The goal of the Johns Hopkins Brain Cancer Biology and Therapy Laboratory (led by Dr. Gregory Riggins) is to locate the genetic and genomic changes that lead to brain cancer. These molecular changes are evaluated for their potential as therapeutic targets and are often mutated genes, or genes that are over-expressed during the development of a brain cancer.
The Riggins Laboratory studies medulloblastomas, the most common malignant brain tumor for children, and glioblastomas, the most common malignant brain tumor for adults. Both tumors are difficult to treat, and new therapies are urgently needed for these cancers.
Our laboratory uses large-scale genomic approaches to locate and analyze the genes that are mutated during brain cancer development. The technologies we now employ are capable of searching nearly all of a cancer genome for molecular alterations that can lead to cancer. The new molecular targets for cancer therapy are first located by large scale gene expression analysis, whole-genome scans for altered gene copy number and high throughput sequence analysis of cancer genomes. The alterations we find are then studied in-depth to determine how they contribute to the development of cancer, whether it is promoting tumor growth, enhancing the ability for the cancer to invade into normal tissue, or preventing the various fail-safe mechanisms programmed into our cells.
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NY-ESO-1 Expression in Meningioma Suggests a Rationale for New Immunotherapeutic Approaches. Baia GS, Caballero OL, Ho JS, Zhao Q, Cohen T, Binder ZA, Salmasi V, Gallia GL, Quinones-Hinojosa A, Olivi A, Brem H, Burger P, Strausberg RL, Simpson AJ, Eberhart CG, Riggins GJ. Cancer Immunol Res. 2013 Nov;1(5):296-302. doi: 10.1158/2326-6066.CIR-13-0029. Epub 2013 Aug 5. PMID: 24777967
Yamashita AS1, Baia GS, Ho JS, Velarde E, Wong J, Gallia GL, Belzberg AJ, Kimura ET, Riggins GJ. Preclinical evaluation of the combination of mTOR and proteasome inhibitors with radiotherapy in malignant peripheral nerve sheath tumors. J Neurooncol. 2014 May;118(1):83-92. PMC4059766.
Roberts NJ, Zhang L, Janku F, Collins A, Bai RY, Staedtke V, Rusk AW, Tung D, Miller M, Roix J, Khanna KV, Murthy R, Benjamin RS, Helgason T, Szvalb AD, Bird JE, Roy-Chowdhuri S, Zhang HH, Qiao Y, Karim B, McDaniel J, Elpiner A, Sahora A, Lachowicz J, Phillips B, Turner A, Klein MK, Post G, Diaz LA Jr, Riggins GJ, Papadopoulos N, Kinzler KW, Vogelstein B, Bettegowda C, Huso DL, Varterasian M, Saha S, Zhou S. Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses. Sci Transl Med. 2014 Aug 13;6(249):249ra111.PMC4399712
Bai RY, Staedtke V, Rudin CM, Bunz F, Riggins GJ.Effective treatment of diverse medulloblastoma models with mebendazole and its impact on tumor angiogenesis. Neuro Oncol. 2015 Apr;17(4):545-54.PMID:2525341
Zhang M, Wang Y, Jones S, Sausen M, McMahon K, Sharma R, Wang Q, Belzberg AJ, Chaichana K, Gallia GL, Gokaslan ZL, Riggins GJ, Wolinksy JP, Wood LD, Montgomery EA, Hruban RH, Kinzler KW, Papadopoulos N, Vogelstein B, Bettegowda C.Somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors. Nat Genet. 2014 Nov;46(11):1170-2.PMC4383254.
Larsen AR, Bai RY, Chung JH, Borodovsky A, Rudin CM, Riggins GJ, Bunz F.Repurposing the antihelmintic mebendazole as a hedgehog inhibitor. Mol Cancer Ther. 2015 Jan;14(1):3-13.PMC4297232
Borodovsky A, Meeker AK, Kirkness EF, Zhao Q, Eberhart CG, Gallia GL, Riggins GJ. A model of a patient-derived IDH1 mutant anaplastic astrocytoma with alternative lengthening of telomeres. J Neurooncol. 2015 Feb;121(3):479-87. PMID:25471051 [PubMed - in process]
Staedtke V, Bai RY, Sun W, Huang J, Kibler KK, Tyler BM, Gallia GL, Kinzler K, Vogelstein B, Zhou S, Riggins GJ. Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats. Oncotarget. 2015 Mar 20;6(8):5536-46. PMID:25849940 [PubMed - in process]
Bai RY, Staedtke V, Wanjiku T, Rudek MA, Joshi AD, Gallia GL, Riggins GJ. Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse Brain Tumor Model. Clin Cancer Res. 2015 Apr 10. [Epub ahead of print]PMID:25862759