Research Summary

Over the past decade, my laboratory has pioneered multiple approaches for perturbing, quantifying, and interpreting cancer heterogeneity in normal and diseased tissues. We investigate phenotypic heterogeneity, whether arising from microenvironment, epigenetic or genetic sources, and its impact on cancer evolution, drug tolerance and effective treatment strategies.

Research Funding

  • April 1, 2025 - March 31, 2030 - Elucidate the landscape of druggable targets for eliminating cancer persister cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA300245
  • April 1, 2020 - March 31, 2025 - Scalable Image-Based Approach for Profiling and Annotating Very Large Compound Libraries” , co-PI . Sponsor: NIH/NCI, Sponsor Award ID: 2R01 CA184984-06A1
  • September 1, 2019 - August 31, 2024 - A drug discovery paradigm for fast-tracking adaptations to high altitude , co-PI . Sponsor: DARPA, Sponsor Award ID: Panacea
  • September 1, 2017 - June 30, 2021 - Reverse-engineering mechanisms of neural circuit wiring in the fly visual system , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01EY028205
  • February 1, 2015 - January 31, 2020 - Systems-level role of GSK3 in colonic epithelium homeostasis and drug resistance , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM112690
  • August 1, 2010 - May 31, 2016 - Lung cancer heterogeneity and its impact on drug resistance. , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA133253
  • July 1, 2004 - May 31, 2015 - On the emergence of polarization and motility responses from chemotactic networks , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM071794
  • September 19, 2008 - August 31, 2014 - Turnkey solution for image phenotype classification , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM085442

Education

University of Pennsylvania, BA, 1985, Mathematics
University of California, San Diego, MA, 1986, Mathematics
University of California, San Diego, PhD, 1990, Mathematics (Advisor: Richard Hamilton)

Honors & Awards

  • 1985
    B.A. Magna Cum Laude, Departmental Honors
  • 1989
    Alfred P. Sloan Doctoral Dissertation Fellowship
  • 1997
    AMS Profiled Industrial Mathematician of the Month
  • 2005
    UTSW endowed scholar: W. W. Caruth, Jr. Scholar in Biomedical Research
  • 2008
    Rita Allen Foundation Scholar: Milton E. Cassel Scholar

Selected Publications

  1. Bao F, Li L, Hammerlindl H, Shen SQ, Hammerlindl S, Altschuler SJ, Wu LF. Transitive prediction of small-molecule function through alignment of high-content screening resources. Nat Biotechnol. 2025 Jul 11. View on PubMed
  2. Li L, Hammerlindl H, Shen SQ, Bao F, Hammerlindl S, Altschuler SJ, Wu LF. A phenopushing platform to identify compounds that alleviate acute hypoxic stress by fast-tracking cellular adaptation. Nat Commun. 2025 Mar 18; 16(1):2684. View on PubMed
  3. Sun X, Kumbier K, Gayathri S, Steri V, Wu LF, Altschuler SJ. Targeting PRMT1 Reduces Cancer Persistence and Tumor Relapse in EGFR- and KRAS-Mutant Lung Cancer. Cancer Res Commun. 2025 01 01; 5(1):119-127. View on PubMed
  4. Sun X, Wu LF, Altschuler SJ, Hata AN. Targeting therapy-persistent residual disease. Nat Cancer. 2024 Sep; 5(9):1298-1304. View on PubMed
  5. Bogdanov A, Salib MN, Chase AB, Hammerlindl H, Muskat MN, Luedtke S, da Silva EB, O'Donoghue AJ, Wu LF, Altschuler SJ, Molinski TF, Jensen PR. Small molecule in situ resin capture provides a compound first approach to natural product discovery. Nat Commun. 2024 Jun 19; 15(1):5230. View on PubMed
  6. Kumbier K, Roth M, Li Z, Lazzari-Dean J, Waters C, Hammerlindl S, Rinaldi C, Huang P, Korobeynikov VA, New York Genome Center ALS Consortium, Phatnani H, Shneider N, Jacobson MP, Wu LF, Altschuler SJ. Identifying FUS amyotrophic lateral sclerosis disease signatures in patient dermal fibroblasts. Dev Cell. 2024 08 19; 59(16):2134-2142.e6. View on PubMed
  7. Waters CS, Angenent SB, Altschuler SJ, Wu LF. A PINK1 input threshold arises from positive feedback in the PINK1/Parkin mitophagy decision circuit. Cell Rep. 2023 10 31; 42(10):113260. View on PubMed
  8. Li L, Shen S, Bickler P, Jacobson MP, Wu LF, Altschuler SJ. Searching for molecular hypoxia sensors among oxygen-dependent enzymes. Elife. 2023 07 26; 12. View on PubMed
  9. Bogdanov A, Salib MN, Chase AB, Hammerlindl H, Muskat MN, Luedtke S, Barbosa da Silva E, O'Donoghue AJ, Wu LF, Altschuler SJ, Molinski TF, Jensen PR. Small Molecule in situ Resin Capture - A Compound First Approach to Natural Product Discovery. bioRxiv. 2023 May 30. View on PubMed
  10. Rinaldi C, Waters CS, Li Z, Kumbier K, Rao L, Nichols RJ, Jacobson MP, Wu LF, Altschuler SJ. Dissecting the effects of GTPase and kinase domain mutations on LRRK2 endosomal localization and activity. Cell Rep. 2023 05 30; 42(5):112447. View on PubMed
  11. Heinrich L, Kumbier K, Li L, Altschuler SJ, Wu LF. Selection of Optimal Cell Lines for High-Content Phenotypic Screening. ACS Chem Biol. 2023 04 21; 18(4):679-685. View on PubMed
  12. Stölzel F, Fordham SE, Nandana D, Lin WY, Blair H, Elstob C, Bell HL, Mohr B, Ruhnke L, Kunadt D, Dill C, Allsop D, Piddock R, Soura EN, Park C, Fadly M, Rahman T, Alharbi A, Wobus M, Altmann H, Röllig C, Wagenführ L, Jones GL, Menne T, Jackson GH, Marr HJ, Fitzgibbon J, Onel K, Meggendorfer M, Robinson A, Bziuk Z, Bowes E, Heidenreich O, Haferlach T, Villar S, Ariceta B, Diaz RA, Altschuler SJ, Wu LF, Prosper F, Montesinos P, Martinez-Lopez J, Bornhäuser M, Allan JM. Biallelic TET2 mutations confer sensitivity to 5'-azacitidine in acute myeloid leukemia. JCI Insight. 2023 Jan 24; 8(2). View on PubMed
  13. Bao F, Deng Y, Wan S, Shen SQ, Wang B, Dai Q, Altschuler SJ, Wu LF. Publisher Correction: Integrative spatial analysis of cell morphologies and transcriptional states with MUSE. Nat Biotechnol. 2022 Aug; 40(8):1295. View on PubMed
  14. Bao F, Deng Y, Wan S, Shen SQ, Wang B, Dai Q, Altschuler SJ, Wu LF. Integrative spatial analysis of cell morphologies and transcriptional states with MUSE. Nat Biotechnol. 2022 08; 40(8):1200-1209. View on PubMed
  15. Sun X, Bieber JM, Hammerlindl H, Chalkley RJ, Li KH, Burlingame AL, Jacobson MP, Wu LF, Altschuler SJ. Modulating environmental signals to reveal mechanisms and vulnerabilities of cancer persisters. Sci Adv. 2022 01 28; 8(4):eabi7711. View on PubMed
  16. Bieber JM, Sanman LE, Sun X, Hammerlindl H, Bao F, Roth MA, Koleske ML, Huang L, Aweeka F, Wu LF, Altschuler SJ. Differential toxicity to murine small and large intestinal epithelium induced by oncology drugs. Commun Biol. 2022 01 27; 5(1):99. View on PubMed
  17. Ji W, Wu LF, Altschuler SJ. Analysis of growth cone extension in standardized coordinates highlights self-organization rules during wiring of the Drosophila visual system. PLoS Genet. 2021 11; 17(11):e1009857. View on PubMed
  18. Sanman LE, Chen IW, Bieber JM, Steri V, Trentesaux C, Hann B, Klein OD, Wu LF, Altschuler SJ. Transit-Amplifying Cells Coordinate Changes in Intestinal Epithelial Cell-Type Composition. Dev Cell. 2021 02 08; 56(3):356-365.e9. View on PubMed
  19. Kochanowski K, Sander T, Link H, Chang J, Altschuler SJ, Wu LF. Systematic alteration of in vitro metabolic environments reveals empirical growth relationships in cancer cell phenotypes. Cell Rep. 2021 01 19; 34(3):108647. View on PubMed
  20. Morinishi L, Kochanowski K, Levine RL, Wu LF, Altschuler SJ. Loss of TET2 Affects Proliferation and Drug Sensitivity through Altered Dynamics of Cell-State Transitions. Cell Syst. 2020 07 22; 11(1):86-94.e5. View on PubMed

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