Honored to work alongside incredible neuro-oncology researchers at HCNL!

A beautiful day in Boston

RT @EAChiocca: As a final reflection on the #MGB CTNS Event, I want to extend a big thank you to everyone who attended and our staff that h…

RT @EAChiocca: The 2025 Prince Mahidol Award Conference in Thailand this past week. Thank you again to Richie Hengswat for the invitation t…

Had a great year doing research with Richie. We already miss Richie as he left to continue his neurosurgery residency.

Snowy night @BrighamWomens

“The core of issues in relationships, teams, and nations lies in Crucial Conversations—high-stakes discussions with opposing views and strong emotions. Ironically, we handle them worst when they matter most.”

RT @EAChiocca: Excited for my upcoming presentations in Thailand at the 2025 Prince Mahidol Award Conference! I will be touching on Immunot…

RT @EAChiocca: Honored to be featured this evening on @WCVB NewsCenter 5 at 6, highlighting our teams’ advances on treating #Glioblastoma.…

RT @EAChiocca: Very excited to announce the publication of our Nature Paper. Please read below! Thank you to all who contributed.

Glioblastoma (GBM) possesses an extreme level of resilience to biochemically targeted therapies, demanding an outside of the box approach that can overcome plastic adaptation and heterogeneity of GBM. Building on the foundation that GBM cells are responsive to mechanical forces, Wang et al. report a mechanical nanosurgery approach to treat chemoresistant glioblastoma using magnetic carbon nanotubes (mCNTs) + precision magnetic field control. Applying precisely controlled magentic field to mCNTs allows them to exert mechanical torque and force to cellular structures of GBM, acting as swarms of nano-scalpels that disturb cellular structure of GBM and kills them. Further, mCNTs can also be used to modulate specific biochemical pathways, allowing combinatory synergy with targeted therapy, chemotherapy, or immunotherapy. Science Advances, 2023

Physician scientists, or physician principle investigators (PIs), have dual roles in research and patient care that enable them to generate novel insights and strategies for disease prevention and treatment. This allowed them to provide countless biomedical innovations, representing over a third of Nobel laureates and Lasker Award winners over the past 30 years. However, they are a dying breed—representing 5% of biomedical workforce in 1980s to 1.5% today. This decline is multifaceted, and it is “imperative to increase and target NIH funding to physician investigators, incorporate an equity lens, and rethink the academic culture that focuses excessively on R01 funding.”

In a study published in Nature, Naghavian et al. report that peptides from certain pathogenic bacteria can be exploited for strong T-cell stimulation against GBM, and the unbiased antigen discovery of tumor infiltrating lymphocytes (TILs) holds promise for developing personalized bacterial tumor vaccines. GBM contains distinct bacterial communities and presents bacteria-specific peptides on its HLA II molecules. Although bacterial peptides eluted from HLA weakly stimulated TILs, an unbiased antigen discovery of TIL-derived CD4+ T-cell clones (TCCs) revealed novel bacteria-derived and microbiota-derived antigens that are highly simulatory for TILs. Further, TCCs showed broad cross-reactivity against a wide range of peptides from pathogenic bacteria, commensal gut microbiota, and GBM-related tumor antigens. Through this T-cell cross-reactivity, immune responses formed against bacteria may also target GBM.

Recent works have revealed that neurons synapse with glioma cells to promote GBM proliferation and invasion, and there have been increasing efforts to target this GBM-neural circuit to create the “next-generation therapeutics” for GBM. In a study published in Nature Cancer, Dong et al. identified that the key regulators of GBM-neuron interactions are EAG2 and Kvb2, which together form voltage-gated potassium channel complex at the GBM-brain interface. Genetic knowdown of the EAG2-Kvb2 complex markedly disrupted GBM-neuron communication and suppressed GBM growth and invasion in Gbm-bearing mice. Furthermore, mechanisms of chemoresistance had a strong correlation with GBM-neuron interaction, and inhibiting EAG2-Kvb2 interaction with an engineered peptide demonstrated robust efficacy in treating TMZ-resistant GBM. Nature Cancer, September 11 2023

Heur et al. combined the two major discoveries in glioblastoma (GBM) biology—intratumoral heterogeneity and neuronal features—and proposed an integrative model of GBM. The periphery of GBM is characterized by unconnected neuronal-like cells that hijack neuronal mechanisms to rapidly invade the normal brain tissue and proliferate along the way. After the first wave of invasion, the “first settler GBM cells” use their tumor microtubes (TMs) to build connections with other tumor cells, forming increasingly dense tumor networks over time. The core of GBM, where these tumor cell networks is the most dense, generate autonomous, rhythmic activation of the tumor promoting pathways (NF-kB and MAPK) through a small-population of “pacemaker-like cells.” This integrated signaling protects GBM from chemotherapy and radiotherapy and allows subsequent plastic adaptation. Clinically, the more solid parts can be resected, but the invading cells will remain, as well as the parts of tumor networks present without any signal abnormalities on current MRI sequences. Therefore, it is paramount to consider a multicafeted treatment approach that targets both the invasion and network interconnectivity to improve therapy for GBM. Cell Press: Trends in Cancer, Aug 2023

RT @MKhasraw: We already have patients enrolled in a trial evaluating this concept in glioblastoma the trial is ope…

The unique membrane lipid composition of glioblastoma (GBM) can be exploited with a safe, highly brain-penetrant, FDA approved selective seretonin reuptake inhibitor (SSRI), fluoxetine. Flouxetine was found to inhibit sphingomyelin phosphodiesterase 1 (SMPD1) acitivity, which subsequently kills GBM cells through inhibition of EGFR signaling and activation of lysosomal stress. When flouxetine was combined with temozolomide (TMZ), it led to massive GBM killing and complete tumor regression in mice. Thus, flouxetine presents as a way to both modulate the psychological stress and reduce tumor growth for GBM patients. Cell Reports, 2021