Paul O'Connor, PhD


Associate Professor, Co-Director Physiology Graduate Program

 PhonDr. Paul O'Connore:  (706) 721-7890  
 Fax:  (706) 721-7299
 Email: paoconnor@augusta.edu
 Office: CB-2206
 Lab: CB-2210

  Learn more about Dr. O'Connor's Research


Education and Training

Monash University, Australia, B.Sc (Hons) 1997-2001 Biomedical Science
Monash University, Department of Physiology, Australia, PhD 2001-2005 Biomedical Sciences (Physiology)
Medical College of Wisconsin, Milwaukee, WI Post-doc 2005-2009 Physiology


Academic Appointments

June 2016 - present: Associate Professor (Tenure), Department of Physiology, Medical College of Georgia, Augusta University

January 2012 - June 2016: Assistant Professor (Tenure track), Department of Physiology, Medical College of Georgia, Augusta University

December 2011 - December 2012: Assistant Professor (Tenure track), Department of Medicine, Section of Experimental Medicine, Georgia Health Sciences Univeristy

2009 - November 2011: Assistant Professor (Research) Department of Physiology, Medical College of Wisconsin


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.
      1. Voltage gated proton channels modulate mitochondrial reactive oxygen species production by complex I in renal medullary thick ascending limb. Redox Biology 2019
      2. 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.
      1. 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 ***
      2. 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.
      1. Vasa recta pericyte density is negatively associated with vascular congestion in the renal medulla following ischemia reperfusion in rats, Am J Physiol 2017.
Technical Illustration of Dr. O'Connor Research titled "Thick Ascending Medullary Limb"
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 pericytes in preventing renal medullary vascular congestion. Pericytes are contractile cells that wrap around capillaries. While generally pericytes are sparsely distributed around capillary vessels, along the descending vasa recta capillaries that supply the renal medulla, pericyes are closely aggregated, covering almost the entirely of these vessels as they descend through the renal outer-medulla. While the physiological function of pericytes remains unclear, we hypothesize that along the descending vasa recta, peristaltic contractions within these cells help to prevent or disrupt red blood cell (RBC) aggregations. The renal medulla is susceptible to aggregation of RBC’s following periods of ischemia which can lead to prolonged hypoxia and cell death. O’Connor laboratory members are investigating methods to promote stimulation of contraction of vasa recta pericytes to determine whether this can reduce RBC congestion and limit renal injury following renal ischemia.

    Vascular Congestion Vascular congestion (dark red) in the renal outer-medulla of the rat 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 ingestion.
  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.

    Technical Image of Dr. O'Connor's research

Honors and awards

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

2018 Medical College of Georgia Exemplary Teaching Award

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

2008 Star Reviewer: Clinical and Experimental Pharmacology and Physiology


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

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

Institutional:
Co-Program director, Physiology Graduate Program


Representative Publications

 Go to Pub Med)

Ray SC, Baban B, Tucker MA, Seaton AJ, Chang KC, Mannon EC, Sun J, Patel B, Wilson K,  Musall JB, Ocasio H, Irsik D, Filosa JA, Sullivan JC, Marshall B, Harris RA and  O’Connor PM. Oral NaHCO3 Activates a Splenic Anti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells.  J Immunol May 15, 2018, 200 (10) 3568-3586; DOI: https://doi.org/10.4049/jimmunol.1701605

Fellner R, Cook A, O'Connor P.M., Zhang S, Pollock D.M, Inscho E. High Salt Diet Blunts Renal Autoregulation by a Reactive Oxygen Species-dependent Mechanism. Am J Physiol: Renal, 2014.

Fellner R, Cook A, O'Connor P.M., Zhang S, Pollock D.M., Inscho E. High Salt Diet Blunts Renal Autoregulation by a Reactive Oxygen Species-dependent Mechanism. Am J Physiol: Renal, 2014.

Jin C, Sun J, Stilphen C.A, Smith S.M.E, Ocasio H, Bermingham B, Darji S, Guha A, Patel R, Geurts A.M, Jacob H.J, Lambert N.A, O'Connor P.M. Hv1 acts as a sodium sensor and promotes superoxide production in medullary thick ascending limb of Dahl salt-sensitive rats. Hypertension 2014 [In Press]

Evans R.G, Harrop G.K, Ngo J.P, Ow C.P.C, O'Connor P.M. Basal renal oxygen consumption and the concept of the efficiency of oxygen utilization for sodium reabsorption. Am J Physiol Renal 2014 Mar;306(5):F551-60.

Sex differences in ET-1 receptor expression and signaling in the IMCD. Jin C, Speed S, Hyndman K.A, O'Connor P.M, Pollock D.M. Am J Physiol Renal 2013 Oct 15;305(8):F1099-10419

The initiation and progression of chronic kidney disease: can we definitively test the chronic hypoxia hypothesis? Evans R.G, O'Connor P.M.

Hypertension 2013 Nov;62(5):827-8 O'Connor P.M., Cowley A.W Jr. Medullary thick ascending limb buffer vasoconstriction of renal outermedullary vasa recta in salt-resistant but not salt-sensitive rats. Hypertension Oct;60(4):965-72 2012.

Feng D., Yang C., Geurtz A., Kurth T., Liang M., Lazar J., Mattson LD., O'Connor P.M., Cowley A.W. Jr. Increased expression of NAD(P)H oxidase subunit p67phox in the renal medulla contributes to oxidative stress and salt-sensitive hypertension. Cell Metab. 2012 Feb 8;15(2):201-8.

Ohsaki Y., O'Connor P.M., Mori T., Ryan R., Dickinson B., Chang C., Lu Y., Ito S., Cowley Jr A.W. Increase of sodium delivery stimulates the mitochondrial respiratory chain H2O2 production in rat renal medullary thick ascending limb. Am J Physiol Renal Physiol. 2012 Jan;302(1):F95-F102.

Schreck, C, O'Connor P.M. NADPH oxidase and renal epithelial ion transport. Am J Physiol Regul Integr Comp Physiol. 2011 May;300(5):R1023-9.

Evans, R. G, Goddard, G, Eppel, G.A, O'Connor, P.M. Factors that render the kidney susceptible to hypoxia during hypoxemia. Am J Physiol Regul Integr Comp Physiol. 2011 Apr;300(4):R931-40.

Evans, R.G, Eppel, G.A, Michaels, S, Burke, S. L, Nematbakhshi, N, Head, G.A, Carroll, J.F, O'Connor, P.M. Multiple mechanisms act to maintain kidney oxygenation in anesthetized rabbits during renal ischemia. Am J Physiol Renal Physiol: 298 (5), F1235-F1243, 2010, Senior Investigator

O'Connor P.M., L Lu, Liang M, Cowley A.W Jr. A novel amiloride sensitive H+ transport pathway mediates enhanced superoxide production in the thick ascending limb of salt-sensitive rats, not Na +/H + exchange. Hypertension: 54(2), 248-54, 2009, Principal Investigator

O'Connor P.M., lu L, Cowley Jr A. W. Enhanced amiloride sensitive superoxide production in renal medullary thick ascending limb of Dahl salt-sensitive rats. Am J Physiol Renal Physiol: 295(3), F726-33, 2008, Principal Investigator.

Abe M, O'Connor PM, Kaldunski M, Liang M, Roman RJ, Cowley AW Jr Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb. Am J Physiol Renal Physiol. 2006 Aug;291(2):F350-7.

O'Connor P.M., Anderson W.P, Kett M.M and Evans R.G. Renal medullary tissue oxygenation is dependent on both cortical and medullary perfusion. Am J Physiol (Renal): 290(3), F688-694, 2006.

Dr. O'Connor's Faculty ProfileLink to Dr. O'Connor on PubMed

Lab meeting schedule

LAB PERSONNEL

Hiram Ocasio
Research Associate

Elinor Mannon
MD/PHD student

Bansari Patel
Research Assistant

Sarah Ray
Graduate Student

Jingping Sun
Research Associate

Katie Wilson
Research Assistant

Dr. O'Connor Lab (2018)Pictured left to right: Elinor Mannon, Sarah Ray, Hiram Ocasio, Dr. Paul O'Connor, Bansari Patel, Katie Wilson, Jingping Sun (2018)
 
Dr. O'Connor Lab (2016)Pictured left to right: Hiram Ocasio, Dr. Paul O'Connor, Jingping Sun, Sarah Ray (2016)
 
2019 ISN ConferencePictured left to right: Elinor Mannon, Ellen Gillis, and Sarah Ray at the International Society of Nephrology Conference in Melbourne. (2019)
 
2019 Melbourne - Dr. O'Connor with students and colleagues
 
O’Connor students and colleagues visiting with Drummond/Sobey laboratories at LaTrobe University, Melbourne Australia (2019)