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, 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/NEI, Sponsor Award ID: R01EY028205
  • February 1, 2015 - January 31, 2019 - Systems-level role of GSK3 in colonic epithelium homeostasis and drug resistance, Principal Investigator. Sponsor: NIH/NIGMS, Sponsor Award ID: R01GM112690

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. 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
  2. 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
  3. 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
  4. Sanman LE, Chen IW, Bieber JM, Thorne CA, Wu LF, Altschuler SJ. Generation and Quantitative Imaging of Enteroid Monolayers. Methods Mol Biol. 2020; 2171:99-113.  View on PubMed
  5. Rajaram S, Roth MA, Malato J, VandenBerg S, Hann B, Atreya CE, Altschuler SJ, Wu LF. A multi-modal data resource for investigating topographic heterogeneity in patient-derived xenograft tumors. Sci Data. 2019 10 31; 6(1):253.  View on PubMed
  6. Hsu CH, Altschuler SJ, Wu LF. Patterns of Early p21 Dynamics Determine Proliferation-Senescence Cell Fate after Chemotherapy. Cell. 2019 07 11; 178(2):361-373.e12.  View on PubMed
  7. Deng Y, Bao F, Dai Q, Wu LF, Altschuler SJ. Scalable analysis of cell-type composition from single-cell transcriptomics using deep recurrent learning. Nat Methods. 2019 04; 16(4):311-314.  View on PubMed
  8. Mender I, LaRanger R, Luitel K, Peyton M, Girard L, Lai TP, Batten K, Cornelius C, Dalvi MP, Ramirez M, Du W, Wu LF, Altschuler SJ, Brekken R, Martinez ED, Minna JD, Wright WE, Shay JW. Telomerase-Mediated Strategy for Overcoming Non-Small Cell Lung Cancer Targeted Therapy and Chemotherapy Resistance. Neoplasia. 2018 08; 20(8):826-837.  View on PubMed
  9. Curtis A. Thorne, Ina W. Chen, Laura E. Sanman, Melanie H. Cobb, Lani F. Wu, Steven J. Altschuler. Planar Enteroids Reveal an Autonomous WNT And BMP Circuit Controlling Intestinal Epithelial Growth and Organization. The FASEB Journal. 2018 Apr 1; 32:659.14-659.14.  View on PubMed
  10. Kochanowski K, Morinishi L, Altschuler S, Wu L. Drug persistence - from antibiotics to cancer therapies. Curr Opin Syst Biol. 2018 Aug; 10:1-8.  View on PubMed
  11. Thurley K, Wu LF, Altschuler SJ. Modeling Cell-to-Cell Communication Networks Using Response-Time Distributions. Cell Syst. 2018 Mar 28; 6(3):355-367.e5.  View on PubMed
  12. Thorne CA, Chen IW, Sanman LE, Cobb MH, Wu LF, Altschuler SJ. Enteroid Monolayers Reveal an Autonomous WNT and BMP Circuit Controlling Intestinal Epithelial Growth and Organization. Dev Cell. 2018 03 12; 44(5):624-633.e4.  View on PubMed
  13. Rajaram S, Heinrich LE, Gordan JD, Avva J, Bonness KM, Witkiewicz AK, Malter JS, Atreya CE, Warren RS, Wu LF, Altschuler SJ. Sampling strategies to capture single-cell heterogeneity. Nat Methods. 2017 Oct; 14(10):967-970.  View on PubMed
  14. Deb D, Rajaram S, Larsen JE, Dospoy PD, Marullo R, Li LS, Avila K, Xue F, Cerchietti L, Minna JD, Altschuler SJ, Wu LF. Combination Therapy Targeting BCL6 and Phospho-STAT3 Defeats Intratumor Heterogeneity in a Subset of Non-Small Cell Lung Cancers. Cancer Res. 2017 06 01; 77(11):3070-3081.  View on PubMed
  15. Zhang ER, Liu S, Wu LF, Altschuler SJ, Cobb MH. Chemoattractant concentration-dependent tuning of ERK signaling dynamics in migrating neutrophils. Sci Signal. 2016 12 13; 9(458):ra122.  View on PubMed
  16. Coster AD, Thorne CA, Wu LF, Altschuler SJ. Examining Crosstalk among Transforming Growth Factor ß, Bone Morphogenetic Protein, and Wnt Pathways. J Biol Chem. 2017 Jan 06; 292(1):244-250.  View on PubMed
  17. Deng Y, Altschuler SJ, Wu LF. PHOCOS: inferring multi-feature phenotypic crosstalk networks. Bioinformatics. 2016 06 15; 32(12):i44-i51.  View on PubMed
  18. Diz-Muñoz A, Thurley K, Chintamen S, Altschuler SJ, Wu LF, Fletcher DA, Weiner OD. Membrane Tension Acts Through PLD2 and mTORC2 to Limit Actin Network Assembly During Neutrophil Migration. PLoS Biol. 2016 06; 14(6):e1002474.  View on PubMed
  19. Ramirez M, Rajaram S, Steininger RJ, Osipchuk D, Roth MA, Morinishi LS, Evans L, Ji W, Hsu CH, Thurley K, Wei S, Zhou A, Koduru PR, Posner BA, Wu LF, Altschuler SJ. Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells. Nat Commun. 2016 Feb 19; 7:10690.  View on PubMed
  20. Kang J, Hsu CH, Wu Q, Liu S, Coster AD, Posner BA, Altschuler SJ, Wu LF. Improving drug discovery with high-content phenotypic screens by systematic selection of reporter cell lines. Nat Biotechnol. 2016 Jan; 34(1):70-77.  View on PubMed

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