Research Summary

The focus of my research group is the protein homeostasis network, a network of over 1,000 different factors in human cells that maintain the proteome in a functional and balanced state. Our goal is to understand how this network functions, and how it is challenged and rewired in disease states, in particular cancer and neurodegenerative diseases. Our functional genomics platform enables us to elucidate dynamic networks and to pinpoint nodes that are potential therapeutic targets. Using biochemistry, biophysics and cell biology, we then "zoom in" on individual nodes of the network to reveal their mechanism of action.

As a postdoctoral scholar in Jonathan Weissman’s lab at UCSF, I spearheaded the development of a functional genomics platform for robust genome-wide screens and genetic interaction maps in mammalian cells (see section C.2 below). Very recently, we have enhanced this platform by developing CRISPR-based technologies enabling both loss-of-function and gain-of-function screens in mammalian cells (see section C.3 below). I am confident that our functional genomics approach will have a particularly high impact in its application to elucidate cancer-relevant cellular pathways. We have successfully used this approach to identify cellular factors that control the sensitivity of cancer cells to drugs (see section C.4 below). This approach can identify biomarkers predictive of clinical responses, predict possible mechanisms of drug resistance, and guide the development of combination therapies.

Research Funding

  • September 1, 2021 - August 31, 2026 - Uncovering the genetic mechanisms of the Chromosome 17q21.31 Tau haplotype on neurodegeneration risk in FTD and PSP , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: U54NS123746
  • July 1, 2021 - June 30, 2026 - Investigating the Functional Impact of AD Risk Genes on Neuro-Vascular Interactions , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01AG072464
  • September 5, 2018 - June 30, 2023 - The Psychiatric Cell Map Initiative: Connecting Genomics, Subcellular Networks, and Higher Order Phenotypes , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01MH115747
  • September 30, 2018 - May 31, 2023 - Systematic elucidation of endosomal trafficking as a therapeutic opportunity in AD using CRISPR-based functional genomics , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AG062359

Education

Marburg University, Germany, Pre-diploma, 06/00, Human Biology
Cambridge University, UK, B.A. (M.A.), First Class Honours, 06/03, Biochemistry
The Rockefeller University, Ph.D., 06/09, Biological Sciences (Cell Biology, Biophysics)
University of California, San Francisco, Postdoctoral Fellow, 07/15, Systems Biology

Honors & Awards

  • 2017
    Named to first cohort of Chan Zuckerberg Biohub Investigators
  • 2016
    Innovative Research Grant, Stand Up To Cancer
  • 2015
    New Innovator Award, NIH
  • 2015
    Allen Distinguished Investigator Award, Paul G. Allen Family Foundation
  • 2014
    Pathway to Independence Award (K99/R00), NIH
  • 2012
    Finalist, Deloitte QB3 Award for Innovation, California Institute for Quantitative Biosciences
  • 2012
    PBBR Postdoctoral Research Fellowship, Program for Breakthrough Biomedical Research, UCSF
  • 2010
    Postdoctoral Fellowship, Jane Coffin Childs Memorial Fund
  • 2006
    David Rockefeller Fellowship, The Rockefeller University
  • 2003
    Predoctoral Fellowship, Howard Hughes Medical Institute

Selected Publications

  1. Rose K, Jepson T, Shukla S, Maya-Romero A, Kampmann M, Xu K, Hurley JH. Tau fibrils induce nanoscale membrane damage and nucleate cytosolic tau at lysosomes. bioRxiv. 2023 Aug 28.  View on PubMed
  2. Yang J, Baron KR, Pride DE, Schneemann A, Guo X, Chen W, Song AS, Aviles G, Kampmann M, Luke Wiseman R, Lander GC. DELE1 oligomerization promotes integrated stress response activation. Nat Struct Mol Biol. 2023 09; 30(9):1295-1302.  View on PubMed
  3. Roberts MA, Deol KK, Mathiowetz AJ, Lange M, Leto DE, Stevenson J, Hashemi SH, Morgens DW, Easter E, Heydari K, Nalls MA, Bassik MC, Kampmann M, Kopito RR, Faghri F, Olzmann JA. Parallel CRISPR-Cas9 screens identify mechanisms of PLIN2 and lipid droplet regulation. Dev Cell. 2023 Sep 25; 58(18):1782-1800.e10.  View on PubMed
  4. Ramani B, Rose IVL, Pan A, Tian R, Ma K, Palop JJ, Kampmann M. Scalable, cell type-selective, AAV-based in vivo CRISPR screening in the mouse brain. bioRxiv. 2023 Jun 27.  View on PubMed
  5. Samelson AJ, Ariqat N, McKetney J, Rohanitazangi G, Parra Bravo C, Goodness D, Tian R, Grosjean P, Abskharon R, Eisenberg D, Kanaan NM, Gan L, Condello C, Swaney DL, Kampmann M. CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis. bioRxiv. 2023 Jun 26.  View on PubMed
  6. Bravo CP, Giani AM, Perez JM, Zhao Z, Samelson A, Wong MY, Evangelisti A, Fan L, Pozner T, Mercedes M, Ye P, Patel T, Yarahmady A, Carling G, Lee VMY, Sharma M, Mok SA, Luo W, Zhao M, Kampmann M, Gong S, Gan L. Human iPSC 4R tauopathy model uncovers modifiers of tau propagation. bioRxiv. 2023 Jun 22.  View on PubMed
  7. Perea V, Baron KR, Dolina V, Aviles G, Rosarda JD, Guo X, Kampmann M, Wiseman RL. Pharmacologic Activation of a Compensatory Integrated Stress Response Kinase Promotes Mitochondrial Remodeling in PERK-deficient Cells. bioRxiv. 2023 May 17.  View on PubMed
  8. Li E, Benitez C, Boggess SC, Koontz M, Rose IVL, Draeger N, Teter OM, Samelson AJ, Ullian EM, Kampmann M. CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions. bioRxiv. 2023 Apr 27.  View on PubMed
  9. Li H, Guglielmetti C, Sei YJ, Zilberter M, Le Page LM, Shields L, Yang J, Nguyen K, Tiret B, Gao X, Bennett N, Lo I, Dayton TL, Kampmann M, Huang Y, Rathmell JC, Heiden MV, Chaumeil MM, Nakamura K. Neurons require glucose uptake and glycolysis in vivo. Cell Rep. 2023 Apr 06; 42(4):112335.  View on PubMed
  10. Sreekanth V, Jan M, Zhao KT, Lim D, Davis JR, McConkey M, Kovalcik V, Barkal S, Law BK, Fife J, Tian R, Vinyard ME, Becerra B, Kampmann ME, Sherwood RI, Pinello L, Liu DR, Ebert BL, Choudhary A. A molecular glue approach to control the half-life of CRISPR-based technologies. bioRxiv. 2023 Mar 20.  View on PubMed
  11. de Majo M, Koontz M, Marsan E, Salinas N, Ramsey A, Kuo YM, Seo K, Li H, Dräger N, Leng K, Gonzales SL, Kurnellas M, Miyaoka Y, Klim JR, Kampmann M, Ward ME, Huang EJ, Ullian EM. Granulin loss of function in human mature brain organoids implicates astrocytes in TDP-43 pathology. Stem Cell Reports. 2023 03 14; 18(3):706-719.  View on PubMed
  12. Rheinberger M, Costa AL, Kampmann M, Glavas D, Shytaj IL, Sreeram S, Penzo C, Tibroni N, Garcia-Mesa Y, Leskov K, Fackler OT, Vlahovicek K, Karn J, Lucic B, Herrmann C, Lusic M. Genomic profiling of HIV-1 integration in microglia cells links viral integration to the topologically associated domains. Cell Rep. 2023 Feb 13; 42(2):112110.  View on PubMed
  13. You SF, Brase L, Filipello F, Iyer AK, Del-Aguila J, He J, D'Oliveira Albanus R, Budde J, Norton J, Gentsch J, Dräger NM, Sattler SM, Kampmann M, Piccio L, Morris JC, Perrin RJ, McDade E, Dominantly Inherited Alzheimer Network, Paul SM, Cashikar AG, Benitez BA, Harari O, Karch CM. MS4A4A modifies the risk of Alzheimer disease by regulating lipid metabolism and immune response in a unique microglia state. medRxiv. 2023 Feb 08.  View on PubMed
  14. Oltion K, Carelli JD, Yang T, See SK, Wang HY, Kampmann M, Taunton J. An E3 ligase network engages GCN1 to promote the degradation of translation factors on stalled ribosomes. Cell. 2023 Jan 19; 186(2):346-362.e17.  View on PubMed
  15. Replogle JM, Bonnar JL, Pogson AN, Liem CR, Maier NK, Ding Y, Russell BJ, Wang X, Leng K, Guna A, Norman TM, Pak RA, Ramos DM, Ward ME, Gilbert LA, Kampmann M, Weissman JS, Jost M. Maximizing CRISPRi efficacy and accessibility with dual-sgRNA libraries and optimal effectors. Elife. 2022 Dec 28; 11.  View on PubMed
  16. Rakin T Nasar, Felipe Luiz Pereira, Song Hua Li, Silvia Miramontes, Martin Kampmann, Kun Leng, William W. Seeley, Salvatore Spina, Bruce L. Miller, Lea Tenenholz Grinberg. Pathological Validation of RORB and CDH9 as Selectively Vulnerable Neurons in Alzheimer’s Disease. Alzheimer's & Dementia. 2022 Dec 20; 18(S3).  View on PubMed
  17. Pantazis CB, Yang A, Lara E, McDonough JA, Blauwendraat C, Peng L, Oguro H, Kanaujiya J, Zou J, Sebesta D, Pratt G, Cross E, Blockwick J, Buxton P, Kinner-Bibeau L, Medura C, Tompkins C, Hughes S, Santiana M, Faghri F, Nalls MA, Vitale D, Ballard S, Qi YA, Ramos DM, Anderson KM, Stadler J, Narayan P, Papademetriou J, Reilly L, Nelson MP, Aggarwal S, Rosen LU, Kirwan P, Pisupati V, Coon SL, Scholz SW, Priebe T, Öttl M, Dong J, Meijer M, Janssen LJM, Lourenco VS, van der Kant R, Crusius D, Paquet D, Raulin AC, Bu G, Held A, Wainger BJ, Gabriele RMC, Casey JM, Wray S, Abu-Bonsrah D, Parish CL, Beccari MS, Cleveland DW, Li E, Rose IVL, Kampmann M, Calatayud Aristoy C, Verstreken P, Heinrich L, Chen MY, Schüle B, Dou D, Holzbaur ELF, Zanellati MC, Basundra R, Deshmukh M, Cohen S, Khanna R, Raman M, Nevin ZS, Matia M, Van Lent J, Timmerman V, Conklin BR, Johnson Chase K, Zhang K, Funes S, Bosco DA, Erlebach L, Welzer M, Kronenberg-Versteeg D, Lyu G, Arenas E, Coccia E, Sarrafha L, Ahfeldt T, Marioni JC, Skarnes WC, Cookson MR, Ward ME, Merkle FT. A reference human induced pluripotent stem cell line for large-scale collaborative studies. Cell Stem Cell. 2022 12 01; 29(12):1685-1702.e22.  View on PubMed
  18. Leng K, Kampmann M. Towards elucidating disease-relevant states of neurons and glia by CRISPR-based functional genomics. Genome Med. 2022 11 18; 14(1):130.  View on PubMed
  19. Kim H, Leng K, Park J, Sorets AG, Kim S, Shostak A, Embalabala RJ, Mlouk K, Katdare KA, Rose IVL, Sturgeon SM, Neal EH, Ao Y, Wang S, Sofroniew MV, Brunger JM, McMahon DG, Schrag MS, Kampmann M, Lippmann ES. Reactive astrocytes transduce inflammation in a blood-brain barrier model through a TNF-STAT3 signaling axis and secretion of alpha 1-antichymotrypsin. Nat Commun. 2022 11 02; 13(1):6581.  View on PubMed
  20. Leng K, Rose IVL, Kim H, Xia W, Romero-Fernandez W, Rooney B, Koontz M, Li E, Ao Y, Wang S, Krawczyk M, Tcw J, Goate A, Zhang Y, Ullian EM, Sofroniew MV, Fancy SPJ, Schrag MS, Lippmann ES, Kampmann M. CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states. Nat Neurosci. 2022 11; 25(11):1528-1542.  View on PubMed

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