Scholars@Duke
Wen-Hsuan Wendy Lin

Wen-Hsuan Wendy Lin

Assistant Professor of Pathology
Pathology
w.wendy.lin@duke.edu
40 Duke Medicine Circle Room 3077, Durham, NC 27710

Selected Publications

Therapeutic targeting of the NOTCH1 and neddylation pathways in T cell acute lymphoblastic leukemia.

Journal Article Proc Natl Acad Sci U S A · April 8, 2025 Gamma Secretase Inhibitors (GSIs) effectively block oncogenic Notch homolog-1 (NOTCH1), a characteristic feature of T cell acute lymphoblastic leukemias (T-ALL). However, their clinical application has been stalled by the induction of severe gastrointestin ... Full text Link to item Cite

Abstract PR05: Single-cell transcriptomics reveals shared and subtype-specific vulnerabilities of the tumor-microenvironment ecosystems in peripheral T-cell lymphomas

Journal Article Blood Cancer Discovery · June 19, 2024 AbstractPeripheral T-cell lymphomas (PTCL) are heterogeneous and highly aggressive hematologic malignancies with dismal outcomes, highlighting the need for novel targeted therapies. PTCLs are characterized b ... Full text Cite

Clinical Utility and Reimbursement of Next-Generation Sequencing-Based Testing for Myeloid Malignancies.

Journal Article J Mol Diagn · January 2024 Next-generation sequencing is becoming increasingly important for the diagnosis, risk stratification, and management of patients with established or suspected myeloid malignancies. These tests are being incorporated into clinical practice guidelines and ma ... Full text Link to item Cite

Role of the S1P Signaling Pathway in the Pathogenesis of Angioimmunoblastic T-Cell Lymphoma

Conference Blood · November 2, 2023 Peripheral T cell lymphomas (PTCLs) are a group of aggressive lymphoid malignancies originating from mature T cells. Angioimmunoblastic T-cell lymphomas (AITL) represent 20% to 30% of all PTCL diagnoses and are associat ... Full text Cite

Reciprocal transmission of activating and inhibitory signals and cell fate in regenerating T cells.

Journal Article Cell Rep · October 31, 2023 The ability of activated progenitor T cells to self-renew while producing differentiated effector cell descendants may underlie immunological memory and persistent responses to ongoing infection. The nature of stem-like T cells responding to cancer and dur ... Full text Link to item Cite

Pharmacologic Inhibition of NT5C2 Reverses Genetic and Nongenetic Drivers of 6-MP Resistance in Acute Lymphoblastic Leukemia.

Journal Article Cancer Discov · November 2, 2022 UNLABELLED: Low-intensity maintenance therapy with 6-mercaptopurine (6-MP) limits the occurrence of acute lymphoblastic leukemia (ALL) relapse and is central to the success of multiagent chemotherapy protocols. Activating mutations in the 5'-nucleotidase c ... Full text Link to item Cite

Oncogenic Vav1-Myo1f induces therapeutically targetable macrophage-rich tumor microenvironment in peripheral T cell lymphoma.

Journal Article Cell Rep · April 19, 2022 Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) comprises heterogeneous lymphoid malignancies characterized by pleomorphic lymphocytes and variable inflammatory cell-rich tumor microenvironment. Genetic drivers in PTCL-NOS include genomic alt ... Full text Link to item Cite

Inflammation and Mortality in COVID-19 Hospitalized Patients With and Without Type 2 Diabetes.

Journal Article J Clin Endocrinol Metab · April 19, 2022 CONTEXT: COVID-19 mortality is increased in patients with diabetes. A common hypothesis is that the relationship of inflammation with COVID-19 mortality differs by diabetes status. OBJECTIVE: The aim of this study was to determine the relationship of infla ... Full text Link to item Cite

A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19.

Journal Article J Clin Invest · July 1, 2021 BACKGROUNDAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.METHODSWe conducted a randomized, double-blind, controlled trial a ... Full text Link to item Cite

Incidental intra-adrenal splenule.

Journal Article Clin Case Rep · July 2021 Splenules can be found in the adrenals and should be considered in the differential diagnosis of adrenal incidentalomas. ... Full text Link to item Cite

Approaching the Interpretation of Discordances in SARS-CoV-2 Testing

Journal Article Open Forum Infectious Diseases · July 1, 2021 The coronavirus disease 2019 pandemic has upended life throughout the globe. Appropriate emphasis has been placed on developing effective therapies and vaccines to curb the pandemic. While awaiting such countermeasures, mitigation efforts coupled with robu ... Full text Cite

Primary differentiated respiratory epithelial cells respond to apical measles virus infection by shedding multinucleated giant cells

Journal Article Proceedings of the National Academy of Sciences · March 16, 2021 SignificanceMeasles virus (MeV) is highly infectious by the respiratory route, but respiratory epithelial cells are thought to be resistant to infection through the exposed apical surface and to require infection ... Full text Cite

Cutaneous T-cell lymphoma of the eyelid masquerading as dermatitis.

Journal Article Orbit · February 2021 Cutaneous T-cell lymphoma (CTCL) may pose a diagnostic challenge for physicians, as clinical presentation and histologic analysis may mimic benign dermatologic conditions. The authors present a case of recurrent CTCL in which the recurrence was limited to ... Full text Link to item Cite

FYN-TRAF3IP2 induces NF-κB signaling-driven peripheral T cell lymphoma.

Journal Article Nat Cancer · January 2021 Angioimmunoblastic T cell lymphoma (AITL) and peripheral T cell lymphoma not-otherwise-specified (PTCL, NOS) have poor prognosis and lack driver actionable targets for directed therapies in most cases. Here we identify FYN-TRAF3IP2 as a recurrent oncogenic ... Full text Link to item Cite

Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum.

Journal Article Nat Immunol · January 2021 Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age1,2. Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are large ... Full text Link to item Cite

A durable protective immune response to wild-type measles virus infection of macaques is due to viral replication and spread in lymphoid tissues.

Journal Article Sci Transl Med · April 1, 2020 Infection with wild-type (WT) measles virus (MeV) is an important cause of childhood mortality that leads to lifelong protective immunity in survivors. WT MeV and the live-attenuated MeV used in the measles vaccine (LAMV) are antigenically similar, but the ... Full text Link to item Cite

Association of persistent wild-type measles virus RNA with long-term humoral immunity in rhesus macaques.

Journal Article JCI Insight · February 13, 2020 Recovery from measles results in life-long protective immunity. To understand induction of long-term immunity, rhesus macaques were studied for 6 months after infection with wild-type measles virus (MeV). Infection caused viremia and rash, with clearance o ... Full text Link to item Cite

Modeling the measles paradox reveals the importance of cellular immunity in regulating viral clearance.

Journal Article PLoS Pathog · December 2018 Measles virus (MV) is a highly contagious member of the Morbillivirus genus that remains a major cause of childhood mortality worldwide. Although infection induces a strong MV-specific immune response that clears viral load and confers lifelong immunity, t ... Full text Link to item Cite

Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway.

Journal Article Cell Rep · January 23, 2018 Unequal transmission of nutritive signaling during cell division establishes fate disparity between sibling lymphocytes, but how asymmetric signaling becomes organized is not understood. We show that receptor-associated class I phosphatidylinositol 3-kinas ... Full text Link to item Cite

Understanding the causes and consequences of measles virus persistence

Journal Article F1000research · January 1, 2018 Measles is an acute systemic viral disease with initial amplification of infection in lymphoid tissue and subsequent spread over 10-14 days to multiple organs. Failure of the innate response to control initial measles virus (MeV) replication is associated ... Full text Cite

Lymphocyte Fate and Metabolism: A Clonal Balancing Act.

Journal Article Trends Cell Biol · December 2017 Activated lymphocytes perform a clonal balancing act, yielding a daughter cell that differentiates owing to intense PI3K signaling, alongside a self-renewing sibling cell with blunted anabolic signaling. Divergent cellular anabolism versus catabolism is em ... Full text Link to item Cite

IRF4 Couples Anabolic Metabolism to Th1 Cell Fate Determination

Journal Article Immunohorizons · September 1, 2017 Anabolic metabolism in lymphocytes promotes plasmablast and cytotoxic T cell differentiation at the expense of self-renewal. Heightened expression and function of the transcription factor IFN regulatory factor 4 (IRF4) accompany enhanced anabolic induction ... Full text Cite

Plasma Cytokines and Chemokines in Zambian Children With Measles: Innate Responses and Association With HIV-1 Coinfection and In-Hospital Mortality.

Journal Article J Infect Dis · March 1, 2017 To identify immune factors present during the acute rash phase of measles and associations with outcome and human immunodeficiency virus type 1 (HIV-1) coinfection, we measured the plasma levels of 22 cytokines and chemokines in Zambian children hospitaliz ... Full text Link to item Cite

CD4+ T cell effector commitment coupled to self-renewal by asymmetric cell divisions.

Journal Article J Exp Med · January 2017 Upon infection, an activated CD4+ T cell produces terminally differentiated effector cells and renews itself for continued defense. In this study, we show that differentiation and self-renewal arise as opposing outcomes of sibling CD4+ T cells. After influ ... Full text Link to item Cite

Anabolism-Associated Mitochondrial Stasis Driving Lymphocyte Differentiation over Self-Renewal.

Journal Article Cell Rep · December 20, 2016 Regeneration requires related cells to diverge in fate. We show that activated lymphocytes yield sibling cells with unequal elimination of aged mitochondria. Disparate mitochondrial clearance impacts cell fate and reflects larger constellations of opposing ... Full text Link to item Cite

CD8+ T Lymphocyte Self-Renewal during Effector Cell Determination.

Journal Article Cell Rep · November 8, 2016 Selected CD8+ T cells must divide, produce differentiated effector cells, and self-renew, often repeatedly. We now show that silencing expression of the transcription factor TCF1 marks loss of self-renewal by determined effector cells and that this require ... Full text Link to item Cite

Asymmetric PI3K Signaling Driving Developmental and Regenerative Cell Fate Bifurcation.

Journal Article Cell Rep · December 15, 2015 Metazoan sibling cells often diverge in activity and identity, suggesting links between growth signals and cell fate. We show that unequal transduction of nutrient-sensitive PI3K/AKT/mTOR signaling during cell division bifurcates transcriptional networks a ... Full text Link to item Cite

Limited in vivo production of type I or type III interferon after infection of macaques with vaccine or wild-type strains of measles virus.

Journal Article J Interferon Cytokine Res · April 2015 The innate immune response to viral infections often includes induction of types I and III interferons (IFNs) and production of antiviral proteins. Measles is a severe virus-induced rash disease, but in vitro studies suggest that in the absence of defectiv ... Full text Link to item Cite

Cutting edge: CXCR4 is critical for CD8+ memory T cell homeostatic self-renewal but not rechallenge self-renewal.

Journal Article J Immunol · August 1, 2014 Central memory (CM) CD8(+) T cells "remember" prior encounters because they maintain themselves through cell division in the absence of ongoing challenge (homeostatic self-renewal), as well as reproduce the CM fate while manufacturing effector cells during ... Full text Link to item Cite

Vaccine-induced measles virus-specific T cells do not prevent infection or disease but facilitate subsequent clearance of viral RNA.

Journal Article mBio · April 15, 2014 Infection with wild-type measles virus (MeV) induces lifelong protection from reinfection, and parenteral delivery of the live attenuated measles vaccine (LAV) also provides protection from measles. The level of neutralizing antibody is a good indicator of ... Full text Link to item Cite

Vaxfectin adjuvant improves antibody responses of juvenile rhesus macaques to a DNA vaccine encoding the measles virus hemagglutinin and fusion proteins.

Journal Article J Virol · June 2013 DNA vaccines formulated with the cationic lipid-based adjuvant Vaxfectin induce protective immunity in macaques after intradermal (i.d.) or intramuscular (i.m.) delivery of 0.5 to 1 mg of codon-optimized DNA encoding the hemagglutinin (H) and fusion (F) pr ... Full text Link to item Cite

Prolonged persistence of measles virus RNA is characteristic of primary infection dynamics.

Journal Article Proc Natl Acad Sci U S A · September 11, 2012 Measles virus (MeV) is the poster child for acute infection followed by lifelong immunity. However, recent work shows the presence of MeV RNA in multiple sites for up to 3 mo after infection in a proportion of infected children. Here, we use experimental i ... Full text Link to item Cite

Measles virus, immune control, and persistence.

Journal Article FEMS Microbiol Rev · May 2012 Measles remains one of the most important causes of child morbidity and mortality worldwide with the greatest burden in the youngest children. Most acute measles deaths are owing to secondary infections that result from a poorly understood measles-induced ... Full text Link to item Cite

Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques.

Journal Article Proc Natl Acad Sci U S A · February 15, 2011 Measles remains an important cause of childhood mortality worldwide. Sustained high vaccination coverage is the key to preventing measles deaths. Because measles vaccine is delivered by injection, hurdles to high coverage include the need for trained medic ... Full text Link to item Cite