About

Susan R. Schwab, PhD, is a professor in the Department of Cell Biology and the Department of Pathology at NYU Grossman School of Medicine. Her research focuses on lymphocyte migration, particularly on the mechanisms that determine how long a lymphocyte remains in a given location, the establishment of gradients that direct immune cell migration, and the differences in trafficking requirements between normal and leukemic T cells. Her work has established the role of sphingosine 1-phosphate (S1P) gradients in guiding T cells out of lymphoid organs and has identified key cells and enzymes involved in controlling these gradients. She has developed novel tools to map S1P gradients and aims to understand their regulation during immune responses, with the goal of translating this knowledge into improved therapies for inflammatory diseases.

Research topics

• Biology
• Immunology
• Cell biology
• Medicine
• Neuroscience
• Pathology
• Internal medicine
• Chemistry
• Cancer research

Selected publications

• BSLD-03 T CELL ACUTE LYMPHOBLASTIC LEUKEMIA ENTRY INTO THE CENTRAL NERVOUS SYSTEM

  Neuro-Oncology Advances · 2025-08-01

  articleOpen accessSenior author

  Abstract Acute lymphoblastic leukemia (ALL) is the most prevalent malignancy in children. Due to ALL’s tendency to invade the central nervous system (CNS), specifically the membrane layers surrounding the brain and spinal cord known as the meninges, standard-of-care treatment includes intrathecal therapy. This can be detrimental to normal neural development, and is not always effective. Among the different subtypes of ALL, our lab focuses on T cell ALL (T-ALL) because it has the highest propensity for aggressive CNS disease. It remains unclear why T-ALL is attracted to the nutrient-limited meninges. Understanding how leukemia cells infiltrate the CNS is essential to furthering the development of targeted therapies for this disease. Recently, B cell ALL (B-ALL) has been shown entering the CNS via skull bridging channels. In addition, effector T cells breach the blood-brain barrier during inflammation. Both of these entry routes require integrins. This raises the question of whether T-ALL uses one of these routes to infiltrate the CNS, and if integrins are required. Using multi-photon and confocal microscopy to visualize the skull and meninges of mice that received Notch1-driven murine T-ALL, we are characterizing a major route of T-ALL entry into the CNS. At early timepoints of disease, we find T-ALL primarily in small clusters in an area of the meninges that lies beneath the occipital region of the skull. Since this is a concentrated area of skull bone marrow, we are investigating whether the T-ALL clusters reflect cells that have recently entered the CNS via bridging channels. We plan to examine what dictates the choice of channels used, and study the directionality of T-ALL movement. In addition, we are using CRISPR to examine the effect of integrin loss on T-ALL CNS infiltration. This work will advance the development of targeted therapeutics for limiting CNS dissemination of T-ALL.

  PublisherOA PDFDOI

• BSLD-04 PROLIFERATION AND SURVIVAL OF T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN THE CENTRAL NERVOUS SYSTEM

  Neuro-Oncology Advances · 2025-08-01

  articleOpen accessSenior author

  Abstract T cell acute lymphoblastic leukemia (T-ALL) has a high incidence of spread to the central nervous system (CNS), particularly the meninges. Although all children diagnosed with T-ALL receive CNS-directed chemotherapy, these treatments induce substantial neurotoxicity, and relapsed disease often originates in the CNS. Development of safer CNS-directed therapeutics warrants a better understanding of molecular events supporting T-ALL survival in the CNS. Our lab recently found that T-ALL expression of integrins VLA4 and LFA1 suppresses proliferation of leukemia cells in the CNS. Additionally, we found that we can stimulate proliferation of integrin-expressing T-ALL using LFA1- and VLA4- blocking antibodies, and that integrin blockade synergizes with chemotherapy targeting proliferating cells. Previous studies have shown that cancer cells may enter a non-proliferative or quiescent state to survive in nutrient-poor environments. Furthermore, in many cases, cancer cells must first be anchored to stromal tissue to receive signals that induce quiescence. We postulate that integrin expression allows T-ALL to contact the meningeal stroma and receive secondary immunosuppressive signaling. We have determined that meningeal cells express the canonical LFA1 and VLA4 ligands, ICAM1 and VCAM1 respectively. We will block these by intrathecal infusion of blocking antibodies to determine if this leads to increased leukemia proliferation. We are also investigating the signals involved in proliferation suppression, and postulate that the expression of T-cell checkpoint molecules might be important. We have carried out bulk RNA-Seq analysis and find that CNS residing T-ALL cells express several checkpoint molecules, including SLAMF6. We are actively testing the importance of these to T-ALL CNS specific proliferation suppression, by antibody blockade and CRISPR knock-out. We expect to identify novel therapeutic targets for T-ALL CNS disease through this study.

  PublisherOA PDFDOI

• S1PR1 inhibition induces proapoptotic signaling in T cells and limits humoral responses within lymph nodes

  Journal of Clinical Investigation · 2024-01-09 · 22 citations

  articleOpen accessSenior author

  Effective immunity requires a large, diverse naive T cell repertoire circulating among lymphoid organs in search of antigen. Sphingosine 1-phosphate (S1P) and its receptor S1PR1 contribute by both directing T cell migration and supporting T cell survival. Here, we addressed how S1P enables T cell survival and the implications for patients treated with S1PR1 antagonists. We found that S1PR1 limited apoptosis by maintaining the appropriate balance of BCL2 family members via restraint of JNK activity. Interestingly, the same residues of S1PR1 that enable receptor internalization were required to prevent this proapoptotic cascade. Findings in mice were recapitulated in ulcerative colitis patients treated with the S1PR1 antagonist ozanimod, and the loss of naive T cells limited B cell responses. Our findings highlighted an effect of S1PR1 antagonists on the ability to mount immune responses within lymph nodes, beyond their effect on lymph node egress, and suggested both limitations and additional uses of this important class of drugs.

  PublisherOA PDFDOI

• Integrin-deficient T cell leukemia accumulates in the central nervous system

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-02

  preprintOpen accessSenior authorCorresponding

  T-cell acute lymphoblastic leukemia (T-ALL) spreads aggressively to the central nervous system (CNS), particularly the leptomeninges. Children with T-ALL are treated with high-dose, CNS-directed chemotherapy, which can cause lasting neurotoxicity and is not always effective. Little is known about how T-ALL enters and persists within the CNS. However, normal T cell migration into the CNS has been extensively studied. Two integrins-VLA-4 and LFA-1-mediate normal T cell entry to the CNS, and VLA-4 blockade effectively treats multiple sclerosis by excluding T cells from the brain. We hypothesized that these integrins would likewise be required for T-ALL CNS entry. Unexpectedly, not only were VLA-4 and LFA-1 dispensable for T-ALL to reach the CNS, integrin-deficient T-ALL accumulated in the CNS compared to control. Mechanistically, integrin loss accelerated T-ALL proliferation in the CNS, suggesting that integrin-mediated interactions may promote quiescence in this space. Integrin blockade synergized with chemotherapy targeting proliferating cells, raising the possibility that combination therapy might be a powerful strategy.

  PublisherOA PDFDOI

• Sphingosine 1-phosphate receptor 1 inhibition induces a pro-apoptotic signaling cascade in T cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-08-22

  preprintOpen accessSenior authorCorresponding

  Effective immunity requires a large, diverse naïve T cell repertoire circulating among lymphoid organs in search of antigen. Sphingosine 1-phosphate (S1P) and its receptor S1PR1 contribute by both directing T cell migration and supporting T cell survival. Here, we address how S1P enables T cell survival, and the implications for patients treated with S1PR1 antagonists. Contrary to expectations, we found that S1PR1 limits apoptosis by maintaining the appropriate balance of BCL2 family members via restraint of JNK activity. Interestingly, the same residues of S1PR1 that enable receptor internalization are required to prevent this pro-apoptotic cascade. Findings in mice were recapitulated in ulcerative colitis patients treated with the S1PR1 antagonist ozanimod, and the loss of naïve T cells limited B cell responses. Our findings highlight an unexpected effect of S1PR1 antagonists on the ability to mount immune responses within lymph nodes, beyond their effect on lymph node egress, and suggest both limitations and novel uses of this important class of drugs.

  PublisherOA PDFDOI

• Get me out of here: <scp>Sphingosine 1‐phosphate</scp> signaling and T cell exit from tissues during an immune response

  Immunological Reviews · 2023-05-22 · 18 citations

  reviewSenior authorCorresponding

  During an immune response, the duration of T cell residence in lymphoid and non-lymphoid tissues likely affects T cell activation, differentiation, and memory development. The factors that govern T cell transit through inflamed tissues remain incompletely understood, but one important determinant of T cell exit from tissues is sphingosine 1-phosphate (S1P) signaling. In homeostasis, S1P levels are high in blood and lymph compared to lymphoid organs, and lymphocytes follow S1P gradients out of tissues into circulation using varying combinations of five G-protein coupled S1P receptors. During an immune response, both the shape of S1P gradients and the expression of S1P receptors are dynamically regulated. Here we review what is known, and key questions that remain unanswered, about how S1P signaling is regulated in inflammation and in turn how S1P shapes immune responses.

  PublisherDOI

• Faculty Opinions recommendation of Visualization of T Cell Migration in the Spleen Reveals a Network of Perivascular Pathways that Guide Entry into T Zones.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2022-04-05

  dataset1st authorCorresponding
  PublisherDOI

• Sphingosine 1-phosphate signaling in perivascular cells enhances inflammation and fibrosis in the kidney

  Science Translational Medicine · 2022 · 57 citations

  • Medicine
  • Biology
  • Cancer research

  Chronic kidney disease (CKD), characterized by sustained inflammation and progressive fibrosis, is highly prevalent and can eventually progress to end-stage kidney disease. However, current treatments to slow CKD progression are limited. Sphingosine 1-phosphate (S1P), a product of sphingolipid catabolism, is a pleiotropic mediator involved in many cellular functions, and drugs targeting S1P signaling have previously been studied particularly for autoimmune diseases. The primary mechanism of most of these drugs is functional antagonism of S1P receptor-1 (S1P1) expressed on lymphocytes and the resultant immunosuppressive effect. Here, we documented the role of local S1P signaling in perivascular cells in the progression of kidney fibrosis using primary kidney perivascular cells and several conditional mouse models. S1P was predominantly produced by sphingosine kinase 2 in kidney perivascular cells and exported via spinster homolog 2 (Spns2). It bound to S1P1 expressed in perivascular cells to enhance production of proinflammatory cytokines/chemokines upon injury, leading to immune cell infiltration and subsequent fibrosis. A small-molecule Spns2 inhibitor blocked S1P transport, resulting in suppression of inflammatory signaling in human and mouse kidney perivascular cells in vitro and amelioration of kidney fibrosis in mice. Our study provides insight into the regulation of inflammation and fibrosis by S1P and demonstrates the potential of Spns2 inhibition as a treatment for CKD and potentially other inflammatory and fibrotic diseases that avoids the adverse events associated with systemic modulation of S1P receptors.

  PublisherOA PDFDOI

• Blood-thirsty: S1PR5 and TRM

  The Journal of Experimental Medicine · 2021-10-29 · 6 citations

  letterOpen accessSenior authorCorresponding

  In this elegant study, Evrard et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210116) find that sphingosine 1-phosphate receptor 5 (S1PR5) powerfully impairs tissue-resident memory T cell (TRM) formation, and that tissue-derived TGF-β limits S1pr5 expression by infiltrating T cells.

  PublisherOA PDFDOI

• Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes

  Cell Reports · 2021-09-01 · 3 citations

  erratumOpen access
  PublisherDOI

Recent grants

• Mapping cancer micro-environments for acute leukemia

  NIH · $2.3M · 2016–2021

• Training Program in Immunology and Inflammation

  NIH · $4.2M · 2012–2027

• Generation of a mouse expressing a photoactivatable Cre recombinase

  NIH · $466k · 2016–2018

• Regulation of T cell exit from non-lymphoid tissues

  NIH · $6.5M · 2010–2027

• A map of sphingosine 1-phosphate distribution

  NIH · $1.7M · 2017–2023

Frequent coauthors

• Jason G. Cyster

  16 shared

• Dan R. Littman

  Howard Hughes Medical Institute

  13 shared

• Victoria Fang

  University of Washington

  11 shared

• Yong Huang

  Sun Yat-sen University

  11 shared

• Ying Xu

  11 shared

• Timothy Hla

  10 shared

• Maria Dufau

  National Institutes of Health

  9 shared

• Takaharu Okada

  Tissue Dynamics (Israel)

  9 shared