Professional Focus
Dr. Nakamura's research interests include investigations in radiosurgery as well as the molecular biology of malignant glioma. She is interested in examining radiotherapy conformality and its impact on tumor control and clinical outcome, particularly with respect to preservation of neurologic function. Because several radiosurgery techniques are currently used to treat central nervous system tumors, she has compared Gamma Knife radiosurgery and Intensity Modulated Radiosurgery for complex skull base lesions in order to understand the dosimetric differences between these modalities, and the implications on normal tissue function. She is extending this research line to include an analysis of Cyberknife radiosurgery plans, which may add to our understanding of the relative merits and indications for radiosurgical techniques.
In addition, Dr. Nakamura has on-going basic science studies and translational studies for the treatment of malignant gliomas. She previously showed that PI3-Kinase based signaling aberrations, which are common in malignant gliomas, can contribute to the notable radioresistance of these tumors through the major signaling molecule PKB/Akt. She has extended these initial findings with mechanistically oriented studies to determine how the PKB/Akt downstream effector mTOR contributes to gliomagenesis. Recent results from her laboratory suggest that mTOR and its regulatory protein raptor, contribute significantly towards transformation in both engineered human glioma models as well as established human malignant glioma cell lines. Although mTOR is known to be involved in regulating cell growth via its nutrient sensing roles, how these functions support tumor development is not understood. Her studies add significant insight into how mTORâ??s physiologic functions may be usurped during transformation, and further, how this mechanism may be therapeutically targeted.
Combined therapy (chemotherapy delivered concurrently with radiotherapy) is a major paradigm in the management of malignant gliomas, and Dr. Nakamura envisions developing her primary findings and using her expertise as a radiation oncologist to develop treatment protocols for CNS tumors. She hopes that understanding the molecular underpinnings of gliomagenesis and the technical aspects of conformal radiotherapy delivery will result in more, and healthier, survivors of central nervous system tumors
Publications
J.S. Lee, A. Jani, C. Pelizzari, R. Weichselbaum, E. Vokes, D. Haraf, G. T.Y. Chen. Volumetric Visualization of Head and Neck CT Data for Treatment Planning. Int J Rad Oncol Biol Phys. 1999 Jun 1; 44(3):693-703.
J.L. Nakamura, L.J. Verhey, V. Smith, P.L. Petti, K.R. Lamborn, D.A. Larson, W.M. Wara, M.W. McDermott, P.K. Sneed. Dose conformity of gamma knife radiosurgery and risk factors for complications. Int J Rad Oncol Biol Phys. 2001 Dec 1; 51(5):1313-9.
J.L. Nakamura, A. Pirzkall, M. Carol, V. Smith, P. Xia, L.J. Verhey, W.M. Wara, P.L. Petti, P.K. Sneed. Comparison of Intensity Modulated Radiosurgery to Gamma Knife for Skull Base Lesions. Int J Rad Oncol Biol Phys 2003 Jan l 55(1):99-109.
J.L. Nakamura, A. Karlsson, N.D. Arvold, A.R. Gottschalk, R.O. Pieper, D. Stokoe, D.A. Haas-Kogan. PKB/Akt mediates radiosensitization by the signaling inhibitor LY294002 in human malignant gliomas. Journal of Neuro-oncology 2005 Feb; 71(3):215-22.
A.R. Gottschalk, A. Doan, J.L. Nakamura, D.A. Haas-Kogan, D. Stokoe. Inhibition of PI3 kinase causes cell death through a PKB dependent mechanism and growth arrest through a PKB independent mechanism. Int J Rad Oncol Biol Phys 2005 Mar 15;61(4):1183-8.
A.R. Gottschalk, A. Doan, J.L. Nakamura, D. Stokoe, D.A. Haas-Kogan. Inhibition of phosphatidylinositol-3-kinase causes increased sensitivity to radiation through a PKB-dependent mechanism. Int J Rad Oncol Biol Phys 2005 Nov15;63(4):1221-7.
A. Panner, J.L. Nakamura, A. T. Parsa, P. Rodriguez-Viciana, M. S. Berger, D. Stokoe, and R. O. Pieper. mTOR-independent translational control of the extrinsic cell death pathway by RalA.. Mol. Cell. Biol. 2006: Oct; 26(20): 7345-57.
J.L. Nakamura, D.A. Haas-Kogan, R.O. Pieper. Glioma invasiveness responds variably to irradiation in a co-culture model. Int J Rad Oncol Biol Phys 2007; 69(3): 880-6.
J.L. Nakamura. The role of EGFR in the ppathogenesis of glioblastoma multiforme.. Expert Opinion on Therapeutic Targets. 2007 Apr; 11(4) 463-72.
N. Kased, K. Huang, J.L. Nakamura, A. Sahgal, D.A. Larson, M.W. McDermott,P.K. Sneed. Gamma Knife Radiosurgery for brainstem metastases: the UCSF experience.. J Neuro-Oncology 2008 Jan; 86(2): 195-205.
J.L. Nakamura, E. Garcia, R.O. Pieper. S6K1 plays a key role in glial transformation. Cancer Research, August 15, 2008.
D.W. Golden, K.R. Lamborn, M.W. McDermott, S. Kunwar, W.M. Wara, J.L. Nakamura, P.K. Sneed. Prognostic Grading for Radiosurgical Treatment of Brain Metastases: Is One System Adequate? J Neurosurgery 2008 Dec (109): 77-86.
N. Kased, D.K. Binder, M.W. McDermott, J.L. Nakamura, K. Huang, M.S. Berger, W.M. Wara, P.K. Sneed. Gamma Knife Radiosurgery for Brain Metastases from Primary Breast Cancer. Int J Rad Oncol Biol Phys 2009 Apr 2 [Epub ahead of print].
Book and Chapters
Nakamura JL, Haas-Kogan DA. PI3Kinase, Akt, mTOR and Internal Signaling Pathways. Handbook of Brain Tumor Chemotherapy. Cambridge: Elsevier, 2006.
Dai CY, Nakamura JL, Haas-Kogan DA, Larson DA. CNS Tumors. In: Hansen EK, Roach MR (Ed.). Handbook of Radiation Oncology. New York: Springer, 2006.
Lee B, Nakamura JL. Bone Tumors. In: Hansen EK, Roach MR (Ed.). Handbook of Radiation Oncology. New York: Springer, 2006.
