Fraser J. Sim PhD
Fraser J. Sim
PhD
Professor; Neuroscience Program Director
Department of Pharmacology and Toxicology
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Myelin Diseases; Neurodegenerative disorders; Neuroscience; Stem Cells
Professional Summary:
My lab investigates the molecular control of cell fate and homeostasis of resident stem and progenitor cells in the human brain. Using a combination of multicolor cell sorting techniques and whole genome analysis, we are characterizing the signaling pathways which regulate the formation and fate of human oligodendrocyte progenitor cells. We are testing the functional significance of these pathways using both pharmacological and viral methods in culture and animal-based models of myelination and demyelination.
Education and Training:
- PhD, Neuroscience, University of Cambridge (2001)
- MA, Natural Sciences, University of Cambridge (1997)
Employment:
- Neuroscience Program Director, JSMBS (2019-present)
- Professor of Pharmacology and Toxicology, Pharmacology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2022-present)
- Associate Professor of Pharmacology and Toxicology, Pharmacology and Toxicology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2015–2022)
- Assistant Professor of Pharmacology and Toxicology, Pharmacology and Toxicology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2009–2015)
- Assistant Professor of Neurology and Neurosurgery, Neurology, University of Rochester (2006–2009)
- Research Assistant Professor, Neurology, University of Rochester (2004–2006)
- Instructor, Neurology, University of Rochester (2003–2004)
- Instructor, Neurology/Neuroscience, Cornell University Medical College (2003)
- Postdoctoral Research Associate, Neurology/Neuroscience, Cornell University Medical College (2002–2003)
- Postdoctoral Research Associate, Department of Clinical Veterinary Medicine, University of Cambridge (2001)
Awards and Honors:
- UB Exceptional Scholar - Sustained Achievement Award (2024)
Research Expertise:
- Neuroscience
UB 2020 Strategic Strengths:
- Molecular Recognition in Biological Systems and Bioinformatics
Grants and Sponsored Research:
- July 2023–June 2028
Programmable Hydrogels for Optimized Human Oligodendrocyte Transplantation in Demyelinating Disease
National Institute of Neurological Disorders and Stroke (NINDS)
Role: Co-Principal Investigator
$2,930,725 - July 2023–June 2026
Molecular mechanisms and therapeutic potential of heparan sulfate proteoglycans in remyelination
DoD CDMRP
Role: Principal Investigator
$998,436 - September 2021–October 2025
Overcoming human-specific obstacles to successful remyelination in multiple sclerosis
Department of Defense (CDMRP)
Role: Principal Investigator - July 2022–June 2024
Induction of Oligodendrocyte Progenitor Cell Differentiation by Blocking Store-Operated Oscillatory Calcium Release
Department of Defense (CDMRP)
Role: Principal Investigator
$238,056 - December 2017–November 2022
Muscarinic Receptor Type 3 Regulation of Oligodendrocyte ProgenitorDifferentiation
NIH/NINDS
Role: Principal Investigator
$1,744,530 - October 2017–September 2021
Targeting extracellular sulfatases to accelerate oligodendrocyte progenitor-based myelin repair and regeneration
National Multiple Sclerosis Society
Role: Principal Investigator
$579,900 - November 2017–October 2018
Modeling human cell-based remyelination in large chronic demyelinating lesions
National Multiple Sclerosis Society
Role: Principal Investigator
$44,000 - October 2013–September 2017
Muscarinic Receptor Regulation of Oligodendrocyte Differentiation
National Multiple Sclerosis Society
Role: Principal Investigator
$554,973 - March 2013–February 2015
Directed Reprogramming of Human Fibroblasts to Oligodendrocyte Progenitors
NYSTEM
Role: Principal Investigator
$329,984 - September 2010–August 2013
Atlas of gene expression by progenitor cells of the human brain and its tumors
NYSTEM
Role: Co-Investigator
$216,690 - May 2012–April 2013
Development of novel cerebral X-ALD model using human ABCD1-null oligodendrocyte progenitors
European Leukodystophy Association
Role: Principal Investigator
$58,792 - September 2010–August 2012
Induction of Oligodendrocyte Fate from Human Neural Stem Cells
NYSTEM
Role: Principal Investigator
$319,907 - July 2007–July 2008
Low-Grade Oligodendroglioma Brain Tumor Research Grant
National Brain Tumor Foundation
Role: Principal Investigator
$50,000 - August 2004–August 2005
Does statin therapy reduce the self-renewal capacity of adult human oligodendrocyte progenitor cells?
National Multiple Sclerosis Society
Role: Principal Investigator
$44,000
Patents:
- CD24 as a brain tumor marker CD24 as a brain tumor stem cell marker and a diagnostic and therapeutic target in primary neural and glial tumors of the brain (2008)
- CD140a sorting Treating Myelin Diseases with Optimized Cell Preparations (2008)
- Human NSC gene expression Genes and signaling pathways differentially active in neural stem cells and neuronal progenitor cells (2006)
- WMPC gene expression Genes differentially expressed by acutely isolated resident progenitor cells of the human white matter (2004)
Journal Articles:
- Cooper JJM, Muthaiah R, Frost JR, Buck GT, Ravichandar R, Gadelkarim F, Raymond FD, Sim FJ. (2024) Clemastine Induces Oligodendrocyte Progenitor Pool Exhaustion and Senescence in the Context of Chronic Demyelination in a Rabbit Model. Annals of neurology (Oct).
- Evans LMP, Gawron J, Sim FJ, Feltri ML, Marziali LN. (2024) Human iPSC-derived myelinating organoids and globoid cells to study Krabbe Disease. bioRxiv : the preprint server for biology (Jul). doi:10.1101/2024.07.19.604372
- Kumar Podder A, Mohamed MA, Seidman RA, Tseropoulos G, Polanco JJ, Lei P, Sim FJ, Andreadis ST. (2024) Injectable shear-thinning hydrogels promote oligodendrocyte progenitor cell survival and remyelination in the central nervous system. Science advances (Jul), 10(28): eadk9918. doi:10.1126/sciadv.adk9918
- Marziali LN, Hwang Y, Palmisano M, Cuenda A, Sim FJ, Gonzalez A, Volsko C, Dutta R, Trapp BD, Wrabetz L, Feltri ML. (2024) p38? MAPK delays myelination and remyelination and is abundant in multiple sclerosis lesions. Brain : a journal of neurology (May), 147(5): 1871-1886. doi:10.1093/brain/awad421
- Ravichandar R, Gadelkarim F, Muthaiah R, Glynos N, Murlanova K, Rai NK, Saraswat D, Polanco JJ, Dutta R, Pal D, Sim FJ. (2024) Dysregulated cholinergic signaling inhibits oligodendrocyte maturation following demyelination. The Journal of neuroscience : the official journal of the Society for Neuroscience (May).
- Evans LMP, Gawron J, Sim FJ, Feltri ML, Marziali LN. (2024) Human iPSC-derived myelinating organoids and globoid cells to study Krabbe disease. PloS one (Jan), 19(12): e0314858. doi:10.1371/journal.pone.0314858
- Cooper JJM, Polanco JJ, Saraswat D, Peirick JJ, Seidl A, Li Y, Ma D, Sim FJ. (2023) Chronic demyelination of rabbit lesions is attributable to failed oligodendrocyte progenitor cell repopulation. Glia (Apr), 71(4): 1018-1035. doi:10.1002/glia.24324
- Mitra S, Thomas SA, Martin JA, Williams J, Woodhouse K, Chandra R, Li JX, Lobo MK, Sim FJ, Dietz DM. (2022) EGR3 regulates opioid-related nociception and motivation in male rats. Psychopharmacology (Nov), 239(11): 3539-3550. doi:10.1007/s00213-022-06226-1
- Seidman RA, Khattab H, Polanco JJ, Broome JE, Sim FJ. (2022) Oscillatory calcium release and sustained store-operated oscillatory calcium signaling prevents differentiation of human oligodendrocyte progenitor cells. Scientific reports (Apr), 12(1): 6160. doi:10.1038/s41598-022-10095-1
- Saraswat D, Shayya HJ, Polanco JJ, Tripathi A, Welliver RR, Pol SU, Seidman RA, Broome JE, O. (2021) Overcoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following experimental demyelination. Nature communications (Mar), 12(1): 1923.
- Saraswat D, Welliver RR, Ravichandar R, Tripathi A, Polanco JJ, Broome J, Hurley E, Dutta R, Feltri ML, Sim FJ. (2021) Heparanome-Mediated Rescue of Oligodendrocyte Progenitor Quiescence following Inflammatory Demyelination. The Journal of neuroscience : the official journal of the Society for Neuroscience (Mar), 41(10): 2245-2263. doi:10.1523/JNEUROSCI.0580-20.2021
- Sekera ER, Saraswat D, Zemaitis KJ, Sim FJ, Wood TD. (2020) MALDI Mass Spectrometry Imaging in a Primary Demyelination Model of Murine Spinal Cord. Journal of the American Society for Mass Spectrometry (Dec), 31(12): 2462-2468.
- Zhang X, Smith NA, Sumowski MT, Anderson JM, Anderson K, Badenoch EA, Brady SJ, Coleman M, Coull RF, Green D, Innes RJ, Laing CM, Mckinley R, Mclennan MS, Murray S, Phillips B, Rae S, Rankin S, Satar I, Shanks S, Sim FJ, Walker N, Howard D, Sniehotta FF, Jackson DM, VaanHolt LM, Hambly C, Speakman JR. (2020) Active travelling to school is not associated with increased total daily physical activity levels, or reduced obesity and cardiovascular/pulmonary health parameters in 10-12-year olds: a cross-sectional cohort study. International journal of obesity (2005) (Jul), 44(7): 1452-1466.
- Tripathi A, Volsko C, Garcia JP, Agirre E, Allan KC, Tesar PJ, Trapp BD, Castelo-Branco G, Sim FJ, Dutta R. (2019) Oligodendrocyte Intrinsic miR-27a Controls Myelination and Remyelination. Cell reports (Oct), 29(4): 904-919.e9. doi:10.1016/j.celrep.2019.09.020
- Wang J, Saraswat D, Sinha AK, Polanco J, Dietz K, O'Bara MA, Pol SU, Shayya HJ, Sim FJ. (2018) Paired Related Homeobox Protein 1 Regulates Quiescence in Human Oligodendrocyte Progenitors. Cell Rep (Dec), 25(12): 3435-3450.
- Welliver RR, Polanco JJ, Seidman RA, Sinha AK, O‘Bara MA, Khaku ZM, Santiago González DA, Nishiyama A, Wess J, Feltri ML, Paez PM, Sim FJ. (2018) Muscarinic receptor M3R signaling prevents efficient remyelination by human and mouse oligodendrocyte progenitor cells. J Neurosci (Jun).
- Martin JA, Caccamise A, Werner CT, Viswanathan R, Polanco JJ, Stewart AF, Thomas SA, Sim FJ, Dietz DM. (2017) A Novel Role for Oligodendrocyte Precursor Cells (OPCs) and Sox10 in Mediating Cellular and Behavioral Responses to Heroin. Neuropsychopharmacology (Dec).
- Pol SU, Polanco JJ, Seidman RA, O‘Bara MA, Shayya HJ, Dietz KC, Sim FJ. (2017) Network-Based Genomic Analysis of Human Oligodendrocyte Progenitor Differentiation. Stem Cell Reports (Aug), 9(2): 710-723.
- Wang ZJ, Martin JA, Gancarz AM, Adank DN, Sim FJ, Dietz DM. (2017) Activin A is increased in the nucleus accumbens following a cocaine binge. Sci Rep (Mar), 7: 43658-43658.
- Poitelon Y, Lopez-Anido C, Catignas K, Berti C, Palmisano M, Williamson C, Ameroso D, Abiko K, Hwang Y, Gregorieff A, Wrana JL, Asmani M, Zhao R, Sim FJ, Wrabetz L, Svaren J, Feltri ML. (2016) YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells. Nat Neurosci (Jul), 19(7): 879-887.
- Dietz KC, Polanco JJ, Pol SU, Sim FJ. (2016) Targeting human oligodendrocyte progenitors for myelin repair. Exp Neurol (Mar).
- Zhou B, Osinski JM, Mateo JL, Martynoga B, Sim FJ, Campbell CE, Guillemot F, Piper M, Gronostajski RM. (2015) Loss of NFIX Transcription Factor Biases Postnatal Neural Stem/Progenitor Cells Toward Oligodendrogenesis. Stem Cells Dev (Sep), 24(18): 2114-2126.
- Abiraman K, Pol SU, O'Bara MA, Chen GD, Khaku ZM, Wang J, Thorn D, Vedia BH, Ekwegbalu EC, Li JX, Salvi RJ, Sim FJ. (2015) Anti-muscarinic adjunct therapy accelerates functional human oligodendrocyte repair. J Neurosci (Feb), 35(8): 3676-3688.
- Douvaras P, Wang J, Zimmer M, Hanchuk S, O'Bara MA, Sadiq S, Sim FJ, Goldman J, Fossati V. (2014) Efficient generation of myelinating oligodendrocytes from primary progressive multiple sclerosis patients by induced pluripotent stem cells. Stem Cell Reports (Aug), 3(2): 250-259.
- Wang J, Pol SU, Haberman AK, Wang C, O‘Bara MA, Sim FJ. (2014) Transcription factor induction of human oligodendrocyte progenitor fate and differentiation. Proc Natl Acad Sci U S A (Jun).
- Dolan JM, Meng H, Sim FJ, Kolega J. (2013) Differential Gene Expression by Endothelial Cells Under Positive and Negative Streamwise Gradients of High Wall Shear Stress. Am J Physiol Cell Physiol (Jul)C854-C866.
- Auvergne RM, Sim FJ, Wang S, Chandler-Militello D, Burch J, Al Fanek Y, Davis D, Benraiss A, Walter K, Achanta P, Johnson M, Quinones-Hinojosa A, Natesan S, Ford HL, Goldman SA. (2013) Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes. Cell Rep (May).
- Wang J, O‘Bara MA, Pol SU, Sim FJ. (2013) CD133/CD140a-based isolation of distinct human multipotent neural progenitor cells and oligodendrocyte progenitor cells. Stem Cells Dev (Mar).
- Pol SU, Lang JK, O‘Bara MA, Cimato TR, McCallion AS, Sim FJ. (2013) Sox10-MCS5 enhancer dynamically tracks human oligodendrocyte progenitor fate. Exp Neurol (Mar).
- Bugiani M, Postma N, Polder E, Dieleman N, Scheffer PG, Sim FJ, van der Knaap MS, Boor I. (2013) Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease. Brain (Jan), 136(Pt 1): 209-222.
- McClain CR, Sim FJ, Goldman SA. (2012) Pleiotrophin Suppression of Receptor Protein Tyrosine Phosphatase-ß/? Maintains the Self-Renewal Competence of Fetal Human Oligodendrocyte Progenitor Cells. J Neurosci (Oct), 32(43): 15066-15075.
- Conway GD, O‘Bara MA, Vedia BH, Pol SU, Sim FJ. (2012) Histone deacetylase activity is required for human oligodendrocyte progenitor differentiation. Glia (Aug).
- Dolan JM, Sim FJ, Meng H, Kolega J. (2012) Endothelial cells express a unique transcriptional profile under very high wall shear stress known to induce expansive arterial remodeling. Am J Physiol Cell Physiol (Apr), 302(8): 1109-1118.
- Sim FJ, McClain CR, Schanz SJ, Protack TL, Windrem MS, Goldman SA. (2011) CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells. Nat Biotechnol (Sep), 29(10): 934-941.
- Johnson MD, Shaw AK, O‘Connell MJ, Sim FJ, Moses HL. (2011) Analysis of transforming growth factor ß receptor expression and signaling in higher grade meningiomas. J Neurooncol (Jun), 103(2): 277-285.
- Persson AI, Petritsch C, Swartling FJ, Itsara M, Sim FJ, Auvergne R, Goldenberg DD, Vandenberg SR, Nguyen KN, Yakovenko S, Ayers-Ringler J, Nishiyama A, Stallcup WB, Berger MS, Bergers G, McKnight TR, Goldman SA, Weiss WA. (2010) Non-stem cell origin for oligodendroglioma. Cancer Cell (Dec), 18(6): 669-682.
- Wang S, Chandler-Militello D, Lu G, Roy NS, Zielke A, Auvergne R, Stanwood N, Geschwind D, Coppola G, Nicolis SK, Sim FJ, Goldman SA. (2010) Prospective identification, isolation, and profiling of a telomerase-expressing subpopulation of human neural stem cells, using sox2 enhancer-directed fluorescence-activated cell sorting. J Neurosci (Nov), 30(44): 14635-14648.
- Johnson MD, Shaw AK, O'Connell MJ, Sim FJ, Moses HL. (2010) Analysis of transforming growth factor ß receptor expression and signaling in higher grade meningiomas. J Neurooncol (Sep).
- Sim FJ, Windrem MS, Goldman SA. (2009) Fate determination of adult human glial progenitor cells. Neuron Glia Biol (Oct)1-11.
- Sim FJ, Lang JK, Ali TA, Roy NS, Vates GE, Pilcher WH, Goldman SA. (2008) Statin treatment of adult human glial progenitors induces PPAR gamma-mediated oligodendrocytic differentiation. Glia (Jul), 56(9): 954-962.
- Lovatt D, Sonnewald U, Waagepetersen HS, Schousboe A, He W, Lin JH, Han X, Takano T, Wang S, Sim FJ, Goldman SA, Nedergaard M. (2007) The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci (Nov), 27(45): 12255-12266.
- Sim FJ, Keyoung HM, Goldman JE, Kim DK, Jung HW, Roy NS, Goldman SA. (2006) Neurocytoma is a tumor of adult neuronal progenitor cells. J Neurosci (Nov), 26(48): 12544-12555.
- Sim FJ, Lang JK, Waldau B, Roy NS, Schwartz TE, Pilcher WH, Chandross KJ, Natesan S, Merrill JE, Goldman SA, Goldmanm SA. (2006) Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation. Ann Neurol (May), 59(5): 763-779.
- Goldman SA, Lang J, Roy N, Schanz SJ, Sim FJ, Wang S, Washco V, Windrem MS. (2006) Progenitor cell-based myelination as a model for cell-based therapy of the central nervous system. Ernst Schering Res Found Workshop (Jan)(60): 195-213.
- Sim FJ, Goldman SA. (2005) White matter progenitor cells reside in an oligodendrogenic niche. Ernst Schering Res Found Workshop (Jan)(53): 61-81.
- Ibanez C, Shields SA, El-Etr M, Leonelli E, Magnaghi V, Li WW, Sim FJ, Baulieu EE, Melcangi RC, Schumacher M, Franklin RJ. (2003) Steroids and the reversal of age-associated changes in myelination and remyelination. Prog Neurobiol (Sep), 71(1): 49-56.
- Sim FJ, Zhao C, Li WW, Lakatos A, Franklin RJ. (2002) Expression of the POU-domain transcription factors SCIP/Oct-6 and Brn-2 is associated with Schwann cell but not oligodendrocyte remyelination of the CNS. Mol Cell Neurosci (Aug), 20(4): 669-682.
- Franklin RJ, Zhao C, Sim FJ. (2002) Ageing and CNS remyelination. Neuroreport (May), 13(7): 923-928.
- Sim FJ, Zhao C, Penderis J, Franklin RJ. (2002) The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci (Apr), 22(7): 2451-2459.
- Smith PM, Sim FJ, Barnett SC, Franklin RJ. (2001) SCIP/Oct-6, Krox-20, and desert hedgehog mRNA expression during CNS remyelination by transplanted olfactory ensheathing cells. Glia (Dec), 36(3): 342-353.
- Kotter MR, Setzu A, Sim FJ, Van Rooijen N, Franklin RJ. (2001) Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination. Glia (Sep), 35(3): 204-212.
- Sim FJ, Hinks GL, Franklin RJ. (2000) The re-expression of the homeodomain transcription factor Gtx during remyelination of experimentally induced demyelinating lesions in young and old rat brain. Neuroscience (Jan), 100(1): 131-139.
Professional Memberships:
- American Association for Cancer Research (2007–present)
- Society for Neuro-Oncology (2007–present)
- International Society for Stem Cell Research (2006–present)
- American Society for Neurochemistry (2005–present)
- Society for Neuroscience (2003–present)
- British Neuropathological Society (2000–2001)
Presentations:
- "HSPG-dependent signaling impairs remyelination following experimental demyelination." Invited Speaker, Neurological Research Institute at Texas Children’s Hospital and Baylor College of Medicine (2024)
- "Muscarinic receptor M3R signaling prevents efficient remyelination by human and mouse oligodendrocyte progenitor cells" 7th Joint ECTRIMS-ACTRIMS (2017)
- "Targeting the inhibitors of remyelination by modulation of HSPG sulfation" 13th Biennial ISN Satellite Meeting on Myelin Biology; Internation Society for Neurochemistry (2017)
- "Transcriptional regulation of human OPC fate" 12th Biennial ISN Satellite Meeting on Myelin Biology; International Society for Neurochemistry Meeting (2015)
- "Muscarinic M3R regulation of human oligodendrocyte progenitor differentiation" Gordon Research Conference on Myelin (2014)
- "Identification and genomic analysis of human neural and oligodendrocyte progenitor cells" Euroglia XI (2013)
- "Transcriptional control of oligodendrocyte fate in human brain" 11th Biennial ISN Satellite Meeting on Myelin Biology; ISN-ASN Meeting (2013)
- "Genomic analyses of human A2B5-defined glioma initiating progenitor cells" Roswell Park Cancer Institute, Molecular and Developmental Genetics Seminar (2010)
- "Human glial progenitor cell isolation and microarray-based molecular characterization: in search of oligoneogenic pathways" SUNY REACH Neurodegenerative Diseases and Stem Cell Therapeutics Symposium (2010)
- "Transcriptional regulation of glial progenitor cells in the developing human brain" 41st Meeting of the American Society for Neurochemistry; American Society for Neurochemistry (2010)
- "Directing human oligodendrocyte progenitor differentiation and repair" Biosymposia, Stem Cells and CNS regeneration; Biosymposia (2007)
- "Fluorescence-based identification, isolation and transplantation of human stem cells" Keio International Symposium on Photonics and Molecular Therapy; Keio University (2007)
- "Stem cell-based repair of the CNS" University of British Columbia, Vancouver, Brain research centre research day (2006)
- "Fate-regulating pathways in adult human oligodendrocyte progenitors" 36th Meeting of the American Society for Neurochemistry; American Society for Neurochemistry (2005)
- "Overcoming environmental and human-specific inhibitors of remyelination in Multiple Sclerosis" Biogen, Invited Speaker
Service Activities:
- Glia, Editorial Board (2021)
- Journal of Clinical Investigation, Nature Communications, Stem Cell Reports, Stem Cells and Development, Scientific Reports, Brain Research (2021)
- NIH, NTRC Panel ad hoc (2/25/21) NIH, ZRG1 MDCN-G (05) Panel ad hoc SEP (3/25/21) NIH, ZNS1 SRB-T(49) for NSD-B Panel ad hoc SEP (7/8/21) NIH, ZRG1 MDCN-T(05) Panel ad hoc SEP (7/20/21) NIH, NTRC Panel ad hoc SEP (10/21/21) NSF Merit Review, ad hoc reviewer (2021) (2021)
- ; Faculty Council Facilities and Space Allocation Policy Committee (2021)
- ; Graduate student education committee (member) (2021)
- ; Neuroscience Program Director (2021)
- ; Natural Sciences Interdisciplinary MS program, Admissions Committee member (2019–2021)
- ; PPBS Steering committee, member (2019–2021)