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.

Research Funding

  • July 1, 2022 - June 30, 2027 - RNA Polymerase II as a Therapeutic Target in Acute Myeloid Leukemia (AML) with RAS Signaling Activation , PI . Sponsor: NIH/NCI, Sponsor Award ID: 1R01CA266422-01A1
  • September 1, 2014 - August 31, 2018 - Investigating Resistance to FLT3 Inhibitors in AML , Principal Investigator . Sponsor: NIH, Sponsor Award ID: K08CA187577

Education

Yale University, CT, BS, 1998, Chemistry

Duke University, MD, 2002, Medicine

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. Othman T, Lo MM, Andreadis CB, Damon LE, Ferng TT, Gaensler KML, Lee JC, Martin TG, Olin RL, Sayre PH, Smith CC, Logan AC. Single-center experience with nelarabine, etoposide, and cyclophosphamide in adults with relapsed/refractory T-acute lymphoblastic leukemia/lymphoma. Leuk Lymphoma. 2025 May 07; 1-4.  View on PubMed
  2. Hoff FW, Huang Y, Welkie RL, Swords RT, Traer E, Stein EM, Lin TL, Patel PA, Collins RH, Baer MR, Duong VH, Blum WG, Arellano ML, Stock W, Odenike O, Redner RL, Kovacsovics T, Deininger MW, Zeidner JF, Olin RL, Smith CC, Foran JM, Schiller GJ, Curran EK, Koenig KL, Heerema NA, Chen T, Martycz M, Stefanos M, Marcus SG, Rosenberg L, Druker BJ, Levine RL, Burd A, Yocum AO, Borate UM, Mims AS, Byrd JC, Madanat YF. Molecular characterization of newly diagnosed acute myeloid leukemia patients aged 60 years or older: a report from the Beat AML clinical trial. Blood Cancer J. 2025 Apr 03; 15(1):55.  View on PubMed
  3. Decker M, Huang BJ, Ware T, Boone C, Tang M, Ybarra J, Ballapuram AC, Taran KA, Chen PY, Amendáriz M, Leung CJ, Harris M, Tjoa K, Hongo H, Abelson S, Rivera J, Ngo N, Herbst DM, Suciu RM, Guijas C, Sedighi K, Andalis T, Roche E, Xie B, Liu Y, Smith CC, Stieglitz E, Niphakis MJ, Cravatt BF, Shannon K. In vivo validation of the palmitoylation cycle as a therapeutic target in NRAS-mutant cancer. bioRxiv. 2025 Mar 21.  View on PubMed
  4. Matthew F Jones, Cheryl A C Peretz, Vanessa E. Kennedy, Elaine Tran, Andrew Koh, Andriana Kotini, Malgorzata Olszewska, Eirini Papapetrou, Catherine C. Smith. AML Derived Induced Pluripotent Stem Cells Reveal a Genotype-Independent Effect of Monocytic Differentiation in Mediating Venetoclax Resistance. Blood. 2024 Nov 5; 144(Supplement 1):1379-1379.  View on PubMed
  5. Timothy T. Ferng, Samantha M. Pintar, Vanessa E. Kennedy, Shaheen Kabir, Theodore C. Tarver, Veronica Steri, Paul Phojanakong, Juwita Hübner, Carolina E. Morales, Jose M. Rivera, Aaron C. Logan, Benjamin Braun, Elliot Stieglitz, Luke A. Gilbert, Catherine C. Smith. CDK8 Inhibition Represses Monocyte-like Gene Expression in Acute Myeloid Leukemia Cells and Antagonizes In Vivo Resistance to FLT3 Inhibition. Blood. 2024 Nov 5; 144(Supplement 1):723-723.  View on PubMed
  6. Bogdan Popescu, Madison Piao, Sydney Abelson, Carolina E. Morales, Khadija Yousuf, Jose M. Rivera, Cheryl A C Peretz, Elliot Stieglitz, Catherine C. Smith. Preclinical Activity of RAS(ON) Multi-Selective Inhibitor RMC-7977 and Therapeutic Combinations in AML with Signaling Mutations. Blood. 2024 Nov 5; 144(Supplement 1):2770-2770.  View on PubMed
  7. Hoff FW, Blum WG, Huang Y, Welkie RL, Swords RT, Traer E, Stein EM, Lin TL, Archer KJ, Patel PA, Collins RH, Baer MR, Duong VH, Arellano ML, Stock W, Odenike O, Redner RL, Kovacsovics T, Deininger MW, Zeidner JF, Olin RL, Smith CC, Foran JM, Schiller GJ, Curran EK, Koenig KL, Heerema NA, Chen T, Martycz M, Stefanos M, Marcus SG, Rosenberg L, Druker BJ, Levine RL, Burd A, Yocum AO, Borate UM, Mims AS, Byrd JC, Madanat YF. Beat-AML 2024 ELN-refined risk stratification for older adults with newly diagnosed AML given lower-intensity therapy. Blood Adv. 2024 10 22; 8(20):5297-5305.  View on PubMed
  8. Kelly L. Schoenbeck, Anand Dhruva, Albert Lee, Anand Parikshak, Catherine Choy Smith, Neil P. Shah, Chloe Evelyn Atreya. Being Present-CML: A mindfulness-based intervention for patients with chronic myeloid leukemia taking tyrosine kinase inhibitors. Journal of Clinical Oncology. 2024 Sep 30; 20(10_suppl):353-353.  View on PubMed
  9. Peretz CAC, Kennedy VE, Walia A, Delley CL, Koh A, Tran E, Clark IC, Hayford CE, D'Amato C, Xue Y, Fontanez KM, May-Zhang AA, Smithers T, Agam Y, Wang Q, Dai HP, Roy R, Logan AC, Perl AE, Abate A, Olshen A, Smith CC. Multiomic single cell sequencing identifies stemlike nature of mixed phenotype acute leukemia. Nat Commun. 2024 Sep 18; 15(1):8191.  View on PubMed
  10. Wintering A, Hecht A, Meyer J, Wong EB, Hübner J, Abelson S, Feldman K, Kennedy VE, Peretz CAC, French DL, Maguire JA, Jobaliya C, Vasquez MR, Desai S, Dulman R, Nemecek E, Haines H, Hammad M, El Haddad A, Kogan SC, Abdullaev Z, Chehab FF, Tasian SK, Smith CC, Loh ML, Stieglitz E. LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia. Haematologica. 2024 08 01; 109(8):2533-2541.  View on PubMed
  11. Matthew F. Jones, Catherine C. Smith. Mechanisms of Resistance to Targeted Therapies in AML. Annual Review of Cancer Biology. 2024 Jun 12; 8(1):81-96.  View on PubMed
  12. Marcello Rotta, Yasmin Abaza, Hetty E Carraway, Bradley W. Christensen, Mitul Gandhi, Paul B. Koller, Ayman H. Qasrawi, Gary J. Schiller, Catherine Choy Smith, Uzma Ahmed, Alexandru Cacovean, Nicole Kowalczyk, Stephan W. Morris, Mona Vimal, Sauji Yachamaneni, Thomas Butler, Eunice S. Wang, Farhad Ravandi-Kashani. Covalent-103: A phase 1, open-label, dose-escalation and expansion study of BMF-500, an oral covalent FLT3 inhibitor, in adults with acute leukemia (AL). Journal of Clinical Oncology. 2024 Jun 1; 42(16_suppl):tps6589-tps6589.  View on PubMed
  13. Levis M, Perl A, Schiller G, Fathi AT, Roboz G, Wang ES, Altman J, Rajkhowa T, Ando M, Suzuki T, Subach RA, Maier G, Madden T, Johansen M, Cheung K, Kurman M, Smith C. A phase 1 study of the irreversible FLT3 inhibitor FF-10101 in relapsed or refractory acute myeloid leukemia. Blood Adv. 2024 05 28; 8(10):2527-2535.  View on PubMed
  14. Kennedy VE, Smith CC. FLT3 targeting in the modern era: from clonal selection to combination therapies. Int J Hematol. 2024 Nov; 120(5):528-540.  View on PubMed
  15. Fieke W Hoff, Ying Huang, Rina Li Welkie, Ronan T. Swords, Elie Traer, Eytan M. Stein, Tara L Lin, Prapti A. Patel, Robert H. Collins, Maria R. Baer, Vu H. Duong, William Blum, Martha Arellano, Wendy Stock, Olatoyosi Odenike, Robert L. Redner, Tibor J. Kovacsovics, Michael W. Deininger, Joshua F. Zeidner, Rebecca Olin, Catherine C. Smith, James M. Foran, Gary J. Schiller, Emily K Curran, Kristin L Koenig, Nyla A. Heerema, Timothy Chen, Molly Martycz, Mona Stefanos, Sonja Gullen Marcus, Leonard Rosenberg, Brian J. Druker, Ross L Levine, Amy Burd, Ashley Owen Yocum, Uma M. Borate, Alice Mims, John C. Byrd, Yazan F. Madanat. Genomic Characterization of Newly Diagnosed Acute Myeloid Leukemia in Patients Age 60 Years and Older; A Report from the Beat AML Master Trial. Blood. 2023 Nov 28; 142(Supplement 1):4296.  View on PubMed
  16. Uma M. Borate, Ying Huang, Rina Li Welkie, Ronan T. Swords, Elie Traer, Eytan M. Stein, Tara L Lin, Yazan F. Madanat, Prapti A. Patel, Robert H. Collins, Maria R. Baer, Vu H. Duong, William Blum, Martha Arellano, Wendy Stock, Olatoyosi Odenike, Robert L. Redner, Tibor J. Kovacsovics, Michael W. Deininger, Joshua F. Zeidner, Rebecca Olin, Catherine C. Smith, James M. Foran, Gary J. Schiller, Emily K Curran, Kristin L Koenig, Nyla A. Heerema, Timothy Chen, Molly Martycz, Mona Stefanos, Sonja Gullen Marcus, Leonard Rosenberg, Brian J. Druker, Ross L Levine, Amy Burd, Ashley Owen Yocum, Alice Mims, John C. Byrd. Influence of Pre-Treatment Features and Therapy Choice By Physicians on Overall Survival in Older Adults with Acute Myeloid Leukemia: A Report from the Beat AML Master Trial. Blood. 2023 Nov 28; 142(Supplement 1):4332.  View on PubMed
  17. Timothy T. Ferng, Samantha M. Pintar, Vanessa E. Kennedy, Theodore C. Tarver, Shaheen Kabir, Veronica Steri, Juan Antonio Camara Serrano, Fernando Salangsang, Paul Phojanakong, Juwita Hübner, Carolina E. Morales, Jose M. Rivera, Aaron C. Logan, Benjamin Braun, Elliot Stieglitz, Luke A. Gilbert, Catherine C. Smith. Mediator Kinase/CDK8 Inhibition As a Strategy to Improve FLT3 Inhibitor Activity in Acute Myeloid Leukemia. Blood. 2023 Nov 28; 142(Supplement 1):4173.  View on PubMed
  18. Vanessa E. Kennedy, Cheryl A C Peretz, Andrew Koh, Elaine Tran, Dalia Dhingra, Saurabh Gulati, Adam Sciambi, Olga Sala-Torra, Lan Beppu, Aaron C. Logan, Alexander Perl, Wendy Stock, Geoffrey L Uy, Ann-Kathrin Eisfeld, Jerald P. Radich, Catherine C. Smith. Multiomic Single-Cell Sequencing May Distinguish BCR-ABL-Mutated Acute Myeloid Leukemia (AML) from Blast Crisis Chronic Myelogenous Leukemia (BC-CML). Blood. 2023 Nov 28; 142(Supplement 1):4334.  View on PubMed
  19. Bogdan Popescu, Elliot Stieglitz, Catherine C. Smith. RAS MULTI(ON) Inhibitor RMC-7977 Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 Inhibitors in AML Models. Blood. 2023 Nov 28; 142(Supplement 1):2793.  View on PubMed
  20. Cheryl A C Peretz, Elaine Tran, Bogdan Popescu, Vanessa E. Kennedy, Tanya Kumar, Lisa McGary, Natalie Tantisira, Eric Wong, Jose M. Rivera, Simayijiang Xirenayi, Elliot Stieglitz, Catherine C. Smith, Juwita Hübner. Threshold Attenuation of Perk Signaling Is Sufficient to Overcome RAS-Mediated FLT3 Inhibitor Resistance. Blood. 2023 Nov 28; 142(Supplement 1):4171.  View on PubMed

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