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.
Awards & Honors
Recent Significant Publications
S.D. Fouse, J.L. Nakamura, C.D. James, S. Chang, J.F. Costello.Sensitivity of primary glioblastoma cells to therapy is patient-specific and independent of the stem cell phenotype.. Neuro-Oncology. 2013. Dec 4 (epub ahead of print). PMID: 24311636
S.E. Braunstein, J.L. Nakamura. Radiotherapy-induced malignancies: Review of epidemiology, pathobiology and evolving technical approaches for mitigating risk.. Frontiers in Oncology. 2013;3:73. PMID: 23565507
M. Wahl, A. Hwang, J. Nakamura, I. Barani, S. Fogh, P. Sneed, M. McDermott, A. Sahgal, L. Ma. Individual Beam Sharpening Improves Composite Dose Fall-off Near a Target for Non-isocentric Cyberknife Radiosurgery.. Technol Cancer Res Treat 2013 Aug;12(4):341-8. PMID: 23369157
Fogh S, Ma L, Gupta N, Sahgal A, Nakamura JL, Barani I, Sneed PK, McDermott M, Larson DA. High-precision volume-staged Gamma Knife surgery and equivalent hypofractionation dose schedules for treating large arteriovenous malformations.. J Neurosurgery 2012 Dec; 117 Suppl: 115-9. PMID: 23205798
F L. Ma, S. Fogh, N. Gupta, A. Hwang, D. Pinnaduwage, J. Nakamura, I. Barani, M. McDermott, P. K. Sneed, D. Larson and A. Sahgal. A technique for achieving submillimeter accuracy of volume-staged stereotactic radiosurgery.. Journal of Radiosurgery and SBRT. 2012; 2(1):11-17.
G. Choi, B. Huang, E. Pinarbasi, S.E. Braunstein, A.E. Horvai, S. Kogan, S. Bhatia, B. Faddegon, J.L. Nakamura. Genetically mediated Nf1 loss in mice promotes diverse radiation-induced tumors modeling second malignant neoplasms. Cancer Res. 2012 Dec 15;72(24):6425-34.PMID: 23071067
Caballero JA, Sneed PK, Lamborn KR, Ma L, Denduluri S, Nakamura JL, Barani IJ, McDermott MW. Prognostic factors for survival in patients treated with stereotactic radiosurgery for recurrent brain metastases after prior whole brain radiotherapy. Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):303-9.PMID: 22079723
Ma L, Lee L, Barani I, Hwang A, Fogh S, Nakamura J, McDermott M, Sneed P, Larson DA, Sahgal A. Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery. Phys Med Biol. 2011 Nov 21;56(22):7247-56.PMID: 22037677
Nakamura JL, Phong C, Pinarbasi E, Kogan SC, Vandenberg S, Horvai AE, Faddegon BA, Fiedler D, Shokat K, Houseman BT, Chao R, Pieper RO, Shannon K., Dose-dependent effects a focal fractionated irradiation on secondary malignant neoplasms in Nf1 mutant mice. Cancer Res. 2011 Jan 1;71(1):106-15.PMID: 21199799
Descovich M, Sneed PK, Barbaro NM, McDermott MW, Chuang CF, Barani IJ, Nakamura JL, Lijun M., A dosimetric comparison between Gamma Knife and CyberKnife treatment plans for trigeminal neuralgia., J Neurosurg. 2010 Dec;113 Suppl:199-206.PMID:21222296
L. Ma, A. Sahgal, C. Chuang, M. Descovich, P. Petti, V. Smith, L. Verhey, N. Barbaro, M. McDermott, K. Huang, J. Nakamura, P. Sneed, D. Larson. Functional Relationship between the volume of a near-target peripheral isodose line and its isodose value for Gamma Knife Radiosurgery. Radiosurgery 2010, Vol. 7, pp.75-83.DOI:10.1159/000288720
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 Nov 15;75(4):1132-40.Epub 2009 Apr 3. PMID:19345514
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, 2008 Aug 15;68(16):6516-23.
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.
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.
Nakamura JL, Haas-Kogan DA, Pieper RO., Glioma invasiveness responds variably to irradiation in a co-culture model, Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):880-6.
Nakamura JL., The epidermal growth factor receptor in malignant gliomas: pathogenesis and therapeutic implications, Expert opinion on therapeutic targets. 2007 Apr;11(4):463-72. Review.