Daniel Lim, MD, PhD
Research Interests: epigenomics of neural development, long non-coding RNAs, and glioma
In addition to cancer-causing mutations to the DNA genome, human glioma cells have many abnormal epigenomic changes that contribute to tumor growth. Epigenomics includes the study of how DNA is “packaged” inside the cell with proteins, forming three-dimensional (3D) structures with our DNA. Inside the nucleus of cells, DNA is wrapped around proteins called histones, forming chromatin, and different chemical modifications to the chromatin help determine whether a gene is turned “on” or “off.” In cancer, abnormalities to such chromatin modifications can cause cancer-genes to get turned on.
The Lim lab studies the regulation of chromatin modifications in neural development to understand the cellular and molecular function of this aspect of epigenomics. A major focus has been on two different chromatin regulators, Mixed Lineage Leukemia-1 (MLL1) and KDM6B, both of which may be key therapeutic targets for glioma, including diffuse intrinsic pontine glioma (DIPG). Recently, the lab has developed new tools to study how chromatin binds specific sub-compartments inside the nucleus, and this “spatial” aspect of epigenomics is also a key driver of tumor growth.
Long non-coding RNAs (lncRNAs) are molecules longer than 200 nucleotides that do not produce proteins, and certain lncRNAs have important biological function and roles in glioma. In addition to discovering the lncRNA Pnky – a powerful regulator of neural stem cell biology – the Lim lab has conducted high-throughput screens for lncRNAs with CRISPR technologies to identify novel therapeutic targets in glioma.
1994: BA, University of California, Berkeley
2001: PhD, Rockefeller University
2002: MD, Cornell University Medical College
2003-2008: Residency, Neurological Surgery, UCSF
2020-present: Professor, Department of Neurological Surgery, UCSF
2015-2020: Associate Professor, Department of Neurological Surgery, UCSF
2008-2015: Assistant Professor, Department of Neurological Surgery, UCSF
2008-Present: Faculty, Biomedical Sciences Graduate School Program, UCSF
2008-Present: Faculty, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCSF
2008-Present: Director, Restorative Neurosurgery, Department of Neurological Surgery, UCSF
2022-2030: Senior Clinician Investigator Award, U.S. Dept. of Veterans Affairs
2010: Kavli Fellow, U.S. National Academy of Sciences
2009: Sontag Distinguished Researcher Award
2009: NIH Director’s New Innovator Award
Maintenance of neural stem cell positional identity by mixed-lineage leukemia 1
Delgado RN, Mansky B, Ahanger SH, Lu C, Andersen RE, Dou Y, Alvarez-Buylla A, Lim DA.
Science. 2020 Apr 3;368(6486):48-53.
Distinct nuclear compartment-associated genome architecture in the developing mammalian brain
Ahanger SH, Delgado RN, Gil E, Cole MA, Zhao J, Hong SJ, Kriegstein AR, Nowakowski TJ, Pollen AA, Lim DA.
Nat Neurosci. 2021 Sep;24(9):1235-1242.
The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells
Ramos AD, Andersen RE, Liu SJ, Nowakowski TJ, Hong SJ, Gertz C, Salinas RD, Zarabi H, Kriegstein AR, Lim DA.
Cell Stem Cell. 2015 Apr 2;16(4):439-447
CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells
Liu SJ, Horlbeck MA, Cho SW, Birk HS, Malatesta M, He D, Attenello FJ, Villalta JE, Cho MY, Chen Y, Mandegar MA, Olvera MP, Gilbert LA, Conklin BR, Chang HY, Weissman JS, Lim DA.
Science. 2017 Jan 6;355(6320):aah7111.
CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma
Liu SJ, Malatesta M, Lien BV, Saha P, Thombare SS, Hong SJ, Pedraza L, Koontz M, Seo K, Horlbeck MA, He D, Birk HS, Jain M, Olsen HE, Akeson M, Weissman JS, Monje M, Gupta N, Raleigh DR, Ullian EM, Lim DA.
Genome Biol. 2020 Mar 31;21(1):83.