Supervisory Bioinformatics Scientist
Children's Hospital of Philadelphia
Jo Lynne’s broad research interests lie in identifying and validating novel coding, noncoding, epigenetic, and/or transcriptional mechanisms contributing to oncogenesis, tumor evolution, and progression/relapse of pediatric high-grade diffuse astrocytic tumors. She combines molecular, genomics, and machine learning approaches to discover and validate novel actionable oncogenic targets and/or pathways with the overall goal of informing current therapeutic regimens leading to future clinical trials.
Children’s Hospital of Philadelphia
Molecular Mechanisms and Functional Impact of Aberrant Splicing in Diffuse Midline Gliomas
A comprehensive approach is needed to advance the understanding and clinical care options for patients with diffuse midline gliomas (DMGs). Using DMG samples provided by the Children’s Brain Tumor Network, researchers seek to identify avenues for new therapies.
High-grade Gliomas (HGG) or astrocytomas in children nearly always result in a dismal prognosis. Although novel therapeutic approaches are currently in development, preclinical testing has been limited, due to a lack of pediatric-specific HGG preclinical models. These models are needed to help test
Diffuse Intrinsic Pontine Glioma
A presumptive diagnosis of DIPG based on classic imaging features, in the absence of a histologic diagnosis, has been routinely employed. Increasingly however, histologic confirmation is obtained for both entry into research studies and molecular characterization of the tumor. New approaches with
Macrophages in SHH Subgroup Medulloblastoma Display Dynamic Heterogeneity That Varies With Treatment Modality
Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, and ontology. Transcriptomic analyses of human medulloblastoma, the most common malignant pediatric brain cancer, showed that medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) have significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated TAMs by single-cell RNA sequencing of autochthonous murine SHH-MB at steady state and under two distinct treatment modalities: molecular-targeted inhibitor and radiation. Our analyses reveal significant TAM heterogeneity, identify markers of ontologically distinct TAM subsets, and show the impact of brain microenvironment on the differentiation of tumor-infiltrating monocytes. TAM composition undergoes dramatic changes with treatment and differs significantly between molecular-targeted and radiation therapy. We identify an immunosuppressive monocyte-derived TAM subset that emerges with radiation therapy and demonstrate its role in regulating T cell and neutrophil infiltration in MB.
Mai T. Dang, Michael V. Gonzalez, Krutika S. Gaonkar, Komal S. Rathi, Patricia Young, Sherjeel Arif, Li Zhai, Zahidul Alam, Samir Devalaraja, Tsun Ki Jerrick To, Ian W. Folkert, Pichai Raman, Jo Lynne Rokita, Daniel Martinez, Jaclyn N. Taroni, Joshua A. Shapiro, Casey S. Greene, Candace Savonen, Fernanda Mafra, Hakon Hakonarson, Tom Curran, Malay Haldar