Martha Stipanuk


Martha Stipanuk

227 Savage Hall
Phone: (607) 255-2683
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Curriculum Vitae
Biographical Statement:

Martha Stipanuk is the James Jamison Professor in Nutrition in the Division of Nutritional Sciences at Cornell University, where she has been a faculty member since 1977. She received her B.S. from the University of Kentucky, her M.S. from Cornell University, and her Ph.D. from the University of Wisconsin-Madison in nutritional biochemistry.

Dr. Stipanuk's professional career has focused on the study of amino acid metabolism, particularly the metabolism of the sulfur-containing amino acid cysteine. Her work has contributed to an understanding of the intermediary pathways of cysteine metabolism in mammalian cells and of the role of various tissues in cysteine metabolism, including glutathione synthesis and taurine production, within the whole body. The Stipanuk laboratory has played a major role in elucidating the physiological function, regulation, structure, and protein coenzyme formation  of cysteine dioxygenase, an iron-dependent enzyme that catalyzes the first step in the cysteinesulfinate-dependent pathway of cysteine catabolism. Cysteine dioxygenase plays a crucial role in regulating cysteine levels, in promoting taurine biosynthesis, and in restricting the metabolism of cysteine through the intermediate hydrogen sulfide, preventing sulfide toxicity and facilitating hydrogen sulfide signaling. The regulation of cysteine dioxygenase abundance and activity state occurs  specifically in response to cysteine levels.  The Stipanuk laboratory is also interested in elucidating the mechanism(s) by which the concentrations of  other amino acids are sensed by cells and how cells respond to changes in amino acid availability.

Dr. Stipanuk has a long-standing interest in teaching and course development in the area of nutrient metabolism. She has developed a multi-authored advanced textbook entitled “Biochemical, Physiological and Molecular Aspects of Human Nutrition” published by Saunders/Elsevier with the 3rd edition released in 2012 and the 4th edition in progress. At Cornell, she teaches graduate courses on “Regulation of Macronutrient Metabolism”  and “Nutritional Regulation of Mammalian Protein Synthesis and Degradation.”

In 2015, she was elected a Fellow of the American Society for Nutrition in recognition of her distinguished career in nutrition science research.

Teaching and Advising Statement:

My current teaching is primarily at the graduate student level.  In this context, I try to focus classwork and assignments on topics relevant to major contemporary research questions in molecular nutrition and metabolism, incorporating use of the literature and development of conceptual mapping of topics to faciliate an understanding of multiple and complex pathways and physiological processes involved in particular research areas.  In advising and mentoring both undergraduates and graduate students, I encourage students to pursue a range of areas of study and experiential learning relevant to their interests and to consider various possibilities for future studies and careers. In addition to using my expertise to serve Cornell students, I translate much of what I have learned teaching Cornell students into content and thinking critically questions for a textbook (now going into its 4th edition) on advanced nutriton and metabolism.

Current Professional Activities:

Cornell University Graduate Field Membership: Nutrition

Member of American Society for Nutrition; Member of Publications Management Committee

Member of the American Society for Biochemistry and Molecular Biology

Member of the American Society for Physiology

Current Research Activities:

Mechanisms of molecular regulation of key enzymes of cysteine metabolism in response to dietary changes; development and characterization of tissue-specific cysteine dioxygenase "knockout" mice; structure-function studies of thiol dioxygenases (cysteine dioxygenase, cysteamine dioxygenase); tissue-specific expression and function of enzymes in taurine and hydrogen sulfide biosynthetic pathways; amino acid deprivation and response to stress; role of amino acids in sensing of nutrient deprivation and activation of stress response pathways.

  • PhD 1977 - University of Wisconsin, Madison; Nutrition and Biochemistry
  • MS 1972 - Cornell University, Nutrition and Biochemistry
  • BS 1970 - University of Kentucky, Home Economics/Education

Courses Taught:

NS 6100 - Nutritional Regulation of Mammalian Protein Synthesis and Degradation

NS 6320 - Regulation of Macronutrient Metabolism

Mentor for graduate student NS 7030 presentation

Research mentor for graduate research

Related Websites:

DNS Home Page

Selected Publications:

  1. Niewiadomski, J., Zhou J.Q., Roman H.B., Liu X., Hirschberger L.L., Locasale J.W., and Stipanuk M.H. (2016) Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice.  Ann N Y Acad Sci, in press.
  2. Jurkowska H., Niewiadomski J., Hirschberger L.L., Roman H.B., Mazor K.M., Liu X., Locasale J.W., Park E., Stipanuk M.H. (2015) Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo. Amino Acids, in press [2015 Oct 20. Epub ahead of print].  
  3. Jurkowska H., Roman H.B., Hirschberger L.L., Sasakura K., Nagano T., Hanaoka K., Krijt J., Stipanuk M.H. (2014) Primary hepatocytes from mice lacking cysteine dioxygenase show increased cysteine concentrations and higher rates of metabolism of cysteine to hydrogen sulfide and thiosulfate. Amino Acids 46:1353-1365.  
  4. Sikalidis A.K., Mazor K.M., Lee J.I., Roman H.B., Hirschberger L.L., Stipanuk M.H. (2014) Upregulation of capacity for glutathione synthesis in response to amino acid deprivation: regulation of glutamate-cysteine ligase subunits. Amino Acids 46:1285-1296. 
  5. Sikalidis A.K., Mazor K.M., Kang M., Liu H., and Stipanuk M.H. (2013) Total 4EBP1 is elevated in liver of rats in response to low sulfur amino acid intake. J Amino Acids 2013:864757. doi: 10.1155/2013/864757.
  6. Driggers C.M., Cooley R.B., Sankaran B., Hirschberger L.L., Stipanuk M.H., and Karplus P.A. (2013) Cysteine dioxygenase structures from pH4 to 9: consistent cys-persulfenate formation at intermediate pH and a Cys-bound enzyme at higher pH. J Mol Biol. 425:3121-3136.
  7. Roman H.B., Hirschberger L.L., Krijt J., Valli A., Kožich V., and Stipanuk M.H. (2013) The cysteine dioxgenase knockout mouse: altered cysteine metabolism in nonhepatic tissues leds to excess H2S/HS- production and evidence of pancreatic and lung toxicity. Antioxid Redox Signal. 19:1321-1336.
  8. Ueki, I., Roman, H.B., Hirschberger, L.L., Junior, C., and Stipanuk, M.H. (2012) Extrahepatic tissues compensate for loss of hepatic taurine synthesis in mice with liver-specific knockout of cysteine dioxygenase. Am J Physiol Endocrinol Metab. 302:E1292-E1299.
  9. Ueki, I., Roman, H.B., Valli, A., Fieselmann, K., Lam, J., Peters, R., Hirschberger, L.L., and Stipanuk, M.H. (2011) Knockout of the cysteine dioxygenase gene results in severe impairment in taurine synthesis and increased catabolism of cysteine to hydrogen sulfide. Am J Physiol Endocrinol Metab. 301: E688-E684.
  10. Stipanuk M.H. and Ueki, I. (2011) Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur. J Inherit Metab Dis. 34:17-32. 
  11. Stipanuk MH, Simmons CR, Karplus PA, Dominy JE Jr. (2011) Thiol dioxygenases: unique families of cupin proteins. Amino Acids 41:91-102.
  12. Sikalidis A.K, Lee J-I., Stipanuk M.H. (2011) Gene expression and integrated stress response in HepG2/C3A cells cultured in amino acid deficient medium. Amino Acids 41:159-171.  
  13. Sikalidis A.K., Stipanuk M.H. (2010) Growing rats respond to a sulfur amino acid-deficien diet by phosphorylation of the a-subunit of eukaryotic initiation factor 2 heterotrimeric complex and induction of adaptive components of the integrated stress response. J Nutr. 140:1080-1085.
  14. Ueki, I. and Stipanuk, M.H. (2009) 3T3-L1 adipocytes and rat adipose tissue have a high capacity for taurine synthesis by the cysteine dioxygenase/cysteinesulfinate decarboxylase and cysteamine dioxygenase pathways.  J. Nutr. 139:207-214.
  15. Stipanuk, M.H., Ueki, I., Dominy, J.E. Jr., Simmons, C.R., and Hirschberger, L.L.  (2009) Cysteine dioxygenase: a robust system for regulation of cellular cysteine levels. Amino Acids 37:55-63. 
  16. Stipanuk, M.H., Dominy, J.E., Jr., Ueki, I., and Hirschberger, L.L. (2008) Measurement of cysteine dioxygenase activity and protein abundance.  Curr. Prot. Toxicol. 6.15.1-6.15.25. 
  17. Simmons, C.R., Krishnamoorthy, K., Granett, S.L., Schuller, D.J., Dominy, J.E. Jr., Begley, T.P., Stipanuk, M.H., and Karplus, P.A. (2008) A putative Fe2+-bound persulfenate intermediate in cysteine dioxygenase. Biochemistry 47:11390-11392. 
  18. Dominy, J.E. Jr., Hwang, J., Guo, S., Hirschberger, L.L., Zhang, S., and Stipanuk, M.H. (2008) Synthesis of amino acid cofactor in cysteine dioxygenase is regulated by substrate and represents a novel post-translational regulation of activity. J. Biol. Chem. 283:12188-12201.
  19. Lee, J-I., Dominy, J.E., Jr., Sikalidis, A. K., Hirschberger, L.L., Wang,W., and Stipanuk, M.H. (2008) HepG2/C3A cells respond to cysteine-deprivation by induction of the amino acid deprivation/integrated stress response pathway.  Physiol. Genomics 33:218-229. 
  20. Dominy,J. E. Jr., Simmons, C.R., Hirschberger, L.L., Hwang, J., Coloso, R.M., Stipanuk, M.H. (2007) Discovery and characterization of a second mammalian thiol dioxygenase: Cysteamine dioxygenase. J. Biol. Chem. 282:25189-25198.
  21. Dominy, J.E., Jr., Hwang, J., and Stipanuk, M.H.  (2007) Overexpression of cysteine dioxygenase reduces intracellular cysteine and glutathione pools in HepG2/C3A cells.  Am. J. Physiol. Endocrinol. Metab. 293:E62-E69.
  22. Stipanuk, M.H., Dominy, J.E. Jr., Lee, J-I., and Coloso, R.M. (2006) Mammalian cysteine metabolism: new insights into regulation of cysteine metabolism.  J. Nutr. 136:1652S-1659S.
  23. Dominy, J.E. Jr., Simmons, C.R., Karplus, P.A., Gehring, A.M., and Stipanuk, M.H. (2006) Identification and characterization of bacterial cysteine dioxygenases: a new route of cysteine degradation for eubacteria.  J. Bacteriol. 188:5561-5569. 
  24. Simmons,C.R., Liu, Q., Huang, Q., Hao, Q., Begley, T.P., Karplus, P.A., and Stipanuk, M.H. (2006) Crystal structure of mammalian cysteine dioxygenase: A novel mononuclear iron center for cysteine thiol oxidation. J. Biol. Chem. 281:18723-18733.  [Issue cover is CDO structure]






Selected Keywords:
cysteine, hydrogen sulfide, sulfur amino acids, taurine, sulfate, sulfide, glutathione, amino acid deprivation, integrated stress response, eukaryotic initiation factor 4E binding protein

The information on this bio page is taken from the CHE Annual Report.