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Michele S. Redell, MD, PhD

Dr. Michele Redell is an Associate Professor of Pediatrics in the section of Pediatric Hematology-Oncology. The focus of her research is to understand and overcome mechanisms of chemotherapy resistance and relapse in pediatric acute myeloid leukemia (AML). Research projects in her lab are focused on understanding the patterns of aberrant STAT pathway signaling, the association of specific signaling patterns with clinical outcome, and interactions between leukemia cells and the bone marrow microenvironment. She also is involved in preclinical evaluation of novel therapeutics targeting chemotherapy resistance mechanisms.

In 2013, Dr. Redell’s group showed for the first time that most pediatric AML patient specimens have abnormally reduced STAT3 responses to ligand stimulation, and that these abnormal response patterns are associated with poor outcome (Redell et al, Blood, 2013). A followup study compared ligand-induced STAT3 signaling patterns in paired samples from diagnosis and relapse, and found that stronger IL-6-induced STAT3 activation at relapse compared to diagnosis was strongly associated with chemotherapy resistant disease (Stevens et al, Haematol, 2015). Further, Dr. Redell’s lab reported that elevated IL-6 levels in the bone marrow of pediatric AML patients at diagnosis are significantly associated with poor event-free survival, particularly for patients who are otherwise classified as “low risk” (Stevens et al, Blood Adv, 2017).

Another project in the lab is to determine the mechanisms by which contact between leukemia cells and stromal cells in the bone marrow protects leukemia cells from chemotherapy. A post-doctoral associate in the lab, Dr. Xin Long, elucidated a mechanism by which a stroma-derived integrin ligand, CYR61, induces the upregulation of the tyrosine kinase SYK in AML cells, leading to increased SYK activity and resistance to mitoxantrone. Importantly, SYK inhibition blocks stroma-mediated resistance (Long et al, Br. J. Haematol, 2015). As a follow up project, Dr. Long further demonstrated that stromal co-culture increases ERK1/2 activity, and the MEK inhibitor selumetinib blocks stroma-mediated chemoresistance (Long et al, Oncotarget, 2017).

Through a collaboration with Dr. Yongcheng Song, a chemist in the Pharmacology Department at Baylor, researchers in the Redell lab demonstrated that the compound SYC-522, which is a specific inhibitor of the histone methyltransferase DOT1L, potentiates chemotherapy-induced apoptosis by inhibiting DNA damage repair signaling. Their paper (Liu et al, PlosOne, 2014) was the first to describe the use of this approach as a strategy for sensitizing AML cells to conventional chemotherapy. Through another collaboration with Zachary Ball in the Chemistry Department at Rice University, the Redell lab has the opportunity to work with novel STAT3 inhibitors with anti-AML activity. Dr. Ball’s tool compound MM-206 inhibits STAT3 phosphorylation and target gene transcription, and prolongs survival in a mouse xenograft model of AML (Minus et al, Angew. Chemie, 2015).

Dr. Redell’s research is funded by the National Cancer Institute, the Cancer Prevention Research Institute of Texas, and the Gillson-Longenbaugh Foundation.

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