via glycopolymer vehicles affords therapeutic infarct size reduction in vivo Molecular therapy : the journal of the American Society of Gene Therapy 2012 ;20(3):601-608