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Kenneth R. Olson, Ph.D.

Emeritus Professor, Cellular & Integrative Physiology
Indiana University School of Medicine - South Bend
Adjunct Professor, Department of Biological Sciences
University of Notre Dame
Concurrent Professor, Department of Chemical Engineering
University of Notre Dame

Ph.D., Michigan State University

         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.

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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. (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.

Peer-reviewed

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).