"The sense of community that is have created among the group of Sontag researchers is truly extraordinary. After every Mid-Winter Retreat, I am newly inspired by the collegiality and collaborative interactions that have developed over the years. Together, we will make important things happen."
- Dr. Daniel A. Lim
- Associate Professor of Neurosurgery, UCSF
- Director of Restorative Neurosurgery, UCSF
- Staff Neurosurgeon, San Francisco VA Medical Center
About DSA-Funded Research
To be malignant, a brain tumor glioma cell needs to express certain genes while repressing others. How do these glioma cells "remember" this abnormal gene expression pattern as they divide, migrate, and divide again? Cancer is conventionally believed to be caused by DNA mutations, however it is increasingly evident that cancer is also driven by epigenetics – heritable patterns of gene expression that are not mediated by DNA mutations in the genome. A current focus of epigenetics is chromatin, which is the structure of DNA wound around chromosomal proteins. This DNA-protein structure is very dynamic, and specific molecular machines – chromatin remodeling factors – catalyze heritable changes that determine whether a gene is expressed or not. I have discovered that one such chromatin remodeling factor, Mixed lineage leukemia-1 (Mll1), helps normal neural stem cells "remember" how to make neurons. There are many similarities between normal neural stem cells and the cancer stem cells found in gliomas. Intriguingly, preliminary data from my lab indicate that Mll1 is critical for tumor growth in a gliomas model system known to harbor cancer stem cells. This proposal investigates how gliomas use Mll1 to "remember" their malignant characteristics. A detailed understanding of how these tumor cells epigenetically maintain their robust cell survival, sustained proliferation, and invasive migration should allow us to interfere with this process, making glioma cells "forget" that they are cancer and revert to an essentially harmless cell type.
"I have known Dan for more than 12 years and can assure you that he is one of the most brilliant neuro-scientist-molecular biologists I have ever met. He is extraordinarily smart and resourceful. I am truly impressed by Dan's intuition, knowledge, experimental abilities, teaching and writing skills and most of all his commitment to combine basic research and medicine."
Arturo Alvarez-Buylla, Ph.D.
University of California, San Francisco
"Dan has all of the qualities that are needed to make for a stellar career in science. He is incredibly hard driving, analytical and is his own hardest critic. I'd be bold enough to venture a guess that very few neurosurgeons have Dan's keen ability to exploit and understand modern Molecular Biology and Biochemical methods."
Michael Botchan, Ph.D.
University of California, Berkeley
- Ramos AD, Diaz A, Nellore A, Delgado RN, Park KY, Gonzales-Roybal G, Oldham MC, Song JS, Lim DA, (2013). Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo, Cell Stem Cell, 12(5): 616-28.
- Hwang WW, Salinas RD, Siu JJ, Kelley KW, Delgado RN, Paredes MF, Alvarez-Buylla A, Oldham, MC, Lim DA, (2014). Distinct and separable roles for EZH2 in neurogenic astroglia, eLIFE, May 27;3:e02439
- Park DH, Sung JH, Salinas RD, Liu SJ, Sun SW, Sgualdino J, Testa G, Matzuk MM, Iwamori N, Lim DA, (2014). Activation of neuronal gene expression by the JMJD3 demethylase is required for adult subventricular zone neurogenesis, Cell Rep., 8(5): 1290-9
- Price JD, Park KY, Chen J, Salinas RD, Cho MJ, Kriegstein A, Lim DA, (2014). The Ink4a/ARF locus is a barrier to neuronal transdifferentiation, J Neurosci., 34(37): 12560-7.