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Dr. Ross Mikkelsen - Pathology - Virginia Commonwealth University

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NAME<br />

<strong>Mikkelsen</strong>, <strong>Ross</strong> B.<br />

eRA COMMONS USER NAME<br />

RMIKKELSEN<br />

BIOGRAPHICAL SKETCH<br />

Provide the following information for the key personnel and other significant contributors.<br />

Follow this format for each person. DO NOT EXCEED FOUR PAGES.<br />

POSITION TITLE<br />

Professor<br />

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)<br />

INSTITUTION AND LOCATION<br />

DEGREE<br />

(if applicable)<br />

YEAR(s)<br />

FIELD OF STUDY<br />

<strong>University</strong> of California at Santa Barbara B.A. 1964­1968 Biology<br />

<strong>University</strong> of California at Santa Barbara Ph.D. 1968­1973 Biology<br />

Tufts <strong>University</strong> School of Medicine, Boston MA Post­doc 1974­1978 Membrane Biochemistry<br />

A. Positions and Honors<br />

Positions and Employment<br />

1973­1975 Research Fellow, Division of Radiobiology, Department of Therapeutic Radiology, Tufts<br />

<strong>University</strong> School of Medicine, Boston, MA<br />

1976­1978 Instructor, Division of Radiobiology, Department of Therapeutic Radiology, Tufts <strong>University</strong><br />

School of Medicine, Boston, MA<br />

1978­1988 Assistant Professor, Division of Radiobiology, Department of Therapeutic Radiology, Tufts<br />

<strong>University</strong> School of Medicine, Boston, MA<br />

1985­1988 Assistant Professor, Department of Physiology, Tufts <strong>University</strong> School of Medicine,<br />

Boston, MA<br />

1988­1995 Associate Professor, Department of Radiation Oncology, <strong>Virginia</strong> <strong>Commonwealth</strong><br />

<strong>University</strong> (VCU), Richmond, VA<br />

1990­1996 Section Chief, Research Section, Department of Radiation Oncology, VCU, Richmond, <strong>Virginia</strong><br />

1989­1995 Associate Professor, Department of Microbiology and Immunology, VCU, Richmond, VA<br />

1995­present Professor, Departments of Radiation Oncology and Microbiology/Immunology, VCU,<br />

Richmond VA<br />

2004­present Professor of Physics, VCU, Richmond, VA<br />

2007­present Chairman, Division of Molecular Radiobiology, VCU, Richmond, VA<br />

Other Experience and Professional Memberships<br />

1992­1994 Malaria Study Section, U.S. Agency for International Development<br />

2001­2003 Radiation Oncology Review Panel, DOD Breast Cancer Program<br />

2004­2006 Radiation Oncology Review Panel, DOD Prostate Cancer Program<br />

2007­ Co­Chairman, Physical Imaging Review Panel, DOD Prostate Cancer Program<br />

2005 Member, NIAID Study Section on Radiation Countermeasures<br />

2006 Member, NIAID ARS Medical Countermeasures Review Committee<br />

2007 Member, NCI Study Section, Lung Cancer and Inflammation<br />

2007 Member, 2008/01 NCI­Subcommittee F ­ Manpower & Training<br />

2008­ Member, 2008 VA Oncology Subcommittee<br />

Honors<br />

1973­1975 Fellow, Damon Runyon­Walter Winchell Memorial Cancer Foundation<br />

1975­1976 Fellow, National Cancer Institute


B. Selected Peer­Reviewed Publications (in chronological order)<br />

1. <strong>Mikkelsen</strong>, R. B., Stedman, T., Schmidt­Ullrich, R., and Lin, P. S. Effects of tamoxifen and protein kinase C<br />

inhibitors on hyperthermic cell killing. Int J Radiat Oncol Biol Phys, 20: 1039­1045, 1991.<br />

2. <strong>Mikkelsen</strong>, R. B. and Gentry, C. A radiation­induced inhibitor of chromosome condensation and nuclear<br />

envelope breakdown in HeLa cells. Radiat Res, 132: 158­161, 1992.<br />

3. Todd, D. G. and <strong>Mikkelsen</strong>, R. B. Ionizing radiation induces a transient increase in cytosolic free [Ca 2+ ] in<br />

human epithelial tumor cells. Cancer Res, 54: 5224­5230, 1994.<br />

4. Grant, S., Freemerman, A. J., Gregory, P. C., Martin, H. A., Turner, A. J., <strong>Mikkelsen</strong>, R., Chelliah, J.,<br />

Yanovich, S., and Jarvis, W. D. Induction of apoptotic DNA fragmentation and c­jun downregulation in human<br />

myeloid leukemia cells by the permeant Ca 2+ chelator BAPTA/AM. Oncol Res, 7: 381­392, 1995.<br />

5. Gatmaitan, Z., Varticovski, L., Ling, L., <strong>Mikkelsen</strong>, R., Steffan, A. M., and Arias, I. M. Studies on fenestral<br />

contraction in rat liver endothelial cells in culture. Am J Pathol, 148: 2027­2041, 1996.<br />

6. Rao, A. S., Freemerman, A. J., Jarvis, W. D., Chelliah, J., Bear, H. D., <strong>Mikkelsen</strong>, R., and Grant, S. Effect<br />

of AS101 on bryostatin 1­mediated differentiation induction, cell cycle arrest, and modulation of drug­induced<br />

apoptosis in human myeloid leukemia cells. Leukemia, 10: 1150­1158, 1996.<br />

7. Schmidt­Ullrich, R. K., <strong>Mikkelsen</strong>, R. B., Dent, P., Todd, D. G., Valerie, K., Kavanagh, B. D., Contessa, J.<br />

N., Rorrer, W. K., and Chen, P. B. Radiation­induced proliferation of the human A431 squamous carcinoma<br />

cells is dependent on EGFR tyrosine phosphorylation. Oncogene, 15: 1191­1197, 1997.<br />

8. Carter, S., Auer, K. L., Reardon, D. B., Birrer, M., Fisher, P. B., Valerie, K., Schmidt­Ullrich, R., <strong>Mikkelsen</strong>,<br />

R., and Dent, P. Inhibition of the mitogen activated protein (MAP) kinase cascade potentiates cell killing by low<br />

dose ionizing radiation in A431 human squamous carcinoma cells. Oncogene, 16: 2787­2796, 1998.<br />

9. Kavanagh, B. D., Dent, P., Schmidt­Ullrich, R. K., Chen, P., and <strong>Mikkelsen</strong>, R. B. Calcium­dependent<br />

stimulation of mitogen­activated protein kinase activity in A431 cells by low doses of ionizing radiation. Radiat<br />

Res, 149: 579­587, 1998.<br />

10. Contessa, J. N., Reardon, D. B., Todd, D., Dent, P., <strong>Mikkelsen</strong>, R. B., Valerie, K., Bowers, G. D., and<br />

Schmidt­Ullrich, R. K. The inducible expression of dominant­negative epidermal growth factor receptor­CD533<br />

results in radiosensitization of human mammary carcinoma cells. Clin Cancer Res, 5: 405­411, 1999.<br />

11. Reardon, D. B., Contessa, J. N., <strong>Mikkelsen</strong>, R. B., Valerie, K., Amir, C., Dent, P., and Schmidt­Ullrich, R. K.<br />

Dominant negative EGFR­CD533 and inhibition of MAPK modify JNK1 activation and enhance radiation<br />

toxicity of human mammary carcinoma cells. Oncogene, 18: 4756­4766, 1999.<br />

12. Todd, D. G., <strong>Mikkelsen</strong>, R. B., Rorrer, W. K., Valerie, K., and Schmidt­Ullrich, R. K. Ionizing radiation<br />

stimulates existing signal transduction pathways involving the activation of epidermal growth factor receptor<br />

and ERBB­3, and changes of intracellular calcium in A431 human squamous carcinoma cells. J Recept Signal<br />

Transduct Res, 19: 885­908, 1999.<br />

13. Tombes, R. M., <strong>Mikkelsen</strong>, R. B., Jarvis, W. D., and Grant, S. Downregulation of delta CaM kinase II in<br />

human tumor cells. Biochim Biophys Acta, 1452: 1­11, 1999.<br />

14. Schmidt­Ullrich, R. K., Dent, P., Grant, S., <strong>Mikkelsen</strong>, R. B., and Valerie, K. Signal transduction and cellular<br />

radiation responses. Radiat Res, 153: 245­257, 2000.<br />

15. Bowers, G., Reardon, D., Hewitt, T., Dent, P., <strong>Mikkelsen</strong>, R. B., Valerie, K., Lammering, G., Amir, C., and<br />

Schmidt­Ullrich, R. K. The relative role of ErbB1­4 receptor tyrosine kinases in radiation signal transduction<br />

responses of human carcinoma cells. Oncogene, 20: 1388­1397, 2001.


16. Lammering, G., Hewit, T. H., Hawkins, W. T., Contessa, J. N., Reardon, D. B., Lin, P. S., Valerie, K., Dent,<br />

P., <strong>Mikkelsen</strong>, R. B., and Schmidt­Ullrich, R. K. Epidermal growth factor receptor as a genetic therapy target for<br />

carcinoma cell radiosensitization. J Natl Cancer Inst, 93: 921­929, 2001.<br />

17. Lammering, G., Valerie, K., Lin, P. S., <strong>Mikkelsen</strong>, R. B., Contessa, J. N., Feden, J. P., Farnsworth, J., Dent,<br />

P., and Schmidt­Ullrich, R. K. Radiosensitization of malignant glioma cells through overexpression of<br />

dominant­negative epidermal growth factor receptor. Clin Cancer Res, 7: 682­690, 2001.<br />

18. Leach, J. K., Van Tuyle, G., Lin, P. S., Schmidt­Ullrich, R., and <strong>Mikkelsen</strong>, R. B. Ionizing radiation­induced,<br />

mitochondria­dependent generation of reactive oxygen/nitrogen. Cancer Res, 61: 3894­3901, 2001.<br />

19. Leach, J. K., Black, S. J., Schmidt­Ullrich, R. K., and <strong>Mikkelsen</strong>, R.B. Activation of constitutive nitric oxide<br />

synthase activity as an early signaling event induced by ionizing radiation. J Biol Chem, 277: 15400­15406,<br />

2002.<br />

20. Contessa, J. N., Hampton, J., Lammering, G., <strong>Mikkelsen</strong>, R. B., Dent, P., Valerie, K., and Schmidt­Ullrich,<br />

R. K. Ionizing radiation activates Erb­B receptor dependent Akt and p70 S6 kinase signaling in carcinoma cells.<br />

Oncogene. 21: 4032­4041, 2002.<br />

21. Ho, K. C., Leach, J. K., Eley, K., <strong>Mikkelsen</strong>, R.B., and Lin, P. S. A simple method of producing low oxygen<br />

conditions with oxyrase for cultured cells exposed to radiation and tirapazimine. Am J Clin Oncol, 26, E86­E91,<br />

2003.<br />

22. <strong>Mikkelsen</strong>, RB and Wardman, P. Biological chemistry of reactive oxygen and nitrogen and radiationinduced<br />

signal transduction mechanisms. Oncogene Reviews, 22, 5734­5754, 2003.<br />

23. Amorino GP, <strong>Mikkelsen</strong> RB, Valerie K, and Schmidt­Ullrich RK. Dominant­negative CREB inhibits<br />

proliferating cell nuclear antigen and DNA repair, leading to increased cellular radiosensitivity. J. Biol. Chem.<br />

278(32), 29394­29399, 2003.<br />

24. <strong>Mikkelsen</strong>, RB. Redox signaling mechanisms and radiation­induced bystander effects. Human and<br />

Experimental Toxicology, 23, 75­81, 2004.<br />

25. Lammering G, Hewit TH, Holmes M, Valerie K, Hawkins W, Lin PS, <strong>Mikkelsen</strong> RB, Schmidt­Ullrich RK.<br />

Inhibition of the Type III Epidermal Growth Factor Receptor Variant Mutant Receptor by Dominant­Negative<br />

EGFR­CD533 Enhances Malignant Glioma Cell Radiosensitivity. Clin Cancer Res. 10(19), 6732­6743, 2004.<br />

26. Sturla L­M, Amorino GP, Alexander MS, <strong>Mikkelsen</strong> RB, Valerie K and Schmidt­Ullrich RK. Requirement of<br />

Tyr992 and Tyr1173 in phosphorylation of the epidermal growth factor receptor by ionizing radiation and<br />

modulation by SHP2, J. Biol. Chem. 280, 14597­604, 2005<br />

27. Barrett, DM, Black SM, Todor H, Schmidt­Ullrich RK, and <strong>Mikkelsen</strong>, RB. Inhibition of Protein Tyrosine<br />

Phosphatases by Mild Oxidative Stresses is Dependent on S­Nitrosylation, J. Biol. Chem. 280, 14453­14461,<br />

2005.<br />

28. Contessa JN, Abell A, <strong>Mikkelsen</strong> RB, Valerie K, Schmidt­Ullrich RK. Compensatory ErbB3/c­Src signaling<br />

enhances carcinoma cell survival to ionizing radiation. Breast Cancer Res Treat. Nov 3, 1­11, 2006.<br />

29. Yakovlev VA and <strong>Mikkelsen</strong> RB A role for CaM­kinases in the cellular response to oxidative stress? Cancer<br />

Biol Ther 5, 1031­2, 2006.<br />

30. Yakovlev VA, Barani IJ, Rabender CS, Black SM, Leach KJ and <strong>Mikkelsen</strong> RB, Tyrosine Nitration of IkBa:<br />

A novel mechanism for NF­kB activation, Biochemistry, 46 (42), 11671 ­11683, 2007.


C. Research Support<br />

Ongoing Research Support<br />

NIH/NCI, 5R01CA65896­11 (<strong>Mikkelsen</strong>) 03/01/1995 – 02/28/09<br />

Radiation, ErbB activation and cellular growth control<br />

The major goals of this project are studying the role of protein tyrosine kinase activation of EGFR as an<br />

immediate early response to radiation and growth regulatory pathways and cellular radiosensitivity.<br />

Role: PI<br />

NIH/NCI T32 CA113277­01, (<strong>Mikkelsen</strong>) 07/01/07­06/30/12<br />

Training in Radiation Oncology Translational Research<br />

Training for 3 post­docs and 1 pre­doc in radiation oncology research.<br />

Role: PI<br />

NIH/NCI, 5RO1CA 90881­05 (<strong>Mikkelsen</strong>) 07/01/02­06/30/13<br />

Radiation­induced Nitric Oxide and Cellular Radiosensitivity<br />

The major goals of this project are to identify and characterize nitric oxide dependent<br />

sensing/amplification mechanisms of cytoplasmic ionization events.<br />

Role: PI

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