Bjoern Schwer, MD, PhD | Developmental & Stem Cell Biology Program

Associate Professor

Suzanne Marie Haderle and Robert Vincent Haderle Endowed Chair

Department of Neurological Surgery

+1 415 476-6786

Our laboratory seeks to gain mechanistic insight into how interrelated processes - namely DNA repair, chromatin regulation, and transcriptional regulation - affect brain physiology. We investigate mechanisms of chromosomal DNA double-strand break formation and repair in neural stem/progenitor cells and other neural cell types in the contexts of neurodevelopment, neural functioning, cellular diversity, and disease. In the latter context, a major current focus is the elucidation of causes of genome instability and chromosomal rearrangements in neural progenitors that give rise to brain cancers.

Research Summary

Genomic instability and DNA repair in neural cells

Websites

Schwer Lab

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

Publications

Endogenous neuronal DNA double-strand breaks are not sufficient to drive brain aging and neurodegeneration.

bioRxiv : the preprint server for biology

Cohen S, Cheradame L, Pratt KJB, Collins S, Barillas A, Carlson A, Ramani V, Legube G, Villeda SA, Mullins RD, Schwer B

PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression.

Scientific reports

Schmidt C, Cohen S, Gudenas BL, Husain S, Carlson A, Westelman S, Wang L, Phillips JJ, Northcott PA, Weiss WA, Schwer B

MDB-32. PRDM6 PROMOTES MEDULLOBLASTOMA FORMATION IN NEUROEPITHELIAL STEM CELLS AND IS A CHROMATIN REPRESSOR BY BINDING TO HISTONE H3 LYSINE 27 TRIMETHYLATION MARKS.

Neuro-oncology

Christin Schmidt, Sarah Cohen, Brian L Gudenas, Sarah Husain, Annika Carlson, Samantha Westelman, Linyu Wang, Joanna J Phillips, Paul A Northcott, William A Weiss, Bjoern Schwer

Type-I-interferon-responsive microglia shape cortical development and behavior.

Cell

Escoubas CC, Dorman LC, Nguyen PT, Lagares-Linares C, Nakajo H, Anderson SR, Barron JJ, Wade SD, Cuevas B, Vainchtein ID, Silva NJ, Guajardo R, Xiao Y, Lidsky PV, Wang EY, Rivera BM, Taloma SE, Kim DK, Kaminskaya E, Nakao-Inoue H, Schwer B, Arnold TD, Molofsky AB, Condello C, Andino R, Nowakowski TJ, Molofsky AV

PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression.

bioRxiv : the preprint server for biology

Schmidt C, Cohen S, Gudenas BL, Husain S, Carlson A, Westelman S, Wang L, Phillips JJ, Northcott PA, Weiss WA, Schwer B

MDB-09. IMPACT OF PRDM6 ON CHROMATIN ACCESSIBILITY, GENE EXPRESSION, AND MEDULLOBLASTOMA FORMATION.

Neuro-oncology

Christin Schmidt, Sarah Husain, Annika Carlson, Sarah Cohen, Samantha Westelman, Linyu Wang, William Weiss, Bjoern Schwer

A type I interferon response defines a conserved microglial state required for effective neuronal phagocytosis.

bioRxiv : the preprint server for biology

Dorman LC, Nguyen PT, Escoubas CC, Vainchtein ID, Xiao Y, Lidsky PV, Nakajo H, Silva NJ, Lagares-Linares C, Wang EY, Taloma SE, Cuevas B, Nakao-Inoue H, Rivera BM, Schwer B, Condello C, Andino R, Nowakowski TJ, Molofsky AV

MODL-32. IMPACT OF PRDM6 ON CHROMATIN ACCESSIBILITY, GENE EXPRESSION, AND MEDULLOBLASTOMA FORMATION.

Neuro-oncology

Christin Schmidt, Sarah Husain, Annika Carlson, Sarah Cohen, Samantha Westelman, Linyu Wang, William Weiss, Bjoern Schwer

Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells.

Scientific reports

Thongthip S, Carlson A, Crossley MP, Schwer B

Editorial: Genomic Instability and Neurodegeneration.

Frontiers in aging neuroscience

Fuchs J, Schwer B, El-Khamisy SF

Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice.

Neuro-oncology

Chuntova P, Hou Y, Naka R, Yamamichi A, Chen T, Goretsky Y, Hatae R, Nejo T, Kohanbash G, Mende AL, Montoya M, Downey KM, Diebold D, Skinner J, Liang HE, Schwer B, Okada H

Topoisomerase I inhibition and peripheral nerve injury induce DNA breaks and ATF3-associated axon regeneration in sensory neurons.

Cell reports

Cheng YC, Snavely A, Barrett LB, Zhang X, Herman C, Frost DJ, Riva P, Tochitsky I, Kawaguchi R, Singh B, Ivanis J, Huebner EA, Arvanites A, Oza V, Davidow L, Maeda R, Sakuma M, Grantham A, Wang Q, Chang AN, Pfaff K, Costigan M, Coppola G, Rubin LL, Schwer B, Alt FW, Woolf CJ

BIOL-11. THE ROLE OF ABERRANT EXPRESSION OF PRDM6 IN THE DEVELOPING CEREBELLUM AND IN GROUP 4 MEDULLOBLASTOMA.

Neuro-oncology

Christin Schmidt, Annika Carlson, William Weiss, Bjoern Schwer

OMIC-03. TRANSLATIONAL CONTROL IN MYC AND MYCN MEDULLOBLASTOMA.

Neuro-oncology

Christin Schmidt, Albertas Navickas, Frederique Zindy, Dana Farmer, Davide Ruggero, Hani Goodarzi, Martine F Roussel, Bjoern Schwer, William Weiss

TMOD-28. NEW APPROACHES FOR ELUCIDATING MEDULLOBLASTOMA DEVELOPMENT VIA HINDBRAIN BLASTOCYST COMPLEMENTATION.

Neuro-oncology

Christin Schmidt, Annika Carlson, William Weiss, Bjoern Schwer

Direct analysis of brain phenotypes via neural blastocyst complementation.

Nature protocols

Dai HQ, Liang Z, Chang AN, Chapdelaine-Williams AM, Alvarado B, Pollen AA, Alt FW, Schwer B

Neural blastocyst complementation enables mouse forebrain organogenesis.

Nature

Chang AN, Liang Z, Dai HQ, Chapdelaine-Williams AM, Andrews N, Bronson RT, Schwer B, Alt FW

DNA double-strand breaks as drivers of neural genomic change, function, and disease.

DNA repair

Alt FW, Schwer B

Three classes of recurrent DNA break clusters in brain progenitors identified by 3D proximity-based break joining assay.

Proceedings of the National Academy of Sciences of the United States of America

Wei PC, Lee CS, Du Z, Schwer B, Zhang Y, Kao J, Zurita J, Alt FW

Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster.

Proceedings of the National Academy of Sciences of the United States of America

Wood JG, Schwer B, Wickremesinghe PC, Hartnett DA, Burhenn L, Garcia M, Li M, Verdin E, Helfand SL

Editorial: DNA damage & immunity.

Mechanisms of ageing and development

Garinis GA, Schwer B, Schumacher B

Recurrently Breaking Genes in Neural Progenitors: Potential Roles of DNA Breaks in Neuronal Function, Degeneration and Cancer.

Transcription-associated processes cause DNA double-strand breaks and translocations in neural stem/progenitor cells.

Proceedings of the National Academy of Sciences of the United States of America

Schwer B, Wei PC, Chang AN, Kao J, Du Z, Meyers RM, Alt FW

Long Neural Genes Harbor Recurrent DNA Break Clusters in Neural Stem/Progenitor Cells.

Cell

Wei PC, Chang AN, Kao J, Du Z, Meyers RM, Alt FW, Schwer B

IgH class switching exploits a general property of two DNA breaks to be joined in cis over long chromosomal distances.

Proceedings of the National Academy of Sciences of the United States of America

Gostissa M, Schwer B, Chang A, Dong J, Meyers RM, Marecki GT, Choi VW, Chiarle R, Zarrin AA, Alt FW

SIRT6 modulates paclitaxel and epirubicin resistance and survival in breast cancer.

Carcinogenesis

Khongkow M, Olmos Y, Gong C, Gomes AR, Monteiro LJ, Yagüe E, Cavaco TB, Khongkow P, Man EP, Laohasinnarong S, Koo CY, Harada-Shoji N, Tsang JW, Coombes RC, Schwer B, Khoo US, Lam EW

Essential developmental, genomic stability, and tumour suppressor functions of the mouse orthologue of hSSB1/NABP2.

PLoS genetics

Shi W, Bain AL, Schwer B, Al-Ejeh F, Smith C, Wong L, Chai H, Miranda MS, Ho U, Kawaguchi M, Miura Y, Finnie JW, Wall M, Heierhorst J, Wicking C, Spring KJ, Alt FW, Khanna KK

Mechanisms of programmed DNA lesions and genomic instability in the immune system.

Cell

Alt FW, Zhang Y, Meng FL, Guo C, Schwer B

Functional redundancy between the XLF and DNA-PKcs DNA repair factors in V(D)J recombination and nonhomologous DNA end joining.

Proceedings of the National Academy of Sciences of the United States of America

Oksenych V, Kumar V, Liu X, Guo C, Schwer B, Zha S, Alt FW

Functional redundancy between repair factor XLF and damage response mediator 53BP1 in V(D)J recombination and DNA repair.

Proceedings of the National Academy of Sciences of the United States of America

Oksenych V, Alt FW, Kumar V, Schwer B, Wesemann DR, Hansen E, Patel H, Su A, Guo C

Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1).

Proceedings of the National Academy of Sciences of the United States of America

Boboila C, Oksenych V, Gostissa M, Wang JH, Zha S, Zhang Y, Chai H, Lee CS, Jankovic M, Saez LM, Nussenzweig MC, McKinnon PJ, Alt FW, Schwer B

Classical and alternative end-joining pathways for repair of lymphocyte-specific and general DNA double-strand breaks.

Advances in immunology

Boboila C, Alt FW, Schwer B

SIRT3 regulates mitochondrial protein acetylation and intermediary metabolism.

Cold Spring Harbor symposia on quantitative biology

Hirschey MD, Shimazu T, Huang JY, Schwer B, Verdin E

SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome.

Molecular cell

Hirschey MD, Shimazu T, Jing E, Grueter CA, Collins AM, Aouizerat B, Stancáková A, Goetzman E, Lam MM, Schwer B, Stevens RD, Muehlbauer MJ, Kakar S, Bass NM, Kuusisto J, Laakso M, Alt FW, Newgard CB, Farese RV, Kahn CR, Verdin E

The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells.

Nature immunology

Ise W, Kohyama M, Schraml BU, Zhang T, Schwer B, Basu U, Alt FW, Tang J, Oltz EM, Murphy TL, Murphy KM

SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production.

Cell metabolism

Shimazu T, Hirschey MD, Hua L, Dittenhafer-Reed KE, Schwer B, Lombard DB, Li Y, Bunkenborg J, Alt FW, Denu JM, Jacobson MP, Verdin E

Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity.

Proceedings of the National Academy of Sciences of the United States of America

Schwer B, Schumacher B, Lombard DB, Xiao C, Kurtev MV, Gao J, Schneider JI, Chai H, Bronson RT, Tsai LH, Deng CX, Alt FW

SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation.

Nature

Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, Grueter CA, Harris C, Biddinger S, Ilkayeva OR, Stevens RD, Li Y, Saha AK, Ruderman NB, Bain JR, Newgard CB, Farese RV, Alt FW, Kahn CR, Verdin E