About

Allison Snyder, MD, is an Assistant Professor of Neurology at the Hospital of the University of Pennsylvania within the Department of Neurology. She completed her undergraduate education with a BA in Chemistry at Bryn Mawr College in 2010 and earned her MD from the University of Rochester School of Medicine and Dentistry in 2014. Her professional focus is on neurology, with a particular emphasis on neurodegenerative diseases and related neurological research. Her work involves advancing understanding of conditions such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, contributing to the scientific community through research on autoimmune responses, disease severity scales, and molecular signatures associated with neurodegeneration.

Research topics

• Biology
• Genetics
• Immunology
• Cancer research
• Cell biology
• Medicine
• Internal medicine
• Neuroscience

Selected publications

• Apoptotic cells promote circulating tumor cell survival and metastasis

  Communications Biology · 2025-07-29 · 5 citations

  articleOpen access

  During tumor progression and especially following cytotoxic therapy, cell death of both tumor and stromal cells is widespread. Despite clinical observations that high levels of apoptotic cells correlate with poorer patient outcomes, the physiological effects of dying cells on tumor progression remain incompletely understood. Here, we report that circulating apoptotic cells robustly enhance tumor cell metastasis to the lungs. Using intravenous metastasis models, we observed that the presence of apoptotic cells, but not cells dying by other mechanisms, supports circulating tumor cell (CTC) survival following arrest in the lung vasculature. Apoptotic cells promote CTC survival by recruiting platelets to the forming metastatic niche. Apoptotic cells externalize the phospholipid phosphatidylserine to the outer leaflet of the plasma membrane, which we found increased the activity of the coagulation initiator Tissue Factor, thereby triggering the formation of platelet clots that protect proximal CTCs. Inhibiting the ability of apoptotic cells to induce coagulation by knocking out Tissue Factor, blocking phosphatidylserine, or administering the anticoagulant heparin abrogated the pro-metastatic effect of apoptotic cells. This work demonstrates a previously unappreciated role for apoptotic cells in facilitating metastasis by establishing CTC-supportive emboli, and suggests points of intervention that may reduce the pro-metastatic effect of apoptotic cells.

  PublisherDOI

• Defining RIPK3-dependent tumor immunosurveillance functions of microglia in brain metastasis 3337

  The Journal of Immunology · 2025-11-01

  articleOpen access1st authorCorresponding

  Abstract Description Metastatic breast cancer accounts for the majority of breast cancer-related deaths. The central nervous system (CNS) is a common site of metastasis that is associated with particularly poor survival prognoses. Metastasis is initiated by disseminated tumor cells (DTCs) that exit the primary tumor, seed distal tissues, evade immunosurveillance, and assume a dormant phenotype before eventually proliferating to form clinically apparent metastases. Notably, the molecular mechanisms underlying effective immunosurveillance of DTCs by CNS-resident macrophages termed microglia remain poorly understood. To investigate signaling pathways involved in microglial activation early on during CNS metastasis, we transcriptionally profiled tumor-targeting vs. non-targeting microglia sorted from the brains of immunocompetent mice seeded with dormant D2.OR mammary carcinoma cells. We found that tumor-targeting microglia exhibit a beneficial inflammatory phenotype characterized by upregulation of receptor-interacting protein kinase 3 (RIPK3) and RIPK3-dependent target genes, which are known to drive protective inflammatory signaling in numerous cell types. Our next steps will determine how RIPK3 activation influences microglial functions in the context of microglial phagocytosis of DTCs, potentially revealing novel therapeutic targets that could be leveraged to restore microglial immunosurveillance and prevent the outgrowth of DTCs into lethal CNS metastases. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

  PublisherOA PDFDOI

• Apoptotic cells promote circulating tumor cell survival and metastasis

  bioRxiv (Cold Spring Harbor Laboratory) · 2024

  • Cancer research
  • Biology
  • Medicine

  During tumor progression and especially following cytotoxic therapy, cell death of both tumor and stromal cells is widespread. Despite clinical observations that high levels of apoptotic cells correlate with poorer patient outcomes, the physiological effects of dying cells on tumor progression remain incompletely understood. Here, we report that circulating apoptotic cells robustly enhance tumor cell metastasis to the lungs. Using intravenous metastasis models, we observed that the presence of apoptotic cells, but not cells dying by other mechanisms, supports circulating tumor cell (CTC) survival following arrest in the lung vasculature. Apoptotic cells promote CTC survival by recruiting platelets to the forming metastatic niche. Apoptotic cells externalize the phospholipid phosphatidylserine to the outer leaflet of the plasma membrane, which we found increased the activity of the coagulation initiator Tissue Factor, thereby triggering the formation of platelet clots that protect proximal CTCs. Inhibiting the ability of apoptotic cells to induce coagulation by knocking out Tissue Factor, blocking phosphatidylserine, or administering the anticoagulant heparin abrogated the pro-metastatic effect of apoptotic cells. This work demonstrates a previously unappreciated role for apoptotic cells in facilitating metastasis by establishing CTC-supportive emboli, and suggests points of intervention that may reduce the pro-metastatic effect of apoptotic cells.

  PublisherOA PDFDOI

• Immune evasion of dormant disseminated tumor cells is due to their scarcity and can be overcome by T cell immunotherapies

  Cancer Cell · 2024 · 71 citations

  • Immunology
  • Biology
  • Cancer research
  PublisherOA PDFDOI

• The Antisocial Network: Cross Talk Between Cell Death Programs in Host Defense

  Annual Review of Immunology · 2021 · 128 citations

  1st authorCorresponding
  • Biology
  • Cell biology
  • Immunology

  Nearly all animal cells contain proteins evolved to trigger the destruction of the cell in which they reside. The activation of these proteins occurs via sequential programs, and much effort has been expended in delineating the molecular mechanisms underlying the resulting processes of programmed cell death (PCD). These efforts have led to the definition of apoptosis as a form of nonimmunogenic PCD that is required for normal development and tissue homeostasis, and of pyroptosis and necroptosis as forms of PCD initiated by pathogen infection that are associated with inflammation and immune activation. While this paradigm has served the field well, numerous recent studies have highlighted cross talk between these programs, challenging the idea that apoptosis, pyroptosis, and necroptosis are linear pathways with defined immunological outputs. Here, we discuss the emerging idea of cell death as a signaling network, considering connections between cell death pathways both as we observe them now and in their evolutionary origins. We also discuss the engagement and subversion of cell death pathways by pathogens, as well as the key immunological outcomes of these processes.

  PublisherOA PDFDOI

• Non-canonical autophagy in dendritic cells restricts cross-presentation and anti-tumor immunity

  bioRxiv (Cold Spring Harbor Laboratory) · 2019-10-02 · 3 citations

  preprintOpen access

  Summary Major Histocompatibility Complex I (MHC-I) molecules classically present peptides derived from endogenous antigens, but exogenous antigens can also gain access to the MHC-I machinery in dendritic cells (DCs), which can activate antigen-specific CD8 + T cells. This process, termed cross-presentation, can be triggered by the uptake of dying autologous cells, including tumor cells, by DCs. The molecular mechanisms that underlie efficient cross-presentation remain largely uncharacterized, and an improved understanding of these mechanisms might reveal novel strategies for anti-tumor therapies. Rubicon (RUBCN) is a molecule required for LC3-associated phagocytosis (LAP), but dispensable for canonical autophagy, and mice lacking this protein develop an autoimmune inflammatory pathology with age. Here, we demonstrate that Rubcn -deficient DCs have increased retention of engulfed cellular cargo in immature phagosomes resulting in increased phagosome-to-cytosol escape and antigen access to proteasome-mediated degradation. As a result, mice selectively lacking Rubcn in DCs mount stronger tumor antigen-specific CD8 + T cell responses and exhibit decreased tumor burden compared to wild type littermates. These findings identify LAP as a key regulator of cross-presentation and suggest that targeting RUBCN might represent a novel strategy for anti-tumor therapy.

  PublisherOA PDFDOI

• The Nucleotide Sensor ZBP1 and Kinase RIPK3 Induce the Enzyme IRG1 to Promote an Antiviral Metabolic State in Neurons

  Immunity · 2019-01-01 · 312 citations

  article
  PublisherDOI

• Myeloid responders to programmed cell death

  The Journal of Immunology · 2019-05-01

  article

  Abstract Necroptosis is a programmed form of cell death that more efficiently primes CD8 T cell responses when compared to apoptosis. This efficiency has been associated with key signaling effects downstream of RIP kinase activation. However, mechanisms whereby these cell-intrinsic signals translate into enhanced adaptive immunity remain unclear. We hypothesized that dying cells would attract and engage with distinct myeloid populations based on which cell death pathway is active, and that these interactions would determine T cell priming ability. By introducing dying cells loaded with non-degradable ‘antigen’ into naïve mice, we have tracked myeloid cells that interacted with necroptotic or apoptotic cell debris up to 72 hrs after injection, corresponding to early detectable differences in T cell priming. Migratory dendritic cells equivalently took up antigen following either necroptosis or apoptosis. However, necroptosis resulted in a greater number of antigen positive macrophages and lymph node resident dendritic cells. Understanding how the immune system recognizes and responds to distinct forms of cell death will benefit investigations into cytotoxic and immunotherapeutic drug combinations.

  PublisherDOI

• Potentiation of anti-tumor immunity by RIPK1/RIPK3-dependent necroptosis

  ResearchWorks at the University of Washington (University of Washington) · 2019-01-01

  dissertationOpen access1st authorCorresponding

  Thesis (Ph.D.)--University of Washington, 2019

  Publisher

• STING is required for host defense against neuropathological West Nile virus infection

  PLoS Pathogens · 2019-08-15 · 46 citations

  articleOpen access

  West Nile Virus (WNV), an emerging and re-emerging RNA virus, is the leading source of arboviral encephalitic morbidity and mortality in the United States. WNV infections are acutely controlled by innate immunity in peripheral tissues outside of the central nervous system (CNS) but WNV can evade the actions of interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, and death. Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. We evaluated the role of STING in host defense to control WNV infection and pathology in a murine model of infection. When challenged with WNV, STING knock out (-/-) mice displayed increased morbidity and mortality compared to wild type (WT) mice. Virologic analysis and assessment of STING activation revealed that STING signaling was not required for control of WNV in the spleen nor was WNV sufficient to mediate canonical STING activation in vitro. However, STING-/- mice exhibited a clear trend of increased viral load and virus dissemination in the CNS. We found that STING-/- mice exhibited increased and prolonged neurological signs compared to WT mice. Pathological examination revealed increased lesions, mononuclear cellular infiltration and neuronal death in the CNS of STING-/- mice, with sustained pathology after viral clearance. We found that STING was required in bone marrow derived macrophages for early control of WNV replication and innate immune activation. In vivo, STING-/- mice developed an aberrant T cell response in both the spleen and brain during WNV infection that linked with increased and sustained CNS pathology compared to WT mice. Our findings demonstrate that STING plays a critical role in immune programming for the control of neurotropic WNV infection and CNS disease.

  PublisherOA PDFDOI

Frequent coauthors

• Andrew Oberst

  17 shared

• Michael Gale

  University of Washington

  8 shared

• Jennifer Martinez

  St. Jude Children's Research Hospital

  6 shared

• Brian P. Daniels

  Rutgers, The State University of New Jersey

  6 shared

• Igor E. Brodsky

  University of Pennsylvania

  6 shared

• Kathryn McGuckin Wuertz

  Armed Forces Research Institute of Medical Science

  6 shared

• Naomi H. Philip

  Yale University

  5 shared

• Meghan A. Wynosky-Dolfi

  University of Pennsylvania

  5 shared

Education

• B.A., Chemistry

  Bryn Mawr College

  2010

• M.D.

  University of Rochester School of Medicine and Dentistry

  2014