"The support of Sontag Foundation was instrumental at the early stage of my career. For me, as a novice in neurooncology, it not only presented a great platform for learning from and brainstorming together with esteemed colleagues, and not only supported the development of my research program but also provided much-needed mentorship. I am truly grateful to Rick Sontag and the amazing team he was able to build for the opportunity to be exposed to great science and meet remarkable individuals that became my role models. Our basic research is now leading toward a clinical trial on GBM, the result I could not dream of only a few years ago, and that could not be achieved without the Sontag Foundation support."
- Dr. Anna M. Krichevsky
- Associate Professor, Neuroscience and Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School
About DSA-Funded Research
Malignant brain tumors remain today a serious clinical and scientific problem. Patients with the most malignant brain tumor, glioblastoma (GBM), have an average survival time of less than one year. Like other cancers, gliomas are diseases caused by dysregulated cell division, maturation, migration and death. However, molecular events that lead to de-regulation of these key processes are not well understood and vary significantly among the patients. Nevertheless, so far glioma therapies aim at targeting tumor cell growth regardless of individual molecular genetics that caused tumor formations and such uniformed approach is clearly inefficient.
Recent discovery of microRNAs (miRNAs), small regulatory RNA molecules, truly revolutionized the field of cancer biology. Since a single miRNA may control functions of multiple cellular proteins, de-regulation of such one (or a few) miRNA(s) may lead to aberrant intracellular metabolism and cancer growth. Our work over the past few years focused on the discovery of miRNAs that contribute to glioma initiation and progression, and today we have mounting evidence indicating that GBM growth is regulated by microRNAs. We have recently examined a number of GBM tumor tissues and identified several miRNAs often de-regulated in gliomas. We hypothesize that normalization of levels of these few key miRNAs can be adopted as a therapy for gliomas. We propose to test this hypothesis and use miRNA "fingerprints" of individual tumors to predict and establish a "corrective personalized therapy" for glioma treatment.
"In comparison with others in her peer group, Anna is stellar. I have no doubt that Anna is at the very beginning of an exceptional future in her chosen field- the biology of brain tumors. Her likelihood to impact the entire field is one of the best bets I can imagine."
Kenneth S. Kosik, M.D.
University of California, Santa Barbara
"Anna has truly pioneered the study of miRNA in brain tumors and opened a new area by discovering the first oncogenic miRNA, miR-21, in glioblastoma. My colleagues and I recognize Dr. Krichevsky as a very bright and creative scientist with an inclination to embark on the most challenging tasks."
Dennis J. Selkoe, M.D.
Harvard Medical School
- Santosh Kesari
- Jun Song
- Kieth Ligon
- Nino Chiocca
- Gabriely G, Yi Ming, Narayan RS, Niers JM, Wurdinger T, Imitola J, Ligon KL, Kesari S, Esau C, Stephens RM, Tannous BA, Krichevsky AM. Human Glioma Growth is Controlled by MicroRNA-10b. Cancer Research. 2011 Apr 6. PMCID: PMC3096675.
- Gabriely G, Teplyuk NM, Krichevsky AM. Context effect: microRNA-10b in cancer cell proliferation, spread and death. Autophagy. 2011 Nov 1. PMID: 21795860.
- Teplyuk NM, Mollenhauer B, Gabriely G, Giese A, Kim E, Smolsky M, Kim RY, Saria MG, Pastorino S, Kesari S, Krichevsky AM. MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. Neuro-Oncology. 2012 PMCID: PMC3367845.
- Teplyuk NT, Uhlmann EJ, Wong HK, , Karmali P, Basu M, Gabriely G, Jain A, Chiocca EA, Stephens R, Marcusson E, Yi M, Krichevsky AM. MicroRNA-10b inhibition reduces E2F1-mediated transcription and miR-15/16 activity in glioblastoma. Oncotarget, 2015 Feb 28;6(6):3770-83. PMCID: PMC4414152.
- Wong HK, El Fatimy R, Onodera C, Uhlmann EJ, Karmali P, Song JS, Tannous B, Krichevsky AM. TCGA analysis predicts microRNA for targeting cancer growth and vascularization in glioblastoma. Mol Ther. 2015 Jul;23(7):1234-47. PMID: 25903473
- Teplyuk NM, Uhlmann EJ, Gabriely G, Volfovsky N, Wang Y, Teng J, Karmali P, Marcusson E, Peter M, Mohan A, Kraytsberg Y, Cialic R, Chiocca EA, Godlewski J, Tannous B, Krichevsky AM. Therapeutic potential of targeting microRNA-10b in established intracranial glioblastoma: first steps toward the clinic. EMBO Mol Med. 2016 Feb 9;8(3):268-87. doi: 10.15252/emmm.201505495. PMID: 26881967