Francine Garrett-Bakelman

Education

  • MD/PhD, Albert Einstein College of Medicine
  • BS, California State University, Fullerton

Primary Appointment

  • Assistant Professor, Biochemistry and Molecular Genetics

Contact

Research Interest(s)

Acute Myeloid Leukemia: molecular and cellular biology events which mediate aberrant epigenetic and transcriptional mechanisms during disease establishment and progression

Research Description

Acute Myeloid Leukemia (AML) is the most common acute leukemia in adults. AML prognosis and overall survival decline in patients older that 60 years of age and in patients who develop disease relapse after initial treatments. Our main research goal is to understand molecular and epigenetic mechanisms responsible for AML disease phenotypes. Through this aim, in the long-term, findings will help identify novel therapeutic targets in AML.

We investigate these questions through the study of samples from AML patients and functional validations in in vitro and in vivo models. Epigenetic (DNA methylation, gene expression, and chromatin assays), molecular and cellular biology techniques are implemented to study how aberrant expression of specific genes contributes to abnormal cellular phenotypes and leukemogenesis. Previous studies have determined that AML progression (from disease diagnosis to relapse) is characterized by significant epigenetic plasticity and differentially expressed genes. Studies are being pursued to identify genes affected by the epigenetic changes observed and how their function contributes to the malignant phenotype.

Postdoctoral positions for a biologist and a computational biology are available in the laboratory.

Selected Publications

  • Chung S, Eng W, Hu W, Khalaj M, Garrett-Bakelman F, Tavakkoli M, Levine R, Carroll M, Klimek V, Melnick A, Park C. CD99 is a therapeutic target on disease stem cells in myeloid malignancies. Science translational medicine. 2017;9(374). PMID: 28123069
  • Glass J, Hassane D, Wouters B, Kunimoto H, Avellino R, Garrett-Bakelman F, Guryanova O, Bowman R, Redlich S, Intlekofer A, Meydan C, Qin T, Fall M, Alonso A, Guzman M, Valk P, Thompson C, Levine R, Elemento O, Delwel R, Melnick A, Figueroa M. Epigenetic Identity in AML Depends on Disruption of Non-promoter Regulatory Elements and is Affected by Antagonistic Effects of Mutations in Epigenetic Modifiers. Cancer discovery. 2017. PMID: 28408400
  • Kunimoto H, McKenney A, Meydan C, Shank K, Nazir A, Rapaport F, Durham B, Garrett-Bakelman F, Pronier E, Shih A, Melnick A, Chaudhuri J, Levine R. Aid is a key regulator of myeloid/erythroid differentiation and DNA methylation in hematopoietic stem/progenitor cells. Blood. 2017;129(13): 1779-1790. PMID: 28077417 | PMCID: PMC5374286
  • Shih A, Meydan C, Shank K, Garrett-Bakelman F, Ward P, Intlekofer A, Nazir A, Stein E, Knapp K, Glass J, Travins J, Straley K, Gliser C, Mason C, Yen K, Thompson C, Melnick A, Levine R. Combination Targeted Therapy to Disrupt Aberrant Oncogenic Signaling and Reverse Epigenetic Dysfunction in IDH2- and TET2-Mutant Acute Myeloid Leukemia. Cancer discovery. 2017;7(5): 494-505. PMID: 28193779 | PMCID: PMC5413413
  • Garrett-Bakelman F, Melnick A. Mutant IDH: a targetable driver of leukemic phenotypes linking metabolism, epigenetics and transcriptional regulation. Epigenomics. 2016;8(7): 945-57. PMID: 27431380 | PMCID: PMC5066133
  • Guryanova O, Shank K, Spitzer B, Luciani L, Koche R, Garrett-Bakelman F, Ganzel C, Durham B, Mohanty A, Hoermann G, Rivera S, Chramiec A, Pronier E, Bastian L, Keller M, Tovbin D, Loizou E, Weinstein A, Gonzalez A, Lieu Y, Rowe J, Pastore F, McKenney A, Krivtsov A, Sperr W, Cross J, Mason C, Tallman M, Arcila M, Abdel-Wahab O, Armstrong S, Kubicek S, Staber P, Gönen M, Paietta E, Melnick A, Nimer S, Mukherjee S, Levine R. DNMT3A mutations promote anthracycline resistance in acute myeloid leukemia via impaired nucleosome remodeling. Nature medicine. 2016;22(12): 1488-1495. PMID: 27841873 | PMCID: PMC5359771
  • Li S, Garrett-Bakelman F, Chung S, Sanders M, Hricik T, Rapaport F, Patel J, Dillon R, Vijay P, Brown A, Perl A, Cannon J, Bullinger L, Luger S, Becker M, Lewis I, To L, Delwel R, Löwenberg B, Döhner H, Döhner K, Guzman M, Hassane D, Roboz G, Grimwade D, Valk P, D'Andrea R, Carroll M, Park C, Neuberg D, Levine R, Melnick A, Mason C. Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nature medicine. 2016;22(7): 792-9. PMID: 27322744 | PMCID: PMC4938719
  • Garrett-Bakelman F, Sheridan C, Kacmarczyk T, Ishii J, Betel D, Alonso A, Mason C, Figueroa M, Melnick A. Enhanced reduced representation bisulfite sequencing for assessment of DNA methylation at base pair resolution. Journal of visualized experiments : JoVE. 2015; e52246. PMID: 25742437 | PMCID: PMC4354670
  • Guryanova O, Lieu Y, Garrett-Bakelman F, Spitzer B, Glass J, Shank K, Martinez A, Rivera S, Durham B, Rapaport F, Keller M, Pandey S, Bastian L, Tovbin D, Weinstein A, Teruya-Feldstein J, Abdel-Wahab O, Santini V, Mason C, Melnick A, Mukherjee S, Levine R. Dnmt3a regulates myeloproliferation and liver-specific expansion of hematopoietic stem and progenitor cells. Leukemia. 2015;30(5): 1133-42. PMID: 26710888 | PMCID: PMC4856586
  • Li S, Garrett-Bakelman F, Perl A, Luger S, Zhang C, To B, Lewis I, Brown A, D'Andrea R, Ross M, Levine R, Carroll M, Melnick A, Mason C. Dynamic evolution of clonal epialleles revealed by methclone. Genome biology. 2014;15(9): 472. PMID: 25260792 | PMCID: PMC4242486
  • Garrett-Bakelman F, Melnick A. Differentiation therapy for IDH1/2 mutant malignancies. Cell research. 2013;23(8): 975-7. PMID: 23732524 | PMCID: PMC3731561
  • Hatzi K, Jiang Y, Huang C, Garrett-Bakelman F, Gearhart M, Giannopoulou E, Zumbo P, Kirouac K, Bhaskara S, Polo J, Kormaksson M, MacKerell A, Xue F, Mason C, Hiebert S, Prive G, Cerchietti L, Bardwell V, Elemento O, Melnick A. A hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters. Cell reports. 2013;4(3): 578-88. PMID: 23911289 | PMCID: PMC3854650
  • Li S, Garrett-Bakelman F, Akalin A, Zumbo P, Levine R, To B, Lewis I, Brown A, D'Andrea R, Melnick A, Mason C. An optimized algorithm for detecting and annotating regional differential methylation. BMC bioinformatics. 2013;14 S10. PMID: 23735126 | PMCID: PMC3622633
  • Magro C, Wang X, Garrett-Bakelman F, Laurence J, Shapiro L, DeSancho M. The effects of Eculizumab on the pathology of malignant atrophic papulosis. Orphanet journal of rare diseases. 2013;8 185. PMID: 24279613 | PMCID: PMC3879088
  • Will B, Vogler T, Bartholdy B, Garrett-Bakelman F, Mayer J, Barreyro L, Pandolfi A, Todorova T, Okoye-Okafor U, Stanley R, Bhagat T, Verma A, Figueroa M, Melnick A, Roth M, Steidl U. Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment. Nature immunology. 2013;14(5): 437-45. PMID: 23563689 | PMCID: PMC3633104
  • Akalin A, Garrett-Bakelman F, Kormaksson M, Busuttil J, Zhang L, Khrebtukova I, Milne T, Huang Y, Biswas D, Hess J, Allis C, Roeder R, Valk P, Löwenberg B, Delwel R, Fernandez H, Paietta E, Tallman M, Schroth G, Mason C, Melnick A, Figueroa M. Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia. PLoS genetics. 2012;8(6): e1002781. PMID: 22737091 | PMCID: PMC3380828
  • Akalin A, Kormaksson M, Li S, Garrett-Bakelman F, Figueroa M, Melnick A, Mason C. methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome biology. 2012;13(10): R87. PMID: 23034086 | PMCID: PMC3491415