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 5, 2018 - June 30, 2023 - The Psychiatric Cell Map Initiative: Connecting Genomics, Subcellular Networks, and Higher Order Phenotypes, Co-Principal Investigator. Sponsor: NIH/NIMH, 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/NIA, Sponsor Award ID: R01AG062359
  • September 30, 2016 - August 31, 2021 - Linking tau proteostasis with neuronal activity in FTD, Co-Investigator. Sponsor: NIH/NINDS, Sponsor Award ID: U54NS100717
  • September 30, 2015 - May 31, 2020 - Rewiring of the human protein homeostasis network in normal and disease contexts, Principal Investigator. Sponsor: NIH/NIGMS, Sponsor Award ID: DP2GM119139

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. Le Vasseur M, Friedman J, Jost M, Xu J, Yamada J, Kampmann M, Horlbeck MA, Salemi MR, Phinney BS, Weissman JS, Nunnari J. Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells. Elife. 2021 May 26; 10.  View on PubMed
  2. Tian R, Abarientos A, Hong J, Hashemi SH, Yan R, Dräger N, Leng K, Nalls MA, Singleton AB, Xu K, Faghri F, Kampmann M. Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis. Nat Neurosci. 2021 07; 24(7):1020-1034.  View on PubMed
  3. Khairunnisa Semesta, Ruilin Tian, Martin Kampmann, Mark Zastrow, Nikoleta Tsvetanova. A high-throughput CRISPR interference screen for dissecting functional regulators of GPCR/cAMP signaling. The FASEB Journal. 2021 May 14; 35(S1).  View on PubMed
  4. Nuñez JK, Chen J, Pommier GC, Cogan JZ, Replogle JM, Adriaens C, Ramadoss GN, Shi Q, Hung KL, Samelson AJ, Pogson AN, Kim JYS, Chung A, Leonetti MD, Chang HY, Kampmann M, Bernstein BE, Hovestadt V, Gilbert LA, Weissman JS. Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing. Cell. 2021 Apr 29; 184(9):2503-2519.e17.  View on PubMed
  5. Ehrenberg AJ, Leng K, Letourneau KN, Hernandez I, Lew C, Seeley WW, Spina S, Miller B, Heinsen H, Kampmann M, Kosik KS, Grinberg LT. Patterns of neuronal Rhes as a novel hallmark of tauopathies. Acta Neuropathol. 2021 05; 141(5):651-666.  View on PubMed
  6. Abrams J, Arhar T, Mok SA, Taylor IR, Kampmann M, Gestwicki JE. Functional genomics screen identifies proteostasis targets that modulate prion protein (PrP) stability. Cell Stress Chaperones. 2021 03; 26(2):443-452.  View on PubMed
  7. Kanfer G, Sarraf SA, Maman Y, Baldwin H, Dominguez-Martin E, Johnson KR, Ward ME, Kampmann M, Lippincott-Schwartz J, Youle RJ. Image-based pooled whole-genome CRISPRi screening for subcellular phenotypes. J Cell Biol. 2021 02 01; 220(2).  View on PubMed
  8. Tian R, Samelson AJ, Rezelj VV, Chen M, Ramadoss GN, Guo X, Kain AM, Tran QD, Lim SA, Lui I, Nunez J, Rockwood SJ, Liu N, Carlson-Stevermer J, Oki J, Maures T, Holden K, Weissman JS, Wells JA, Conklin B, Vignuzzi M, Kampmann M. BRD2 inhibition blocks SARS-CoV-2 infection in vitro by reducing transcription of the host cell receptor ACE2. bioRxiv. 2021 Jan 19.  View on PubMed
  9. Leng K, Li E, Eser R, Piergies A, Sit R, Tan M, Neff N, Li SH, Rodriguez RD, Suemoto CK, Leite REP, Ehrenberg AJ, Pasqualucci CA, Seeley WW, Spina S, Heinsen H, Grinberg LT, Kampmann M. Molecular characterization of selectively vulnerable neurons in Alzheimer's disease. Nat Neurosci. 2021 02; 24(2):276-287.  View on PubMed
  10. Semesta KM, Tian R, Kampmann M, von Zastrow M, Tsvetanova NG. A high-throughput CRISPR interference screen for dissecting functional regulators of GPCR/cAMP signaling. PLoS Genet. 2020 10; 16(10):e1009103.  View on PubMed
  11. Bennett NK, Nguyen MK, Darch MA, Nakaoka HJ, Cousineau D, Ten Hoeve J, Graeber TG, Schuelke M, Maltepe E, Kampmann M, Mendelsohn BA, Nakamura JL, Nakamura K. Defining the ATPome reveals cross-optimization of metabolic pathways. Nat Commun. 2020 08 28; 11(1):4319.  View on PubMed
  12. Newberry RW, Arhar T, Costello J, Hartoularos GC, Maxwell AM, Naing ZZC, Pittman M, Reddy NR, Schwarz DMC, Wassarman DR, Wu TS, Barrero D, Caggiano C, Catching A, Cavazos TB, Estes LS, Faust B, Fink EA, Goldman MA, Gomez YK, Gordon MG, Gunsalus LM, Hoppe N, Jaime-Garza M, Johnson MC, Jones MG, Kung AF, Lopez KE, Lumpe J, Martyn C, McCarthy EE, Miller-Vedam LE, Navarro EJ, Palar A, Pellegrino J, Saylor W, Stephens CA, Strickland J, Torosyan H, Wankowicz SA, Wong DR, Wong G, Redding S, Chow ED, DeGrado WF, Kampmann M. Robust Sequence Determinants of a-Synuclein Toxicity in Yeast Implicate Membrane Binding. ACS Chem Biol. 2020 08 21; 15(8):2137-2153.  View on PubMed
  13. Ramkumar P, Abarientos AB, Tian R, Seyler M, Leong JT, Chen M, Choudhry P, Hechler T, Shah N, Wong SW, Martin TG, Wolf JL, Roybal KT, Pahl A, Taunton J, Wiita AP, Kampmann M. CRISPR-based screens uncover determinants of immunotherapy response in multiple myeloma. Blood Adv. 2020 07 14; 4(13):2899-2911.  View on PubMed
  14. Kampmann M. CRISPR-based functional genomics for neurological disease. Nat Rev Neurol. 2020 Sep; 16(9):465-480.  View on PubMed
  15. Jost M, Chen Y, Gilbert LA, Horlbeck MA, Krenning L, Menchon G, Rai A, Cho MY, Stern JJ, Prota AE, Kampmann M, Akhmanova A, Steinmetz MO, Tanenbaum ME, Weissman JS. Pharmaceutical-Grade Rigosertib Is a Microtubule-Destabilizing Agent. Mol Cell. 2020 07 02; 79(1):191-198.e3.  View on PubMed
  16. Khairunnisa Mentari Semesta, Ruilin Tian, Martin Kampmann, Mark von Zastrow, Nikoleta G. Tsvetanova. A High-throughput CRISPR Interference Screen to Dissect Functional Regulators of GPCR/cAMP Signaling. The FASEB Journal. 2020 Apr 1; 34(S1):1-1.  View on PubMed
  17. Rauch JN, Luna G, Guzman E, Audouard M, Challis C, Sibih YE, Leshuk C, Hernandez I, Wegmann S, Hyman BT, Gradinaru V, Kampmann M, Kosik KS. LRP1 is a master regulator of tau uptake and spread. Nature. 2020 04; 580(7803):381-385.  View on PubMed
  18. Newberry RW, Leong JT, Chow ED, Kampmann M, DeGrado WF. Deep mutational scanning reveals the structural basis for a-synuclein activity. Nat Chem Biol. 2020 06; 16(6):653-659.  View on PubMed
  19. Guo X, Aviles G, Liu Y, Tian R, Unger BA, Lin YT, Wiita AP, Xu K, Correia MA, Kampmann M. Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway. Nature. 2020 03; 579(7799):427-432.  View on PubMed
  20. Oh E, Mark KG, Mocciaro A, Watson ER, Prabu JR, Cha DD, Kampmann M, Gamarra N, Zhou CY, Rape M. Gene expression and cell identity controlled by anaphase-promoting complex. Nature. 2020 03; 579(7797):136-140.  View on PubMed

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