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Paul Hess

Paul Hess

Verified

North Carolina State University · Clinical Sciences

Active 1921–2026

h-index28
Citations3.2k
Papers10017 last 5y
Funding$490k
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About

Sarah Ho is the Director of Student Engagement at the College of Veterinary Medicine at NC State University. She is involved in fostering a lively campus community that emphasizes student achievement, well-being, and extracurricular development. Her role includes supporting students through various programs and initiatives aimed at enriching their academic and personal experiences, including study abroad opportunities, research projects, and community building activities. Her focus is on creating a welcoming, collaborative environment that nurtures inquisitive, empathetic, and ethically driven future veterinarians.

Research topics

  • Biology
  • Genetics
  • Computational biology
  • Internal medicine
  • Medicine
  • Ecology
  • Cancer research
  • Oncology
  • Evolutionary biology
  • Surgery
  • Pathology

Selected publications

  • A Manifold-Based Measure of Transcriptional Entropy for Quantifying Aging in Single Cells

    bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-24

    articleOpen access

    Characterizing cellular aging is essential for understanding age-related diseases. While tissue-level studies reveal broad age-associated changes, they often reflect compositional shifts rather than cell-level reprogramming. The cellular damage hypothesis posits that aging involves the accumulation of DNA, chromatin, and other damage across molecular layers, increasing transcriptional entropy. Existing supervised methods for detecting cellular senescence yield cell type-specific senescence scores but rely on labeled data and lack generalizability. Here, we introduce a first-principles framework for quantifying transcriptional entropy in single cells as each cell's deviation from a transcriptomic manifold, capturing breakdown of transcriptional coordination. This unsupervised approach identifies aging-affected cell types and distinguishes two cellular aging mechanisms: loss of expression precision and activation of stress-response pathways in high entropy cells. Applied to Tabula Muris Senis and SenNet Multiome datasets, transcriptional entropy correlates with chromatin-based mitotic age and highlights regenerative tissue compartments as most affected by aging.

  • Phase 1 Dose Escalation of Single‐Agent Mechlorethamine in Dogs With Lymphoma

    Veterinary and Comparative Oncology · 2025-11-06

    articleOpen access

    ABSTRACT Mechlorethamine is commonly prescribed to dogs at 3 mg/m 2 . The minimal toxicity observed indicates that higher doses of mechlorethamine are likely tolerable. The primary objective of this study was to determine the maximally tolerated dose (MTD) of mechlorethamine in dogs with lymphoma. The secondary objectives were to describe the toxicity associated with increased mechlorethamine dose and to evaluate the response in treatment‐naive dogs treated at the MTD. Dogs with histologically or cytologically confirmed intermediate to large cell lymphoma were enrolled using a 3 + 3 dose escalation model, starting at 3.5 mg/m 2 mechlorethamine IV, with planned dose increments of 10%–15% between cohorts. Adverse events were monitored per VCOG‐CTCAE guidelines. Dose‐limiting toxicity was defined as any grade 3 or 4 adverse event. Thirty dogs were enrolled across nine cohorts. Two dogs treated at 12.3 mg/m 2 developed asymptomatic grade 4 neutropenia 7 days after mechlorethamine administration, leading to a MTD of 10.7 mg/m 2 . Low‐grade vomiting, diarrhoea, and inappetence were recorded amongst dogs at several dose levels and were managed with supportive medications. Six of 10 chemotherapy‐naïve dogs treated at the MTD, representing a separate cohort, showed partial responses (PR) 7 days post‐administration; however, PR was also observed at dosages ranging from 3.5 to 12.3 mg/m 2 in pre‐treated patients. A higher dose of mechlorethamine than previously reported can be safely administered as a single agent to dogs. Increasing the dose of mechlorethamine in combination therapies might offer greater therapeutic benefits.

  • Cancer subclone detection based on DNA copy number in single-cell and spatial omic sequencing data

    Nature Methods · 2025-09-01 · 6 citations

    article
  • Optimizing canine T cell activation, expansion, and transduction

    PLoS ONE · 2025-09-11 · 1 citations

    articleOpen accessCorresponding

    Dogs are becoming an important model for human cancers, and successfully troubleshooting issues with genetically modified T cell immunotherapy for round cell and solid neoplasms in dogs provides a unique opportunity to improve efficacy, safety, and affordability for humans as well. Unfortunately, T cell activation in dogs for optimal viral transduction has not been determined, restricting advancements in canine T cell immunotherapy. Two αCD3 and two αCD28 antibody clones for canine T cell stimulation have been described in the literature, but no studies have been undertaken to evaluate which αCD3/αCD28 combination is most effective, nor has anyone directly compared the efficacy of the two most popular antibody presentation strategies: antibody-coated plates and antibody-conjugated beads. In evaluating the effects of plate- or bead-bound αCD3 stimulation alone versus αCD3/αCD28 in combination, we tested 12 possible antibody stimulation strategies in addition to evaluating two largely unexplored mitogens in canine T cell transduction, phorbol myristate acetate (PMA) with ionomycin and concanavalin A (ConA). We investigated the impact of these stimulation strategies on canine T cell activation, expansion, and transduction. For stimulation strategies producing the best results, we also examined how each strategy affected the proportions of CD4/CD8 T cell subsets and regulatory T cell (Treg) prevalence. We determined that, in general, plate-bound antibodies were far superior to bead-bound antibodies for canine T cell stimulation, and that plate-bound αCD3 clone CA17.6F9 in combination with αCD28 clone 5B8 or the mitogen PMA with ionomycin produced better activation and expansion profiles, better transduction, and more desirable T cell subsets that are more likely to improve patient outcomes in dogs suffering from round cell and solid tumors.

  • Optimizing canine T cell activation, expansion, and transduction

    bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-30

    preprintOpen access

    Abstract Dogs are becoming an important model for human cancers, and successfully troubleshooting issues with genetically modified T cell immunotherapy for round cell and solid neoplasms in dogs provides a unique opportunity to improve efficacy, safety, and affordability for humans as well. Unfortunately, T cell activation in dogs for optimal viral transduction has not been determined, restricting advancements in canine T cell immunotherapy. Two αCD3 and two αCD28 antibody clones for canine T cell stimulation have been described in the literature, but no studies have been undertaken to evaluate which αCD3/αCD28 combination is most effective, nor has anyone directly compared the efficacy of the two most popular antibody presentation strategies: antibody-coated plates and antibody-conjugated beads. In evaluating the effects of plate- or bead-bound αCD3 stimulation alone versus αCD3/αCD28 in combination, we tested 12 possible antibody stimulation strategies in addition to evaluating two largely unexplored mitogens in canine T cell transduction, phorbol myristate acetate (PMA) with ionomycin and concanavalin A (ConA). We investigated the impact of these stimulation strategies on canine T cell activation, expansion, and transduction. For stimulation strategies producing the best results, we also examined how each strategy affected the proportions of CD4/CD8 T cell subsets and regulatory T cell (T reg ) prevalence. We determined that, in general, plate-bound antibodies were far superior to bead-bound antibodies for canine T cell stimulation, and that plate-bound αCD3 clone CA17.6F9 in combination with αCD28 clone 5B8 or the mitogen PMA with ionomycin produced better activation and expansion profiles, better transduction, and more desirable T cell subsets that are more likely to improve patient outcomes in dogs suffering from round cell and solid tumors.

  • Immunological responses and clinical outcomes in dogs with osteosarcoma receiving standard therapy and a Listeria vaccine expressing HER2

    Molecular Therapy · 2025-02-15 · 9 citations

    articleOpen access
  • 855 Interim results from a comparative oncology safety study evaluating intravesical chitosan/interleukin-12 immunotherapy in client-owned dogs with invasive urothelial carcinoma

    Regular and Young Investigator Award Abstracts · 2025-11-01

    articleOpen access

    Table 1 Adverse events following intravesical chitosan/interleukin-12 immunotherapy in client-owned dogs with invasive urothelial carcinoma

  • Winning Poster: Insertion and maintenance of peripherally inserted central catheter for a pediatric epidermolysis bullosa patient: A case report

    Journal of Pediatric Nursing · 2025-09-01

    article
  • Assessing mutation-origin neopeptide prediction tools in canine cancer using the model MHC class Ia allomorphs, DLA-88*508:01 and *034:01 9302

    The Journal of Immunology · 2025-11-01

    articleOpen access1st authorCorresponding

    Abstract Description Pet dogs with osteosarcoma and bladder cancer are valid models for immunotherapy development. Lacking are any methodologic studies for finding canine neoantigen CTL. Our hypothesis is that actionable, mutant neopeptides are contained in canine cancer immunopeptidomes. We used standard in silico analyses and pMHC surface stabilization (pMHC-SS) assays to validate tools to identify neopeptides and cognate CTL. Two class Ia (DLA-88) allomorphs, prevalent in cancer-prone breeds and used to train NetMHCpan, were studied. Binding scores of viral MHC-associated peptides (MAPs) compared to NetMHCpan outputs established the best correlated parameter (BA score) and predictive cut-off value. In tests of predictive power, most putative binding neopeptides, generated from a published mammary tumor mutanome, bound in the flow assay. NetCHOP provided added benefits, despite overlapping c-terminal preferences of the allomorphs and canine proteasome. Rigor of the optimized tools to predict mutant MAPs for a model canine sarcoma was assessed comparing exome, transcriptome, and mass spectrometry data. Twenty-two mutant MAPs were predicted; none were found. The pMHC-SS assay was also used to evaluate peptide exchange in DLA-88 for custom neoepitope tetramers. Motif-matching dipeptides and low-affinity leaving peptides facilitated swapping (100% efficiency). Conventional neopeptide prediction methods are helpful in dogs. The rarity of mutant MAPs is a challenge to immunotherapy in both species. Funding Sources NIH U01CA272258 Topic Categories Veterinary and Comparative Immunology (VET)

  • Elevated serum gamma‐glutamyltransferase activity and immunohistochemistry in two dogs with renal carcinoma

    Veterinary Clinical Pathology · 2024-07-26

    articleOpen access

    During a 3-year time period, a 15-year-old male castrated Terrier mix (dog 1) and a 6-year-old female spayed Labrador Retriever (dog 2) presented to the North Carolina State Veterinary Hospital with similar blood work abnormalities and no significant physical examination findings. A CBC, chemistry panel, and urinalysis performed on both dogs were relatively unremarkable, other than a marked increase in serum gamma-glutamyltransferase (GGT) activity. Through imaging, both patients were diagnosed with a renal mass, and histopathology of both masses revealed a carcinoma. Immunohistochemical staining of the renal mass in both dog 1 and dog 2 were intensely positive for GGT. Dog 1 had the affected kidney removed, which normalized the GGT value. Dog 2 was euthanized, and metastasis to the lung was noted upon postmortem examination. There have been limited case studies documenting an elevation in serum GGT in dogs diagnosed with renal carcinoma. While renal carcinoma is uncommon in dogs, it is an important differential to keep in mind when there is a marked increase in serum GGT without accompanying increases in other measured liver enzymes. In addition, serum GGT can serve as a helpful biomarker for disease resolution and recurrence, as surgical removal of the renal mass (dog 1) led to the resolution of the elevated serum GGT. To our knowledge, this is the first report demonstrating IHC staining for GGT in a canine renal carcinoma.

Recent grants

Frequent coauthors

  • Mark L. Kahn

    California University of Pennsylvania

    23 shared
  • Adam Buntzman

    19 shared
  • Jennifer C. Holmes

    North Carolina State University

    17 shared
  • Grace E. Kissling

    16 shared
  • Jennifer A. Neel

    16 shared
  • Carol B. Grindem

    16 shared
  • Ellen Young

    14 shared
  • Jeffrey A. Frelinger

    University of North Carolina Health Care

    13 shared

Awards & honors

  • Regular and Young Investigator Award Abstracts (2025)
  • Morris Animal Foundation
  • Resume-aware match score
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  • AI-drafted outreach

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