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Jackson Lab

 

A major interest of the Jackson Lab is the biochemistry, molecular/cell biology, and physiology/pharmacology of adenosine.  In this regard, the Jackson Lab is investigating:

1.      Production of adenosine from the metabolism of 3’,5’-cAMP to 5’-AMP (i.e., the 3’,5’-cAMP-adenosine pathway);

2.      Production of adenosine from the metabolism of 2’,3’-cAMP to 2’-AMP and 3’-AMP (i.e., the 2’,3’-cAMP-adenosine pathway);

3.      Regulation of adenosine levels by guanosine (i.e., the guanosine-adenosine mechanism);

4.      Regulation of renal function by adenosine;

5.      Regulation of renal sympathetic neurotransmission by adenosine;

6.      Regulation vascular smooth muscle cell proliferation and glomerular mesangial cell proliferation by adenosine;

7.      Regulation of the immune system (particularly T lymphocytes) by adenosine;

8.      Regulation of inflammation by adenosine;

9.      Role of adenosine in cancer;

10.  Role of adenosine in traumatic brain injury.

Another major interest in the Jackson Lab is the regulation of arterial blood pressure and the pathophysiology of hypertension.  In this regard, the Jackson Lab is investigating:

11.  Role of adenosine in the cardiovascular system and kidneys in hypertension;

12.  Regulation of cAMP metabolism in the cardiovascular system and kidneys in hypertension;

13.  Role of RACK1 (Receptor for Activated C Kinase 1) in the cardiovascular system and kidneys in hypertension;

14.  Role of dipeptidyl peptidase IV in the cardiovascular system and kidneys in hypertension.

15.  Cross talk between G-protein signal transduction pathways in the cardiovascular system and kidneys in hypertension.

 

Edwin K. Jackson, PhD

Purine Pharmacology:  Adenosine is an endogenous purine that regulates most physiological systems.  We are investigating (using a variety of molecular, analytical, cellular and physiological tools and using several strains of genetically modified animals, as well as conducting studies in patients): 1) the production of adenosine from 3’,5’-cAMP and 2’,3’-cAMP (the cAMP-adenosine pathways; see Figure 1); 2) the modulation of adenosine levels by guanosine;3) the roles of adenosine in regulating the sympathetic nervous system, heart, vascular system, kidneys, bladder, brain and immune system;4)  the effects of adenosine on cardiac fibroblasts, vascular smooth muscle cells, vascular endothelial cells, glomerular mesangial cells, renal epithelial cells, T cells and B cells; 5) the role of exosomes in adenosine biochemistry; 6) how to modulate the adenosine system with drugs to treat cardiovascular and renal diseases, traumatic brain injury, cancer and HIV infected patients.
Figure 1

 
Cardiovascular and Renal Pharmacology:  Our recent studies indicate that NPY1-36 (a peptide released from sympathetic nerves) and PYY1-36 (a peptide released from the intestines) trigger proliferation of and extracellular matrix production by preglomerular vascular smooth muscle cells (PGVSMCs) and glomerular mesangial cells (GMCs) in kidneys from genetically-hypertensive animals, a phenomenon mediated via Y1 receptors and that involves signaling by RACK1 (receptor for activated C kinase 1).  Dipeptidyl peptidase IV (DPPIV) metabolizes NPY1-36 and PYY1-36 (Y1 receptor agonists) to NPY3-36 and PYY3-36 (inactive at Y1 receptors).  We are investigating whether a new class of antidiabetic drugs (DPPIV inhibitors) may adversely affect the kidneys of hypertensive subjects by preventing the conversion of PYY1-36 and NPY1-36 to less active metabolites and thereby promoting inappropriate cell proliferation and extracellular matrix production (see Figure 2). 

Figure 2

Headshot of Edwin K. Jackson, PhD
Edwin K. Jackson, PhD
Distinguished Professor

Headshot of Shawn Kotermanski
Shawn Kotermanski
Senior Research Specialist

Headshot of Zaichuan Mi
Zaichuan Mi
Research V

Edwin K. Jackson, PhD

Journal Articles

Verrier JD, TC Jackson, DG Gillespie, K Janesko-Feldman, R Bansal, A-K Nave, PM Kochanek and EK Jackson.  Oligodendrocyte expressed CNPase is essential to the extracellular 2’,3’-cAMP-adenosine pathway. Glia 61:1595-1606, 2013.
Jackson EK and Z Mi.  In Vivo cardiovascular pharmacology of 2’,3’-cAMP, 2’-AMP, and 3’-AMP in the rat. Journal of Pharmacology and Experimental Therapeutics 346:190-200, 2013.
Saze Z, PJ Schuler, C-S Hong, D Cheng, EK Jackson and TL Whiteside.  Adenosine production by human B cells and B cell-mediated suppression of activated T cells. Blood 122:9-18, 2013.
Jackson EK, D Cheng, TC Jackson, JD Verrier and DG Gillespie. Extracellular guanosine regulates extracellular adenosine levels.  American Journal of Physiology-Cell Physiology 304: C406-C421, 2013. 
Cheng D, X Zhu, GD Gillespie and EK Jackson. Role of RACK1 in the differential proliferative effects of neuropeptide Y1-36 and peptide YY1-36 in SHR versus WKY preglomerular vascular smooth muscle cells.  American Journal of Physiology-Renal Physiology 304: F770-F780, 2013. 
Jackson EK and DG Gillespie.  Extracellular 2’,3’-cAMP-adenosine pathway in proximal tubular,  thick ascending limb and collecting duct epithelial cells.   American Journal of Physiology-Renal Physiology 304: F49-F55, 2013. 
Jackson EK, D Cheng, SP Tofovic and Z Mi. Endogenous adenosine contributes to renal sympathetic neurotransmission via postjunctional A1-receptor-mediated coincident signaling.  American Journal of Physiology – Renal Physiology 302: F466-FF76, 2012.
Verrier JD, TC Jackson, PM Kochanek and Jackson EK. The brain in vivo expresses the 2’,3’-cAMP-adenosine pathway.  Journal of Neurochemistry 122: 115-125, 2012. 
Jackson EK, SJ Kochanek and DG Gillespie.  Dipeptidyl peptidase IV regulates proliferation of preglomerular vascular smooth muscle and mesangial cells.  Hypertension 60: 757-764, 2012.
Jackson EK and DG Gillespie. Extracellular 2’,3’-cAMP and 3’,5’-cAMP stimulate proliferation of preglomerular vascular endothelial cells and renal epithelial cells.  American Journal of Physiology – Renal Physiology 303: F954-F962, 2012.