- Pediatric Hematology-Oncology
Boards, Advisory Committees, Professional Organizations
Member, American Society of Pediatric Hematology Oncology (2022 - Present)
MS, Medical College of Wisconsin, Clinical and Translational Science (2022)
Fellowship: Medical College of Wisconsin Hematology/Oncology Fellowship Program (2022) WI
Board Certification: American Board of Pediatrics, Pediatrics (2019)
Residency: Medical College of Wisconsin Dept of Pediatrics (2019) WI
Medical Education: University of Cincinnati College of Medicine (2012) OH
Potential clinical use of azacitidine and MEK inhibitor combination therapy in PTPN11-mutated juvenile myelomonocytic leukemia.
Molecular therapy : the journal of the American Society of Gene Therapy
Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative neoplasm of childhood. The molecular hallmark of JMML is hyperactivation of the Ras/MAPK pathway with the most common cause being mutations in the gene PTPN11, encoding the protein tyrosine phosphatase SHP2. Current strategies for treating JMML include using the hypomethylating agent, 5-azacitidine (5-Aza) or MEK inhibitors trametinib and PD0325901 (PD-901), but none of these are curative as monotherapy. Utilizing an Shp2E76K/+ murine model of JMML, we show that the combination of 5-Aza and PD-901 modulates several hematologic abnormalities often seen in JMML patients, in part by reducing the burden of leukemic hematopoietic stem and progenitor cells (HSC/Ps). The reduced JMML features in drug-treated mice were associated with a decrease in p-MEK and p-ERK levels in Shp2E76K/+ mice treated with the combination of 5-Aza and PD-901. RNA-sequencing analysis revealed a reduction in several RAS and MAPK signaling-related genes. Additionally, a decrease in the expression of genes associated with inflammation and myeloid leukemia was also observed in Shp2E76K/+ mice treated with the combination of the two drugs. Finally, we report two patients with JMML and PTPN11 mutations treated with 5-Aza, trametinib, and chemotherapy who experienced a clinical response because of the combination treatment.
View details for DOI 10.1016/j.ymthe.2023.01.030
View details for PubMedID 36739480
- Real-world experience in treating pediatric relapsed/refractory or therapy-related myeloid malignancies with decitabine, vorinostat, and FLAG therapy based on a phase 1 study run by the TACL consortium PEDIATRIC BLOOD & CANCER 2022; 69 (10)
Outcomes of Hispanic and non-Hispanic white pediatric and young adult patients with B-cell acute lymphoblastic leukemia after commercial tisagenlecleucel.
LIPPINCOTT WILLIAMS & WILKINS. 2022
View details for Web of Science ID 000863680300019