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

January 2012 - present: Assistant Professor (Tenure track), Department of Physiology, 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, Milwaukee, WI.


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 lab, we utilize a number of approaches to study kidney function from the level of the awake animal down to cellular and molecular pathways. Approaches we utilize include measurements of renal function in conscious animals (Blood pressure telemetry, glomerular filtration rate), isolation and microperfusion of renal tubules and vessels, live cell fluorescent imaging, cell culture, immunohistochemistry as well as numerous molecular and genetic approaches. Much of the recent focus of our laboratory has been directed toward the role of the voltage-gated channel Hv1, which we were the first to localize to the kidney, in renal physiology and pathophysiology. We utilize a unique ‘Hv1 knockout’ mutant rat model, in which the Hv1 gene was mutated using state of the art zinc finger nuclease gene targeting technology to study the function of this channel. One of the great benefits of this approach is we have been able to ‘knock out’ Hv1 in an animal model of hypertensive renal disease (the Dahl salt-sensitive (SS) rat), allowing us to study the contribution of this pathway to the development of renal injury and hypertension in a naturally occurring model of disease.

Technical Illustration of Dr. O'Connor Research titled "Thick Ascending Medullary Limb"

We are the first to localize the voltage-gated proton channel Hv1 to the apical membrane of renal medullary thick ascending limb tubular segments in humans and rats.

Currently we are investigating the role of this novel renal channel in the development of hypertensive kidney injury using a state of the art Hv1 mutant Dahl salt-sensitive rat model in which the channel has been deleted.

We are also investigating the role of this channel in electrolyte and acid/base homeostatis secondary to its potential role in the regulation of Na, Cl, and NH4+ reabsorption and reactive oxygen species production by the mTAL.


Current Projects

Investigation of the role of Hv1 in the development of renal injury in hypertensive Dahl SS rats. Hypertensive Hv1-/- rats have significantly reduced renal injury compared to wild-type animals. Evidence from our laboratory 

indicates that Hv1 activity may promote injury in high salt fed/acid states via changes in renal auto regulation and/or promotion of excess free radicals by NADPH oxidase. These pathways, as well as the factors that activate Hv1 in the kidney, are being investigated. 

The role of Hv1 in medullary thick ascending limb (mTAL) NH4+ and Na reabsorption. The Hv1 channel is specific to protons and only opens under relative physiological extremes (cellular depolarization/acidification). We recently localized Hv1 to the apical membrane of the renal medullary thick ascending limb segment of the nephron. Current projects are investigating the ability of Hv1 to contribute to both NH4+ and Na reabsorption by NKCC2 in this region of the nephron and how disruption in these pathways may contribute to disease states such as hypertension.

The role of Hv1 as an intracellular Na sensor and its contribution to diseases including ischemic stroke and Lupus nephritis). Evidence from our recent studies in cells that express Hv1 (macrophages/mTAL) indicates that Hv1 may act as an intracellular Na sensor, promoting the activity of NADPH oxidase and cellular reactive oxygen species production when intracellular Na is low. Along with our collaborators, current studies focus on the molecular mechanisms mediating this Na sensing phenotype (Susan Smith) and how disruptions in these pathways may contribute to disease states including ischemic stroke (Ergul, Li) or Lupus nephritis. 


Honors and awards

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, Cardio-Renal Section April 2012, 2013


Editorial Boards:

Clinical and Experimental Pharmacology and Physiology (2008  - Current)

American Journal of Physiology – Renal (2010 – Current)

Frontiers in Physiology: Genomic Physiology (2010 - Current)

Physiological Reports (2013 inaugural member - Current)

*Representative Publications*

 (Go to Pub Med)

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 [In Press]

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 [In Press]

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.