Paul O'Connor, PhD

Professor

 Phone:  (706) 721-7890  
 Fax:  (706) 721-7299
 Email: paoconnor@augusta.edu
 Office: CB-2206
 Lab: CB-2210

 

 

Research Interests

Our laboratory’s interests lie in the physiological pathways involved in the regulation of kidney function and how disruptions in these pathways can lead to disease. In the laboratory, we utilize a number of approaches to study kidney function from the level of the awake animal down to cellular and molecular pathways. Dr. O’Connor’s early work focused on the mechanisms that regulate renal oxygen tension and are highlighted in Brenner and Rectors the Kidney 9th Edition.

Major research contributions from the O’Connor laboratory include:

1. Identification and characterization of the voltage-gated proton channel in the kidney including identification of mitochondrial derived reactive oxygen species as the source of Hv1 dependent reactive oxygen species in the kidney.

    a. Voltage gated proton channels modulate mitochondrial reactive oxygen species production by complex I in renal medullary thick ascending limb. Redox Biology 2019

    b. Hv1 acts as a sodium sensor and promotes superoxide production in medullary thick ascending limb of Dahl salt-sensitive rats. Hypertension 2014

2. Demonstrating the NaHCO3 ingestion promotes a systemic anti-inflammatory response in rats and healthy human subjects and that stimulation of gastric acid secretion may promote the cholinergic anti-inflammatory pathway.

    a. Oral NaHCO3 activates the splenic anti-inflammatory pathway; evidence vagal signals are transmitted via mesothelial cells. Journal of Immunology 2018. *** Most downloaded article of 2018 in JI ***

    b. A basic solution to activate the cholinergic anti-inflammatory pathway via the mesothelium? Pharmacologic Research 2019.

3. Demonstrating that vasa recta pericytes protect the kidney from vascular congestion following periods of ischemia.

    a. Vasa recta pericyte density is negatively associated with vascular congestion in the renal medulla following ischemia reperfusion in rats, Am J Physiol 2017.

_{Voltage-gated proto channel (Hv1) expression in medullary thick ascending limb (mTAL) of the human kidney}

 

 

Current Projects

Current projects in the O’Connor laboratory focus on three major themes:

1. Investigating the role of vasa recta in renal medullary vascular congestion.  The renal medulla is susceptible to aggregation of RBC’s following periods of ischemia which can lead to prolonged hypoxia and cell death. The O’Connor laboratory is investigating methods to prevent vascular congestion and determine whether this can reduce long term renal injury as well as cardiovascular consequences following renal ischemia.

 

Renal vascular congestion is caused by a mismatch between cortical and medullary perfusion

 

^{Vascular congestion (dark red) in the renal outer-medulla of the rat and human kidney following a period of ischemia}

2. Determining the mechanisms through which NaHCO3 ingestion slows the decline in renal function in CKD.A number of small clinical trials have demonstrated that oral ingestion of NaHCO₃ markedly slows the decline in kidney function in CKD patients. The mechanisms underlying this protective effect of NaHCO₃ supplementation however, remain unclear. Our group has shown that ingestion of NaHCO₃ promotes an anti-inflammatory polarization within the innate immune system, promoting more regulatory or M2 macrophages and less classically activated or inflammatory M1 macrophages in the kidney. Our data indicate that this anti-inflammatory effect of NaHCO₃ ingestion requires the spleen and may be related to activation of the cholinergic anti-inflammatory pathway, an innate anti-inflammatory pathway that can be promoted by electrical stimulation of the vagal nerve. As inflammation may play an important role in the progression of CKD, cost-effective and simple interventions that can modulate the immune system and promote renal protection may be of great benefit to CKD patients. O’Connor laboratory members are currently investigating how NaHCO₃ ingestion promotes an anti-inflammatory response in the kidney and, in collaborations with the Baban and Harris groups, whether this occurs in CKD patients and may underlie the protective effect of NaHCO₃

3. Investigating the role of mesothelial cell communication toward splenic capsular fibrosis and anti-inflammatory signaling in the spleen. In investigating the role of the spleen in polarization of the immune system to NaHCO₃, we found that simply moving the spleen during surgery was sufficient to abolish the renal anti-inflammatory response. This observation prompted us to investigate how anti-inflammatory signals reach the splenic parenchyma. We found that mesothelial cells appear to form connections to the splenic capsule and that when these connections are broken, mesothelial cells on the splenic capsule proliferate and hypertrophy. This response is then followed by the development of splenic capsular fibrosis. Remarkably, these mesothelial cells stain positive for the pan neuronal marker PGP9.5 and contain ultrastructural organelles similar to those observed in neurons. These observations led us to hypothesize that specialized mesothelial cells may act to communicate anti-inflammatory signals to the spleen. O’Connor laboratory members are currently investigating whether mesothelial cells are able to transmit signals to the splenic capsule and whether disruption of this signaling results in splenic capsular fibrosis and immune dysregulation.

 

Jenny Nguyen received the Barbara A. Horowitz and John M. Horowitz Outstanding Undergraduate Abstract Award titled, "'Assessment of temporal changes in glomerular filtration rate in male and female rats using transcutaneous FITC-sinistrin clearance." The competition was held at the APS meeting located in Long Beach, CA April 2024 and Ms. Nguyen represented the O'Connor Lab. Congratulations to Jenny Nguyen!

Awards and Honors

2019 Hamilton Scholar in Physiology - for contributions to the Department of Physiology and Medical College of Georgia

2019 Medical College of Georgia Distinguished Faculty Award for Basic Science Teaching

2017-18 Medical College of Georgia Exemplary Teaching Award (PBL)

2018 Excellence in Teaching Award (Augusta University Graduate School)

2015 Arthur Guyton Award for Excellence in Integrative Physiology, American Physiological Society

2014 New Investigator Awardee for the Water and Electrolyte Homeostasis Section of the American Physiological Society

2013 Elected Fellow of the American Heart Association

2012 Kidney Council New Investigator Award American Heart Association, Council for High Blood Pressure Research

2012 Renal Section Research Recognition Award, American Physiological Society

Selected Professional Services

Grant Reviewer:
American Heart Association (AHA), Cardio-Renal Section
Department of Veterans Affairs, Nephrology Study section
National Institutes of Health (NIH), Re-building a kidney consortium

Associate Editor:

Molecular Medicine (2020-2023). Molecular Medicine is a peer-reviewed open access medical journal published by The Feinstein Institute for Medical Research. IF 4.096 https://molmed.biomedcentral.com/about

Comprehensive Physiology (2020-present). Comprehensive Physiology occupies a unique niche among physiology journals and in the APS community as a co-production of APS and Wiley Publishing Co. It is in the top 5 journals in physiology, with an I.F of 6.604.

Editorial Boards:
American Journal of Physiology, Renal Physiology
Physiological Reports

Institutional:
Co-Program director, Physiology Graduate Program

 

Related Links

• Cells that make our insides slick also calm our spleens (MedicalXpress) 
• The Journal of Immunology’s (The JI’s) most-downloaded article in 2018.
• Could a Daily Dose of Baking Soda Combat Autoimmune Disease? (ReachMD)
• Drinking baking soda could be an inexpensive, safe way to combat autoimmune disease (EurekAlert!)
• Baking soda could help fight autoimmune disease (Channel 12 WRDW)
• Beyond Capacity (MCG Medicine)
• $9.4 million grant helps scientists explore how cell death fuels high blood pressure (JagWire)

 

 

 

 

 

 

 

 

 

 

 

 

^{Men's Journal - September 2018 Vol 27, No. 9 page 111}