About

Nathan D Seligson is a Clinical Assistant Professor in the Department of Pharmacotherapy and Translational Research at the University of Florida College of Pharmacy. He earned his Doctor of Pharmacy degree from the University of South Florida and completed a pharmacy practice residency. Following this, he completed a post-doctoral fellowship in translational hematology and oncology, focusing on precision medicine in sarcoma. His clinical practice includes activities as a clinical pharmacogenomics specialist and a hematology/oncology research scientist at Nemours Children's Specialty Care in Jacksonville, Florida. Dr. Seligson's research centers on understanding cancer biology and tumor evolution to provide actionable molecular subtyping and pharmacogenomic therapy guidance in sarcoma. He has been published as a first author in leading journals such as JAMA Open Network, The Oncologist, and npj Precision Medicine. His teaching includes courses on clinical applications of precision medicine in oncology and selected topics in pharmacy. His background combines clinical practice, research in precision medicine, and education in pharmacogenomics and oncology.

Research topics

• Biology
• Medicine
• Genetics
• Bioinformatics
• Internal medicine
• Cancer research
• Computational biology
• Pharmacology
• Immunology
• Oncology
• Pathology
• Cell biology

Selected publications

• Abstract 5424: Detection of rare oncogenic fusions through concurrent DNA and RNA next-generation sequencing in a pan-cancer clinical setting.

  Cancer Research · 2026-04-03

  article

  Abstract Background: Concurrent DNA and RNA testing is the gold standard for detection of oncogenic gene fusions with an associated targeted therapy. However, rare fusions without such therapies can also impact patient care by informing diagnosis, prognosis, or potential resistance to therapy. Targeted panel DNA assays are typically optimized for a small number of fusion genes, making use of RNA testing particularly salient for rare fusions. Here we quantify the benefit of concurrent DNA and RNA testing over DNA alone for such fusions, in a large real-world dataset of 74,182 patients with advanced cancer. Methods: We retrospectively analyzed deidentified records from the Tempus multimodal database of metastatic solid tumor samples from non-pediatric patients who underwent testing with both targeted panel DNA-next generation sequencing (NGS) and whole-exome RNA-NGS assays (Tempus xT and xR, respectively). Fusions both on and off the xT panel without an associated targeted therapy were considered for the study. Fusions were identified through the Tempus bioinformatic workflow, which runs RNA-NGS and DNA-NGS pipelines concurrently, followed by pathologist review. Results: Of the 74,182 patients in the cohort, 4,776 (6.4%) had at least one oncogenic fusion without an FDA-approved targeted therapy, with a total of 4,845 such fusions in the dataset. Of these fusions, 85.0% (4,119/4,845) involved genes present on the xT panel, with 56.6% (2,744) involving genes optimized for detecting rearrangements on the xT panel. Across all fusions in the study, 2,561 (52.9%) were detected by RNA-NGS only. For rare fusions involving genes on the xT panel and those with optimized detection in xT, 44.7% (1,841/4,119) and 23.9% (656/3,744) were detected in RNA only, respectively. The most common fusions in this dataset were TMPRSS2-ERG (n=2,247) with 23.4% detected only in RNA. RNA-only detection rates were particularly high for ESR1-CCDC170 (211/213, 99.1%) and PTPRK-RSPO3 (280/280, 100%). TMPRSS2 is optimized for fusion detection by xT, ESR1 is on xT but not targeted for rearrangements, and PTPRK- RSPO3 does not appear on xT. Conclusions: We show that RNA testing greatly enhances detection of rare fusions without an associated FDA-approved targeted therapy in a real-world setting. This benefit of RNA testing is most apparent for fusions not on a DNA-NGS targeted panel, but fusions targeted on the xT panel also showed increased detection with concurrent RNA testing. Among the fusions with high rates of RNA-only detection, ESR1-CCDC170 is associated with more aggressive ER+ breast cancers, and PTPRK-RSPO3 may modulate WNT signaling in colorectal cancer. Other clinically relevant fusions also showed enhanced detection from RNA-NGS. Overall, these findings suggest RNA testing could enhance detection of rare oncogenic fusions to better inform patient care. Citation Format: Lisa Gai, Molly Murnane, Malvika Pillai, Matthew Campbell, Bradley Bowles, Kyle A. Beauchamp, Rotem Ben-Shachar, Gregory Omerza, Razelle Kurzrock, Nathan David Seligson, Halla S. Nimeiri, Justin Guinney. Detection of rare oncogenic fusions through concurrent DNA and RNA next-generation sequencing in a pan-cancer clinical setting [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 5424.

  PublisherDOI

• P502: Application of pharmacogenomic testing in pediatric kidney transplant patients

  Genetics in Medicine Open · 2026-01-01

  articleOpen accessSenior author

  Introduction: Genome sequencing (GS) is increasingly utilized as a first-tier diagnostic tool for patients with suspected genetic disorders.The American Academy of Pediatrics and the American College of Medical Genetics and Genomics jointly recommended GS as a first-tier diagnostic test for children with intellectual disability, global developmental delay, and congenital anomalies.This policy shift marks a major step forward in the early identification of genetic conditions, moving comprehensive sequencing from specialty-based testing to a standard component of pediatric evaluation.However, with the potential shift in ordering patterns of GS, the present utilization remains under-characterized at a population level.Methods: We conducted a secondary data analysis of de-identified clinical GS orders from our laboratory, encompassing pediatric patients regardless of clinical indication.The dataset included patient-level variables such as age, sex at birth, and insurance coverage.Distance between the patient's home address zip code and the institution's zip code was calculated, and Rural-Urban Commuting Area codes were assigned.Descriptive statistics were used to calculate mean and median for continuous variables.The Pearson chi-square ( 2 ) test was applied to examine associations between categorical variables, and the Mann-Whitney U test was used to evaluate differences in continuous variables across groups.Results: The dataset included over 5000 pediatric patients recently tested through GS.The mean age at testing was 5.54 years (SD = 5.3), with a median of 3.96 years.The cohort was 60.0% male.The mean distance a patient lived from the institution where genetic testing was ordered was 62.0 miles (SD = 108.9),with a median of 28.6 miles.There were 203 patients who lived over 200 miles from the ordering institution and 440 patients who lived in a different state than the ordering institution.Approximately 19.8% of patients lived in rural areas, and 2.1% of the ordering institutions were located in rural areas.The median distance to clinic was 74.1 miles (M = 96.5,SD = 94.8) for those in rural areas compared to 19.3 miles (M = 53.7,SD = 110.4)for those in urban areas (P < .001).The mean age at time of testing was 5.76 years (SD = 5.3) for those who lived in rural areas and 6.00 years (SD = 5.3) for those in urban areas.Trio testing had the highest utilization (64.3%), followed by duo testing (20.6%) and proband-only testing (15.1%).Almost all rapid GS were through hospital billing (98.0%).Payer source did not differ significantly between rural and urban groups.Patients with commercial insurance had higher rates of trio GS (78.8%) than those with Medicaid (58.8%) or medical institution billing (62.6%), with a significant difference between test type and insurance coverage (P < .001).Conclusion: GS is guideline-recommended as a first-tier test and has been shown in previous studies to help resolve the diagnostic odyssey.Expanding access to comprehensive GS-including trio and rapid testing-within Medicaid and commercial programs across the US would likely increase patient access to timely genetic diagnoses.We observed significantly longer distances for testing for rural patients which impacts equitable access.Further, longer travel distances create added financial and practical barriers, including lost wages, lodging costs, and meal expenses, which can be prohibitive for many families, especially those using Medicaid.Equal access to GS can likely only be achieved if additional testing pathways are made available to patients living in rural communities.

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• Opportunities for Pharmacogenomics in Pediatrics: Prescribing Trends of Psychiatric Medications With Pharmacogenomic Implications at a Multistate Pediatric Health System

  The Journal of Pediatric Pharmacology and Therapeutics · 2025-04-01 · 1 citations

  article

  The Clinical Pharmacogenetics Implementation Consortium (CPIC) has published guidelines providing pharmacogenomic (PGx) recommendations for more than 100 drugs; however, limited data exist describing prescribing patterns of these medications in pediatric populations. With increasing evidence describing the benefits of PGx testing to tailor drug therapy in psychiatric conditions, along with a worsening mental health crisis in pediatrics, it is vital to assess the prevalence of medication prescribing and potential impact of implementing PGx testing in this population. Here we describe prescribing patterns of psychiatric drugs classified as CPIC level A/B from January 1, 2010, through December 31, 2020, across Nemours Children's Health, a multistate pediatric health care system. We identified 21,442 unique patients who received at least 1 indicated medication during this period. The most frequently prescribed medications were amitriptyline and sertraline. Overall prescribing was highest in the departments of neurology, primary care, and psychiatry with selective serotonin reuptake inhibitors (SSRIs) being the most frequently prescribed medication class. These findings indicate ample opportunity for PGx implementation targeting these medications. Identification of high-prescribing departments and specific medications prescribed will help focus PGx implementation and education efforts.

  PublisherDOI

• Revisiting <i>CDKN2A</i> dysregulation in Ewing sarcoma

  Molecular Oncology · 2025-03-13 · 1 citations

  articleOpen accessSenior authorCorresponding

  Ewing sarcoma (EwS) is a rare and aggressive malignancy, which frequently affects children. One of the few recurrent genomic variants in EwS is genomic copy number deletion of CDKN2A; however, the clinical consequences of dysregulation of CDKN2A in EwS are unclear. In this study, we revisit CDKN2A to investigate its role as a potential prognostic biomarker in EwS using data from EwS pre-clinical models as well as clinical samples from patients with EwS. We demonstrate the potential essentiality of CDKN2A dysregulation and sustained downstream CDK4/CCND1 activity. Finally, we present evidence that high expression of CDKN2A is a negative prognostic biomarker at diagnosis in EwS in three independent datasets. Our data may suggest that the role of CDKN2A may change across the clinical context of EwS, however, further study is necessary to validate the function of CDKN2A expression in EwS.

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• Preferences for implementing pharmacogenomics in pediatric primary care: a discrete choice experiment

  Pediatric Research · 2025-08-16 · 1 citations

  article
  PublisherDOI

• Revumenib for Relapsed or Refractory Acute Leukemia With a <i>KMT2A</i> Translocation

  Annals of Pharmacotherapy · 2025-05-28 · 4 citations

  reviewSenior authorCorresponding

  Objective: To review the pharmacology, efficacy, and safety of revumenib (Revuforj) for relapsed or refractory (r/r) acute leukemia with a lysine methyltransferase 2A ( KMT2A) gene rearrangement or translocation ( KMT2Ar ). Data Sources: A literature search was conducted using PubMed/MEDLINE, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and April 23, 2025. Keywords included Revuforj, revumenib, SNDX-5613, KMT2A , MLL1 , and menin. Study Selection and Data Extraction: All English-language studies involving revumenib for r/r acute leukemia with a KMT2Ar were included. Data Synthesis: Revumenib, a protein-protein inhibitor that interrupts the interaction between the KMT2A protein and the scaffold protein menin, was granted approval by the Food and Drug Administration (FDA) for r/r acute leukemia with KMT2Ar based on a phase 2 clinical trial in adult and pediatric patients (n = 57), which reported a complete remission or complete remission with partial hematologic recovery of 22.8%. Common grade 3/4 adverse reactions reported for revumenib include infectious (febrile neutropenia 33%; infection 29%; bacterial infection 20%) and hematologic events (differentiation syndrome 13%; hemorrhage 9%; thrombosis 5%). Grade 3/4 QT prolongation, the primary dose-limiting adverse effect, was present in 12% of patients. Differentiation syndrome, related to revumenib’s antileukemic effect, was observed in 29% of patients (grade 3/4: 13%; grade 5: &lt;1%). We also include long-term follow-up for a total of 104 and 135 patients for efficacy and safety results, respectively. Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs: In the high-risk disease of r/r acute leukemia with KMT2Ar , given limited treatment options, revumenib appears to be a viable, novel treatment option demonstrating clinical efficacy and a manageable adverse effect profile that can be utilized as a bridge to stem cell transplant. Existing therapy options in this setting may include additional traditional chemotherapy, chimeric antigen receptor T-cell therapy (CAR-T), antibody-drug conjugates (eg, gemtuzumab, inotuzumab), bispecific T-cell engager (BiTE) therapies (eg, blinatumomab), DNA methyltransferase inhibitors (eg, azacitidine, decitabine), histone deacetylase inhibitors (eg, vorinostat, panobinostat), and BCL-2 inhibitors (venetoclax). Conclusions: Revumenib is an innovative targeted treatment with promising activity in r/r acute leukemia with KMT2Ar .

  PublisherDOI

• A patient-derived CRISPR platform reveals selective dependencies in Acute Myeloid Leukemia

  Blood · 2025-11-03

  article

  Abstract Introduction: CRISPR/Cas9 screening is a powerful tool used to delineate genes critical for AML progression and drug resistance. However, most of the studies have been performed in cell lines and PDX models. While cell lines fail to represent the genetic, epigenetic, and phenotypic heterogeneity of primary leukemic cells, PDX models are limited by variable engraftment efficiency, time-consuming processes, and high costs. To overcome these challenges, we pioneered an integrated approach combining bioinformatics and CRISPR/Cas9 screening to uncover genetic drivers and vulnerabilities in AML using patient-derived primary cells in culture. Insights from our study could inform the development of targeted therapies and improve patient outcomes. Methods Custom CRISPR/Cas9 screen targeting 2,440 genes associated with AML, leukemic stemness, and the druggable genome was performed using mononuclear cells (MNCs) isolated from peripheral blood or bone marrow from 9 AML patients. Briefly, the cells were transduced with custom library and cultured for 24-30 days. After an initial few days in suspension, a subset of MNCs from 5 of 9 patients transitioned to an adherent state 5-7 days post-transduction. Both adherent and suspension cells were collected at different time points, sgRNA was quantified and sequenced using the Illumina NovaSeq X Plus. sgRNA abundance was analyzed using the RRA algorithm of the MAGeCK computational tool and genes with significant negative or positive enrichment in each patient was identified by comparing early versus late time points and adherent versus suspension cell fractions. Results In a subset of patient samples, AML cells transitioned from suspension to an adherent phenotype during long-term culture, a state previously associated with increased chemotherapy resistance due to interactions with endothelial niches. Our CRISPR/Cas9 screen revealed that this adherent cell population harbored distinct genetic dependencies, including consistent negative enrichment of EDNRA and SOD1.These genes were selectively essential in the adherent fraction but not in suspension cells, suggesting context-specific vulnerabilities. The identification of these targets offers new opportunities to therapeutically disrupt chemo resistant AML niches, potentially enhancing the efficacy of existing treatments and reducing relapse risk. EDNRA has been implicated in many cancers and in context of AML, it is a downstream target of HOXA9 and MEIS1. Our results indicate that EDNRA knockout inhibits AML cell proliferation and growth, highlighting its potential as a therapeutic target. Furthermore, EDNRA is overexpressed in AML compared to normal cells, and since FDA approved EDNRA inhibitors such as Macitentan, Bosentan, Ambrisentan, and Clazosentan are already being used to treat pulmonary arterial hypertension, this presents a promising opportunity to evaluate these inhibitors as potential chemotherapy-sensitizing agents for high-risk AML.SOD1 plays a critical role in eliminating toxic radicals generated within biological systems and has been associated with poor outcomes in AML. SOD1 has been identified as a synthetic lethal target in PPM1D-mutant leukemia cells, corroborating our findings. TRAPPC9, SUZ12, and ERG were significant genes with negative enrichment when comparing adherent and suspension fractions across 5 patient samples. These genes have a higher expression in primary AML cells compared to normal controls, implying potential roles in disease progression. SDHA was identified as a significant negatively enriched gene in the suspension cell fraction in 4 of 9 patients. It exhibited elevated expression in AML cells compared to controls, and its deficiency has been linked to the development of drug resistance in AML, emphasizing its role in both drug resistance and disease progression. Conclusion This study demonstrates the establishment of a scalable platform for CRISPR screening in primary AML cells for identification of more conserved vulnerabilities that may be exploited therapeutically, with EDNRA as a potential target. Ongoing work includes validating key targets with the goal of advancing therapeutic strategies. Future studies will expand CRISPR screening to a broader set of patient samples with diverse cytogenetic profiles and incorporate CROP-seq technology to perform single-cell CRISPR screens, providing deeper insights into the molecular mechanisms underlying AML progression and relapse.

  PublisherDOI

• Upregulation of POLE and proficient DNA repair are features of CIC::DUX4 sarcomas

  npj Precision Oncology · 2025-06-20 · 1 citations

  articleOpen access1st authorCorresponding

  CIC::DUX4 translocation-positive sarcomas (CDS) are rare, highly proliferative tumors associated with chemotherapy resistance. Without a clear understanding of the molecular pathways driving CDS, no effective treatment regimens have been developed. Here, we identify protection against DNA damage through upregulation of POLE and DNA repair pathways specific to CDS. These data may explain the high proliferation rate and chemotherapy resistance of these tumors and suggest targeted treatment strategies for CDS.

  PublisherOA PDFDOI

• Genomic, transcriptomic, and immunogenomic landscape of over 1300 sarcomas of diverse histology subtypes

  Nature Communications · 2025-05-06 · 7 citations

  articleOpen access

  Given their rarity and diversity, a fundamental understanding of the genomic underpinnings for many sarcoma subtypes is still lacking. To better define the molecular landscape of this group of diseases, we perform matched whole exome sequencing and RNA sequencing on a cohort of 1340 sarcoma tumor specimens. We identify recurrent somatic mutations and observe an increased mutational burden in metastatic vs. primary samples (p < 0.001). We observe frequent copy number alterations including whole genome doubling, with this feature being more common in metastatic tumors (p = 0.026). Estimation of immune cell abundances followed by hierarchical clustering identifies five immune subtypes ranging from low to high and we observe inferior overall survival in immune deplete clusters compared to immune enriched (p < 0.01). Interestingly, GIST predominantly form a distinct “immune intermediate” cluster that is marked by a specific enrichment for NK cells (FDR < 0.01). Sarcoma is a highly heterogeneous disease, which can be caused by a large variety of mutations. Here, the authors utilise multi-omics to characterise a cohort of 1,340 sarcoma tissue specimens to identify key somatic mutations and identify immune subtypes.

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• Systemic mRNA vaccines elicit rapid immune activation in canine brain tumors

  Journal for ImmunoTherapy of Cancer · 2025-11-01

  articleOpen access

  Malignant glioma is considered invariably recalcitrant, thus necessitating development of new therapeutic approaches. Spontaneously arising canine glioma exhibits important molecular and pathological similarities to malignant pediatric glioma, making it an invaluable model for testing novel therapies. We evaluated safety and activity of RNA lipid particle aggregates (LPAs) designed to provoke cancer immunogenicity in 10 dogs with histologically confirmed glioma. Vaccine manufacturing was feasible in all subjects and generally well tolerated. Median survival time was 123 and 155 days in dogs receiving three (Group A) or four (Group B) vaccines, respectively; this was increased from historical reporting of subjects receiving palliative care. Responding animals had a robust cytokine response following infusions. In animals receiving non-specific RNA-LPAs, there was localization of messenger RNA (mRNA) payloads to the brain tumor microenvironment and a rapid shift in immunologic gene signatures consistent with a viral response. These data demonstrate the ability to induce rapid viremic response in the tumor microenvironment following a single peripherally administered mRNA vaccine. Since RNA-LPAs are amenable to repeat boosts, these formulations may overcome challenges of tumor immunosuppression and therapeutic access and are currently under evaluation in first-in-human trials (NCT04573140, NCT06389591).

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Frequent coauthors

• James L. Chen

  Tempus Labs (United States)

  19 shared

• John L. Hays

  The Ohio State University

  18 shared

• Kelsey J. Cook

  Florida College

  17 shared

• Sherri Z. Millis

  15 shared

• Jatinder K. Lamba

  Florida College

  11 shared

• Ming Poi

  Caris Life Sciences (United States)

  10 shared

• Junan Li

  Comprehensive Blood & Cancer Center

  8 shared

• Yan W. Asmann

  8 shared