CONTACT INFORMATION http://www.loyola.org
W. Keith Jones
Ph.D.
  • Professor
  • Department Chairperson, Molecular Pharmacology and Therapeutics
  • Molecular Pharmacology and Therapeutics
Research Keywords
  • Cancer/Carcinogenesis
  • Cardiovascular System
Research Summary

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.

  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 cardioproteciotn 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 initiatiors 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.
Publications

Consumption of high fat diet acutely prior to ischemia/reperfusion results in cardioprotection through NF-kappaB dependent regulation of autophagic pathwaysHaar,L.; Ren,X.; Liu,Y.; Koch,S. E.; Goines,J.; Tranter,M.; Engevik,M. A.; Nieman,M. L.; Rubinstein,J.; Jones,W. K.American journal of physiology.Heart and circulatory physiology 2014 ; ( ):

Cardiac-specific Suppression of NF-kappaB Signaling Prevents Diabetic Cardiomyopathy via Inhibition of the Renin-Angiotensin SystemThomas,C. M.; Yong,Q. C.; Mattar Rosa,R.; Seqqat,R.; Gopal,S.; Casarini,D. E.; Jones,W. K.; Gupta,S.; Baker,K. M.; Kumar,R.American journal of physiology.Heart and circulatory physiology 2014 ; ( ):

Toward an integrated public health approach for epilepsy in the 21st centuryKoh,H. K.; Kobau,R.; Whittemore,V. H.; Mann,M. Y.; Johnson,J. G.; Hutter,J. D.; Jones,W. K.Preventing Chronic Disease 2014 ;11( ):E146

Novel role of transient receptor potential vanilloid 2 in the regulation of cardiac performanceRubinstein,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.American journal of physiology.Heart and circulatory physiology 2014 ;306(4):H574-84

Increased fibrosis and progression to heart failure in MRL mice following ischemia/reperfusion injurySmiley,D.; Smith,M. A.; Carreira,V.; Jiang,M.; Koch,S. E.; Kelley,M.; Rubinstein,J.; Jones,W. K.; Tranter,M.Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 2014 ;23(6):327-334

Azelastine desensitization of transient receptor potential vanilloid 1: A potential mechanism explaining its therapeutic effect in nonallergic rhinitisSingh,U.; Bernstein,J. A.; Haar,L.; Luther,K.; Jones,W. K.American Journal of Rhinology & Allergy 2014 ;28(3):215-224

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 studyKoch,S. E.; Haworth,K. J.; Robbins,N.; Smith,M. A.; Lather,N.; Anjak,A.; Jiang,M.; Varma,P.; Jones,W. K.; Rubinstein,J.Ultrasound in medicine & biology 2013 ;39(11):2034-2043

Probenecid as a noninjurious positive inotrope in an ischemic heart disease murine modelKoch,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.JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS 2013 ;18(3):280-289

Novel role of HAX-1 in ischemic injury protection involvement of heat shock protein 90Lam,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.Circulation research 2013 ;112(1):79-89

NF-kappaB mediated miR-26a regulation in cardiac fibrosisWei,C.; Kim,I. K.; Kumar,S.; Jayasinghe,S.; Hong,N.; Castoldi,G.; Catalucci,D.; Jones,W. K.; Gupta,S.Journal of cellular physiology 2013 ;228(7):1433-1442

Paracrine effect of Wnt11-overexpressing mesenchymal stem cells on ischemic injuryZuo,S.; Jones,W. K.; Li,H.; He,Z.; Pasha,Z.; Yang,Y.; Wang,Y.; Fan,G. C.; Ashraf,M.; Xu,M.STEM CELLS AND DEVELOPMENT 2012 ;21(4):598-608

Probenecid: novel use as a non-injurious positive inotrope acting via cardiac TRPV2 stimulationKoch,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.Journal of Molecular and Cellular Cardiology 2012 ;53(1):134-144

In vivo delivery of nucleic acids via glycopolymer vehicles affords therapeutic infarct size reduction in vivoTranter,M.; Liu,Y.; He,S.; Gulick,J.; Ren,X.; Robbins,J.; Jones,W. K.; Reineke,T. M.Molecular therapy : the journal of the American Society of Gene Therapy 2012 ;20(3):601-608

Cardiac-specific genetic inhibition of nuclear factor-kappaB prevents right ventricular hypertrophy induced by monocrotalineKumar,S.; Wei,C.; Thomas,C. M.; Kim,I. K.; Seqqat,R.; Kumar,R.; Baker,K. M.; Jones,W. K.; Gupta,S.American journal of physiology.Heart and circulatory physiology 2012 ;302(8):H1655-66

Languages
  • French