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Carolyn A. Felix, MD
Leader, Normal and Malignant Hematopoiesis Research Affinity Group
Dr. Felix uses molecular, biochemical, cellular and in vivo methods to investigate the pathobiology of leukemias with KMT2A (MLL) translocations. Leukemias with these translocations affect infants and young children or occur as a complication of type II topoisomerase (TOP2) poison chemotherapies used for anti-cancer treatment. She aims to develop better treatment and prevention approaches for these leukemias, which have a poor prognosis.
Bio
The pathobiology of leukemias with KMT2A (MLL) translocations is the central focus of Dr. Felix’s dynamic research program. A pioneer in panhandle polymerase chain reaction (PCR) cloning strategies as well as new high-throughput sequencing technology, Dr. Felix aims to better understand those translocations in order to develop more effective treatments and preventative strategies.
In addition, Dr. Felix and her team are investigating molecularly targeted agents to surmount cell death resistance, and are developing models in zebrafish embryos as a developmental tool to recapitulate leukemogenesis in infants.
Her KMT2A-R leukemia research program encompasses TOP2 DNA damage mechanisms, molecular epidemiology, disease biomarkers, and developmental origins of the translocations and novel treatments.
Among her career achievements, Dr. Felix:
- Invented panhandle PCR technologies to clone KMT2A genomic translocation breakpoint junctions and KMT2A fusion transcripts and, using this technology, discovered new KMT2A partner genes and traced origins of translocations
- Discovered that KMT2A translocation breakpoints are TOP2 cleavage sites in vitro and in cells
- Invented high-throughput sequencing technology to surmount key challenge of removing covalently attached DNA from TOP2 enzyme at the cleavage site in order to be able to resolve TOP2 cleavage at single base precision genome-wide in cells
- Made major discoveries with new high-throughput sequencing technology indicating that TOP2A cleavage is associated with genes involved in oncogenic translocations, and with key factors in the transcriptome and epigenome
- Discovered that targeting EIF4E with ribavirin reduces proliferation and survival, downregulates EIF4E targets and enhances chemosensitivity in infant acute lymphoblastic leukemia
Education and Training
BS, Boston College (Biology/Chemistry), 1977
MD, Boston University, 1981
Titles and Academic Titles
Leader, Normal and Malignant Hematopoiesis Research Affinity Group
Joshua Kahan Endowed Chair in Pediatric Leukemia Research
Attending Physician
Professor of Pediatrics
Professional Memberships
Association of American Physicians, 2006-
Professional Awards
ASPHO Young Investigator Award, 1990
ASCO Young Investigator Award, 1992
Eastern PA Chapter LLS Distinguished Leadership Award, 2000
Eagles Fly for Leukemia Award for Excellence in Treatment of Pediatric Cancer, 2006
Publication Highlights
PubMed:
Urtishak KA, Wang LS, Culjkovic-Kraljacic B, Davenport JW, Porazzi P, Vincent TL, Teachey DT, Tasian SK, Moore JS, Seif AE, Jin S, Barrett JS, Robinson BW, Chen IL, Harvey RC, Carroll MP, Carroll AJ, Heerema NA, Devidas M, Dreyer ZE, Hilden JM, Hunger SP, Willman CL, Borden KLB, Felix CA. Targeting EIF4E signaling with ribavirin in infant acute lymphoblastic leukemia. Oncogene. 2018 Nov; PMID: 30478448
Yu X, Davenport JW, Urtishak KA, Carillo ML, Gosai SJ, Kolaris CP, Byl JAW, Rappaport EF, Osheroff N, Gregory BD, Felix CA. Genome-wide TOP2A DNA cleavage is biased toward translocated and highly transcribed loci. Genome Res. 2017 Jul; 27(7):1238-1249. PMID: 28385713
Urtishak KA, Robinson BW, Rappaport EF, Sarezky MD, Biegel JA, Nichols KE, Wilmoth DM, Wang LS, Stern JW, Felix CA. Unique Familial MLL(KMT2A)-Rearranged Precursor B-Cell Infant Acute Lymphoblastic Leukemia in Non-twin Siblings. Pediatr Blood Cancer. 2016 Jul; 63(7):1175-80. PMID: 26999444
Urtishak KA, Edwards AY, Wang LS, Hudome A, Robinson BW, Barrett JS, Cao K, Cory L, Moore JS, Bantly AD, Yu QC, Chen IM, Atlas SR, Willman CL, Kundu M, Carroll AJ, Heerema NA, Devidas M, Hilden JM, Dreyer ZE, Hunger SP, Reaman GH, Felix CA. Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia. Blood. 2013 Apr; 121(14):2689-703. PMID: 23393050
Robinson BW, Germano G, Song Y, Abrams J, Scott M, Guariento I, Tiso N, Argenton F, Basso G, Rhodes J, Kanki JP, Look AT, Balice-Gordon RJ, Felix CA. mll ortholog containing functional domains of human MLL is expressed throughout the zebrafish lifespan and in haematopoietic tissues. Br J Haematol. 2011 Feb; 152(3):307-21. PMID: 21155757