About

Harley I. Kornblum is a professor in the Departments of Pediatrics, Psychiatry and Biobehavioral Sciences, Pediatric Neurology, and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles. His laboratory focuses on neurodevelopment, neural repair, and brain tumors, investigating the factors that drive these processes. He is one of the co-discoverers of stem cell-like cells in brain tumors, which are thought to be critical in the resistance of brain tumors to therapies. His research aims to find means to overcome this therapeutic resistance. In addition to brain tumors, Dr. Kornblum’s work is relevant to autism, spinal cord injury, stroke, cerebral palsy, and other developmental disorders of the nervous system. His research contributes to understanding the mechanisms underlying these conditions and exploring potential therapeutic strategies.

Research topics

• Biology
• Cancer research
• Chemistry
• Cell biology
• Medicine

Selected publications

• <b>Acute rapamycin treatment reveals novel mechanisms of dysfunction in a maternal inflammation mouse model</b>

  Figshare · 2026-04-17

  articleOpen accessSenior author

  Data from Nature Communications accepted manscript (behavior, westernblot, slice electrophysiology, immunostaining, brain wet weight). Abstract/description of paper: Maternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and brain inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that alter or prevent physical brain changes. Here, we have focused on the acute effects of rapamycin to uncover novel mechanisms of dysfunction related to mTOR pathway signaling. We find that within 2 hours, rapamycin treatment could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity and brain community structure, repetitive behaviors, and sensory over-responsivity in adult offspring with persistent mild brain overgrowth. These CNS-mediated effects are also associated with alteration of the expression of several ASD-, ion channel-, and epilepsy-associated genes in the same time frame. Reduction of microglia with CSF1R inhibitors or inhibition of NADPH oxidase in young animals reduces the development of some of the behavioral phenotypes, but neither is as effective as acute mTOR inhibition. Our findings indicate that mTOR dysregulation in MIR offspring is a key contributor to various levels of brain dysfunction. However, we demonstrate that the adult MIR brain is also amenable to rapid normalization of these functional changes which results in the rescue of both core and comorbid ASD-like behaviors in adult animals without requiring long-term physical alterations to the brain. Restoring excitatory/inhibitory imbalance and sensory functional network modularity may therefore be important targets for therapeutically addressing both primary sensory and compensatory repetitive behavior phenotypes.

  PublisherDOI

• Abstract 6234: Characterizing the competitive interactions between glioblastoma and oligodendrocyte progenitor cells

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Resection of glioblastoma (GBM) often only includes the contrast-enhancing (CE) solid portion of the tumor and radiation therapy also targets this region. These therapies leave behind infiltrating tumor cells that lay beyond the CE border in the non-enhancing region (NE) with the capacity to propagate the tumor following therapy. Non-transformed cell types in the brain have been shown to promote GBM progression via a variety of mechanisms. We performed single nucleus RNA-sequencing (snRNA-seq) on 17 biopsies from the NE and CE regions of seven different primary IDH WT glioblastoma tumors during maximal resection surgery. While some oligodendrocyte progenitor cells (OPCs) are present in the NE region, they are almost absent in the CE region, a finding corroborated by our prior study of recurrent tumors. OPCs, the most common cycling cells in the brain, share many genes with GBM and the interaction between the two cell types has yet to be described on a single cell level. Prior work has demonstrated that in the developing and adult brain young, more fit OPCs can outcompete older OPCs leading us to hypothesize that brain tumor cells can compete with non-transformed OPCs. To explore possible interactions between GBM and OPCs we utilized predictive cell-cell interaction software, finding that OPCs express transcripts that are predicted to respond to GBM signals to induce proliferation, migration and differentiation. Compared to snRNA-seq of healthy OPCs, the OPCs from our biopsies were more likely to be proliferative, migratory, and differentiated. To assess possible enrichment of pathways associated with a more competitive state, we performed differential expression between OPCs contained in our biopsies and GBM cells. This revealed a significant enrichment of the YAP1 pathway which is associated with a more competitive state. GBM cells were predicted to be activated by OPCs to proliferate, migrate and have increase synaptic activity. To investigate how soluble factors secreted by OPCs and GBM cells influence each other by culturing each cell population in conditioned media (CM) derived from the opposite cell type. OPCs treated with GBM CM have shown increased proliferation and GBM cells treated with OPC CM have shown decreased proliferation, possibly due to younger nature of OPCs that were differentiated from iPSCs. Our findings support the hypothesis that there are complex and possibly competitive interactions between OPCs and GBM cells, extending the concept of “cancer neuroscience”. Further studies are ongoing to establish the nature and mechanisms of these interactions. Citation Format: Lindsey A. Dudley, Sunlan Lu, Beatrice O'Brien, Carol Watkins, Travis Perryman, Riki Kawaguchi, Steve A. Goldman, Kunal S. Patel, Harley I. Kornblum. Characterizing the competitive interactions between glioblastoma and oligodendrocyte progenitor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6234.

  PublisherDOI

• Acute rapamycin treatment reveals novel mechanisms of dysfunction in a maternal inflammation mouse model

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-14

  datasetOpen accessSenior author

  Abstract Maternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and brain inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that alter or prevent physical brain changes. Here, we have focused on the acute effects of rapamycin to uncover novel mechanisms of dysfunction related to mTOR pathway signaling. We find that within 2 hours, rapamycin treatment could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity and brain community structure, repetitive behaviors, and sensory over-responsivity in adult offspring with persistent mild brain overgrowth. These CNS-mediated effects are also associated with alteration of the expression of several ASD-, ion channel-, and epilepsy-associated genes in the same time frame. Reduction of microglia with CSF1R inhibitors or inhibition of NADPH oxidase in young animals reduces the development of some of the behavioral phenotypes, but neither is as effective as acute mTOR inhibition. Our findings indicate that mTOR dysregulation in MIR offspring is a key contributor to various levels of brain dysfunction. However, we demonstrate that the adult MIR brain is also amenable to rapid normalization of these functional changes which results in the rescue of both core and comorbid ASD-like behaviors in adult animals without requiring long-term physical alterations to the brain. Restoring excitatory/inhibitory imbalance and sensory functional network modularity may therefore be important targets for therapeutically addressing both primary sensory and compensatory repetitive behavior phenotypes.

  PublisherDOI

• Critical role of cell competition in gliomagenesis

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-16

  articleOpen access

  ABSTRACT Malignant glioma is incurable. Using a mouse genetic mosaic system to generate sporadic Trp53,Nf1 -null OPCs, we previously identified oligodendrocyte precursor cell (OPC) as a cell-of-origin of glioma. Here, we report that pre-malignant Trp53,Nf1 -null OPCs outcompete wildtype counterparts during their expansion. Blocking competition by mutating/strengthening wildtype OPCs impeded both pre-malignant progression and malignant expansion of glioma. “In-tissue” phosphoproteomic profiling revealed an enrichment of phosphopeptides related to RNA splicing and protein translation at the peak of cell competition, suggesting that competitiveness may stem from unique protein species. Among candidates was mTORC1, whose pharmacological inhibition or genetic disruption resulted in a loss of competitiveness in our mouse model. Finally, analysis of patient biopsies and interrogating the role of individual gliomagenic mutations in OPC competition supported its relevance in human gliomas. Together, these findings identified the driving role of competitive interactions among OPCs in gliomagenesis, and suggest unconventional therapeutic strategies to target this process.

  PublisherDOI

• <b>Acute rapamycin treatment reveals novel mechanisms of dysfunction in a maternal inflammation mouse model</b>

  Figshare · 2026-04-17

  articleOpen accessSenior author

  Data from Nature Communications accepted manscript (behavior, westernblot, slice electrophysiology, immunostaining, brain wet weight). Abstract/description of paper: Maternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and brain inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that alter or prevent physical brain changes. Here, we have focused on the acute effects of rapamycin to uncover novel mechanisms of dysfunction related to mTOR pathway signaling. We find that within 2 hours, rapamycin treatment could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity and brain community structure, repetitive behaviors, and sensory over-responsivity in adult offspring with persistent mild brain overgrowth. These CNS-mediated effects are also associated with alteration of the expression of several ASD-, ion channel-, and epilepsy-associated genes in the same time frame. Reduction of microglia with CSF1R inhibitors or inhibition of NADPH oxidase in young animals reduces the development of some of the behavioral phenotypes, but neither is as effective as acute mTOR inhibition. Our findings indicate that mTOR dysregulation in MIR offspring is a key contributor to various levels of brain dysfunction. However, we demonstrate that the adult MIR brain is also amenable to rapid normalization of these functional changes which results in the rescue of both core and comorbid ASD-like behaviors in adult animals without requiring long-term physical alterations to the brain. Restoring excitatory/inhibitory imbalance and sensory functional network modularity may therefore be important targets for therapeutically addressing both primary sensory and compensatory repetitive behavior phenotypes.

  PublisherDOI

• Temporal Mapping of Radiation-Induced Neural Injury and Mitigation in Human Cortical Organoids

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-06

  articleOpen access

  Background: Radiation therapy is a standard-of-care oncological treatment for central nervous system (CNS) malignancies. However, as survival outcomes improve, radiation-induced injury to normal brain tissue has increased in clinical significance. CNS radiation injury is a delayed, multifactorial process characterized by impaired neurogenesis, reactive gliosis, and persistent functional deficits. Mechanistic exploration and development of effective radiation mitigators have been limited by the lack of scalable, human-relevant models. Methods: Mature human iPSC-derived cortical organoids were exposed to single-dose or clinically relevant fractionated radiation (5 x 2 Gy). DNA damage, apoptosis, and growth dynamics were assessed longitudinally. Structural organization, synaptic integrity, and neuroinflammatory responses were evaluated by immunofluorescence and real-time PCR. Transcriptomic profiling was performed at 72 hours and 2 weeks after fractionated radiation to capture acute and delayed effects. Two candidate radiation mitigators, NSPP and amisulpride, were tested for their therapeutic effects within the organoid system. Results: Cortical organoids exhibited partial recovery following single doses up to 4 Gy or fractioned irradiation. Transcriptomic analyses revealed that radiation not only reduced overall cell viability but also reshaped lineage trajectories, characterized by depletion of neural stem/progenitor populations, loss of neuronal identity, enhanced gliogenesis, increased inflammatory cytokines, and disrupted cortical layering and synaptic integrity. Treatment with NSPP or amisulpride attenuated injury-associated transcriptional and structural alterations. Conclusion: Human cortical organoids recapitulate key features of radiation-induced neural injury, recovery, and therapeutic modulation, providing a robust, scalable, and human-relevant platform for studying CNS radiation biology and preclinical screening of candidate radiation mitigators. Key points: Human iPSC-derived cortical organoids enable study of human CNS radiation responses.Organoids recover after single-dose and fractionated radiation relevant to clinical exposure.The platform supports scalable, human-relevant testing of radiation mitigation strategies.

  PublisherOA PDFDOI

• Acute rapamycin treatment reveals novel mechanisms of dysfunction in a maternal inflammation mouse model

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-14

  datasetOpen accessSenior author

  Abstract Maternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and brain inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that alter or prevent physical brain changes. Here, we have focused on the acute effects of rapamycin to uncover novel mechanisms of dysfunction related to mTOR pathway signaling. We find that within 2 hours, rapamycin treatment could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity and brain community structure, repetitive behaviors, and sensory over-responsivity in adult offspring with persistent mild brain overgrowth. These CNS-mediated effects are also associated with alteration of the expression of several ASD-, ion channel-, and epilepsy-associated genes in the same time frame. Reduction of microglia with CSF1R inhibitors or inhibition of NADPH oxidase in young animals reduces the development of some of the behavioral phenotypes, but neither is as effective as acute mTOR inhibition. Our findings indicate that mTOR dysregulation in MIR offspring is a key contributor to various levels of brain dysfunction. However, we demonstrate that the adult MIR brain is also amenable to rapid normalization of these functional changes which results in the rescue of both core and comorbid ASD-like behaviors in adult animals without requiring long-term physical alterations to the brain. Restoring excitatory/inhibitory imbalance and sensory functional network modularity may therefore be important targets for therapeutically addressing both primary sensory and compensatory repetitive behavior phenotypes.

  PublisherDOI

• Supplementary Figure S1 from &lt;i&gt;(R)&lt;/i&gt;-2-Hydroxyglutarate Inhibits KDM5 Histone Lysine Demethylases to Drive Transformation in &lt;i&gt;IDH&lt;/i&gt;-Mutant Cancers

  2025-12-11

  articleOpen access

  &lt;p&gt;Characterization of isogenic TF-1 cell lines expressing TET2-targeting shRNAs.&lt;/p&gt;

  PublisherOA PDFDOI

• Supplementary Table S11 from &lt;i&gt;(R)&lt;/i&gt;-2-Hydroxyglutarate Inhibits KDM5 Histone Lysine Demethylases to Drive Transformation in &lt;i&gt;IDH&lt;/i&gt;-Mutant Cancers

  2025-12-11

  articleOpen access

  &lt;p&gt;Supplementary Table S11 shows the characteristics of the primary glioma patient samples.&lt;/p&gt;

  PublisherDOI

• Supplementary Figure S3 from &lt;i&gt;(R)&lt;/i&gt;-2-Hydroxyglutarate Inhibits KDM5 Histone Lysine Demethylases to Drive Transformation in &lt;i&gt;IDH&lt;/i&gt;-Mutant Cancers

  2025-12-11

  articleOpen access

  &lt;p&gt;Trimethyl-H3K4 is not enriched upon knock-down of TET2 in TF-1 cells.&lt;/p&gt;

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01NS052563

  NIH · $2.4M · 2017

• NIH Grant K08NS001837

  NIH · $477k · 2001

• NIH Grant R56NS052563

  NIH · $231k · 2011

• UCLA SPORE in Brain Cancer

  NIH · $35.6M · 2017–2027

• NIH Grant R21MH062800

  NIH · $459k · 2002

Frequent coauthors

• Linda M. Liau

  194 shared

• David A. Nathanson

  158 shared

• Timothy F. Cloughesy

  University of California, Los Angeles

  146 shared

• Paul S. Mischel

  Stanford University

  133 shared

• Frank Pajonk

  119 shared

• William H. Yong

  University of California, Los Angeles

  119 shared

• Albert Lai

  University of California, Los Angeles

  100 shared

• Dan R. Laks

  94 shared