University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Catherine Smith, MD

Catherine Smith, MD

Assistant Professor, Division of Hematology/Oncology, Department of Medicine, UCSF

Cancer Center Program Memberships

Hematopoietic Malignancies

Research Summary

My laboratory focuses on identification of therapeutic resistance mechanisms and novel treatment strategies for acute myeloid leukemia (AML). We have a particular emphasis on AML associated with mutations in Fms-like Tyrosine Kinase-3 (FLT3). FLT3 is mutated in ~30% of AML, with constitutively activating FLT3 internal tandem duplication (ITD) mutations conferring a poor prognosis. We employ a prototypical “bedside to bench and back” approach to the problem of cancer drug resistance, founded on the belief that the ultimate pathway to improved cancer therapy begins with translational studies that utilize samples from patients who have undergone therapy in real time. This strategy allows us to interrogate how tumors can evolve under the selective pressure of cancer therapy and allows us to devise ways to circumvent these evolutionary adaptations.

We have the following specific research focuses at the current time:

1) Rational discovery and screening of novel FLT3 inhibitors coupled with analysis of resistance mechanisms to clinically relevant FLT3 inhibitors currently in clinical trials.

2) Identification and validation of non-FLT3 dependent mechanisms of FLT3 inhibitor resistance through genomic analysis of patients treated on FLT3 inhibitor clinical trials.

3) Study of the role of AML genetic tumor heterogeneity in response and resistance to FLT3 inhibitor therapy.

4) Understanding the molecular mechanism of recurrent cyclin D3 mutations in mediating resistance to FLT3 inhibitor therapy.

Education

Yale University, CT, BS, 1998, Chemistry
Duke University, MD, 2002, Medicine


Professional Experience

  • 7/2002-6/2005
    Residency, Internal Medicine, Brigham and Women's Hospital, Harvard Medical School
  • 7/2005-6/2006
    Clinical Instructor, Department of Medicine, University of California at San Francisco
  • 7/2006-7/2009
    Fellow, Division of Hematology/Oncology, Department of Medicine, University of California at San Francisco
  • 8/2009-6/2011
    Adjunct Instructor, Division of Hematology/Oncology, Department of Medicine, University of California at San Francisco
  • 7/2011-present
    Assistant Professor, Division of Hematology/Oncology, Department of Medicine, University of California at San Francisco

Honors & Awards

  • 2010
    Leukemia and Lymphoma Society Special Fellow in Clinical Research Career Development Award
  • 2010
    European Hematology Association/American Society of Hematology Translational Research Training Program Award
  • 2009
    American Society of Hematology Research Training Award for Fellows, Finalist
  • 2002
    American Medical Women's Association, Inc. Janet M. Glasgow Memorial Achievement Citation Awarded to graduating women medical students who graduate in the top 10% of their class.
  • 2002
    E. E. Owen, M.D. Clinical Scholar Award Awarded to 2 graduating medical students for clinical excellence.
  • 2001
    William G. Anylan Scholarship Awarded to 4th year medical students deserving recognition based on academics, service to the medical school and commitment to the profession.
  • 2000
    Alpha Omega Alpha
  • 2000-2001
    Howard Hughes Medical Institute Research (HHMI) Medical Student Training Fellowship
  • 1998
    Cum Laude, Yale University
  • 1998
    Howard Douglass Moore Prize Awarded for excellence in the field of chemistry at Yale University.
  • 1998
    Michael T. Manzella Award Presented to the senior who through the qualities of kindness, dedication and courage most inspired classmates in Timothy Dwight College at Yale.
  • 1997
    National Institutes of Health (NIH) Summer Research Internship
  • 1996
    Howard Hughes Medical Institute (HHMI) Summer Research Fellowship

Selected Publications

  1. Tarver TC, Hill JE, Rahmat L, Perl AE, Bahceci E, Mori K, Smith CC. Gilteritinib is a clinically active FLT3 inhibitor with broad activity against FLT3 kinase domain mutations. Blood Adv. 2020 Feb 11; 4(3):514-524.
    View on PubMed
  2. Smith CC. The growing landscape of FLT3 inhibition in AML. Hematology Am Soc Hematol Educ Program. 2019 Dec 06; 2019(1):539-547.
    View on PubMed
  3. Benjamin Demaree, Cyrille Delley, Cheryl Peretz, Harish Vasudevan, David Ruff, Aik Ooi, Catherine C. Smith, Adam Abate. Combined Single-Cell DNA Genotyping and Protein Quantification (DAb-seq) in Acute Myeloid Leukemias Reveals Distinct Immunophenotypic Subsets Among Pathogenic Clones. Blood. 2019 Nov 13; 134(Supplement_1):2088-2088.
    View on PubMed
  4. Kelly L. Schoenbeck, Giselle Salmasi, Miguel Carlos Cerejo, Patricia A. Cornett, Lloyd E. Damon, Aaron C. Logan, Rebecca L. Olin, Andrew D. Leavitt, Catherine C. Smith. Direct Oral Anticoagulant Use and Outcomes in Patients with High and Intermediate Risk BCR-ABL-Negative Myeloproliferative Neoplasms. Blood. 2019 Nov 13; 134(Supplement_1):1165-1165.
    View on PubMed
  5. Varun Mittal, Mimi Lo, Lloyd E. Damon, Karin L. Gaensler, Thomas G. Martin, Rebecca L. Olin, Catherine C. Smith, Aaron C. Logan. Efficacy of Venetoclax Combination Therapy with Hypomethylating Agents in Patients with Relapsed Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation. Blood. 2019 Nov 13; 134(Supplement_1):5089-5089.
    View on PubMed
  6. Cheryl A Cohler Peretz, Lisa H F McGary, Tanya F Kumar, J Hunter Jackson, Jose Jacob, Robert Durruthy-Durruthy, Chunxiao Zhang, Mark J. Levis, Alexander E. Perl, Anskar Yu Hung Leung, Catherine C. Smith. Single Cell Sequencing Reveals Evolution of Tumor Heterogeneity of Acute Myeloid Leukemia on Quizartinib. Blood. 2019 Nov 13; 134(Supplement_1):1440-1440.
    View on PubMed
  7. Kelly L. Schoenbeck, Miguel Carlos Cerejo, Patricia A. Cornett, Lloyd E. Damon, Karin L. Gaensler, Andrew D. Leavitt, Aaron C. Logan, Gabriel N. Mannis, Rebecca L. Olin, Giselle Salmasi, Peter H. Sayre, Neil P. Shah, Anand Dhruva, Chloe E. Atreya, Catherine C. Smith. Symptom Assessment in Patients with BCR-ABL-Negative Myeloproliferative Neoplasms at an Academic Medical Institution. Blood. 2019 Nov 13; 134(Supplement_1):5859-5859.
    View on PubMed
  8. Chao AK, Meyer JA, Lee AG, Hecht A, Tarver T, Van Ziffle J, Koegel AK, Golden C, Braun BS, Sweet-Cordero EA, Smith CC, Dvorak CC, Loh ML, Stieglitz E. Fusion driven JMML: a novel CCDC88C-FLT3 fusion responsive to sorafenib identified by RNA sequencing. Leukemia. 2020 Feb; 34(2):662-666.
    View on PubMed
  9. Huang LW, Sheng Y, Andreadis C, Logan AC, Mannis GN, Smith CC, Gaensler KML, Martin TG, Damon LE, Steinman MA, Huang CY, Olin RL. Functional Status as Measured by Geriatric Assessment Predicts Inferior Survival in Older Allogeneic Hematopoietic Cell Transplantation Recipients. Biol Blood Marrow Transplant. 2020 Jan; 26(1):189-196.
    View on PubMed
  10. McMahon CM, Ferng T, Canaani J, Wang ES, Morrissette JJD, Eastburn DJ, Pellegrino M, Durruthy-Durruthy R, Watt CD, Asthana S, Lasater EA, DeFilippis R, Peretz CAC, McGary LHF, Deihimi S, Logan AC, Luger SM, Shah NP, Carroll M, Smith CC, Perl AE. Clonal Selection with RAS Pathway Activation Mediates Secondary Clinical Resistance to Selective FLT3 Inhibition in Acute Myeloid Leukemia. Cancer Discov. 2019 Aug; 9(8):1050-1063.
    View on PubMed
  11. Smith CC. Roman warfare: targeting of support cells in AML. Blood. 2019 02 07; 133(6):506-507.
    View on PubMed
  12. Li-Wen Huang, Chiung-Yu Huang, Charalambos Andreadis, Aaron C. Logan, Gabriel N. Mannis, Catherine C. Smith, Karin M. Gaensler, Thomas G. Martin, Lloyd E. Damon, Michael A. Steinman, Rebecca L. Olin. Functional Status Is Associated with Outcomes after Allogeneic Stem Cell Transplantation for Older Patients with Hematologic Malignancies. Blood. 2018 Nov 29; 132(Supplement 1):3599-3599.
    View on PubMed
  13. Mark J. Levis, Alexander E. Perl, Jessica K. Altman, Jorge E. Cortes, Catherine C. Smith, Maria R. Baer, David F. Claxton, Joseph G. Jurcic, Ellen K. Ritchie, Stephen A. Strickland, Raoul Tibes, Jason E. Hill, Matt Rosales, Erkut Bahceci. Impact of Minimal Residual Disease and Achievement of Complete Remission/Complete Remission with Partial Hematologic Recovery (CR/CRh) on Overall Survival Following Treatment with Gilteritinib in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) with FLT3 Mutations. Blood. 2018 Nov 29; 132(Supplement 1):1458-1458.
    View on PubMed
  14. Dennis J. Eastburn, Christine M. McMahon, Robert Durruthy-Durruthy, Martin Carroll, Catherine C. Smith, Alexander E. Perl. Longitudinal Monitoring of AML Tumors with High-Throughput Single-Cell DNA Sequencing Reveals Rare Clones Prognostic for Disease Progression and Therapy Response. Blood. 2018 Nov 29; 132(Supplement 1):1476-1476.
    View on PubMed
  15. Cortes J, Perl AE, Döhner H, Kantarjian H, Martinelli G, Kovacsovics T, Rousselot P, Steffen B, Dombret H, Estey E, Strickland S, Altman JK, Baldus CD, Burnett A, Krämer A, Russell N, Shah NP, Smith CC, Wang ES, Ifrah N, Gammon G, Trone D, Lazzaretto D, Levis M. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018 07; 19(7):889-903.
    View on PubMed
  16. Mark J. Levis, Catherine Choy Smith, Koji Ishizuka, Ken Kobayashi, Meena Arunachalam, Yibin Wang, Deborah Lazzaretto, Jorge E. Cortes. Post hoc exploratory analysis of two phase 2 trials of quizartinib monotherapy in patients (pts) with FLT3 -ITD–mutated (mu) relapsed/refractory (R/R) AML with or without prior 1st-generation FLT3 tyrosine kinase inhibitors (TKI) treatment. Journal of Clinical Oncology. 2018 May 20; 36(15_suppl):7017-7017.
    View on PubMed
  17. Perl AE, Altman JK, Cortes J, Smith C, Litzow M, Baer MR, Claxton D, Erba HP, Gill S, Goldberg S, Jurcic JG, Larson RA, Liu C, Ritchie E, Schiller G, Spira AI, Strickland SA, Tibes R, Ustun C, Wang ES, Stuart R, Röllig C, Neubauer A, Martinelli G, Bahceci E, Levis M. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol. 2017 08; 18(8):1061-1075.
    View on PubMed
  18. Jessica K. Altman, Alexander E. Perl, Jorge E. Cortes, Catherine Choy Smith, Mark Robert Litzow, Jason E Hill, Richard A. Larson, Charles Liu, Ellen K. Ritchie, Stephen Anthony Strickland, Eunice S. Wang, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark J. Levis. Deep molecular response to gilteritinib to improve survival in FLT3 mutation-positive relapsed/refractory acute myeloid leukemia. Journal of Clinical Oncology. 2017 May 20; 35(15_suppl):7003-7003.
    View on PubMed
  19. Smith CC, Paguirigan A, Jeschke GR, Lin KC, Massi E, Tarver T, Chin CS, Asthana S, Olshen A, Travers KJ, Wang S, Levis MJ, Perl AE, Radich JP, Shah NP. Heterogeneous resistance to quizartinib in acute myeloid leukemia revealed by single-cell analysis. Blood. 2017 07 06; 130(1):48-58.
    View on PubMed
  20. Catherine Choy Smith, Mark J. Levis, Mark Robert Litzow, Alexander E. Perl, Jessica K. Altman, Stan Gill, Geoffrey Yuen, Peter Bonate, Takeshi Kadokura, Angela Joubert James, Charles Liu, Itsuro Nagase, Ogert Fisniku, Erkut Bahceci. Pharmacokinetics and pharmacodynamics of gilteritinib in patients with relapsed or refractory acute myeloid leukemia. Journal of Clinical Oncology. 2016 May 20; 34(15_suppl):7026-7026.
    View on PubMed

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