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. Huang LW, Shi Y, Andreadis C, Logan AC, Mannis GN, Smith CC, Gaensler KML, Martin TG, Damon LE, Boscardin WJ, Steinman MA, Olin RL. Association of geriatric measures and global frailty with cognitive decline after allogeneic hematopoietic cell transplantation in older adults. J Geriatr Oncol. 2023 Sep 05; 14(8):101623.  View on PubMed
  2. Shallis RM, Daver N, Altman JK, Komrokji RS, Pollyea DA, Badar T, Bewersdorf JP, Bhatt VR, de Botton S, de la Fuente Burguera A, Carraway HE, Desai P, Dillon R, Duployez N, El Chaer F, Fathi AT, Freeman SD, Gojo I, Grunwald MR, Jonas BA, Konopleva M, Lin TL, Mannis GN, Mascarenhas J, Michaelis LC, Mims AS, Montesinos P, Pozdnyakova O, Pratz KW, Schuh AC, Sekeres MA, Smith CC, Stahl M, Subklewe M, Uy GL, Voso MT, Walter RB, Wang ES, Zeidner JF, Žucenka A, Zeidan AM. Standardising acute myeloid leukaemia classification systems: a perspective from a panel of international experts. Lancet Haematol. 2023 Sep; 10(9):e767-e776.  View on PubMed
  3. Catherine Choy Smith, Pankit Vachhani, Guillermo Garcia-Manero, Nicole Renee Grieselhuber, Guru Subramanian Guru Murthy, Astha Bhatia, Jatinder Arora, Hooman Izadi, Anthony Fiorino, Raajit Rampal. A phase 1/2 dose escalation study of the BCL-2 inhibitor ZN-d5 and the WEE1 inhibitor azenosertib (ZN-c3) in patients (Pts) with acute myeloid leukemia (AML). Journal of Clinical Oncology. 2023 Jun 1; 41(16_suppl):tps7077-tps7077.  View on PubMed
  4. Peretz CAC, Kennedy VE, Walia A, Delley CL, Koh A, Tran E, Clark IC, Hayford CE, D'Amato C, Xue Y, Fontanez KM, Roy R, Logan AC, Perl AE, Abate A, Olshen A, Smith CC. Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification. bioRxiv. 2023 May 18.  View on PubMed
  5. Clark IC, Fontanez KM, Meltzer RH, Xue Y, Hayford C, May-Zhang A, D'Amato C, Osman A, Zhang JQ, Hettige P, Ishibashi JSA, Delley CL, Weisgerber DW, Replogle JM, Jost M, Phong KT, Kennedy VE, Peretz CAC, Kim EA, Song S, Karlon W, Weissman JS, Smith CC, Gartner ZJ, Abate AR. Microfluidics-free single-cell genomics with templated emulsification. Nat Biotechnol. 2023 Mar 06.  View on PubMed
  6. Jerry Lee, Raja Rajalingam, Denice Kong, Weiyun Ai, Charalambos B. Andreadis, Lloyd E. Damon, Neil Dunavin, Karin M. Gaensler, Lawrence D. Kaplan, Thomas G. Martin, Rebecca L. Olin, Peter H. Sayre, Catherine C. Smith, Jeffrey L. Wolf, Aaron C. Logan. 304 HLA-DPB1 Mismatch Permissiveness and Activating KIR Haplotypes Have Different Impact on Allogeneic Hematopoietic Cell Transplant Survival Outcomes in Acute Leukemias and Myelodysplastic Syndrome. Transplantation and Cellular Therapy. 2023 Feb 1; 29(2):s232-s233.  View on PubMed
  7. Daver N, Perl AE, Maly J, Levis M, Ritchie E, Litzow M, McCloskey J, Smith CC, Schiller G, Bradley T, Tiu RV, Naqvi K, Dail M, Brackman D, Siddani S, Wang J, Chyla B, Lee P, Altman JK. Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemia. J Clin Oncol. 2022 12 10; 40(35):4048-4059.  View on PubMed
  8. Timothy T. Ferng, Daisuke Terada, Makoto Ando, Theodore C. Tarver, Fihr Chaudhary, Kimberly C. Lin, Aaron C. Logan, Catherine C. Smith. Abstract LB516A: The irreversible FLT3 inhibitor FF-10101 is active against a diversity of FLT3 inhibitor resistance mechanisms. Cancer Research. 2022 Jun 15; 82(12_Supplement):lb516a-lb516a.  View on PubMed
  9. Perl AE, Hosono N, Montesinos P, Podoltsev N, Martinelli G, Panoskaltsis N, Recher C, Smith CC, Levis MJ, Strickland S, Röllig C, Groß-Langenhoff M, Chou WC, Lee JH, Yokoyama H, Hasabou N, Lu Q, Tiu RV, Altman JK. Clinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib. Blood Cancer J. 2022 05 30; 12(5):84.  View on PubMed
  10. Ferng TT, Terada D, Ando M, Tarver TC, Chaudhary F, Lin KC, Logan AC, Smith CC. The Irreversible FLT3 Inhibitor FF-10101 Is Active Against a Diversity of FLT3 Inhibitor Resistance Mechanisms. Mol Cancer Ther. 2022 05 04; 21(5):844-854.  View on PubMed
  11. Smith CC, Levis MJ, Perl AE, Hill JE, Rosales M, Bahceci E. Molecular profile of FLT3-mutated relapsed/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib. Blood Adv. 2022 04 12; 6(7):2144-2155.  View on PubMed
  12. Huang LW, Sheng Y, Andreadis C, Logan AC, Mannis GN, Smith CC, Gaensler KML, Martin TG, Damon LE, Huang CY, Olin RL. Patterns and Predictors of Functional Decline after Allogeneic Hematopoietic Cell Transplantation in Older Adults. Transplant Cell Ther. 2022 06; 28(6):309.e1-309.e9.  View on PubMed
  13. Bogdan Popescu, Carlos Stahlhut, Theodore C. Tarver, Timothy T. Ferng, Cheryl Peretz, Sydney Wishner, Paul Phojanakong, Veronica Steri, Eric B. Wong, Jose M. Rivera, Elliot Stieglitz, Catherine C. Smith. Allosteric SHP2 Inhibitor RMC4550 Synergizes with Venetoclax in FLT3 and KIT Mutant Acute Myeloid Leukemia. Blood. 2021 Nov 5; 138(Supplement 1):2231-2231.  View on PubMed
  14. Kelly L. Schoenbeck, Anand Dhruva, Albert Lee, Neha G. Goyal, Adrienne K. Yang, Sa Ra Park, Catherine C. Smith, Neil P Shah, Chloe E. Atreya. Being Present-CML: A Distress Reduction Intervention for Patients with Chronic Myeloid Leukemia Taking Tyrosine Kinase Inhibitors. Blood. 2021 Nov 5; 138(Supplement 1):4051-4051.  View on PubMed
  15. Timothy T. Ferng, Theodore C. Tarver, Shaheen Kabir, Benjamin Braun, Aaron C. Logan, Luke A. Gilbert, Catherine C. Smith. RNA Polymerase II Is a Therapeutic Target to Overcome FLT3 Inhibitor Resistance Mediated By the Bone Marrow Microenvironment. Blood. 2021 Nov 5; 138(Supplement 1):2236-2236.  View on PubMed
  16. Cheryl A C Peretz, Vanessa E Kennedy, Rhonda E. Ries, Soheil Meshinchi, Catherine C. Smith. Single Cell Sequencing of Pediatric Acute Myeloid Leukemia Reveals Clonal Evolution to Relapse on Combination Chemotherapy with Sorafenib. Blood. 2021 Nov 5; 138(Supplement 1):3470-3470.  View on PubMed
  17. Naval Daver, Alexander E. Perl, Joseph Maly, Mark Levis, Ellen Ritchie, Mark R. Litzow, James McCloskey, Catherine C. Smith, Gary J. Schiller, Terrence Bradley, Ramon V. Tiu, Kiran Naqvi, Monique Dail, Satya Siddani, Jing Wang, Brenda Chyla, Paul Lee, Jessica K. Altman. Venetoclax in Combination with Gilteritinib Demonstrates Molecular Clearance of FLT3 mutation in Relapsed/Refractory FLT3 -Mutated Acute Myeloid Leukemia. Blood. 2021 Nov 5; 138(Supplement 1):691-691.  View on PubMed
  18. Alexander E Perl, Jessica K Altman, Naoko Hosono, Pau Montesinos, Nikolai Podoltsev, Giovanni Martinelli, Catherine C Smith, Mark J Levis, Christoph Röllig, Marco Groß-Langenhoff, Nahla Hasabou, Qiaoyang Lu, Ramon V Tiu. AML-091: Clinical Outcomes in Patients with Relapsed/Refractory Acute Myeloid Leukemia Treated with Gilteritinib Who Received Prior Midostaurin or Sorafenib. Clinical Lymphoma Myeloma & Leukemia. 2021 Sep 1; 21:s280.  View on PubMed
  19. Jessica K. Altman, Naval Daver, Joseph Maly, Mark Levis, Ellen Ritchie, Mark Litzow, James McCloskey, Catherine C. Smith, Gary Schiller, Terrence Bradley, Ramon V. Tiu, Kiran Naqvi, Satya Siddani, Jing Wang, Paul Lee, Alexander E. Perl. AML-162: Efficacy and Safety of Venetoclax in Combination with Gilteritinib for Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia: Updated Analyses of a Phase 1b Study. Clinical Lymphoma Myeloma & Leukemia. 2021 Sep 1; 21:s285.  View on PubMed
  20. James AJ, Smith CC, Litzow M, Perl AE, Altman JK, Shepard D, Kadokura T, Souda K, Patton M, Lu Z, Liu C, Moy S, Levis MJ, Bahceci E. Correction to: Pharmacokinetic Profile of Gilteritinib: A Novel FLT-3 Tyrosine Kinase Inhibitor. Clin Pharmacokinet. 2021 Sep; 60(9):1251.  View on PubMed

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