Research Summary

I have over 20 years of experience performing research and developing advanced technologies. I bring to my biology research a blend of experimental science, engineering, and mathematics. In 1994, I left a mathematics faculty position at Princeton to join the fledgling Research Division at Microsoft. At Microsoft I co-ran an advanced technology team (with Dr. Steven Altschuler) that worked on problems ranging from video compression, to data mining, to speech recognition. In 2000, I moved into biology. I was recruited by Rosetta Inpharmatics, where I developed new approaches for predicting gene function and mechanisms of drug perturbation. I moved to Harvard University in 2001 to immerse myself in the world of experimental biology and then to UTSW in 2005 to establish my independent laboratory. In 2014, I moved my laboratory to UCSF as a Professor in the Department of Pharmaceutical Chemistry.

Over the past decade, my laboratory has pioneered multiple approaches for quantifying and interpreting cellular heterogeneity. I have been fascinated by the functional consequences of cell individuality in normal and diseased tissues. I was stunned by the phenotypic diversity that can arise both within and across cancer clones from a single patent population and can be used to predict mechanisms of drug action. Traditionally, this phenotypic heterogeneity, whether arising from microenvironment, epigenetic, or genetic sources, has been viewed as an impediment to understanding and treating cancer. I was therefore very surprised by our ability to use quantitative measurements of heterogeneity to predict drug responses. Since uncovering these results, my lab has been focused on identifying which components of cell-to-cell differences are unimportant and which contain functional information. Currently, my lab’s research program focuses on understanding the dynamic responses of cancer cells to drugs, and identifying molecular bases for drug resistance.

Research Funding

  • April 1, 2020 - March 31, 2025 - Scalable Image-Based Approach for Profiling and Annotating Very Large Compound Libraries, Principal Investigator. 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, Principal Investigator. Sponsor: DARPA, Sponsor Award ID: Panacea
  • August 1, 2014 - July 31, 2019 - A scalable image-based approach for profiling and annotating very large compound, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA184984
  • August 1, 2014 - July 31, 2018 - (PQD1) An Iterative Approach for Overcoming Evolving Targeted Therapy Resistance, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA185404

Education

National Taiwan University, BA, 1985, Mathematics
University of California, San Diego, MA, 1987, Mathematics
University of California, San Diego, PhD, 1990, Mathematics (Advisor: Dr. Richard Hamilton)

Honors & Awards

  • 2004
    Thomas T. Hoopes Thesis Prize for best undergraduate thesis at Harvard (Maciag)
  • 2005
    UTSW endowed scholar: Cecil H. and Ida Green Scholar in Biomedical Computational Science
  • 2008
    Simmons Cancer Center Best Poster Award (Singh and Ku)
  • 2009
    Gilman Postdoc of the Year Award (Loo)
  • 2010
    UTSW Postdoc of the Year Award (Loo)

Selected Publications

  1. 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.  View on PubMed
  2. 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.  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.  View on PubMed
  4. Sanman LE, Chen IW, Bieber JM, Thorne CA, Wu LF, Altschuler SJ Generation and Quantitative Imaging of Enteroid Monolayers.  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.  View on PubMed
  6. Hsu CH, Altschuler SJ, Wu LF Patterns of Early p21 Dynamics Determine Proliferation-Senescence Cell Fate after Chemotherapy.  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.  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.  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.  View on PubMed
  10. Kochanowski K, Morinishi L, Altschuler S, Wu L Drug persistence - from antibiotics to cancer therapies.  View on PubMed
  11. Thurley K, Wu LF, Altschuler SJ Modeling Cell-to-Cell Communication Networks Using Response-Time Distributions.  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.  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.  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.  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.  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.  View on PubMed
  17. Deng Y, Altschuler SJ, Wu LF PHOCOS: inferring multi-feature phenotypic crosstalk networks.  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.  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.  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.  View on PubMed

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