Rishi Lulla
A5051462497- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Chromatin Remodeling and Cancer
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Ocular Oncology and Treatments
- Cancer-related molecular mechanisms research
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- Cancer therapeutics and mechanisms
- Cancer Mechanisms and Therapy
- Tryptophan and brain disorders
- Circular RNAs in diseases
- Brain Metastases and Treatment
- Cancer-related Molecular Pathways
- Genetics and Neurodevelopmental Disorders
- Lung Cancer Treatments and Mutations
- interferon and immune responses
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
- Melanoma and MAPK Pathways
- Radiation Therapy and Dosimetry
Brown University
2018-2025
Hasbro Children's Hospital
2018-2024
Providence College
2019-2024
Rhode Island Hospital
2021-2024
Lifespan
2021-2023
Warren Alpert Foundation
2023
UCSF Benioff Children's Hospital
2022
University of California, San Francisco
2022
University Children's Hospital Zurich
2022
Children's Cancer Center
2022
Diffuse midline gliomas (including diffuse intrinsic pontine glioma, DIPG) are highly morbid glial neoplasms of the thalamus or brainstem that typically arise in young children and not surgically resectable. These tumors characterized by a high rate histone H3 mutation, resulting replacement lysine 27 with methionine (K27M) genes encoding variants H3.3 (H3F3A) H3.1 (HIST1H3B). Detection these gain-of-function mutations has clinical utility, as they associated distinct tumor biology outcomes....
A limited number of reports have investigated the role microRNAs in osteosarcoma. In this study, we performed miRNA expression profiling osteosarcoma cell lines, tumor samples, and normal human osteoblasts. Twenty-two differentially expressed were identified using high throughput real-time PCR analysis, 4 (miR-135b, miR-150, miR-542-5p, miR-652) confirmed validated a different group tumors. Both miR-135b miR-150 been previously shown to be important cancer. We hypothesize that dysregulation...
p53 is a promising target in human cancer. p28 cell-penetrating peptide that preferentially enters cancer cells and binds to both wild-type mutant protein, inhibiting COP1-mediated ubiquitination proteasomal degradation. This results increased levels of p53, which induces cell cycle arrest at G2/M. We conducted phase I study determine the maximum-tolerated dose (MTD) describe dose-limiting toxicities (DLTs) pharmacokinetics (PKs) children. Children aged 3–21 years with recurrent or...
Radiation therapy is the most commonly used postsurgical treatment for primary malignant brain tumors. Consequently, investigating efficacy of chemotherapeutics combined with radiation treating tumors high clinical relevance. In this study, we examined cyclin-dependent kinase 4/6 inhibitor palbociclib, when in combination human atypical teratoid rhabdoid tumor (ATRT) as well glioblastoma (GBM).Evaluation antitumor activity vitro was based upon results from cell proliferation assays,...
Introduction We have examined expression of microRNAs (miRNAs) in ependymomas to identify molecular markers value for clinical management. miRNAs are non-coding RNAs that can block mRNA translation and affect stability. Changes the been correlated with many human cancers. Materials Methods utilized TaqMan Low Density Arrays evaluate 365 normal brain tissue. first demonstrated similarity profiles paired frozen tissue (FT) paraffin-embedded specimens (FFPE). compared miRNA 34 FFPE ependymoma...
To investigate molecular alterations in choroid plexus tumors (CPT) using a genome-wide high-throughput approach to identify diagnostic and prognostic signatures that will refine tumor stratification guide therapeutic options.One hundred CPTs were obtained from multi-institutional tissue clinical database. Copy-number (CN), DNA methylation, gene expression assessed for 74, 36, 40 samples, respectively. Molecular subgroups correlated with parameters outcomes.Unique distinguished carcinomas...
BACKGROUNDPatients with diffuse midline gliomas (DMGs), including intrinsic pontine glioma (DIPG), have dismal outcomes. We previously described the H3.3K27M mutation as a shared neoantigen in HLA-A*02.01+, H3.3K27M+ DMGs. Within Pacific Pediatric Neuro-Oncology Consortium, we assessed safety and efficacy of an H3.3K27M-targeted peptide vaccine.METHODSNewly diagnosed patients, aged 3-21 years, HLA-A*02.01+ status were enrolled stratum A (DIPG) or B (nonpontine DMG). Vaccine was administered...
Gene-mediated cytotoxic immunotherapy (GMCI) is a tumor-specific immune stimulatory strategy implemented through local delivery of aglatimagene besadenovec (AdV-tk) followed by anti-herpetic prodrug. GMCI induces T-cell dependent tumor immunity and synergizes with radiotherapy. Clinical trials in adult malignant gliomas demonstrated safety potential efficacy. This the first trial pediatric brain tumors. phase I dose escalation study was conducted to evaluate patients 3 years age or older...
Pediatric brain tumors are the leading cause of cancer-related death in children United States and contribute a disproportionate number potential years life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary The Children's Brain Tumor Network (CBTN) is multi-institutional international clinical research consortium created advance therapeutic development through collection rapid distribution biospecimens data via open-science...
Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, Children's Brain Tumor Network (CBTN) Pacific Neuro-Oncology Consortium (PNOC) created a systematic process tumor biobanking, model generation, sequencing with immediate access to harmonized data. We leverage data establish OpenPBTA, an open collaborative project over 40 scalable...
Abstract Background Survivors of pediatric brain tumors are at risk for impaired development in multiple neuropsychological domains. The purpose this study was to compare outcomes tumor patients who underwent X-ray radiotherapy (XRT) versus proton (PRT). Methods Pediatric either XRT or PRT and received posttreatment age-appropriate evaluation—including measures intelligence (IQ), attention, memory, visuographic skills, academic parent-reported adaptive functioning—were identified....
Radiotherapy (RT) has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all patients show evidence of disease progression within months completing RT. No further clinical benefit achieved using alternative radiation strategies. Here, we tested hypothesis that histone demethylase inhibition by GSK-J4 enhances radiation-induced DNA damage, making it a potential radiosensitizer in DIPG.Experimental Design: We evaluated effects on genes...
Diffuse midline glioma (DMG) is a highly morbid pediatric brain tumor. Up to 80% of DMGs harbor mutations in histone H3-encoding genes, associated with poor prognosis. We previously showed the feasibility detecting H3 circulating tumor DNA (ctDNA) liquid biome children diagnosed DMG. However, detection low levels ctDNA dependent on platform sensitivity and sample type. To address this, we optimized specificity across two commonly used digital droplet PCR (ddPCR) platforms (RainDance BioRad),...
Pediatric diffuse midline glioma is a highly morbid glial neoplasm that may arise in the thalamus or brainstem (also known as intrinsic pontine DIPG). Because tumor anatomic location precludes surgical resection, diagnosis and treatment based on MR imaging analysis of biopsy specimens. Up to 80% pediatric gliomas harbor histone H3 mutation resulting replacement lysine 27 with methionine (K27M) genes encoding variant H3.3 (H3F3A) H3.1 (HIST1H3B). H3K27M mutant responds more poorly associated...
ONC201/TIC10 activates TRAIL signaling through ATF4 and the integrated stress response (ISR). ONC201 demonstrated tumor regressions disease stability in patients with histone H3K27M-mutated midline-glioma. H3K27M-mutation prevents H3K27-methylation on mutated allele. EZH2 inhibitors (EZH2i) reduce H3K27 methylation have anti-tumor effects. We hypothesized sensitivity apoptosis may increase by reducing EZH2i or HDACi as mimics of H3K27M-mutation. EPZ-6438 (tazemetostat) PF-06821497 vorinostat...
Small molecule imipridones including ONC201, ONC206 and ONC212 have anti-cancer activity mediated in part through the integrated stress response, induction of TRAIL its receptor DR5, activation mitochondrial caseinolytic protease ClpP with impaired oxidative phosphorylation. ONC201 provides clinical benefit a subset patients histone H3K27M-mutated diffuse glioma (DG). We hypothesized that EZH2 inhibitors (EZH2i) may sensitize tumors to by mimicking H3K27M mutation. EZH1 is homolog...
// Frank Eckerdt 1 , Elspeth Beauchamp 1,2 Jonathan Bell Asneha Iqbal 1,3 Bing Su 4,5 Rikiro Fukunaga 6 Rishi R. Lulla Stewart Goldman and Leonidas C. Platanias 1, 2 Robert H. Lurie Comprehensive Cancer Center Division of Hematology- Oncology, Feinberg School Medicine, Northwestern University, Chicago, IL,USA Department Jesse Brown VA Medical Center, IL, USA 3 Hematology Ann & Children’s Hospital 4 Immunobiology, Yale University New Haven, CT, 5 Shanghai Institute Immunology...
The PIM family of proteins encodes serine/threonine kinases with important roles in protein synthesis and cancer cell metabolism. In glioblastoma (GBM) lines, siRNA-mediated knockdown or pharmacological inhibition by SGI-1776 AZD-1208 results reduced phosphorylation classic effectors also elements the PI3K/mTOR pathway, suggesting interplay between mTOR signals GBM cells. Combination kinase inhibitors BYL-719, an inhibitor specific for PI3K catalytic isoform p110α, enhanced antineoplastic...