A. Personal Information:

Name: Maria Teresa Cristina Runnegar

Business Address
Division of Gastrointestinal and Liver Diseases
Department of Medicine
University of Southern California
Health Sciences Campus
Mudd Memorial Building 401
1333 San Pablo Avenue
Los Angeles CA 90033

Business Telephone
(323) 442-3231

E-mail: runnegar@hsc.usc.edu

B. Education:

High School
Lourdes' Hill School for Girls and E.T.C., Brisbane, Australia, 1958-59

College or University
University of Queensland, Brisbane, Australia, BSc with First Class Honors, 1966
University of New England, Armidale, Australia, BA, 1981

Graduate School
University of Queensland, Brisbane,Australia, PhD, 1968

Honors and Awards
University Medal for outstanding academic achievement, University of Queensland, Brisbane, Australia, 1966
Commonwealth Postgraduate Award, 1966-68

C. Professional Background:

Academic Appointments

Teaching Fellow of Biochemistry, University of Queensland, 1964-65
Tutor and Part-time Lecturer of Biochemistry, University of New England 1970-72, 1976-78
Research Associate in Biochemistry, University of New England 1973-75, 1979-1980
Research Fellow in Biochemistry, University of New England 1981-1987
Visiting Assistant Professor of Microbiology, University of California, Los Angeles 1987-1989
Lecturer of Microbiology,University of California, Los Angeles 1989-1990
Associate Professor of Research Medicine, University of Southern California, Los Angeles 1990-present

D. Society Memberships:

Australian Biochemical Society, 1965-
Society of Toxicology, 1994-
American Society for Cell Biology, 1995-
American Association for the Study of Liver Diseases, 1995-

E. Consultantships:

Californian

Consultant, California State Department of Health Services, Berkeley, in the investigation of the occurrence and effects on public health of toxic blooms in water supplies statewide, and on the development of strategies to minimize the impact of such blooms, 1990-present

Other

Consultant to many Water Supply Authorities, and Departments of Health in the States of New South Wales, Victoria, South Australia and Queensland in Australia. Tested toxic blooms in potable water supplies, advised on the control and public health implications of such blooms, 1978-1987.

F. Research Activities:

Complete Bibliography

Appended

Major Areas of Research Interest

Cellular targets of microcystin action in hepatocytes. Effect of protein phosphatase inhibitors in the regulation of microtubule dependent vesicle transport in hepatocytes (collaboration with Dr Sarah Hamm-Alvarez, University of Southern California, Los Angeles)

Metabolic consequences of protein phosphatase inhibition in the liver. Transport of xenobiotic organic anions into liver. Mode of action of the novel cyanobacterial toxin cylindrospermopsin. effects on GSH synthesis and metabolism and cytotoxicity in hepatocytes, histological and EM changes in mice dosed with the alkaloid (collaboration with Professor Wanda Hasckek, University of Illinois, Champaign Urbana).

biosynthetic pathway for the alkaloid in the cyanobacterium Cylindrospermopsis raciborskii, (collaboration with Professor Richard Moore, University of Hawaii, Honolulu).

Research Grants in Past Five Years

1. Microcystins, Natural Environmental Toxins: Mode of Action Principal Investigator National Institutes of Health: NIEHS Direct costs $ 688,865 1990-1996

2. Microcystins, Natural Environmental Toxins: Mode of Action Principal Investigator National Institutes of Health: NIDDK Direct costs $ 470,604 1996-99

BIBLIOGRAPHY

1. de Jersey J, Runnegar MTC and Zerner B. Oxazolinones as enzyme acylating agents. Biochem Biophys Res Comm 25: 383-388, 1966.

2. Runnegar MTC, Blakeley RL, Fernley RT, Webb EC and Zerner B. The system: hydroxylamine-oxygen-cupric ion. A model hydroxylase in the inactivation of ox and pig liver carboxylesterases. Biochim Biophys Acta 167: 632-634, 1967.

3. Runnegar MTC, Scott K, Webb EC and Zerner B. Carboxylesterases (E.C. 3.1.1) purification and titration of ox liver carboxylesterase. Biochemistry 8: 2013-2018, 1969.

4. Runnegar MTC, Webb EC and Zerner B. Carboxylesterases (E.C. 3.1.1) dissociation of ox liver carboxylesterase. Biochemistry 8: 2018-2026, 1969.

5. Stoops JK, Horgan DJ, Runnegar MTC, de Jersey J, Webb EC and Zerner B. Carboxylesterases (E.C. 3.1.1) kinetic studies on carboxylesterases. Biochemistry 8: 2026-2033, 1969.

6. Inkerman PA, Scott K, Hamilton SE, Bennett EA and Zerner B. Carboxylesterases (E.C. 3.1.1) purification and titration of chicken, sheep and horse liver carboxylesterases. Can J Biochem 53: 536-546, 1975.

7. Elleman TC, Falconer IR, Jackson ARB and Runnegar MTC. Isolation, characterization and pathology of the toxin from a Microcystis aeruginosa (Anacystis cyanea) bloom. Aust J Biol Sci 31: 209-218, 1978.

8. Falconer IR, Jackson ARB, Langley J, Runnegar MT. Liver pathology in mice in poisoning by the blue-green alga Microcystis aeruginosa. Aust J Biol Sci 34: 179-187, 1981.

9. Runnegar MTC, Falconer IR and Silver J. Deformation of isolated rat hepatocytes by a peptide hepatotoxin from the blue-green alga Microcystis aeruginosa. N-S Arch Pharmacol 317: 268-272, 1981.

10. Runnegar MTC and Falconer IR. The in vivo and in vitro biological effects of the peptide hepatotoxin from the blue-gren alga Microcystis aeruginosa. S Afric J Science 78: 363-366, 1982.

11. Falconer IR, Beresford AM and Runnegar MT. Evidence of liver damage by toxin from a bloom of blue- green alga, Microcystis aeruginosa. Med J Aust 1: 511-514, 1983.

12. Jackson ARB, McInnes A, Falconer IR and Runnegar MT. Clinical and pathological changes in sheep experimentally poisoned by the blue-green alga Microcystis aeruginosa. Vet Pathol 21: 102-113, 1984.

13. Hawkins PR, Runnegar MTC, Jackson ARB and Falconer IR. Severe hepatotoxicity caused by the tropical cyanobacterium (blue-green alga) Cylindrospermopsis raciborskii (Woloszynska) Seenaya and Subba Raju isolated from a domestic water supply reservoir. J Appl Environ Microbiol 50: 1292-1295, 1985.

14. Botes DP, Wessels L, Kruger H, Runnegar MTC, Santikarn S, Smith RJ, Barna JCJ and Williams DM. Structural studies on cyanoginosins-LR,-YR,-YA, and-YM, peptide toxins from Microcystis aeruginosa. J Chem Soc, Perkin Trans 2747-2748, 1985.

15. Runnegar MTC and Falconer IR. Effect of toxin from the cyanobacterium Microcystis aeruginosa on ultrastructural morphology and actin polymerization in isolated hepatocytes. Toxicon 24: 109-115, 1986.

16. Jackson ARB, Runnegar MTC, Cumming RB and Brunner JF. Experimental acute intoxication of young layer and broiler chickens with the cyanobacterium (blue green alga) Microcystis aeruginosa. Avian Pathol 15: 741-748, 1986.

17. Runnegar MTC, Falconer IR, Buckley T and Jackson ARB. Lethal potency and tissue distribution of 125I-labelled toxic peptides from the blue-green alga Microcystis aeruginosa. Toxicon 24: 506-509, 1986.

18. Falconer IR, Buckley T and Runnegar MTC. Biological half-life, organ distribution and excretion of 125I-labelled toxic peptide from the blue-green alga Microcystis aeruginosa. Aust J Biol Sci 39: 17-21, 1986.

19. Runnegar MTC, Andrews J, Gerdes RG and Falconer IR. Injury to hepatocytes induced by a peptide toxin from the cyanobacterium Microcystis aeruginosa. Toxicon 25: 1235-1239, 1987.

20. Falconer IR and Runnegar MTC. Effects of the peptide toxin from Microcystis aeruginosa on intracellular calcium, pH and membrane integrity in mammalian cells. Chem-Biol Interactions 63: 215-225, 1987.

21. Runnegar MTC, Jackson ARB and Falconer IR. Toxicity of the cyanobacterium Nodularia spumigena Mertens. Toxicon 26: 143-151, 1988.

22. Falconer IR, Smith JV, Jackson ARB, Jones A and Runnegar MTC. Oral toxicity of a bloom of the cyanobacterium Microcystis aeruginosa administered to mice over periods up to 1 year. J Toxicol Environ Health 24: 291-305, 1988.

23. Runnegar MTC, Jackson ARB and Falconer IR. Toxicity to mice and sheep of a bloom of the cyanobacterium (blue-green alga) Anabaena circinalis. Toxicon 26: 599-602, 1988.

24. Falconer IR, Runnegar MTC, Buckley TH, Huyn VL and Bradshaw P. Use of powdered and granular activated carbon to remove toxicity from drinking water containing cyanobacterial blooms. Amer Waterworks Assoc J. 81: 102-105, 1989.

25. Runnegar MTC, Gerdes RG and Falconer IR. The uptake of the cyanobacterial hepatotoxin microcystin by isolated rat hepatocytes. Toxicon 29: 43-51, 1991.

26. Ohtani I, Moore RE and Runnegar MTC. Cylindrospermopsin, a potent hepatotoxin from the blue- green alga Cylindrospermopsis raciborskii. J Amer Chem Soc 114: 7942-44, 1992.

27. Moore RE, Ohtani I, Moore BS, de Koning CB, Yoshida WY, Runnegar MTC and Carmichael WW. Cyanobacterial toxins. Gazz. Chem. Ital. 123: 329-336, 1993.

28. Runnegar MT, Kong S and Berndt N. Protein phosphatase inhibition and in vivo hepatotoxicity of microcystins. Amer. J. Physiol. 265: G224-G230, 1993.

29. Runnegar MT, Kong S, Zhong Y-Z, Ge J-L and Lu, S. The role of glutathione in the toxicity of a novel cyanobacterial alkaloid cylindrospermopsin in cultured rat hepatocytes. Biochem. Biophys. Res. Comm. 201: 235-241, 1994.

30. Runnegar MT, Kong S, Zhong Y-Z and Lu, S. Inhibition of GSH synthesis by cyanobacterial alkaloid cylindrospermopsin in cultured hepatocytes. Biochem. Pharmacol. 49: 219-225, 1995.

31. Runnegar MT, Maddatu T, DeLeve LD, Berndt N and Govindarajan S. Differential toxicity of the protein phosphatase inhibitors Microcystin and Calyculin A. J. Pharm. Exp. Ther.: 273: 545-553, 1995.

32. Runnegar MT, Berndt and Kaplowitz N. Microcystin uptake and inhibition of protein phosphatases: effect of chemoprotectants and self- inhibition in relation to known hepatic transporters. Tox. & Appl. Pharmac.: 134: 264-272, 1995.

33. Runnegar MT, Berndt N, Kong S, Lee EYC and Zhang L. In vivo and in vitro binding of microcystin to protein phosphatases 1 and 2A. Biochem. Biophys. Res. Comm. 216: 162-169. 1995

34. Hamm-Alvarez SF, Wei X, Berndt N and Runnegar M. Microcystin and okadaic acid differentially alter microtubule-dependent vesicle transport and microtubule subpopulations in hepatocytes: evidence for PP1 and PP2A dependent mechanisms. Amer J Physiol 271: C929-C943, 1996

35. Runnegar M, Wei X, Berndt N and Hamm-Alvarez SF. Transferrin receptor recycling in hepatocytes is regulated by protein phosphatase 2A, possibly through effects on microtubule-dependent transport. Hepatology 26: 176-185, 1997.

36. Solter PF, Wollenberg GK, Chu FS and Runnegar MT. Prolonged sublethal exposure to the protein phosphatase inhibitor microcystin-LR, results in multiple hepatotoxic effects. Submitted to Veterinary Pathology