Sandeep Mittal, MD, FRCSC, FACS
Chair, Department of Neurosurgery
Professor, Departments of Neurosurgery and Oncology, Wayne State University
Leader, Neuro-Oncology Multidisciplinary Team, Karmanos Cancer Center
Co-Director, WSU/DMC Comprehensive Epilepsy Center
Director, Translational Neuro-Oncology Research Laboratory, Karmanos Cancer Institute
4160 John R Street, Suite 930
Detroit, MI 48201
Mentoring: Anthony Guastella (Year 4)
- Brain tumor neurobiology
- Epileptogenesis in tumor-associated epilepsy
- Immunotherapy for malignant gliomas
- Molecular imaging of primary and metastatic brain tumors
- Oncogenic drivers that lead to development of brain metastases
Dr. Mittal is Director of the Translational Neuro-Oncology Research Laboratory located at the Hudson-Webber Cancer Research Center, Karmanos Cancer Institute. The lab has several ongoing research projects focusing on brain tumor neurobiology for primary tumors meningiomas and glioblastomas and metastatic brain tumors derived from primary breast or lung cancer. We take advantage of our unique capability to utilize freshly-resected patient brain tumor specimens. In addition to traditional tissue studies, we also generate in vivo models of human brain tumors. in collaboration with Lisa A. Polin, PhD and the Animal Model and Therapeutics Evaluation Core (Karmanos Cancer Institute/Wayne State University).
MENINGIOMA – As part of our NIH-funded collaboration with Csaba Juhász, MD PhD, (Depts. of Pediatrics and Neurology), we have expanded our studies of tryptophan metabolism in brain tumors to include meningiomas (http://www.ncbi.nlm.nih.gov/pubmed/26092774). These tumors, arising from the arachnoid cap cells, are the most common primary brain tumor, and we have found that the kynurenine pathway of tryptophan metabolism is prominent and that molecular imaging with our radiotracer 11C-alpha-methyl-tryptophan (AMT) correlates with levels of tryptophan metabolizing enzymes. Furthermore, we have generated patient-derived xenograft models of human meningioma in immunocompromised mice (http://www.ncbi.nlm.nih.gov/pubmed/26174772) from our cell line KCI-MENG1, generated from a WHO Grade I meningioma tumor specimen. We are also developing a model from a WHO Grade III meningioma tumor specimen, KCI-MENG3.
GLIOBLASTOMA – Patient survival after glioblastoma diagnosis is dismal despite aggressive treatment strategies including surgery, radiotherapy, and chemotherapy. We have therefore developed patient-derived xenograft models that closely mimic the human disease. Our pre-clinical models share the same imaging characteristics with the 11C-alpha-methyl-tryptophan (AMT) radiotracer and will be invaluable for our translational studies of tryptophan metabolism. Anthony's award winning poster from the 2015 International Society for Tryptophan Research meeting highlights our pre-clinical glioblastoma models.
These pre-clinical models of human glioblastoma will also be used for immunotherapy studies using bispecific antibody-armed T cells in collaboration with Larry Lum, MD, DSc and Archana Thakur, PhD. In glioblastoma, EGFR amplification is found in ~50% of tumors. Our preliminary studies have used EGFR-targeted armed T cells co-injected with U87 glioblastoma cells. The T cells prevented the development of intracranial tumors and led to healthy survival in mice.
BREAST CANCER BRAIN METASTASES – Our recent study of breast cancer brain metastases in collaboration with Aliccia Bollig-Fischer, PhD, identified copy number variations of potential oncogenic drivers that were specific to the metastatic brain lesions, and were not the predominant drivers of the primary breast cancers. At the time of publication, this was the largest data set specifically assaying copy number variation in metastatic brain tumors derived from breast cancer (http://www.ncbi.nlm.nih.gov/pubmed/25970776). We are also developing patient-derived xenograft models of metastatic brain tumors from the different molecular subtypes of primary breast cancer. Hormone-negative, HER2+ and triple negative breast cancer have higher incidence rates of metastatic brain lesions than hormone-positive breast cancers. We currently have two mouse xenograft models of breast cancer brain metastases that are profiles, with several others in development. Studies are planned in collaboration with Nerissa Viola-Villegas, PhD, using the Her2+ model.
LUNG CANCER BRAIN METASTASES – Metastatic brain tumors derived from primary lung cancer are the most common brain tumor type. We have therefore developed a series of patient-derived xenograft models from patient specimens of lung cancer brain metastases. Pilot studies using the radiotracer 11C-alpha-methyl-tryptophan (AMT) in mice bearing these xenografts are underway.
In addition to the subcutaneous tumors shown above, we have also developed one of these tumor models into an orthotopic model by stereotactic injection of tumor cells into the mouse brain. Studies are planned in collaboration with Larry H. Matherly, PhD, to use this mouse model in pre-clinical studies of agents that target the proton-coupled folate transporter.
Kamson DO, Lee TJ, Varadarajan K, Robinette NL, Muzik O, Chakraborty PK, Snyder M, Barger GR, Mittal S, Juhász C. Clinical significance of tryptophan metabolism in the nontumoral hemisphere in patients with malignant glioma. J Nucl Med. 2014;55:1605-10.
Jain A, Hoeprich M, Mittal M, Kupsky WJ, Mittal S. Spontaneous intratumoral infarction - an unusual evolution of a falcine meningioma. Clin Neuropathol. 2014 Aug 27. [Epub ahead of print]
Xie Q, Mittal S, Berens ME. Targeting adaptive glioblastoma: an overview of proliferation and invasion. Neuro Oncol. 2014 Jul 30. [Epub ahead of print]
Ahmad A, Sethi S, Chen W, Ali-Fehmi R, Mittal S, Sarkar FH. Up-regulation of microRNA-10b is associated with the development of breast cancer brain metastasis. Am J Transl Res. 2014;6:384-90
Dholariya YN, Bansod YB, Vora RM, Mittal SS, Shirsat AE, Bhingare CL. Design and optimization of bilayered tablet of Hydrochlorothiazide using the Quality-by-Design approach. Int J Pharm Investig. 2014;4:93-101.
Mittal S, Pandey AK. Cerium oxide nanoparticles induced toxicity in human lung cells: role of ROS mediated DNA damage and apoptosis. Biomed Res Int. 2014;2014:891934.
Juhász C, Dwivedi S, Kamson DO, Michelhaugh SK, Mittal S. Comparison of amino acid positron emission tomographic radiotracers for molecular imaging of primary and metastatic brain tumors. Mol Imaging. 2014 Aug;13.
Shah AK, Mittal S. Invasive electroencephalography monitoring: Indications and presurgical planning. Ann Indian Acad Neurol. 2014;17:S89-94.
Shah AK, Mittal S. Evaluation of magnetic resonance imaging-negative drug-resistant epilepsy. Ann Indian Acad Neurol. 2014;17:S80-8.
Kamson DO, Mittal S, Robinette NL, Muzik O, Kupsky WJ, Barger GR, Juhász C. Increased tryptophan uptake on PET has strong independent prognostic value in patients with a previously treated high-grade glioma.Neuro Oncol. 2014;16:1373-83.
Brown EC, Muzik O, Rothermel R, Juhász C, Shah AK, Fuerst D, Mittal S, Sood S, Asano E. Evaluating signal-correlated noise as a control task with language-related gamma activity on electrocorticography. Clin Neurophysiol. 2014;125:1312-23.
Mittal S, Shah AK, Barkmeier DT, Loeb JA. Systems biology of human epilepsy applied to patients with brain tumors. Epilepsia. 2013;54:35-9.
Marupudi NI, Mittal M, Mittal S. Delayed pneumocephalus-induced cranial neuropathy.Case Rep Med. 2013;2013:105087.
Kumar G, Mittal S, Moudgil SS, Kupsky WJ, Shah AK. Histopathological evidence that hippocampal atrophy following status epilepticus is a result of neuronal necrosis. J Neurol Sci. 22=013;334:186-91.
Kamson DO, Mittal S, Buth A, Muzik O, Kupsky WJ, Robinette NL, Barger GR, Juhász C. Differentiation of glioblastomas from metastatic brain tumors by tryptophan uptake and kinetic analysis: a positron emission tomographic study with magnetic resonance imaging comparison. Mol Imaging. 2013;12:327-37.
Mittal S, Mittal M, Montes JL, Farmer JP, Andermann F. Hypothalamic hamartomas. Part 2. Surgical considerations and outcome. Neurosurg Focus. 2013;34:E7.
Mittal S, Mittal M, Montes JL, Farmer JP, Andermann F. Hypothalamic hamartomas. Part 1. Clinical, neuroimaging, and neurophysiological characteristics. Neurosurg Focus. 2013;34:E6.
Juhász C, Buth A, Chugani DC, Kupsky WJ, Chugani HT, Shah AK, Mittal S. Successful surgical treatment of an inflammatory lesion associated with new-onset refractory status epilepticus. Neurosurg Focus. 2013;34:E5.
Kojima K, Brown EC, Matsuzaki N, Rothermel R, Fuerst D, Shah A, Mittal S, Sood S, Asano E. Gamma activity modulated by picture and auditory naming tasks: intracranial recording in patients with focal epilepsy. Clin Neurophysiol. 2013;124:1737-44.
Burghardt T, Basha MM, Fuerst D, Mittal S. Crying with sorrow evoked by electrocortical stimulation. Epileptic Disord. 2013;15:72-5.
A complete list of Dr. Mittal's publications can be found here: http://mypub.org/mittal.
Education and Training:
10/1993 to 05/1997 - Doctor of Medicine & Master of Surgery (MD,CM), Faculty of Medicine, McGill University, Montreal, Quebec, Canada
07/1997 to 06/2004 - Neurosurgery Residency Training Program, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
07/2001 to 06/2003 - Clinical and Research Fellowship, Developmental Neurobiology, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
07/2004 to 06/2005 - Clinical Fellowship, Epilepsy Surgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
07/2005 to 06/2006 - Clinical Fellowship, Neuro-Oncological Surgery and Image-Guided Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
Cancer Biology Courses Taught:
CB7240 Principles of Cancer Therapy