Daniel A. Lim MD, PhD

Daniel Lim MD, PhD

• Associate Professor in Residence of Neurological Surgery 

• Director of Restorative Neurosurgery

Faculty, Biomedical Sciences Graduate program

• Faculty, Developmental and Stem Cell Biology Graduate program

• Faculty, Herbert W. Boyer Program in Biological Sciences (PIBS)

Faculty, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research

tl_files/Lim Lab 2.jpg

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. In the future he 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.

In addition to his basic science interests, Lim has a clinical interest in stereotactic neurosurgery and has worked with Paul Larson MD and Phillip Starr MD, PhD to study deep brain stimulation for movement disorders including Parkinson’s disease, essential tremor, and atypical tremors resulting from multiple sclerosis or stroke.

Education, Training, and Previous Positions

1994: AB, University of California, Berkeley
2000: PhD, Rockefeller University
2002: MD, Cornell University Medical College
2003-2008: Neurosurgical Residency, University of California, San Francisco

Selected Professional Memberships and Appointments

American Board of Neurological Surgery, Diplomate
American Association of Neurological Surgeons, Fellow (FAANS)
Congress of Neurological Surgeons  

Selected Honors and Awards

1990: National Merit scholarship
1990-1994: University of California Regent's scholarship
1993: Howard Hughes Medical Institute, undergraduate fellow
1993-present: Phi Beta Kappa, Alpha Chapter
1994: Yanaba-Jung Memorial Research Award (for undergraduate thesis), UC Berkeley
1999-2002: President, Chairman of the Board of Directors, The Millennium Kids Foundation
2009: NIH Director’s New Innovator Award
2009: Sontag Distinguished Researcher Award
2010: Kavli Fellow, U.S. National Academy of Sciences

Selected Recent Publications

Cho SW, Xu J, Sun R, Mumbach MR, Carter AC, Chen YG, Yost KE, Kim J, He J, Nevins SA, Chin SF, Caldas C, Liu SJ, Horlbeck MA, Lim DA, Weissman JS, Curtis C, Chang HY. Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element. Cell. 2018 Apr 25. pii: S0092-8674(18)30400-8. doi: 10.1016/j.cell.2018.03.068. [Epub ahead of print] PubMed PMID: 29731168.

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. Single-cell profiling of human gliomas reveals macrophage ontogeny as a basis for regional differences in macrophage activation in the tumor microenvironment. Genome Biol. 2017 Dec 20;18(1):234. doi: 10.1186/s13059-017-1362-4. PubMed PMID: 29262845; PubMed Central PMCID: PMC5738907.

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. Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Science. 2017 Dec 8;358(6368):1318-1323. doi: 10.1126/science.aap8809. PubMed PMID: 29217575.

Delgado RN, Lim DA. Maintenance of Positional Identity of Neural Progenitors in the Embryonic and Postnatal Telencephalon. Front Mol Neurosci. 2017 Nov 13;10:373. doi: 10.3389/fnmol.2017.00373. eCollection 2017. PubMed PMID: 29180952; PubMed Central PMCID: PMC5693875.

Andersen RE, Lim DA. Forging our understanding of lncRNAs in the brain. Cell Tissue Res. 2018 Jan;371(1):55-71. doi: 10.1007/s00441-017-2711-z. Epub 2017 Oct 27. Review. PubMed PMID: 29079882.

Cebrián-Silla A, Alfaro-Cervelló C, Herranz-Pérez V, Kaneko N, Park DH, Sawamoto K, Alvarez-Buylla A, Lim DA, García-Verdugo JM. Unique Organization of the Nuclear Envelope in the Post-natal Quiescent Neural Stem Cells. Stem Cell Reports. 2017 Jul 11;9(1):203-216. doi: 10.1016/j.stemcr.2017.05.024. Epub 2017 Jun 22. PubMed PMID: 28648897; PubMed Central PMCID: PMC5511107.

Cohen-Pfeffer JL, Gururangan S, Lester T, Lim DA, Shaywitz AJ, Westphal M, Slavc I. Intracerebroventricular Delivery as a Safe, Long-Term Route of Drug Administration. Pediatr Neurol. 2017 Feb;67:23-35. doi: 10.1016/j.pediatrneurol.2016.10.022. Epub 2016 Nov 10. Review. PubMed PMID: 28089765.

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. CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells. Science. 2017 Jan 6;355(6320). pii: aah7111. doi: 10.1126/science.aah7111. Epub 2016 Dec 15. PubMed PMID: 27980086; PubMed Central PMCID: PMC5394926.

Müller S, Liu SJ, Di Lullo E, Malatesta M, Pollen AA, Nowakowski TJ, Kohanbash G, Aghi M, Kriegstein AR, Lim DA, Diaz A. Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas. Mol Syst Biol. 2016 Nov 25;12(11):889. doi: 10.15252/msb.20166969. PubMed PMID: 27888226; PubMed Central PMCID: PMC5147052.

Delgado RN, Lu C, Lim DA. Maintenance of neural stem cell regional identity in culture. Neurogenesis (Austin). 2016 May 9;3(1):e1187321. doi: 10.1080/23262133.2016.1187321. eCollection 2016. PubMed PMID: 27606338; PubMed Central PMCID: PMC4973606.

Diaz A, Liu SJ, Sandoval C, Pollen A, Nowakowski TJ, Lim DA, Kriegstein A. SCell: integrated analysis of single-cell RNA-seq data. Bioinformatics. 2016 Jul 15;32(14):2219-20. doi: 10.1093/bioinformatics/btw201. Epub 2016 Apr 19. PubMed PMID: 27153637; PubMed Central PMCID: PMC4937196.

Liu SJ, Nowakowski TJ, Pollen AA, Lui JH, Horlbeck MA, Attenello FJ, He D, Weissman JS, Kriegstein AR, Diaz AA, Lim DA. Single-cell analysis of long non-coding RNAs in the developing human neocortex. Genome Biol. 2016 Apr 14;17:67. doi: 10.1186/s13059-016-0932-1. PubMed PMID: 27081004; PubMed Central PMCID: PMC4831157.

Rowland NC, Kalia SK, Kalia LV, Larson PS, Lim DA, Bankiewicz KS. Merging DBS with viral vector or stem cell implantation: "hybrid" stereotactic surgery as an evolution in the surgical treatment of Parkinson's disease. Mol Ther Methods Clin Dev. 2016 Jan 13;3:15051. doi: 10.1038/mtm.2015.51. eCollection 2016. Review. PubMed PMID: 26817024; PubMed Central PMCID: PMC4714520.

Ramos AD, Attenello FJ, Lim DA. Uncovering the roles of long noncoding RNAs in neural development and glioma progression. Neurosci Lett. 2016 Jun 20;625:70-9. doi: 10.1016/j.neulet.2015.12.025. Epub 2015 Dec 28. Review. PubMed PMID: 26733304; PubMed Central PMCID: PMC5094911.

Pollen AA, Nowakowski TJ, Chen J, Retallack H, Sandoval-Espinosa C, Nicholas CR, Shuga J, Liu SJ, Oldham MC, Diaz A, Lim DA, Leyrat AA, West JA, Kriegstein AR. Molecular identity of human outer radial glia during cortical development. Cell. 2015 Sep 24;163(1):55-67. doi: 10.1016/j.cell.2015.09.004. PubMed PMID: 26406371; PubMed Central PMCID: PMC4583716.

Delgado RN, Lim DA. Embryonic Nkx2.1-expressing neural precursor cells contribute to the regional heterogeneity of adult V-SVZ neural stem cells. Dev Biol. 2015 Nov 15;407(2):265-74. doi: 10.1016/j.ydbio.2015.09.008. Epub 2015 Sep 24. PubMed PMID: 26387477; PubMed Central PMCID: PMC4663161.

Lim DA. Transcriptional and epigenetic insights from stem cells and developing tissues. Development. 2015 Aug 1;142(15):2549-53. doi: 10.1242/dev.122424. PubMed PMID: 26243867.

Rolston JD, Ramos AD, Heath S, Englot DJ, Lim DA. Thalamotomy-Like Effects From Partial Removal of a Ventral Intermediate Nucleus Deep Brain Stimulator Lead in a Patient With Essential Tremor: Case Report. Neurosurgery. 2015 Nov;77(5):E831-6; discussion E836-7. doi: 10.1227/NEU.0000000000000906. PubMed PMID: 26200771; PubMed Central PMCID: PMC5267577.

Ramos AD, Andersen RE, Liu SJ, Nowakowski TJ, Hong SJ, Gertz CC, Salinas RD, Zarabi H, Kriegstein AR, Lim DA. The long noncoding RNA pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells. Cell Stem Cell 2015;16(4):439-47.

Rowland NC, Starr PA, Larson PS, Ostrem JL, Marks WJ Jr, Lim DA. Combining cell transplants or gene therapy with deep brain stimulation for Parkinson's disease. Mov Disord. 2015 Feb;30(2):190-5.

Lim DA, Alvarez-Buylla A. Adult neural stem cells stake their ground. Trends Neurosci. 2014 Oct;37(10):563-71.

Price JD, Park KY, Chen J, Salinas RD, Cho MJ, Kriegstein AR, Lim DA. The Ink4a/Arf locus is a barrier to direct neuronal transdifferentiation. J Neurosci. 2014 Sep 10;34(37):12560-7.

Park DH, Hong SJ, Salinas RD, Liu SJ, Sun SW, Sgualdino J, Testa G, Matzuk MM, Iwamori N, Lim DA. Activation of neuronal gene expression by the JMJD3 demethylase is required for postnatal and adult brain neurogenesis. Cell Rep. 2014 Sep 11;8(5):1290-9.

Silvestrini MT, Yin D, Martin AJ, Coppes VG, Mann P, Larson PS, Starr PA, Zeng X, Gupta N, Panter SS, Desai TA, Lim DA. Interventional magnetic resonance imaging-guided cell transplantation into the brain with radially branched deployment. Mol Ther. 2015 Jan;23(1):119-29.

Andersen RE, Lim DA. An ingredient for the elixir of youth. Cell Res. 2014 Dec;24(12):1381-2.

Benitah SA, Bracken A, Dou Y, Huangfu D, Ivanova N, Koseki H, Laurent L, Lim DA, Meshorer E, Pombo A, Sander M, Xu GL. Stem cell epigenetics: looking forward. Cell Stem Cell. 2014 Jun 5;14(6):706-9.

Potts MB, Siu JJ, Price JD, Salinas RD, Cho MJ, Ramos AD, Hahn J, Margeta M, Oldham MC, Lim DA. Analysis of Mll1 deficiency identifies neurogenic transcriptional modules and Brn4 as a factor for direct astrocyte-to-neuron reprogramming. Neurosurgery. 2014 Oct;75(4):472-82; discussion 482.

Hwang WW, Salinas RD, Siu JJ, Kelley KW, Delgado RN, Paredes MF, Alvarez-Buylla A, Oldham MC, Lim DA. Distinct and separable roles for EZH2 in neurogenic astroglia. Elife. 2014 May 27;3:e02439.

Cheng JS, Lim DA, Chang EF, Barbaro NM. A review of percutaneous treatments for trigeminal neuralgia. Neurosurgery. 2014 Mar;10 Suppl 1:25-33; discussion 33.

Gonzales-Roybal G, Lim DA. Chromatin-based epigenetics of adult subventricular zone neural stem cells. Front Genet. 2013 Oct 8;4:194.

Cheng JS, Lim DA, Chang EF, Barbaro NM. A Review of Percutaneous Treatments for Trigeminal Neuralgia. Neurosurgery. 2013 Sep 23. [Epub ahead of print] PubMed PMID: 24064481.

Potts MB, Silvestrini MT, Lim DA. Devices for cell transplantation into the central nervous system: Design considerations and emerging technologies. Surg Neurol Int. 2013 Mar 19;4(Suppl 1):S22-30.

Ramos AD, Diaz A, Nellore A, Delgado RN, Park KY, Gonzales-Roybal G, Oldham MC, Song JS, Lim DA. Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo. Cell Stem Cell. 2013 May 2;12(5):616-28.

Silvestrini MT, Yin D, Coppes VG, Mann P, Martin AJ, Larson PS, Starr PA, Gupta N, Panter SS, Desai TA, Lim DA. Radially branched deployment for more efficient cell transplantation at the scale of the human brain. Stereotact Funct Neurosurg. 2013;91(2):92-103.

Gupta N, Henry RG, Strober J, Kang SM, Lim DA, Bucci M, Caverzasi E, Gaetano L, Mandelli ML, Ryan T, Perry R, Farrell J, Jeremy RJ, Ulman M, Huhn SL, Barkovich AJ, Rowitch DH. Neural stem cell engraftment and myelination in the human brain. Sci Transl Med. 2012 Oct 10;4(155):155ra137. Erratum in: Sci Transl Med. 2012 Dec 19;4(165):165er8.

Diaz A, Park K, Lim DA, Song JS. Normalization, bias correction, and peak calling for ChIP-seq. Stat Appl Genet Mol Biol. 2012 Mar 31;11(3):Article 9.

Potts MB, Lim DA. An old drug for new ideas: metformin promotes adult neurogenesis and spatial memory formation. Cell Stem Cell. 2012 Jul 6;11(1):5-6.

Crowell AL, Ryapolova-Webb ES, Ostrem JL, Galifianakis NB, Shimamoto S, Lim DA, Starr PA. Oscillations in sensorimotor cortex in movement disorders: an electrocorticography study. Brain. 2012 Feb;135(Pt 2):615-30.

Sugiarto S, Persson AI, Munoz EG, Waldhuber M, Lamagna C, Andor N, Hanecker P, Ayers-Ringler J, Phillips J, Siu J, Lim DA, Vandenberg S, Stallcup W, Berger MS, Bergers G, Weiss WA, Petritsch C. Asymmetry-defective oligodendrocyte progenitors are glioma precursors. Cancer Cell. 2011 Sep 13;20(3):328-40.

Johnston MA, Lim DA. Keeping them quiet: BMPs maintain adult neural stem cell quiescence. Cell Stem Cell. 2010 Jul 2;7(1):9-10.

Oh MC, Lim DA. Novel treatment strategies for malignant gliomas using neural stem cells. Neurotherapeutics. 2009 Jul;6(3):458-64.

Lim DA, Huang YC, Swigut T, Mirick AL, Garcia-Verdugo JM, Wysocka J, Ernst P, Alvarez-Buylla A. Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells. Nature. 2009 Mar 26;458(7237):529-33.

Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, Vandenberg SR, Ginzinger DG, James CD, Costello JF, Bergers G, Weiss WA, Alvarez-Buylla A, Hodgson JG. miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med. 2008 Jun 24;6:14.