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| Medical Degree: |
M.D., Cornell University Medical College, 1991
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| Medical Board Certification: |
Anatomic Pathology, American Board of Pathology, 1997
Neuropathology, American Board of Pathology, 1997
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| Fellowship: |
Research, Howard Hughes Medical Institute, 1996 - 1998
Neuropathology, UCLA School of Medicine, 1993 - 1995
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| Residency: |
Anatomic & Clinical Pathology, UCLA School of Medicine, 1992 - 1996
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| Internship: |
Psychiatry, UCLA Neuropsychiatric Hospital, 1991 - 1992
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| Laboratory Address: |
David Geffen School of Medicine at UCLA
10833 Le Conte Avenue
Los Angeles, CA 90095
UNITED STATES
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| Work Address: |
Office
CHS 13-317
Campus 173216
Los Angeles, CA 90095
UNITED STATES
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Fax Number:
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(310) 267-2058
Office/Lab Fax
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Work Phone Number:
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(310) 794-7512
Mischel Laboratory
(310) 825-2339
Michelle Martinez, Administrative Assistant
(310) 825-2783
Mischel Laboratory
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Molecular pathogenesis of brain tumors
In cancer, genetic and epigenetic alterations result in cascades of deregulated molecular events leading to genetically complex highly individual tumors. The complexity is daunting, but finding consistencies that can be therapeutically exploited is necessary for the development and clinical application of new treatments. The critical need is to develop strategies for identifying reliable biochemical signatures for key deregulated molecules, focusing on the molecules that can be therapeutically exploited singly or in combination. Traditional pathological examination is unlikely to provide sufficient insight about underlying molecular alterations to guide selection of patients for these molecularly targeted therapies. My research program is built around identifying molecular subsets that can be used to inform treatment decisions. To move beyond traditional pathologic analysis of glioblastoma we have: 1) identified clinically relevant molecular subsets of glioblastoma (Mischel et al., Oncogene 2003; Shai et al., Oncogene 2003; Freije et al., Cancer Research 2004); 2) begun to dissect the modular structure of gene co-expression networks so that novel pathways can be identified and targeted (Mischel et al., 2004); 3) identified genetic alterations that can modify response to targeted molecular therapy in glioblastoma (Wang et al., Oncogene 2004; Lu et al., Laboratory Investigation 2004) and 4) developed approaches for determining the relevant signal transduction pathway profiles that can be used to select patients for targeted molecular therapy (Choe et al., Cancer Research 2003; Wang et al., 2004, under review and Mellinghoff et al., under review). Based on this work, we were invited to submit a review on molecular classification of brain cancer in Nature Reviews Neuroscience (Mischel et al., Nature Reviews Neuroscience, 2004).
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Molecular pathogenesis of brain tumors
In cancer, genetic and epigenetic alterations result in cascades of deregulated molecular events leading to genetically complex highly individual tumors. The complexity is daunting, but finding consistencies that can be therapeutically exploited is necessary for the development and clinical application of new treatments. The critical need is to develop strategies for identifying reliable biochemical signatures for key deregulated molecules, focusing on the molecules that can be therapeutically exploited singly or in combination. Traditional pathological examination is unlikely to provide sufficient insight about underlying molecular alterations to guide selection of patients for these molecularly targeted therapies. My research program is built around identifying molecular subsets that can be used to inform treatment decisions. To move beyond traditional pathologic analysis of glioblastoma we have: 1) identified clinically relevant molecular subsets of glioblastoma (Mischel et al., Oncogene 2003; Shai et al., Oncogene 2003; Freije et al., Cancer Research 2004); 2) begun to dissect the modular structure of gene co-expression networks so that novel pathways can be identified and targeted (Mischel et al., 2004); 3) identified genetic alterations that can modify response to targeted molecular therapy in glioblastoma (Wang et al., Oncogene 2004; Lu et al., Laboratory Investigation 2004) and 4) developed approaches for determining the relevant signal transduction pathway profiles that can be used to select patients for targeted molecular therapy (Choe et al., Cancer Research 2003; Wang et al., 2004, under review and Mellinghoff et al., under review). Based on this work, we were invited to submit a review on molecular classification of brain cancer in Nature Reviews Neuroscience (Mischel et al., Nature Reviews Neuroscience, 2004).
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Dr. Mischel graduated from the University of Pennsylvania with a B.A. in Philosophy in 1984. He received his M.D. from Cornell University Medical College in 1991, graduating Alpha Omega Alpha. Dr. Mischel was trained in Anatomic Pathology and Neuropathology at UCLA. Dr. Mischel did his post-doctoral research in the laboratory of Dr. Louis F. Reichardt at the Howard Hughes Medical Institute at UCSF, studying basic signal transduction biology in the developing nervous system. Dr. Mischel joined the active faculty of UCLA as an Assistant Professor in 1998, Associate Professor with tenure in 2004 and was promoted to Professor in 2006. Also in 2006, Dr. Mischel became Joint- Professor for the Molecular & Medical Pharmacology Department. Dr. Mischel is the recipient of a number of awards including the Pfizer New Faculty Award in Neuroscience, Stop Cancer Next Generation Award, the Johnny Mercer Foundation Award and he is currently a finalist for the Burroughs Welcome Fund Clinical Scientist Award in Translational Research.
Expertise: Dr. Mischel is a board certified neuropathologist with expertise in signal transduction biology. His laboratory has expertise in quantitative analysis of signal transduction pathways, stem-cell related pathways, and gene expression networks in clinical samples. His laboratory focuses on the development and application of molecularly targeted therapies for glioblastoma and on the application of emerging technologies to identify the patients most likely to benefit from these new treatments.
Please visit the Mischel Lab Click here:
Visit the UCLA Pathology Site here: Pathology
Visit the Jonnson Cancer Center here:
JCC
Visit UCLA Molecular & Medical Pharmacology Site here: Pharmacology
Visit the UCLA ACCESS Faculty page here:
ACCESS
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Tso CL, Freije WA, Day A, Chen Z, Merriman B, Perlina A, Lee Y, Dia EQ, Yoshimoto K, Mischel PS, Liau LM, Cloughesy TF, Nelson SF. Distinct Transcription Profiles of Primary and Secondary Glioblastoma Subgroups.
Cancer Research.
2006; 66(1):
159-67.
Carlson MR, Zhang B, Fang Z, Mischel PS, Horvath S, Nelson SF. Gene connectivity, function, and sequence conservation: predictions from modular yeast co-expression networks.
BMC Genomics.
2006; 7(1):
40.
Wang C-C, Liao Y-P, Mischel PS, Iwamoto KS, Cacalano NA, McBride WH. HDJ-2 as a target for radiosensitization of glioblastoma multiforme cells by the farnesyltransferase inhibitor, R115777 and the role of the p53/p21 pathway..
Cancer Research.
2006; in press:
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Pope WB, Lai A, Nghiemphu P, Mischel P, Cloughesy TF MRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy.
Neurology.
2006; 66(8):
1258-60.
Mischel PS, Cloughesy TF, Mellinghoff IK. PTEN loss as a mechanism of resistance to EGFR tyrosine kinases inhibitors.
Clinical Cancer Research.
2006; Invited Review:
.
Wang C-C, Liao Y-P, Mischel PS, Iwamoto KS, Cacalano NA, McBride WH. Primary gioblastoma express mesenchymal stem-like properties.
2006; In press:
.
Tso CL, Shintaku P, Chen J, Chen Z, Yoshimoto K, Mischel PS, Cloughesy TF, Liau LM, Nelson SF Primary gioblastoma express mesenchymal stem-like properties.
Molecular Cancer Research.
2006; In Press:
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Wang M, Lu K, Zhu S, Dia E, Vivanco I, Shackleford G, Cavenee W, Mellinghoff I, Cloughesy TF, Sawyers C, Mischel PS. mTOR inhibition promotes response to EGFR kinase inhibitors in PTEN-deficient and PTEN-intact glioblastoma cells..
Cancer Research.
2006; In Press:
.
Liau LM, Prins RM, Kiertscher SM, Odesa SK, Kremen TJ, Giovannone AJ, Lin JW, Chute DJ, Mischel PS, Cloughesy TF and Roth MD Dendritic Cell Vaccination in Glioblastoma Patients Induces Systemic and Intracranial T-cell Responses Modulated by the Local CNS Tumor Microenvironment.
Clinical Cancer Research.
2005; 11(15):
5515-5525.
Lu KV, Jong KA, Kim GY, Singh J, Dia EQ, Yoshimoto K, Wang MY, Cloughesy TF, Nelson SF and Mischel PS Differential induction of glioblastoma migration and growth by two forms of pleiotrophin.
Journal of Biological Chemistry.
2005; 280(29):
26953-64.
Chen W, Cloughesy TF, Kamdar N, Satyamurthy, Bergscheider M, Liau L, Mischel P, Czernin J, Phelps ME, Silverman DHS. Imaging Proliferation in Brain Tumors with FLT-PET.
Journal of Nuclear Medicine.
2005; 46(6):
945-952.
Pope WB, Sayre J, Perlina A, Villablanca P, Mischel PS, Cloughesy TF MR imaging correlates of survival in patients with high grade gliomas. American Journal of Neuroradiology .
American Journal of Neuroradiology.
2005; 26(10):
2466-2474.
Pope WB, Sayer J, Perlina A, Villablanca JP, Mischel PS, Cloughesy TF. Magnetic Resonance Imaging Correlates of Survival in Patients with High Grade Gliomas.
American Journal of Neuroradiology.
2005; 26(10):
2466-2474.
Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JHY, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao PN, Beroukhim R, Peck TC, Lee JC, Sellers WR, StokoeD , Prados M, Cloughesy TF, Sawyers CL and Mischel PS. Molecular determinants of EGFR kinase inhibitor response in glioblastoma.
New England Journal of Medicine.
2005; 353(19):
2012-2024.
Stillman BN, Mischel PS, Baum LG. New Roles for Galectins in Brain Tumors-From Prognostic Markers to Therapeutic Targets.
2005; (15):
124-132.
Mehrian Shai R, Reichardt JK, Ya-Hsuan H, Kremen TJ, Liau LM, Cloughesy TF, Mischel PS, Nelson SF Robustness of gene expression profiling in glioma specimen samplings and derived cell lines.
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2005; 20(136 (1-2)):
99-103.
Frieje WA, Castro-Vargas FE, Fang Z, Horvath S, Cloughesy TF, Liau LM, Mischel PS, Nelson SF. Gene Expression Profiling of Gliomas Strongly Predicts Survival.
Cancer Res. .
2004; 15, 64(18):
6503-6510.
Lu KV, Jong K, Rajasekaran AK, Cloughesy TF, Mischel PS. Upregulation of Tissue Inhibitor of Metalloproteinases (TIMP)-2 Promotes Matrix Metalloproteinase (MMP)-2 Activation and Cell Invasion in Human Glioblastoma Cell Line..
2004; 84(1):
8-20.
Mischel PS, Cloughesy TF Targeted molecular therapy of GBM.
Brain Pathol.
2003; 13(1):
52-61.
Choe G, Horvath S, Cloughesy TF, Crosby K, Seligson D, Palotie A, Inge L, Smith B, Sawyers CL, Mischel PS. Analysis of the P13K Signaling Pathway in Glioblastoma Patients.
2003; 63(11):
2742-2746.
Shai R, Shi T, Kremen TJ, Horvath S, Liau LM, Cloughesy TF, Mischel PS*, Nelson SF*, (*Co-Senior authors) Gene Expression Profiling Identites Distinct Subtypes of Glioblastoma.
2003; 22(31):
4918-4923.
Mischel PS, Shai R, Shi T, Horvath S, Lu KV, Choe G, Seligson D, Kremen TJ, Palotie A, Liau L, Cloughesy T, Nelson SF Identification of Molecular Subtypes of Glioblastoma by Gene Expression Profiling .
Oncogene. .
2003; 217;2(15):
2361-2372.
Mischel PS, Nelson SF, Cloughesy TF Molecular analysis of glioblastoma: pathway profiling and its implications for patient therapy..
Cancer biology & therapy. .
2003; 2(3):
242-7.
Mischel PS, Umbach JA, Eskandari S, Smith SG, Gundersen CB, Zampighi GA. Nerve growth factor signals via pre-existing TrkA receptor oligomers..
Biophysical Journal
2002; 83(2):
968-976.
Liau LM, Black KL, Martin NA, Sykes SN, Brontstein JM, Joubin-Steele L, Mischel PS, Belldegrun A, Cloughesy TF Treatment of a glioblastoma patient by vaccination with autologous dendritic cells pulsed with allogenic major histocompatibility complex class I-matched tumor peptides.
Neurosurgical Focus .
2001; (9):
1-5.
Vinters HV, Park SH, Johnson MW, Mischel PS, Catania M, Kerfoot C Cortical dysplasia, genetic abnormalities and neurocutaneous syndromes.
Dev. Neuroscience .
1999; (21):
248-59.
Bakshi R, Mazziotta JC, Mischel PS, Jahan R, Seligson DB, Vinters HV Lymphomatosis cerebri presenting as a rapidly progressive dementia: clinical, neuroimaging and pathologic findings.
Dement Geriatr Cogn Disord.
1999; 10(2):
152-7.
Vinters HV, Farrell MA, Mischel PS, Anders KA Diagnostic Neuropathology..
1998;
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Mischel PS, Vinters HV Focal Cortical Dysplasia..
Neurobase
1998;
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Mischel PS, VInters HV Neuropathology of developmental disorders..
Epilepsy: A comprehensive textbook
1998;
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Mathern GL, Babb TL, Mischel PS, Vinters HV, Pretorius JK, Leite JP and Peacock WJ Childhood generalized and mesial temporal epilepsies demonstrate different amounts and patterns of hippocampal neuron loss and mossy fiber synaptic reorganization.
Brain.
1997; (119):
965-87.
Menchine M, Emelin JK, Mischel PS, Haag TA, Norman MG, Pepkowitz SH, Welsh CT, Townsend JJ, Vinters HV Tissue and cell-type specific expression of the Tuberous Sclerosis Gene, TSC2, in human tissues. .
Modern Pathology.
1997; (9):
1071-80.
Kaufer D, Mendez MF, Mischel PS, Verity MA, Benson DF Alien hand syndrome in adult onset orthochromatic leukodystrophy.
Behavioral Neurology .
1996; (9):
5-10.
De Salles, Solberg AA, Mischel TD, Massoud P, Plasencia TF, Goetsch A, De Souza SE, Vinuela F Arteriovenous malformation animal model for radiosurgery: the rete mirabile.
AJNR Am J Neuroradiol.
1996; 17(8):
1451-8.
Mischel PS, Nguyen L, Vinters HV Cerebral cortical dysplasia associated with pediatric epilepsy..
Journal of Neuropathology and Experimental Neurology
1995; 54:
137-53.
Mischel PS, Vinters HV Coccidioidomycosis: Selected neuropathologic and vasculopathic manifestations and their clinical correlates..
Clinical Infectious Diseases
1995; 20(2):
400-405.
McPherson SE, Kuratani JD, Cummings JL, Shih J, Mischel PS and Vinters HV Creutzfeldt-Jakob Disease with mixed transcortical aphasia.
Behavioral Neurology .
1994; (7):
197-203.
Wang Y, Zhu S, Cloughesy TF, Liau LM, Mischel PS p53 disruption profoundly alters the response of human glioblastoma cells to DNA topoisomerase I inhibition..
Oncogene. .
2004; 12, 23(6):
1283-90.
Mischel PS, Smith SG, Vining ER, Valletta JS, Mobley WC, Reichardt LF The extracellular domain of p75NTR is necessary to inhibit neurotrophin-3 signaling through TrkA..
The Journal of biological chemistry. .
2001; 276(14):
11294-301.
Jahan R, Mischel PS, Curran JG, Peacock WJ, Shields DW, Vinters HV Bilateral neuropathologic changes in a child with hemimegalencephaly..
Pediatric neurology. .
1997; 17(4):
344-9.
Farahani K, Mischel PS, Black KL, De Salles AA, Anzai Y, Lufkin RB Hyperacute thermal lesions: MR imaging evaluation of development in the brain..
Radiology. .
1995; 196(2):
517-20.
Geschwind DH, FitzPatrick M, Mischel PS, Cummings JL Sneddon's syndrome is a thrombotic vasculopathy: neuropathologic and neuroradiologic evidence..
Neurology. .
1995; 45(3 Pt 1):
557-60.
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