Daniel A. Lim MD, PhD
Assistant Professor in Residence of Neurological Surgery
Director of Restorative Neurosurgery
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 Association of Neurological Surgeons
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
Selected Recent Publications
Lim DA, Huang Y-C, Swigut T, Mirick AL, Garcia-Verdugo JM, Wysocka J, Ernst P, Alvarez-Buylla A. Chromatin remodeling factor Mll1 is essential for neurogenesis from postnatal neural stem cells. Nature 2009;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;6:14.
Lim DA, Cha S, Mayo MC, Chen MH, Keles E, Vandenberg S, Berger MS. Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro Oncol 2007;9(4):424-9.
Lim DA, Khandhar SM, Heath S, Ostrem JL, Ringel N, Starr P. Multiple Target Deep Brain Stimulation for Multiple Sclerosis Related and Poststroke Holmes' Tremor. Stereotact Funct Neurosurg 2007;85(4):144-149.
Lim DA, Huang YC, Alvarez-Buylla A. The adult neural stem cell niche: lessons for future neural cell replacement strategies. Neurosurg Clin N Am 2007;18(1):81-92.
Lim DA, Suarez-Farinas M, Naef F, Hacker CR, Menn B, Takebayashi H, Magnasco M, Patil N, Alvarez-Buylla A. In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis. Mol Cell Neurosci 2006;31(1):131-48.
Palma V, Lim DA, Dahmane N, Sanchez P, Brionne TC, Herzberg CD, Gitton Y, Carleton A, Alvarez-Buylla A, Ruiz i Altaba A. Sonic hedgehog controls stem cell behavior in the postnatal and adult brain. Development 2005;132(2):335-44.
Alvarez-Buylla A, Lim DA. For the long run: maintaining germinal niches in the adult brain. Neuron 2004;41(5):683-6.
Caporaso GL, Lim DA, Alvarez-Buylla A, Chao MV. Telomerase activity in the subventricular zone of adult mice. Mol Cell Neurosci 2003;23(4):693-702.
Tramontin AD, Garcia-Verdugo JM, Lim DA, Alvarez-Buylla A. Postnatal development of radial glia and the ventricular zone (VZ): a continuum of the neural stem cell compartment. Cereb Cortex 2003;13(6):580-7.
Gritti A, Bonfanti L, Doetsch F, Caille I, Alvarez-Buylla A, Lim DA, Galli R, Verdugo JM, Herrera DG, Vescovi AL. Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents. J Neurosci 2002;22(2):437-45.
Lim DA, Flames N, Collado L, Herrera DG. Investigating the use of primary adult subventricular zone neural precursor cells for neuronal replacement therapies. Brain Res Bull 2002;57(6):759-64.
Naef F, Lim DA, Patil N, Magnasco M. DNA hybridization to mismatched templates: a chip study. Phys Rev E Stat Nonlin Soft Matter Phys 2002;65(4 Pt 1):040902.
Li XC, Jarvis ED, Alvarez-Borda B, Lim DA, Nottebohm F. A relationship between behavior, neurotrophin expression, and new neuron survival. Proc Natl Acad Sci U S A. 2000;97(15):8584-9.
Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM, Alvarez-Buylla A. Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 2000;28(3):713-26.
Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999;97(6):703-16.
Lim DA, Alvarez-Buylla A. Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis. Proc Natl Acad Sci U S A 1999;96(13):7526-31.