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Kenneth R. Olson, Ph.D.

Professor of Physiology (Emeritus), Indiana University School of Medicine - South Bend
Adjunct Professor, Department of Biological Sciences, University of Notre Dame
Concurrent Professor, Department of Chemical and Biomolecular Engineering, University of Notre Dame

Education

University of Wisconsin-LaCrosse; BS; Majors in Chemistry and Biology;  1969

Michigan State University; MS; Physiology;  1970

Michigan State University; Ph.D.; Physiology;  1972

 

Academic Appointments

Research Associate--Michigan State University (1972-1973)


Assistant Professor--Rutgers University (1973-1975)


Assistant Professor--Indiana University School of Medicine, South Bend Center (1975-1979); Adjunct Assistant Professor, Department of Biological Sciences, University of Notre Dame (1975-1979)


Associate Professor--Indiana University School of Medicine, South Bend Center (1979-1984);
Adjunct Associate Professor, Department of Biological Sciences, University of Notre Dame (1979-1984)


Professor--Indiana University School of Medicine - South Bend (1984-2010);
Adjunct Professor, Department of Biological Sciences, University of Notre Dame (1984-Present)

Assistant Director for Research; Indiana University School of Medicine, South Bend Center (1990-2006)


Concurrent Professor; Department of Chemical Engineering, University of Notre Dame (1998-Present)

Emeritus Professor; Indiana University School of Medicine - South Bend (2010-Present)

         Blood vessels are uniquely designed to detect low oxygen (hypoxia) and regulate blood flow accordingly.  Hypoxia dilates systemic vessels (e.g., coronary arteries) to match oxygen delivery with metabolic demand and pulmonary arteries constrict to optimize gas exchange in the lung.  My laboratory has identified a novel oxygen “sensing” mechanism using hydrogen sulfide (H2S).

         Known for centuries as a toxic and malodorous gas with the smell of rotten eggs, hydrogen sulfide (H2S) has recently come to the fore as an endogenously produced signaling molecule in the cardiovascular, nervous, and gastrointestinal systems.  My research involves three aspects of H2S biology; 1) the role of H2S in oxygen sensing in the cardiovascular system, 2) H2S production and metabolism in tissues, and 3) the applicability of a variety of newly developed H2S-donating drugs in cancer biology.

H2S and oxygen sensing

            Vertebrate cardiorespiratory homeostasis is inextricably dependent upon specialized cells that provide feedback on oxygen status in the tissues, blood, and on occasion the environment. These “oxygen sensing” cells include chemoreceptors and oxygen sensitive chromaffin cells that initiate cardiorespiratory reflexes, vascular smooth muscle cells that adjust perfusion to metabolism (in the brain heart skeletal muscle, etc.) or to pulmonary ventilation.  There are also other cells that condition themselves in response to episodic hypoxia.  Identification of how these cells sense oxygen and transduce this into the appropriate physiological response has enormous clinical applicability in a variety of areas such as, mitigating consequences of heart attack and stroke, or countering hypoxia related pulmonary hypertension as a result of COPD, sleep apnea or other hypoxia-related respiratory disorders.  Despite intense research, however, there is no consensus on how cells detect a fall in oxygen and then couple this to the appropriate physiological response, i.e., the oxygen “sensor”.  Our research has shown that the oxygen sensing mechanism consists of a delicate balance between constitutive production of biologically active H2S in the cell and its oxidation (destruction) by the cell’s mitochondria. Thus the concentration of this important signaling molecule is inversely and inexorably coupled to oxygen availability. Our research has focused on pulmonary arteries of a variety of terrestrial vertebrates and hypoxia-tolerant diving mammals and birds (seals, sea lions and penguins) as well as respiratory and systemic (coronary, cerebral and visceral) vessels from all vertebrate classes including the most primitive hagfish and lamprey.  These studies not only provide an extensive profile of blood vessel responses to hypoxia and H2S but they give us a window into the evolutionary development of vascular oxygen sensing.  We are also examining this oxygen sensing mechanism in neuroepithelial cells of the fish gill which is homologous to the glomus cells of the mammalian carotid body.

olson_fig-1.jpg

H2S and oxygen sensing

            Vertebrate cardiorespiratory homeostasis is inextricably dependent upon specialized cells that provide feedback on oxygen status in the tissues, blood, and on occasion the environment. These “oxygen sensing” cells include chemoreceptors and oxygen sensitive chromaffin cells that initiate cardiorespiratory reflexes, vascular smooth muscle cells that adjust perfusion to metabolism (in the brain heart skeletal muscle, etc.) or to pulmonary ventilation.  There are also other cells that condition themselves in response to episodic hypoxia.  Identification of how these cells sense oxygen and transduce this into the appropriate physiological response has enormous clinical applicability in a variety of areas such as, mitigating consequences of heart attack and stroke, or countering hypoxia related pulmonary hypertension as a result of COPD, sleep apnea or other hypoxia-related respiratory disorders.  Despite intense research, however, there is no consensus on how cells detect a fall in oxygen and then couple this to the appropriate physiological response, i.e., the oxygen “sensor”.  Our research has shown that the oxygen sensing mechanism consists of a delicate balance between constitutive production of biologically active H2S in the cell and its oxidation (destruction) by the cell’s mitochondria. Thus the concentration of this important signaling molecule is inversely and inexorably coupled to oxygen availability. Our research has focused on pulmonary arteries of a variety of terrestrial vertebrates and hypoxia-tolerant diving mammals and birds (seals, sea lions and penguins) as well as respiratory and systemic (coronary, cerebral and visceral) vessels from all vertebrate classes including the most primitive hagfish and lamprey.  These studies not only provide an extensive profile of blood vessel responses to hypoxia and H2S but they give us a window into the evolutionary development of vascular oxygen sensing.  We are also examining this oxygen sensing mechanism in neuroepithelial cells of the fish gill which is homologous to the glomus cells of the mammalian carotid body.

 

 

 

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Recent Publications (out of >160)

Reviews

Olson, K.R. (2014) Hydrogen sulfide as an oxygen sensor. Antioxid. Redox Signal. [Epub ahead of print]

Olson,K.R., DeLeon,E. And Lui,F. (2014) Controversies and conundrums in hydrogen sulfide biology. Nitric Oxide doi: 10.1016/j.niox.2014.05.012

Olson, K.R. (2013) Hydrogen sulfide as an oxygen sensor. Clin.Chem.Lab.Med. 51:623-632. Doi:10.1515

Calzia, E., Radermacher, P. and Olson, K.R. (2012) Endogenous H2S in hemorrhagic shock: innocent bystander or central player? Critical Care 16:183.

Olson, K.R. (2012) A Practical Look at the Chemistry and Biology of Hydrogen Sulfide Antioxidants and Redox Signaling 17:32-44 (doi:10.1089/ars.2011.4401).

Olson, K.R. (2012) Mitochondrial adaptations to utilize hydrogen sulfide for energy and signaling. J.Comp.Physiol. 182:881-897.

Olson, K.R., Donald, J.A., Dombkowski, R.A., Perry, S.F. (2012) Evolutionary and Comparative Aspects of Nitric Oxide, Carbon Monoxide and Hydrogen Sulfide. Resp. Physiol.Neurobiol. 184:117-129. doi.org/10.1016/j.resp.2012.04.004.

Fago, A., Jensen, F.B., Tota, B., Feelisch, M., Olson, K.R., Helbo, S., Lefevre, S., Mancardi, D., Palumbo, A., Sandvik, G.K., Skovgaard, N. (2012) Integrating nitric oxide, nitrite and hydrogen sulfide signaling in the physiological adaptations to hypoxia: A comparative approach. Comp. Biochem. Physio.l A Mol. Integr. Physiol. 162(1):1-6. doi:10.1016/j.cbpa.2012.01.011

Kashfi, K. and Olson, K.R. (2012) Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras. Biochem. Pharmacol. 85:689-703.

Olson, K.R. (2011) Hydrogen sulfide is an oxygen sensor in the carotid body. Respir.Physiol Neurobiol.179:103-110 (doi:10.1016/j.resp.2011.09.010).

Olson, K.R. (2011) Hydrogen sulfide is an oxygen sensor in the carotid body. Respiratory Physiol.Neurobiol. Doi:10.1016.

Olson, K.R. (2011) The Therapeutic Potential of Hydrogen Sulfide: Separating Hype from Hope. Am.J.Physiol.Regul Integr Comp Physiol. 301:R297-R312.

Olson, K.R., Whitfield, N.L. (2010) Hydrogen sulfide and oxygen sensing in the cardiovascular system. Antioxidents and Redox Signaling 12:1219-1234.

Olson, K.R. and Donald, J.A. (2009) Nervous control of circulation - the role of gasotransmitters, NO, CO, and H2S. Acta Histochemica 111:244-256.

Olson, K.R. (2009) Is Hydrogen Sulfide a Circulating “Gasotransmitter” in Vertebrate Blood? Biochem.Biophys.Acta-Bioenergetics 1787:856-863.

Olson, K.R. (2008) Hydrogen Sulfide and Oxygen Sensing: Implications in Cardiorespiratory Control. J.Exp.Biol. 211:2727-2734.

Book Chapter

Olson, K.R. (2013) Chapter 2. Hydrogen sulfide as an oxygen sensor.  In: H. Kimura (ed) Hydrogen sulfide and its therapeutic Applications. DOI 10.1007/978-3-7091-1550-3_2. Wein: Springer-Verlag. pp. 37-62.

Peer-reviewed

Olson.K.R., DeLeon,E.R., Gao,Y., Hurley,K., Sadauskas,V, Batz,C. And Stoy,G.F. (2013) Thiosulfate: a Readily Accessible Source of Hydrogen Sulfide in Oxygen Sensing. Am.J.Physiol.Regul Integr Comp Physiol. 305: R592.-R603. 

Olson, K.R. (2013) Hydrogen Sulfide: two feet on the gas and none on the brake? Frontiers in Physiology 4:1-3.  doi: 10.3389

Olson, K.R. (2013) A Theoretical examination hydrogen sulfide metabolism and its potential in autocrine/paracrine oxygen sensing. Resp. Physiol. Neurobiol. 186: 173-179.

Skovgaard, N, Olson, K.R. (2012) Hydrogen sulfide mediates hypoxic vasoconstriction through a production of mitochondrial ROS in trout gills. Am.J.Physiol.Regul Integr Comp Physiol. 303:R487-R494. 

Chattopadhyay,M., Kodel,R. Olson,K.R., Kashfi,K. (2012) NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model. Biochem.Biophys.Res.Commun. 491:523-528.

Madden,J.A.; Ahlf,S.B.; Dantuma,M.W.; Olson,K.R.; Roerig,D.L.(2012) Precursors and inhibitors of hydrogen sulfide synthesis affect acute hypoxic pulmonary vasoconstriction in the intact lung. J.Appl.Physiol. 112:411-418 (doi: 10.1152/japplphysiol.01049.2011).

Dombkowski,R.A. Naylor,M.G. Shoemaker,E. Smith,M. DeLeon,E.R. Stoy,G.F. Gao,Y., Olson,K.R.  (2011) Hydrogen sulfide (H2S) and hypoxia inhibit salmonid gastrointestinal motility: evidence for H2S as an oxygen sensor. J.Exp.Biol. 214:4030-4040.

DeLeon,E.R. Stoy,G.F., Olson,K.R.(2012) Passive loss of hydrogen sulfide in biological experiments.Anal.Biochem. 421:203-207 (doi:10.1016/j.ab.2011.10.016)

Dombkowski, R.A., Naylor, M.G., Shoemaker, E., Smith, M., DeLeon, E.R., Stoy,G.F., Gao, Y. and Olson, K.R. (2011) Hydrogen sulfide (H2S) and hypoxia inhibit salmonid gastrointestinal motility: evidence for H2S as an oxygen sensor. J.Exp.Biol. (In press).

Olson, K.R., Whitfield, N.L., Bearden, S.E., St.Leger, J., Nilson, E., Gao, Y., Madden, J.A. (2010) Hypoxic pulmonary vasodilation: A paradigm shift with a hydrogen sulfide mechanism. Am.J.Physiol.Regul Integr Comp Physiol. 298:R51 -R60.

Olson, K.R., Forgan, L.G., Dombkowski, R.A. and Forster, M.E. (2008) Oxygen Dependency of Hydrogen Sulfide-mediated Vasoconstriction in Cyclostome Aortas. J.Exp.Biol. 211:2205-2213.

Olson, K.R., Healy, M., Qin, Z., Vulesevic, B., Duff, D.W., Whitfield, N.L., Yang, G., Wang, R., and  Perry, S.F., (2008) Hydrogen Sulfide as an Oxygen Sensor in Trout Gill Chemoreceptors Am.J.Physiol. Regul Integr Comp Physiol 295:R669-R680.

Whitfield, N.L., Kreimier, E.L., Verdial, F.C., Skovgaard, N., Olson, K.R. (2008) A Reappraisal of H2S/sulfide concentration in vertebrate blood and its potential significance in ischemic preconditioning and vascular signaling. Am.J.Physiol.Regul Integr Comp Physiol. 294:R1930 -R1937.

Russell, M.J., Dombkowski, R.A. and Olson, K.R. (2007) Effects of hypoxia on vertebrate blood vessels. J.Exp.Zool. 309(2):55-63.

Dombkowski, R.A., Doellman, M.M., Head, S.K. and Olson, K.R. (2006) Hydrogen sulfide mediates hypoxia-induced relaxation of trout urinary bladder smooth muscle. J. Exp. Biol. 209: 3234-3240.

 Olson, K.R., Dombkowski, R.A., Russell, M.J., Doellman, M.M., Head, S.K. and Madden, J.A. (2006) Hydrogen sulfide as an oxygen sensor/transducer in vertebrate hypoxic vasoconstriction and hypoxic vasodilation. J.Exp.Biol. 209:4011-4023.

 Dombkowski, R.A.. Russell, M.J., Schulman, A.A., Doellman, M.M., and Olson, K.R. (2005) The vertebrate phylogeny of hydrogen sulfide vasoactivity.   Am.J.Physiol Regul Integr Comp Physiol 288:R243-R252. (Epub 9/2/04).

Dombkowski, R.A, Russell, M.J., and Olson, K.R. (2004) Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout.  Am.J.Physiol Regul Integr Comp Physiol 286:R678-R685. (Epub 12/17/03).

Dombkowski, R.A.. Russell, M.J., Schulman, A.A., Doellman, M.M., and Olson, K.R. (2005) The vertebrate phylogeny of hydrogen sulfide vasoactivity. Am.J.Physiol Regul Integr Comp Physiol 288:R243-R252. (Epub 9/2/04)

Smith, M.P., Dombkowski, R.A., Wincko, J.T. and Olson, K.R. (2006) Effect of pH on Rainbow Trout Blood Vessels and Gill Vascular Resistance. J.Exp.Biol. 209: 2586-2594.

Olson, K.R., Dombkowski, R.A., Russell, M.J., Doellman, M.M., Head, S.K. and Madden, J.A. (2006) Hydrogen sulfide as an oxygen sensor/transducer in vertebrate hypoxic vasoconstriction and hypoxic vasodilation. J.Exp.Biol. 209:4011-4023.

Dombkowski, R.A., Doellman, M.M., Head, S.K. and Olson, K.R. (2006) Hydrogen sulfide mediates hypoxia-induced relaxation of trout urinary bladder smooth muscle. J. Exp. Biol. 209: 3234-3240.

Chen, X., Moon, T.W., Olson, K.R., Dombkowski, R.A., and Perry, S.F. (2007)The effects of salt-induced hypertension on α1-adrenoreceptor expression and cardiovascular physiology in the rainbow trout (Oncorhynchus mykiss). Am.J.Physiol Regul Integr Comp Physiol 293:R1384-R1392. (Epub 06/07)

Olson, K.R. and Hoagland, T.M. (2008) Effects of Freshwater/Saltwater Adaptation and Dietary Salt on Fluid Compartments, Blood Pressure and Venous Capacitance in Trout. Am.J.Physiol Regul Integr Comp Physiol: 294:R1061-R1067.

Russell, M.J., Dombkowski, R.A. and Olson, K.R. (2007) Effects of hypoxia on vertebrate blood vessels. J.Exp.Zool. 309(2):55-63.

Olson, K.R., Forgan, L.G., Dombkowski, R.A. and Forster, M.E. (2008) Oxygen Dependency of Hydrogen Sulfide-mediated Vasoconstriction in Cyclostome Aortas. J.Exp.Biol. 211:2205-2213.

Olson, K.R., Healy, M., Qin, Z., Vulesevic, B., Duff, D.W., Whitfield, N.L., Yang, G., Wang, R., and Perry, S.F., (2008) Hydrogen Sulfide as an Oxygen Sensor in Trout Gill Chemoreceptors Am.J.Physiol. Regul Integr Comp Physiol 295:R669-R680.

Johnson, K.E., Olson, K.R., (2009) Responses of the trout cardiac natriuretic peptide system to manipulation of salt and water balance. Am.J.Physiol. Regul Integr Comp Physiol 296:R1170-R1179.

Foster, J.M., Forster, M.E., Olson, K.R. (2008) Different sensitivities of arteries and veins to vasoactive drugs in a hagfish, Eptatretus cirrhatus". Comp.Biochem.Physiol. 148:107-111.

Whitfield, N.L., Kreimier, E.L., Verdial, F.C., Skovgaard, N., Olson, K.R. (2008) A Reappraisal of H2S/sulfide concentration in vertebrate blood and its potential significance in ischemic preconditioning and vascular signaling. Am.J.Physiol.Regul Integr Comp Physiol. 294:R1930 -R1937.

Conklin, D.J., Lillywhite, H.B., Bishop, B., Hargens, A.R., Olson, K.R. (2009) Rhythmic contractility in the hepatic portal "corkscrew" vein of the rat snake. Comp. Biochem. Physiol. 152:389-397.

Dombkowski, R.A., Whitfield, N.L., Motterlini, R., Gao, Y. and Olson, K.R. (2009) Effects of carbon monoxide on trout and lamprey vessels. Am.J.Physiol.Regul Integr Comp Physiol. 296:R114 -R149.

Johnson,K.R. and Olson.K.R. (2009) The response of non-traditional natriuretic peptide production sites to salt and water manipulations in the rainbow trout. J.Exp.Biol. 212:2991-2997.

Wegner,N.C., Sepulveda,C.A., Olson.K.R. ,Hyndman,K.A. and Graham,J.B. (2010) Functional Morphology of the Gills of the Shortfin Mako, Isurus oxyrinchus, a Lamnid Shark. J.Morphol. 271:937-938.

Johnson,K.R.; Hoagland,T.M.; Olson,K.R. (2011) Endogenous vascular synthesis of B-type and C-type natriuretic peptides in the rainbow trout. J.Exp.Biol. 214:2709-2717.

Olson, K.R., Whitfield, N.L., Bearden, S.E., St.Leger, J., Nilson, E., Gao, Y., Madden, J.A. (2010) Hypoxic pulmonary vasodilation: A paradigm shift with a hydrogen sulfide mechanism. Am.J.Physiol.Regul Integr Comp Physiol. 298:R51-R60.

DeLeon,E.R. Stoy,G.F., Olson,K.R.(2012) Passive loss of hydrogen sulfide in biological experiments.Anal.Biochem. 421:203-207 (doi:10.1016/j.ab.2011.10.016)

Dombkowski,R.A. Naylor,M.G. Shoemaker,E. Smith,M. DeLeon,E.R. Stoy,G.F. Gao,Y., Olson,K.R. (2011) Hydrogen sulfide (H2S) and hypoxia inhibit salmonid gastrointestinal motility: evidence for H2S as an oxygen sensor. J.Exp.Biol. 214:4030-4040.

Madden,J.A.; Ahlf,S.B.; Dantuma,M.W.; Olson,K.R.; Roerig,D.L.(2012) Precursors and inhibitors of hydrogen sulfide synthesis affect acute hypoxic pulmonary vasoconstriction in the intact lung. J.Appl.Physiol. 112:411-418 (doi: 10.1152/japplphysiol.01049.2011).

Chattopadhyay,M., Kodel,R. Olson,K.R., Kashfi,K. (2012) NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model. Biochem.Biophys.Res.Commun. 491:523-528.

Skovgaard, N, Olson, K.R. (2012) Hydrogen sulfide mediates hypoxic vasoconstriction through a production of mitochondrial ROS in trout gills. Am.J.Physiol.Regul Integr Comp Physiol. 303:R487-R494.

*Olson, K.R. (2013) A Theoretical examination hydrogen sulfide metabolism and its potential in autocrine/paracrine oxygen sensing. Resp. Physiol. Neurobiol. 186: 173-179.

*Olson, K.R. (2013) Hydrogen Sulfide: two feet on the gas and none on the brake? Frontiers in Physiology 4:1-3. doi: 10.3389/fphys.2013.00002.

*Olson.K.R., DeLeon,E.R., Gao,Y., Hurley,K., Sadauskas,V, Batz,C. And Stoy,G.F. (2013) Thiosulfate: a Readily Accessible Source of Hydrogen Sulfide in Oxygen Sensing. Am.J.Physiol.Regul Integr Comp Physiol. 305: R592-R603.

Agne,A.M., Baldin,J.P., Benjamin,A.R., Orogo-Wenn,M.C., Wichmann,L., Olson,K.R., Walters,D.V., Althaus,M. (2015) Hydrogen sulfide decreases beta-adrenergic agonist-stimulated lung liquid clearance by inhibiting ENaC-mediated transepithelial sodium absorption. Am.J.Physiol.Regul Integr Comp Physiol. 308: R636-R649.


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