Michael Oldham PhD

Michael Oldham, PhD

Assistant Professor of Neurological Surgery

Principal Investigator, UCSF Brain Tumor Center

Dr. Oldham is a neuroscientist and Principal Investigator in the Department of Neurological Surgery and Brain Tumor Center at UCSF. The overarching goal of his research is to understand the molecular basis of cellular identity in the human brain in health and disease, with a particular focus on glioma and other types of brain tumors His laboratory develops and applies standardized approaches for deconstructing complex biological systems using novel computational and experimental strategies. His group explores the idea that by analyzing gene coexpression relationships in heterogeneous tissue samples, it is possible to isolate robust transcriptional signatures of distinct cell types and cellular processes in silico.

As a graduate student, Dr. Oldham performed the first analysis of gene coexpression relationships in the human brain and revealed a reproducible structure to the human brain transcriptome, including robust transcriptional signatures corresponding to distinct cell types. As a UCSF Sandler Fellow, he developed a novel strategy called GCASS (Gene Coexpression Analysis of Serial Sections) for identifying transcriptional signatures of distinct cell types in a single tissue specimen that does not require cell labeling, isolation, or purification. As a proof of principle, he used this strategy to identify a transcriptional signature of human neural stem cells during cortical development in a study that was recently published in Nature.

Education, Training, and Previous Positions

1996: BS, Duke University
2009: PhD, University of California Los Angeles
2010: Postdoctoral Scholar, University of California Los Angeles
2010-2015: UCSF Sandler Fellow, Department of Neurology and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research
2015-Present: Assistant Professor, Department of Neurological Surgery, UCSF

Selected Honors and Awards

2002-2003: Pre-doctoral Fellowship, Neuroscience Ph.D. Program, UCLA
2008: Eva Kavan Prize for Excellence in Research on the Brain, Brain Research Institute, UCLA
2009: UCSF Sandler Fellow, UCSF
2010: Travel Fellow, Winter Conference on Brain Research, Breckenridge, CO
2012: Young Investigator, Sage Commons Congress, San Francisco, CA

Selected Recent Publications

Preuss TM, Cáceres M, Oldham MC, Geschwind DH. Human brain evolution: insights from microarrays. Nature reviews. Genetics. 2004; 5(11):850-60. PubMed [journal] PMID: 15520794

Oldham MC, Geschwind DH. Evolutionary genetics: the human brain -- adaptation at many levels. European journal of human genetics : EJHG. 2005; 13(5):520-2. PubMed [journal] PMID: 15756295

Oldham MC, Geschwind DH. Deconstructing language by comparative gene expression: from neurobiology to microarray. Genes, brain, and behavior. 2006; 5 Suppl 1:54-63. PubMed [journal] PMID: 16417618

Oldham MC, Geschwind DH. Comparative genomics: grasping human transcriptome evolution: what does it all mean? Heredity. 2006; 96(5):339-40. PubMed [journal] PMID: 16552432

Oldham MC, Horvath S, Geschwind DH. Conservation and evolution of gene coexpression networks in human and chimpanzee brains. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103(47):17973-8. PubMed [journal] PMID: 17101986, PMCID: PMC1693857

Abrahams BS, Tentler D, Perederiy JV, Oldham MC, Coppola G, et al. Genome-wide analyses of human perisylvian cerebral cortical patterning. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(45):17849-54. PubMed [journal] PMID: 17978184, PMCID: PMC2077018

Spiteri E, Konopka G, Coppola G, Bomar J, Oldham M, et al. Identification of the transcriptional targets of FOXP2, a gene linked to speech and language, in developing human brain. American journal of human genetics. 2007; 81(6):1144-57. PubMed [journal] PMID: 17999357, PMCID: PMC2276350

Miller JA, Oldham MC, Geschwind DH. A systems level analysis of transcriptional changes in Alzheimer's disease and normal aging. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008; 28(6):1410-20. NIHMSID: NIHMS175627 PubMed [journal] PMID: 18256261, PMCID: PMC2902235

Oldham MC, Konopka G, Iwamoto K, Langfelder P, Kato T, et al. Functional organization of the transcriptome in human brain. Nature neuroscience. 2008; 11(11):1271-82. NIHMSID: NIHMS135318 PubMed [journal] PMID: 18849986, PMCID: PMC2756411

Winden KD, Oldham MC, Mirnics K, Ebert PJ, Swan CH, et al. The organization of the transcriptional network in specific neuronal classes. Molecular systems biology. 2009; 5:291. PubMed [journal] PMID: 19638972, PMCID: PMC2724976

Mumford JA, Horvath S, Oldham MC, Langfelder P, Geschwind DH, et al. Detecting network modules in fMRI time series: a weighted network analysis approach. NeuroImage. 2010; 52(4):1465-76. NIHMSID: NIHMS210084 PubMed [journal] PMID: 20553896, PMCID: PMC3632300

Cai C, Langfelder P, Fuller TF, Oldham MC, Luo R, et al. Is human blood a good surrogate for brain tissue in transcriptional studies? BMC genomics. 2010; 11:589. PubMed [journal] PMID: 20961428, PMCID: PMC3091510

Langfelder P, Luo R, Oldham MC, Horvath S. Is my network module preserved and reproducible? PLoS computational biology. 2011; 7(1):e1001057. PubMed [journal] PMID: 21283776, PMCID: PMC3024255

Iwamoto K, Bundo M, Ueda J, Oldham MC, Ukai W, et al. Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons. Genome research. 2011; 21(5):688-96. PubMed [journal] PMID: 21467265, PMCID: PMC3083085

Rosen EY, Wexler EM, Versano R, Coppola G, Gao F, et al. Functional genomic analyses identify pathways dysregulated by progranulin deficiency, implicating Wnt signaling. Neuron. 2011; 71(6):1030-42. NIHMSID: NIHMS316126 PubMed [journal] PMID: 21943601, PMCID: PMC3633414

Oldham MC, Langfelder P, Horvath S. Network methods for describing sample relationships in genomic datasets: application to Huntington's disease. BMC systems biology. 2012; 6:63. PubMed [journal] PMID: 22691535, PMCID: PMC3441531

Konopka G, Friedrich T, Davis-Turak J, Winden K, Oldham MC, et al. Human-specific transcriptional networks in the brain. Neuron. 2012; 75(4):601-17. NIHMSID: NIHMS387484 PubMed [journal] PMID: 22920253, PMCID: PMC3645834

Han K, Gennarino VA, Lee Y, Pang K, Hashimoto-Torii K, et al. Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. Genes & development. 2013; 27(5):485-90. PubMed [journal] PMID: 23431031, PMCID: PMC3605462

Ramos AD, Diaz A, Nellore A, Delgado RN, Park KY, et al. Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo. Cell stem cell. 2013; 12(5):616-28. NIHMSID: NIHMS456366 PubMed [journal] PMID: 23583100, PMCID: PMC3662805

Molofsky AV, Glasgow SM, Chaboub LS, Tsai HH, Murnen AT, et al. Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions. Glia. 2013; 61(9):1518-32. NIHMSID: NIHMS536168 PubMed [journal] PMID: 23840004, PMCID: PMC3909648

Qiu H, Lee S, Shang Y, Wang WY, Au KF, et al. ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects. The Journal of clinical investigation. 2014; 124(3):981-99. PubMed [journal] PMID: 24509083, PMCID: PMC3938263

Parchem RJ, Ye J, Judson RL, LaRussa MF, Krishnakumar R, et al. Two miRNA clusters reveal alternative paths in late-stage reprogramming. Cell stem cell. 2014; 14(5):617-31. NIHMSID: NIHMS567928 PubMed [journal] PMID: 24630794, PMCID: PMC4305531

Hwang WW, Salinas RD, Siu JJ, Kelley KW, Delgado RN, et al. Distinct and separable roles for EZH2 in neurogenic astroglia. eLife. 2014; 3:e02439. PubMed [journal] PMID: 24867641, PMCID: PMC4032491

Potts MB, Siu JJ, Price JD, Salinas RD, Cho MJ, et al. Analysis of Mll1 deficiency identifies neurogenic transcriptional modules and Brn4 as a factor for direct astrocyte-to-neuron reprogramming. Neurosurgery. 2014; 75(4):472-82; discussion 482. NIHMSID: NIHMS684259 PubMed [journal] PMID: 24887289, PMCID: PMC4420187

Lui JH, Nowakowski TJ, Pollen AA, Javaherian A, Kriegstein AR, et al. Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex. Nature. 2014; 515(7526):264-8. NIHMSID: NIHMS636238 PubMed [journal] PMID: 25391964, PMCID: PMC4231536

Parchem RJ, Moore N, Fish JL, Parchem JG, Braga TT, et al. miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability. Cell reports. 2015; 12(5):760-73. PubMed [journal] PMID: 26212322

Pollen AA, Nowakowski TJ, Chen J, Retallack H, Sandoval-Espinosa C, et al. Molecular identity of human outer radial glia during cortical development. Cell. 2015; 163(1):55-67. NIHMSID: NIHMS721046 PubMed [journal] PMID: 26406371, PMCID: PMC4583716

Kelley KW, Oldham MC. Transcriptional architecture of the human brain. Nat Neurosci. 2015 Dec;18(12):1699-701. doi: 10.1038/nn.4178. PubMed PMID: 26605877.

Lui H, Zhang J, Makinson SR, Cahill MK, Kelley KW, Huang HY, Shang Y, Oldham MC, Martens LH, Gao F, Coppola G, Sloan SA, Hsieh CL, Kim CC, Bigio EH, Weintraub S, Mesulam MM, Rademakers R, Mackenzie IR, Seeley WW, Karydas A, Miller BL, Borroni B, Ghidoni R, Farese RV Jr, Paz JT, Barres BA, Huang EJ. Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation. Cell. 2016 May 5;165(4):921-35. doi: 10.1016/j.cell.2016.04.001. Epub 2016 Apr 21. PubMed PMID: 27114033; PubMed Central PMCID: PMC4860138.

Mitra I, Tsang K, Ladd-Acosta C, Croen LA, Aldinger KA, Hendren RL, Traglia M, Lavillaureix A, Zaitlen N, Oldham MC, Levitt P, Nelson S, Amaral DG, Hertz-Picciotto I, Fallin MD, Weiss LA. Pleiotropic Mechanisms Indicated for Sex Differences in Autism. PLoS Genet. 2016 Nov 15;12(11):e1006425. doi: 10.1371/journal.pgen.1006425. eCollection 2016 Nov. Erratum in: PLoS Genet. 2017 Jun 7;13(6):e1006831. PubMed PMID: 27846226; PubMed Central PMCID: PMC5147776.

Raju CS, Spatazza J, Stanco A, Larimer P, Sorrells SF, Kelley KW, Nicholas CR, Paredes MF, Lui JH, Hasenstaub AR, Kriegstein AR, Alvarez-Buylla A, Rubenstein JL, Oldham MC. Secretagogin is Expressed by Developing Neocortical GABAergic Neurons in Humans but not Mice and Increases Neurite Arbor Size and Complexity. Cereb Cortex. 2017 Apr 26:1-13. doi: 10.1093/cercor/bhx101. [Epub ahead of print] PubMed PMID: 28449024.

Hu JK, Du W, Shelton SJ, Oldham MC, DiPersio CM, Klein OD. An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice. Cell Stem Cell. 2017 Jul 6;21(1):91-106.e6. doi: 10.1016/j.stem.2017.03.023. Epub 2017 Apr 27. PubMed PMID: 28457749; PubMed Central PMCID: PMC5501749.

Seidel K, Marangoni P, Tang C, Houshmand B, Du W, Maas RL, Murray S, Oldham MC, Klein OD. Resolving stem and progenitor cells in the adult mouse incisor through gene co-expression analysis. Elife. 2017 May 5;6. pii: e24712. doi: 10.7554/eLife.24712. PubMed PMID: 28475038; PubMed Central PMCID: PMC5419740.

Mitra I, Tsang K, Ladd-Acosta C, Croen LA, Aldinger KA, Hendren RL, Traglia M, Lavillaureix A, Zaitlen N, Oldham MC, Levitt P, Nelson S, Amaral DG, Hertz-Picciotto I, Fallin MD, Weiss LA. Correction: Pleiotropic Mechanisms Indicated for Sex Differences in Autism. PLoS Genet. 2017 Jun 7;13(6):e1006831. doi: 10.1371/journal.pgen.1006831. eCollection 2017 Jun. PubMed PMID: 28591140; PubMed Central PMCID: PMC5462340.

Sorrells SF, Paredes MF, Cebrian-Silla A, Sandoval K, Qi D, Kelley KW, James D, Mayer S, Chang J, Auguste KI, Chang EF, Gutierrez AJ, Kriegstein AR, Mathern GW, Oldham MC, Huang EJ, Garcia-Verdugo JM, Yang Z, Alvarez-Buylla A. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature. 2018 Mar 15;555(7696):377-381. doi: 10.1038/nature25975. Epub 2018 Mar 7. PubMed PMID: 29513649.

Griveau A, Seano G, Shelton SJ, Kupp R, Jahangiri A, Obernier K, Krishnan S, Lindberg OR, Yuen TJ, Tien AC, Sabo JK, Wang N, Chen I, Kloepper J, Larrouquere L, Ghosh M, Tirosh I, Huillard E, Alvarez-Buylla A, Oldham MC, Persson AI, Weiss WA, Batchelor TT, Stemmer-Rachamimov A, Suvà ML, Phillips JJ, Aghi MK, Mehta S, Jain RK, Rowitch DH. A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment. Cancer Cell. 2018 Apr 6. pii: S1535-6108(18)30125-9. doi: 10.1016/j.ccell.2018.03.020. [Epub ahead of print] PubMed PMID: 29681511.