Photo of Khalid Shah,  MS, PhD

Khalid Shah, MS, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-4821
Fax: (617) 643-7212


kshah@helix.mgh.harvard.edu

Khalid Shah, MS, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Radiology, Harvard Medical School
  • Neurologist, Radiology and Neurology, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Successful treatment of CNS pathologies remains one of the greatest challenges. The recognition that different stem cell types, including mesenchymal and neural stem cells can integrate appropriately throughout the mammalian brain following transplantation has unveiled new possibilities for their use in neural transplantation. Our laboratory has shown that different stem cell types home to sites of cerebral pathology and thus can be armed with therapeutic transgenes, a strategy that can be used to inhibit tumor growth by targeting angiogenesis or selectively inducing apoptosis in proliferating tumor cells in the brain.

Our research is based on developing clinically translatable models of both primary and metastatic brain tumors and stem cell based therapeutics that simultaneously target cell death and proliferation pathways in an effort to eradicate brain tumors. We have engineered different stem cells types (i) to secrete therapeutic protein, S-TRAIL (secreted tumor necrosis factor receptor-apoptosis inducing ligand) to specifically induce apoptosis in tumor cells and antiangiogenic TSP-1 (thrombospondin-1) to inhibit tumor angiogenesis. These stem cells are then used to populate primary tumors and their secondary microinvasive deposits in the brain. Recently our laboratory has also focused on targeting tumors that are resistant to TRAIL and different oncolytic viruses. As such we have developed stem cell deliverable bi-modal therapeutic molecules like EGFR targeting nanobody (ENb)-TRAIL and oncolytic herpes virus (oHSV) bearing TRAIL (oHSV-TRAIL) and shown their efficacy in mouse models of aggressive and invasive brain tumors. Inherently linked to the brain tumor therapy paradigm, we employ fluorescent/bioluminescent imaging markers and optical imaging techniques to track stem cells, image apoptosis and changes in tumor volumes in real time in vivo. We also explore the use of microRNAs inhibitors to target brain tumor specific microRNAs and the combination of clinically approved drugs, microRNA inhibitors and shRNAs with therapeutic stem cells in a variety of brain tumor models.

Publications

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  • Bagci-Onder T, Du W, Figueiredo JL, Martinez-Quintanilla J, Shah K. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells. Brain 2015; 138:1710-21. PubMed
  • Choi SH, Tamura K, Khajuria RK, Bhere D, Nesterenko I, Lawler J, Shah K. Antiangiogenic variant of TSP-1 targets tumor cells in glioblastomas. Mol Ther 2015; 23:235-43. PubMed
  • Stuckey DW, Hingtgen SD, Karakas N, Rich BE, Shah K. Engineering toxin-resistant therapeutic stem cells to treat brain tumors. Stem Cells 2015; 33:589-600. PubMed
  • Martinez-Quintanilla J, He D, Wakimoto H, Alemany R, Shah K. Encapsulated stem cells loaded with hyaluronidase-expressing oncolytic virus for brain tumor therapy. Mol Ther 2015; 23:108-18. PubMed
  • Bhere D, Shah K. Stem Cell-Based Therapies for Cancer. Adv Cancer Res 2015; 127:159-89. PubMed
  • Stuckey DW, Shah K. Stem cell-based therapies for cancer treatment: separating hope from hype. Nat Rev Cancer 2014; 14:683-91. PubMed
  • Redjal N, Zhu Y, Shah K. Combination of Systemic Chemotherapy with Local Stem Cell Delivered S-TRAIL in Resected Brain Tumors. Stem Cells 2014. PubMed
  • Sullivan JP, Nahed BV, Madden MW, Oliveira SM, Springer S, Bhere D, Chi AS, Wakimoto H, Rothenberg SM, Sequist LV, Kapur R, Shah K, Iafrate AJ, Curry WT, Loeffler JS, Batchelor TT, Louis DN, Toner M, Maheswaran S, Haber DA. Brain Tumor Cells in Circulation Are Enriched for Mesenchymal Gene Expression. 2014. PubMed
  • Srivastava J, Robertson CL, Rajasekaran D, Gredler R, Siddiq A, Emdad L, Mukhopadhyay ND, Ghosh S, Hylemon PB, Gil G, Shah K, Bhere D, Subler MA, Windle JJ, Fisher PB, Sarkar D. AEG-1 regulates retinoid X receptor and inhibits retinoid signaling. Cancer Res 2014; 74:4364-77. PubMed
  • Duebgen M, Martinez-Quintanilla J, Tamura K, Hingtgen S, Redjal N, Wakimoto H, Shah K. Stem cells loaded with multimechanistic oncolytic herpes simplex virus variants for brain tumor therapy. Journal of the National Cancer Institute 2014. PubMed
  • Kuruppu D, Brownell AL, Shah K, Mahmood U, Tanabe KK. Molecular imaging with bioluminescence and PET reveals viral oncolysis kinetics and tumor viability. Cancer Res 2014. PubMed
  • Zhu Y, Shah K. Multiple lesions in receptor tyrosine kinase pathway determine glioblastoma response to pan-ERBB inhibitor PF-00299804 and PI3K/mTOR dual inhibitor PF-05212384. Cancer Biol Ther 2014. PubMed
  • Du W, Uslar L, Sevala S, Shah K. Targeting c-Met Receptor Overcomes TRAIL-Resistance in Brain Tumors. PLoS ONE 2014; 9:e95490. PubMed
  • Stuckey DW, Shah K. TRAIL on trial: preclinical advances in cancer therapy. Trends Mol Med 2013; 19:685-94. PubMed
  • Martinez-Quintanilla J, Bhere D, Heidari P, He D, Mahmood U, Shah K. In vivo Imaging of the Therapeutic Efficacy and Fate of Bimodal Engineered Stem Cells in Malignant Brain Tumors. Stem Cells 2013. PubMed
  • Tamura K, Wakimoto H, Agarwal AS, Rabkin SD, Bhere D, Martuza RL, Kuroda T, Kasmieh R, Shah K. Multimechanistic tumor targeted oncolytic virus overcomes resistance in brain tumors. Mol Ther 2013; 21:68-77. PubMed
  • Guo Y, Yuan H, Cho H, Kuruppu D, Jokivarsi K, Agarwal A, Shah K, Josephson L. High efficiency diffusion molecular retention tumor targeting. PLoS ONE 2013; 8:e58290. PubMed
  • Shah K. Encapsulated stem cells for cancer therapy. Biomatter 2013. PubMed
  • Hingtgen S, Figueiredo JL, Farrar C, Duebgen M, Martinez-Quintanilla J, Bhere D, Shah K. Real-time multi-modality imaging of glioblastoma tumor resection and recurrence. J. Neurooncol. 2013; 111:153-61. PubMed
  • Srivastava J, Siddiq A, Emdad L, Santhekadur PK, Chen D, Gredler R, Shen XN, Robertson CL, Dumur CI, Hylemon PB, Mukhopadhyay ND, Bhere D, Shah K, Ahmad R, Giashuddin S, Stafflinger J, Subler MA, Windle JJ, Fisher PB, Sarkar D. Astrocyte elevated gene-1 promotes hepatocarcinogenesis: Novel insights from a mouse model. Hepatology 2012; 56:1782-91. PubMed
  • van de Water JA, Bagci-Onder T, Agarwal AS, Wakimoto H, Roovers RC, Zhu Y, Kasmieh R, Bhere D, Van Bergen En Henegouwen PM, Shah K. Therapeutic stem cells expressing variants of EGFR-specific nanobodies have antitumor effects. Proc Natl Acad Sci U S A 2012; 109:16642-7. PubMed
  • Kauer TM, Figueiredo JL, Hingtgen S, Shah K. Encapsulated therapeutic stem cells implanted in the tumor resection cavity induce cell death in gliomas. Nat Neurosci 2012; 15:197-204. PubMed
  • Hingtgen S, Kasmieh R, Elbayly E, Nesterenko I, Figueiredo JL, Dash R, Sarkar D, Hall D, Kozakov D, Vajda S, Fisher PB, Shah K. A first-generation multi-functional cytokine for simultaneous optical tracking and tumor therapy. PLoS ONE 2012; 7:e40234. PubMed
  • Nesterenko I, Wanningen S, Bagci-Onder T, Anderegg M, Shah K. Evaluating the Effect of Therapeutic Stem Cells on TRAIL Resistant and Sensitive Medulloblastomas. PLoS ONE 2012; 7:e49219. PubMed
  • Shah K. Mesenchymal stem cells engineered for cancer therapy. Adv Drug Deliv Rev 2011. PubMed
  • Shah K. In vivo imaging of the dynamics of different variants of EGFR in glioblastomas. Methods Mol Biol 2010; 680:153-64. PubMed
  • Shah K. Imaging fate of stem cells at a cellular resolution in the brains of mice. Methods Mol Biol 2010; 680:91-101. PubMed
  • Bagci-Onder T, Wakimoto H, Anderegg M, Cameron C, Shah K. A dual PI3K/mTOR inhibitor, PI-103, cooperates with stem cell-delivered TRAIL in experimental glioma models. Cancer Res 2011; 71:154-63. PubMed
  • van Eekelen M, Sasportas LS, Kasmieh R, Yip S, Figueiredo JL, Louis DN, Weissleder R, Shah K. Human stem cells expressing novel TSP-1 variant have anti-angiogenic effect on brain tumors. Oncogene 2010; 29:3185-95. PubMed
  • Hamed HA, Yacoub A, Park MA, Eulitt PJ, Dash R, Sarkar D, Dmitriev IP, Lesniak MS, Shah K, Grant S, Curiel DT, Fisher PB, Dent P. Inhibition of Multiple Protective Signaling Pathways and Ad.5/3 Delivery Enhances mda-7/IL-24 Therapy of Malignant Glioma. Mol Ther 2010; 18:1130-42. PubMed
  • Yoo BK, Chen D, Su ZZ, Gredler R, Yoo J, Shah K, Fisher PB, Sarkar D. Molecular mechanism of chemoresistance by astrocyte elevated gene-1. Cancer Res 2010; 70:3249-58. PubMed
  • Hingtgen SD, Kasmieh R, van de Water J, Weissleder R, Shah K. Determining Multiple Aspects of Stem Cell-Based Therapies Using Novel Diagnostic and Therapeutic Multifunctional Molecules. Stem Cells 2010; 28:832-41. PubMed
  • Emdad L, Sarkar D, Lee SG, Su ZZ, Yoo BK, Dash R, Yacoub A, Fuller CE, Shah K, Dent P, Bruce JN, Fisher PB. Astrocyte elevated gene-1: a novel target for human glioma therapy. Mol Cancer Ther 2010; 9:79-88. PubMed
  • Piccirillo SG, Binda E, Fiocco R, Vescovi AL, Shah K. Brain cancer stem cells. J Mol Med 2010; 87:1087-95. PubMed
  • Yoo BK, Gredler R, Vozhilla N, Su ZZ, Chen D, Forcier T, Shah K, Saxena U, Hansen U, Fisher PB, Sarkar D. Identification of genes conferring resistance to 5-fluorouracil. Proc Natl Acad Sci U S A 2009; 106:12938-43. PubMed
  • Kumar AT, Chung E, Raymond SB, van de Water JA, Shah K, Fukumura D, Jain RK, Bacskai BJ, Boas DA. Feasibility of in vivo imaging of fluorescent proteins using lifetime contrast. Opt Lett 2009; 34:2066-8. PubMed
  • Wakimoto H,Kesari S,Farrell CJ,Curry WT Jr,Zaupa C,Aghi M,Kuroda T,Stemmer-Rachamimov A,Shah K,Liu TC,Jeyaretna DS,Debasitis J,Pruszak J,Martuza RL,Rabkin SD. Human glioblastoma-derived cancer stem cells: establishment of invasive glioma models and treatment with oncolytic herpes simplex virus vectors. Cancer Res 2009; 69:3472-81. PubMed
  • Sasportas LS,Kasmieh R,Wakimoto H,Hingtgen S,van de Water JA,Mohapatra G,Figueiredo JL,Martuza RL,Weissleder R,Shah K. Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci U S A 2009; 106:4822-7. PubMed
  • Shah K. Imaging neural stem cell fate in mouse model of glioma. Curr Protoc Stem Cell Biol 2009; Chapter 5:Unit 5A.1. PubMed
  • Hingtgen S,Ren X,Terwilliger E,Classon M,Weissleder R,Shah K. Targeting multiple pathways in gliomas with stem cell and viral delivered S-TRAIL and Temozolomide. Mol Cancer Ther 2008; 7:3575-85. PubMed
  • Dent P, Yacoub A, Park M, Sarkar D, Shah K, Curiel DT, Grant S. Searching for a cure: Gene therapy for glioblastoma. Cancer Biol Ther 2008; 7:1335-40. PubMed
  • Yip S, Shah K. Stem-cell based therapies for brain tumors. Curr Opin Mol Ther 2008; 10:334-42. PubMed
  • Deliolanis NC,Kasmieh R,Wurdinger T,Tannous BA,Shah K,Ntziachristos V. Performance of the red-shifted fluorescent proteins in deep-tissue molecular imaging applications. J Biomed Opt 2008; 13:044008. PubMed
  • Yacoub A, Hamed H, Emdad L, Dos Santos W, Gupta P, Broaddus WC, Ramakrishnan V, Sarkar D, Shah K, Curiel DT, Grant S, Fisher PB, Dent P. MDA-7/IL-24 Plus Radiation Enhance Survival in Animals with Intracranial Primary Human GBM Tumors. Cancer Biol Ther 2008; 7:917-33. PubMed
  • Albrecht BK, Harmange JC, Bauer D, Berry L, Bode C, Boezio AA, Chen A, Choquette D, Dussault I, Fridrich C, Hirai S, Hoffman D, Larrow JF, Kaplan-Lefko P, Lin J, Lohman J, Long AM, Moriguchi J, O'Connor A, Potashman MH, Reese M, Rex K, Siegmund A, Shah K, Shimanovich R, Springer SK, Teffera Y, Yang Y, Zhang Y, Bellon SF. Discovery and Optimization of Triazolopyridazines as Potent and Selective Inhibitors of the c-Met Kinase. J Med Chem 2008; 51:2879-82. PubMed
  • Shah K, Hingtgen S, Kasmieh R, Figueiredo JL, Garcia-Garcia E, Martinez-Serrano A, Breakefield X, Weissleder R. Bimodal viral vectors and in vivo imaging reveal the fate of human neural stem cells in experimental glioma model. J Neurosci 2008; 28:4406-13. PubMed
  • Corsten MF, Shah K. Therapeutic stem-cells for cancer treatment: hopes and hurdles in tactical warfare. Lancet Oncol 2008; 9:376-84. PubMed
  • Hink MA, Shah K, Russinova E, de Vries SC, Visser AJ. Fluorescence fluctuation analysis of Arabidopsis thaliana somatic embryogenesis receptor-like kinase and brassinosteroid insensitive 1 receptor oligomerization. Biophys J 2007; 94:1052-62. PubMed
  • Corsten MF, Miranda R, Kasmieh R, Krichevsky AM, Weissleder R, Shah K. MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. Cancer Res 2007; 67:8994-9000. PubMed
  • Arwert E, Hingtgen S, Figueiredo JL, Bergquist H, Mahmood U, Weissleder R, Shah K. Visualizing the Dynamics of EGFR Activity and Antiglioma Therapies In vivo. Cancer Res 2007; 67:7335-42. PubMed
  • Minami Y, Shimamura T, Shah K, Laframboise T, Glatt KA, Liniker E, Borgman CL, Haringsma HJ, Feng W, Weir BA, Lowell AM, Lee JC, Wolf J, Shapiro GI, Wong KK, Meyerson M, Thomas RK. The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272. Oncogene 2007; 26:5023-7. PubMed
  • Kock N, Kasmieh R, Weissleder R, Shah K. Tumor therapy mediated by lentiviral expression of shBcl-2 and S-TRAIL. Neoplasia 2007; 9:435-42. PubMed
  • Shah K, Breakefield XO. HSV Amplicon Vectors for Cancer Therapy. Curr Gene Ther 2006; 6:361-70. PubMed
  • Shah K, Tung CH, Breakefield XO, Weissleder R. In vivo imaging of S-TRAIL-mediated tumor regression and apoptosis. Mol Ther 2005; 11:926-31. PubMed
  • Shah K. Current advances in molecular imaging of gene and cell therapy for cancer. Cancer Biol Ther 2005; 4:518-23. PubMed
  • Shah K, Weissleder R. Molecular optical imaging: applications leading to the development of present day therapeutics. NeuroRx 2005; 2:215-25. PubMed
  • Shah K, Bureau E, Kim DE, Yang K, Tang Y, Weissleder R, Breakefield XO. Glioma therapy and real-time imaging of neural precursor cell migration and tumor regression. Ann Neurol 2004; 57:34-41. PubMed
  • Shah K, Jacobs A, Breakefield XO, Weissleder R. Molecular imaging of gene therapy for cancer. Gene Ther 2004; 11:1175-87. PubMed
  • Shah K, Tung CH, Yang K, Weissleder R, Breakefield XO. Inducible release of TRAIL fusion proteins from a proapoptotic form for tumor therapy. Cancer Res 2004; 64:3236-42. PubMed
  • Kim DE, Schellingerhout D, Ishii K, Shah K, Weissleder R. Imaging of stem cell recruitment to ischemic infarcts in a murine model. Stroke 2004; 35:952-7. PubMed
  • Messerli SM, Prabhakar S, Tang Y, Shah K, Cortes ML, Murthy V, Weissleder R, Breakefield XO, Tung CH. A novel method for imaging apoptosis using a caspase-1 near-infrared fluorescent probe. Neoplasia 2004; 6:95-105. PubMed
  • Shah K, Hsich G, Breakefield XO. Neural precursor cells and their role in neuro-oncology. Dev Neurosci 2005; 26:118-30. PubMed
  • Shah K, Tung CH, Chang CH, Slootweg E, O'Loughlin T, Breakefield XO, Weissleder R. In Vivo Imaging of HIV Protease Activity in Amplicon Vector-transduced Gliomas. Cancer Res 2004; 64:273-8. PubMed
  • Shah K, Tang Y, Breakefield X, Weissleder R. Real-time imaging of TRAIL-induced apoptosis of glioma tumors in vivo. Oncogene 2003; 22:6865-72. PubMed
  • Tang Y, Shah K, Messerli SM, Snyder E, Breakefield X, Weissleder R. In vivo tracking of neural progenitor cell migration to glioblastomas. Hum Gene Ther 2003; 14:1247-54. PubMed
  • Regan MM, Brick AJ, Choueiri TK, Clement JM, Kwabi C, Shah K, Amato A, McDermott DF, Atkins MB, Signoretti S. Carbonic anhydrase IX (CA IX) and pathologic features as predictors of outcome in patients (pts) with metastatic renal cell carcinoma (mRCC) receiving VEGF-targeted therapy J Clin Oncol 2008.
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