Meet Jared Hysinger – Tissue Navigator
When I first started as tissue navigator, I saw distance between medical research and clinical practice. Yet, conversations with families throughout the donation process have erased that distance. In medical science there is a term, “bench to bed side.” This refers to the process of taking scientific discoveries made at a lab bench and implementing them in the context of patient care – either through improved therapies or increased awareness of the underlying biology behind human diseases. However, the role of a tissue navigator has shown that this process is not one-way. Patients have a unique role in informing how scientists research their diseases. By donating tissue, patients provide scientists with a real sample of their unique disease. We can compare it to others and with their own healthy tissue to find similarities and improve our treatment strategies.
One of our lab’s promising trials using GD2 CAR T cells to target DIPG cells was borne out of experiments done with patient tissue. Autopsy derived cell lines from patients showed how a molecule called GD2 was found in much higher quantities on the surface of DIPG cells compared with others. By targeting T cells against this marker, the lab has shown promising results in reducing tumors in human patients. Yet, there is still so much more to learn and more work to be done developing these treatments. Gift From a Child has showed me how many more important advancements like these are waiting to be made from future patient tissue.
For both the families of deceased patients and myself, conversations during the unimaginable death of a child are hard on the mind and soul. However, many families expressed they found hope and purpose in the impact their loved-one’s donation could have on science. I too, found both hope and purpose in hearing their stories. Conversations with families as a tissue navigator provided a deep meaningfulness to medical science by directly connecting the science with the patient community it impacts. While the loss of a child is unimaginable, helping families through the post-mortem donation process showed the power of the pediatric tumor community. Working together as families, care providers, and scientists I am honored to be a part of helping prevent this tragedy from continuing to touch more families.
(Also, as an aside, the photos show the reason I love being from California. You can go from sandy beaches to snowy mountains in the same winter day and it’s sunny in both places. Would highly recommend a hike to Mount Tamalpais for anyone visiting the Bay Area and looking for an awe-inspiring vista.)
Jared Hysinger
Recent Publications from Centers of Excellence
Harmonization of Post-mortem Donations for Pediatric Brain Tumors and Molecular Characterization of Difuse Midline Gliomas
Children diagnosed with brain tumors have the lowest overall survival of all pediatric cancers. To address the paucity of tissue for biological studies, we have established a comprehensive protocol for the coordination and processing of donated specimens at postmortem. Since 2010, 60 postmortem pediatric brain tumor donations from 26 institutions were coordinated and collected. Patient derived xenograft models and cell cultures were successfully created (76% and 44% of attempts respectively), irrespective of postmortem processing time. Histological analysis of mid-sagittal whole brain sections revealed evidence of treatment response, immune cell infiltration and the migratory path of infiltrating H3K27M DMG cells into other midline structures and cerebral lobes. Sequencing of primary and disseminated tumors confirmed the presence of oncogenic driver mutations and their obligate partners. Our findings highlight the importance of postmortem tissue donations as an invaluable resource to accelerate research, potentially leading to improved outcomes for children with aggressive brain tumors. Read Full Publication
Dr. Monje-Deisseroth and her team at Stanford University recently published a paper detailing how gliomas are able to “hijack” the brain's communication system.
Published in Nature: High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron–glioma synapses. Read More
Congratulations to two of our Center of Excellence teams lead by Dr Javad Nazarian and Dr. Michelle Monje on their recent groundbreaking research publication. Due in part to increased access to post-mortem tissuethe teams were able to study a larger sample of DIPG tumors. Diffuse intrinsic pontine glioma is a lethal pediatric brain cancer characterized by H3K27M histone mutation. Nagaraja et al. characterize a large cohort of rare primary tumors and normal pontine tissue to reveal active regulatory element heterogeneity dependent upon the histone variant and cell context in which the mutation occurs. Read More
Research Breakthroughs Resulting from Autopsy Tissue
Donovan_et_al_Locoregional_delivery_CAR-T_cells_Nat_Med2020_opt
Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas_2018
Non-inflammatory tumor microenvironment of diffuse intrinsic pontine glioma_2018
Intertumoral Heterogeneity within Medulloblastoma Subgroups_Sick Kids Publication_June 2017
A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma (DIPG)_March 2017
Neural Precursor-Derived Pleiotrophin Mediates Subventricular Zone Invasion by Glioma_Aug 2017
Divergent clonal selection dominates medulloblastoma at recurrence
Models Pave the Way for Improved Outcomes in Medulloblastoma_August 2016
Functionally defined therapeutic targets in diffuse intrinsic pontine glioma_June 2015
Neuronal Activity Promotes Glioma Growth through Neuroligin-3 Secretion_May 2015 Cell
Stanford Research Paper: Electrical and synaptic integration of glioma into neural circuits
Rapid autopsy of a patient with recurrent anaplastic ependymoma.
Next-Generation Rapid Autopsies Enable Tumor Evolution Tracking and Generation of Preclinical Models
Why Autopsy Tissue is Needed to Empower Research
Pediatric Brain Cancer Tissue Donation article_2016
Overcoming Autopsy Barriers in Pediatric Cancer Research
Study on Collection of autopsy tissue in DIPG patients_Oct 2010
Next-Generation Rapid Autopsies Enable Tumor Evolution Tracking_January 2018
The clinical, research, and social value of autopsy after any cancer death
Gift from a Child
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