About

Greg Nolan is the Director of Academic Advising at the College of the Liberal Arts at Penn State University. His background includes studying South Africa extensively, having taken several classes on the country, studying Nelson Mandela, traveling there, and visiting Robben Island. These experiences have significantly shaped his approach to working with students. Nolan's personal interests include college memories of studying abroad in South Africa and supporting collegiate hockey. He enjoys spending time at the ponds at the Hintz Family Alumni Center with his husband and twin toddlers. His favorite colors are orange, pink, and purple, and he prefers the Monkey Business flavor at Berkey Creamery.

Research topics

• Biology
• Computational biology
• Genetics
• Medicine
• Computer Science
• Cell biology
• Bioinformatics
• Evolutionary biology
• Pathology
• Internal medicine
• Artificial Intelligence
• World Wide Web
• Endocrinology
• Risk analysis (engineering)
• Data science
• Immunology
• Anatomy

Selected publications

• CD39 ⁺ CD49a ⁺ CD103 ⁺ cytotoxic tissue-resident natural killer cells infiltrate and control solid epithelial tumor growth in mice

  Science Translational Medicine · 2026-05-06

  article

  Human tissue-resident natural killer (NK) cells (trNK cells), broadly defined by markers of tissue residency, such as CD49a [ integrin α 1 ( ITGA1 )] and CD103 [ integrin α E ( ITGAE )], are increasingly recognized for their immunoregulatory role in host control of infection, malignancy, and autoimmunity. Although the importance of transforming growth factor–β in trNK cell differentiation has been demonstrated, the context in which the differentiation of CD49a + CD103 + trNK cells occurs can result in either an immunosuppressive phenotype (e.g., decidual NK cells) or a highly cytotoxic one (e.g., some tumor trNK subsets). To understand this dichotomy better, we used a multiomic approach to molecularly characterize these cells. We identified a cytotoxic trNK (ctrNK) cell population, characterized by the expression of CD39. These ctrNK cells exhibited superior cytolytic activity against tumor target cells, enhanced capacity to infiltrate into solid tumor microenvironments, and augmented ability to control solid tumor growth in vivo compared with conventionally activated peripheral NK cells. This heightened cytolytic and infiltrative functionality of ctrNK cells appeared to be conferred, in part, by the expression of CD103 and by avidity for tumor targets. Because adoptive immune cell therapy of solid tumor malignancies has been challenged by the inefficiency of ex vivo expanded immune cells to infiltrate immunosuppressive solid tumor microenvironments, our observations that ctrNK cells can be differentiated and expanded ex vivo present a potential platform for adoptive cell therapy of solid tumor malignancies.

  PublisherDOI

• Epstein-Barr virus orchestrates spatial reorganization and immunomodulation in the classic Hodgkin lymphoma tumor microenvironment

  Cell Reports Medicine · 2026-03-31

  articleOpen access

  Classic Hodgkin lymphoma (cHL) is composed of rare malignant Hodgkin and Reed-Sternberg (HRS) cells within a T-cell-rich tumor microenvironment (TME). Epstein-Barr virus (EBV) is present in ∼25% of cases, but its contribution to pathogenesis and immunomodulation remains unclear due to technical barriers. Using complementary spatial proteomics and transcriptomics across multi-institutional cohorts, we systematically map key EBV-linked TME reorganization. EBV-positive cHL exhibits distinct immunological features, including memory CD8 T cell enrichment, heightened T cell dysfunction spatially correlated with HRS proximity, and terminally exhausted T cell signatures contrasting with progenitor-exhausted patterns in EBV-negative disease. We identify EBV-encoded LMP1 as a factor in T cell dysfunction through enhanced HRS:CD8 interactions, and its expression level correlates with T cell terminal exhaustion in a distance-dependent manner. This spatial framework dissects viral-mediated immune evasion in the cHL TME, highlighting potential therapeutic opportunities to target virus-associated T cell dysfunction for precision immunotherapy in virus-associated malignancies.

  PublisherDOI

• Immune Checkpoint Therapy Drives Maturation of a Cellular Neighborhood Nucleated by T Cell-APC Triads Enabling Spatially Compartmentalized Tumor Immunity

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-12

  articleOpen access

  Spatially organized immune hubs of T cells and antigen-presenting cells (APCs) have been linked to immune checkpoint therapy (ICT) efficacy, yet the mechanisms underlying their function remain unclear. Using CODEX multiplex imaging, we longitudinally characterized the dynamic evolution of intratumoral cellular neighborhoods (CN) defined by triad interactions of CD4 and CD8 T cells with two distinct myeloid APC populations: cDC1s and IFN-gamma-activated macrophages. We termed this CN the immunity-promoting CN (IP-CN) and tracked its progressive development during tumor rejection induced by anti-CTLA-4/anti-PD-1 therapy. A coordinated IFN-gamma; and TNF-alpha signaling signature accompanied the IP-CN assembly. Over time, the IP-CN underwent functional maturation, forming specialized sub-neighborhoods that compartmentalized proliferating T cells at the tumor periphery versus cytotoxic T effector cells interacting with tumor cell targets. Our findings reveal a spatiotemporal mechanism by which the IP-CN sustains and amplifies cytotoxic T cell responses, demonstrating how T cell-APC neighborhoods orchestrate tumor immunity.

  PublisherOA PDFDOI

• Author Reply to Peer Reviews of Natural Killer Cell Receptor Signaling and Activation Depend on Cell Cycle Stages

  2026-01-08

  peer-review
  PublisherDOI

• Lymph node colonization induces tissue remodeling via immunosuppressive fibroblast-myeloid cell niches supporting metastatic tolerance

  Cancer Cell · 2026-01-29 · 3 citations

  articleOpen accessSenior author

  Lymph node (LN) colonization in cancer is linked to poor prognosis. Evidence suggests that LN colonization induces systemic immunosuppression, facilitating distant metastasis. We investigated LN-mediated immunosuppression in patients with head-and-neck cancer using spatial proteomics, spatial transcriptomics, and an in vivo model of melanoma LN metastasis. Both primary tumors and paired LNs of nodal-positive patients exhibit enhanced interferon-γ signaling and an enrichment of immunosuppressive myeloid cells and cancer-associated fibroblasts (CAFs). The spatial intersection of these myeloid-CAF-enriched niches with perifollicular T cell zones and LN follicles is linked to enhanced T cell dysfunction and Treg activation therein, thereby driving architectural LN remodeling. These immune suppressive changes extend to adjacent non-tumor-involved LN regions and nearby tumor-free LNs, but were not detected in LNs of non-cancer patients, reflecting a systemic effect that compromises anti-tumor immunity beyond the tumor-involved LN. Hence, our findings establish LN colonization as an active driver of systemic immunosuppression, facilitating metastatic progression.

  PublisherDOI

• Estimating time since influenza virus exposure using single-cell proteomic data

  Frontiers in Immunology · 2026-03-19

  articleOpen access

  Introduction: Determining when the onset of a respiratory infection occurred is important for effective clinical management and can aid in mapping transmission events. However, current diagnostic assays report only pathogen detection status and do not provide any information about the timing of infection, in part because of the lack of biomarkers that inform time since exposure. Methods: To address this gap, we developed immune-based predictive models of infection timing and shedding status using data from a controlled human challenge with influenza A/California/2009 (H1N1), in which major immune cell subsets were longitudinally profiled across multiple time points before and after viral challenge using 42-marker mass cytometry panels. Random forest machine learning models were trained to address two predictive objectives: (1) distinguishing virus shedders from non-shedders and (2) estimating days post-infection challenge (DPC) from immune profiles. Model performance was evaluated within the primary challenge cohort and independently validated using data from a separate controlled human influenza challenge study using the same virus. Results: Our analysis revealed that single-cell immune population dynamics alone encode a robust and reproducible temporal structure following influenza infection, enabling accurate estimation of virus exposure timing. Discussion: These findings provide foundational insight into host immune responses during influenza infection and represent an early step toward a future class of immune-based diagnostics that could extend beyond pathogen detection to inform infection timing and the duration of periods associated with contagiousness.

  PublisherOA PDFDOI

• Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma

  Nature Cancer · 2026-03-25

  articleOpen access

  Lymph node (LN) function requires the organization of cells into higher-order spatial units. However, the principles governing LN architecture in health and disease remain poorly understood. Here, we used single-cell and spatial mapping to investigate the mechanisms directing immune cell organization in human LNs and its disruption in architecturally distinct lymphoma entities: indolent follicular lymphoma (FL) and aggressive diffuse large B cell lymphoma (DLBCL). Our data substantiate the central role of LN-resident stromal cells in chemokine-driven lymphocyte zonation and reveal an inflammatory feedback loop fueled by tumor-reactive T cells that triggers stromal remodeling, progressive loss of homeostatic chemokine gradients, and tissue disorganization from a non-malignant state to FL and DLBCL. Loss of homeostatic chemokines was associated with adverse patient survival, identifying the underlying architectural rearrangement as a key event during lymphomagenesis. Collectively, our results highlight the principles of LN organization and suggest how lymphoma-induced microenvironmental reprogramming drives the loss of tissue organization.

  PublisherDOI

• Comparative single-cell immune responses in peripheral blood and lymph node of immunized SARS-CoV-2 challenged infant rhesus macaques

  UNC Libraries · 2025-09-25

  articleOpen access

  A better understanding of post-exposure immune responses in vaccinated individuals, particularly infants, is needed. Using a rhesus macaque model, we compared recipients of mRNA- or protein-based SARS-CoV-2 vaccines administered in infancy with unvaccinated controls 7 days post-SARS-CoV-2 virus challenge. Mass cytometry profiling of peripheral blood mononuclear cells and dissociated mediastinal lymph node cells at 7 days post-challenge revealed tissue-specific differences between groups, representing a snapshot of immune activity at this point. Vaccinated animals showed lower frequencies of activated CD8+ T cells in blood and lower levels of monocyte and B cell subsets in lymph nodes, aligning with lower viral loads and milder pathology. Plasmacytoid dendritic cells—commonly depleted in circulation during severe human COVID-19—were preserved in the blood of vaccinated groups. Ex vivo stimulation demonstrated heightened inflammatory cell signaling from unvaccinated rhesus macaques, correlating with worse clinical outcomes. These findings enhance our understanding of a critical nonhuman primate model and underscore the utility of single-cell, tissue-level analyses in evaluating next-generation pediatric SARS-CoV-2 vaccine strategies.

  PublisherDOI

• Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation

  Immunity · 2025-09-13 · 7 citations

  articleOpen access

  T cell dysregulation, and mast cell enrichment. We identified key immune-epithelial interactions in tissue remodeling, particularly involving basal progenitor and tuft cells. A distinct basal cell trajectory was implicated in nasal polyp formation. Orthogonal validation with spatial transcriptomics from >100 individuals with CRS revealed conserved tissue remodeling features. Our study provides insights into CRS pathophysiology, highlighting immune-epithelial interactions as potential therapeutic targets in chronic inflammation, also serving as a resource for dissecting immune disease mechanisms.

  PublisherDOI

• Fluid-Squid: DIY Multiplexed Imaging of Cells and Tissues

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-10

  preprintOpen access

  Recent advances in multiplexed single-cell characterization have revolutionized our insight into cell biology, but many available technologies remain limited by high costs or a lack of customizability. To address these challenges, we developed Fluid-Squid, a cost-effective, quantitative imaging platform that integrates automated fluidics to support customizable, do-it-yourself multiplexed imaging workflows. Using Fluid-Squid, we successfully imaged fresh frozen human intestinal tissues with a 36-plex oligonucleotide-barcoded antibody panel and further demonstrated the feasibility of lyophilizing such multiplexed panels. We also adapted existing multiplexed imaging workflows to characterize individual cells to identify immune cell populations, phenotype, and antigen-specific cells from mouse splenocytes and human peripheral blood mononuclear cells (PBMCs) with a 39-antibody panel. To further expand its utility, we developed a barcoding strategy that allows for the pooling and simultaneous staining of multiple samples, reducing time, costs, and batch effects in single-cell experiments. This approach facilitated rapid titration to optimize antibody concentrations and assess the impact of various blood preparation methods on cell type retention. Overall, our work provides a new open-source framework for automated fluidics and microscopy in a flexible, cost-effective platform, empowering adaptable multiplexed characterization of both single cells and tissues.

  PublisherOA PDFDOI

Recent grants

• Administrative Core

  NIH · $92.6M · 2003–2029

• NIH Grant U54CA143907

  NIH · $5.8M · 2016

• NIH Grant P01AI041520

  NIH · $4.5M · 2001

• Balanced signaling cues to guide cell transitions in the blood lineage continuum

  NIH · $2.9M · 2015–2021

• NIH Grant R21DK073928

  NIH · $422k · 2007

Frequent coauthors

• Sean C. Bendall

  168 shared

• Wendy J. Fantl

  127 shared

• Nikolay Samusik

  114 shared

• Matthew H. Spitzer

  Parker Institute for Cancer Immunotherapy

  111 shared

• Yury Goltsev

  105 shared

• Sizun Jiang

  Broad Institute

  100 shared

• Erin F. Simonds

  89 shared

• Kara L. Davis

  Stanford University

  87 shared

Education

• Post-Graduate Research, Genetics

  Stanford University

  1990

• Grade Student , Genetics

  Stanford University

  1989

• B.S. Biology, specialization in Genetics , Genetics

  Cornell University

  1983