Research Interests: neural stem cells, neurogenesis, long non-coding RNAs
The focus of Dr. Lim’s research is on neural stem cells and neurogenesis. He is particularly interested in the molecular biology of the population of neural stem cells found in the subventricular zone (SVZ). For neural stem cells to make neurons, daughter cells need to express certain sets of genes while repressing others. The maintenance of such lineage-specific transcriptional programs is in part regulated by chromatin structure – the “packaged” state of DNA with histone proteins. Recently, Dr. Lim’s work has revealed that the chromatin remodeling factor called Mixed Lineage Leukemia-1 (MLL1) is essential for postnatal neural stem cells to make new neurons. Currently, his work focuses on the molecular mechanisms by which MLL1 specifies a transcriptional program instructive for neurogenesis.
The Lim Laboratory also studies long non-coding RNAs (lncRNAs), which transcripts under 200 nucleotides long, with no evidence of protein coding potential. It is becoming clear that lncRNAs can have critical biological functions and roles in human neurological disease. Many lncRNAs interact with chromatin regulators and appear to regulate their function. The Lim Lab recently identified Pnky, a novel lncRNA transcript that is a potent regulator of neural stem cells in the embryonic and postnatal brain. Dr. Lim continues to study the function of this lncRNA in vivo and the molecular mechanisms by which it regulates neurogenesis.
In the future, Dr. Lim hopes to define the genetic programs and molecular mechanisms that guide the formation of neurons and glia from SVZ neural stem cells, and translate these discoveries into cell-based and genetic therapies for human neurological diseases.
1994: BA, University of California, Berkeley
2001: PhD, Rockefeller University
2002: MD, Cornell University Medical College
2003-2008: Residency, 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
2015-Present: Associate Professor, Department of Neurological Surgery, UCSF
2010: Kavli Fellow, U.S. National Academy of Sciences
2009: Sontag Distinguished Researcher Award
2009: NIH Director’s New Innovator Award
1999-2002: President, Chairman of the Board of Directors, The Millennium Kids Foundation
1994: Yanaba-Jung Memorial Research Award (for undergraduate thesis), UC Berkeley
1993-present: Phi Beta Kappa, Alpha Chapter
1993: Howard Hughes Medical Institute, undergraduate fellow
1990-1994: University of California Regent's scholarship
Single-cell profiling of human gliomas reveals macrophage ontogeny as a basis for regional differences in macrophage activation in the tumor microenvironment
Müller S, Kohanbash G, Liu SJ, Alvarado B, Carrera D, Bhaduri A, Watchmaker PB, Yagnik G, Di Lullo E, Malatesta M, Amankulor NM, Kriegstein AR, Lim DA, Aghi M, Okada H, Diaz A.
Genome Biol.2017 Dec 20;18(1):234.
Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex
Nowakowski TJ, Bhaduri A, Pollen AA, Alvarado B, Mostajo-Radji MA, Di Lullo E, Haeussler M, Sandoval-Espinosa C, Liu SJ, Velmeshev D, Ounadjela JR, Shuga J, Wang X, Lim DA, West JA, Leyrat AA, Kent WJ, Kriegstein AR.
Science. 2017 Dec 8;358(6368):1318-1323.
Maintenance of Positional Identity of Neural Progenitors in the Embryonic and Postnatal Telencephalon
Delgado RN, Lim DA.
Front Mol Neurosci. 2017 Nov 13;10:373. eCollection 2017.