Dr. Oscar Silva is an academic hematopathologist who completed anatomic and clinical pathology residency and hematopathology fellowship at Stanford in 2020. Prior to Stanford, he received his MD and PhD from the University of California, Los Angeles – California Institute of Technology Medical Scientist Training Program (UCLA-Caltech MSTP) and his B.A. from Santa Clara University. Dr. Silva strives to provide excellent patient care and medical student, resident and fellow education. His current interests include the diagnosis of difficult hematolymphoid neoplasms and the identification and characterization of markers of diagnostic and prognostic importance in hematolymphoid neoplasia.

Clinical Focus

  • Hematopathology
  • Anatomical and Clinical Pathology
  • Pathology

Academic Appointments

  • Clinical Assistant Professor, Pathology

Professional Education

  • Board Certification: American Board of Pathology, Pathology (2020)
  • Fellowship: Stanford University Hemapathology Fellowship (2018) CA
  • Residency: Stanford University Pathology Residency (2020) CA
  • Medical Education: UCLA David Geffen School Of Medicine Registrar (2015) CA
  • M.D., University of California, Los Angeles (2015)
  • Ph.D, University of California, Los Angeles, Immunology (2013)

All Publications

  • Low-cost transcriptional diagnostic to accurately categorize lymphomas in low- and middle-income countries. Blood advances Valvert, F. n., Silva, O. n., Solórzano-Ortiz, E. n., Puligandla, M. n., Siliézar Tala, M. M., Guyon, T. n., Dixon, S. L., López, N. n., López, F. n., Carías Alvarado, C. C., Terbrueggen, R. n., Stevenson, K. E., Natkunam, Y. n., Weinstock, D. M., Briercheck, E. L. 2021; 5 (10): 2447–55


    Inadequate diagnostics compromise cancer care across lower- and middle-income countries (LMICs). We hypothesized that an inexpensive gene expression assay using paraffin-embedded biopsy specimens from LMICs could distinguish lymphoma subtypes without pathologist input. We reviewed all biopsy specimens obtained at the Instituto de Cancerología y Hospital Dr. Bernardo Del Valle in Guatemala City between 2006 and 2018 for suspicion of lymphoma. Diagnoses were established based on the World Health Organization classification and then binned into 9 categories: nonmalignant, aggressive B-cell, diffuse large B-cell, follicular, Hodgkin, mantle cell, marginal zone, natural killer/T-cell, or mature T-cell lymphoma. We established a chemical ligation probe-based assay (CLPA) that quantifies expression of 37 genes by capillary electrophoresis with reagent/consumable cost of approximately $10/sample. To assign bins based on gene expression, 13 models were evaluated as candidate base learners, and class probabilities from each model were then used as predictors in an extreme gradient boosting super learner. Cases with call probabilities < 60% were classified as indeterminate. Four (2%) of 194 biopsy specimens in storage <3 years experienced assay failure. Diagnostic samples were divided into 70% (n = 397) training and 30% (n = 163) validation cohorts. Overall accuracy for the validation cohort was 86% (95% confidence interval [CI]: 80%-91%). After excluding 28 (17%) indeterminate calls, accuracy increased to 94% (95% CI: 89%-97%). Concordance was 97% for a set of high-probability calls (n = 37) assayed by CLPA in both the United States and Guatemala. Accuracy for a cohort of relapsed/refractory biopsy specimens (n = 39) was 79% and 88%, respectively, after excluding indeterminate cases. Machine-learning analysis of gene expression accurately classifies paraffin-embedded lymphoma biopsy specimens and could transform diagnosis in LMICs.

    View details for DOI 10.1182/bloodadvances.2021004347

    View details for PubMedID 33988700

  • RNA splicing programs define tissue compartments and cell types at single cell resolution. eLife Olivieri, J. E., Dehghannasiri, R., Wang, P. L., Jang, S., de Morree, A., Tan, S. Y., Ming, J., Ruohao Wu, A., Tabula Sapiens Consortium, Quake, S. R., Krasnow, M. A., Salzman, J. 2021; 10


    The extent splicing is regulated at single-cell resolution has remained controversial due to both available data and methods to interpret it. We apply the SpliZ, a new statistical approach, to detect cell-type-specific splicing in >110K cells from 12 human tissues. Using 10x data for discovery, 9.1% of genes with computable SpliZ scores are cell-type-specifically spliced, including ubiquitously expressed genes MYL6 and RPS24. These results are validated with RNA FISH, single-cell PCR, and Smart-seq2. SpliZ analysis reveals 170 genes with regulated splicing during human spermatogenesis, including examples conserved in mouse and mouse lemur. The SpliZ allows model-based identification of subpopulations indistinguishable based on gene expression, illustrated by subpopulation-specific splicing of classical monocytes involving an ultraconserved exon in SAT1. Together, this analysis of differential splicing across multiple organs establishes that splicing is regulated cell-type-specifically.

    View details for DOI 10.7554/eLife.70692

    View details for PubMedID 34515025

  • The RNA-binding protein IGF2BP3 is critical for MLL-AF4-mediated leukemogenesis. Leukemia Tran, T. M., Philipp, J., Bassi, J. S., Nibber, N., Draper, J. M., Lin, T. L., Palanichamy, J. K., Jaiswal, A. K., Silva, O., Paing, M., King, J., Katzman, S., Sanford, J. R., Rao, D. S. 2021


    Despite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes. Here, we find that the RNA-binding protein IGF2BP3, which is overexpressed in MLL-translocated leukemia, strongly amplifies MLL-Af4-mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4-driven leukemia and greatly attenuates disease, with a minimal impact on baseline hematopoiesis. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. At the molecular level, IGF2BP3 regulates a complex posttranscriptional operon governing leukemia cell survival and proliferation. IGF2BP3-targeted mRNA transcripts include important MLL-Af4-induced genes, such as those in the Hoxa locus, and the Ras signaling pathway. Targeting of transcripts by IGF2BP3 regulates both steady-state mRNA levels and, unexpectedly, pre-mRNA splicing. Together, our findings show that IGF2BP3 represents an attractive therapeutic target in this disease, providing important insights into mechanisms of posttranscriptional regulation in leukemia.

    View details for DOI 10.1038/s41375-021-01346-7

    View details for PubMedID 34321607

  • Polytypic T-cell prolymphocytic leukemia. Blood Ames, E., Silva, O. 2021; 137 (15): 2125

    View details for DOI 10.1182/blood.2021010694

    View details for PubMedID 33856441

  • Classic Hodgkin lymphoma in Guatemalan children of age less than six years: analysis of immune regulatory pathways and the tumor microenvironment. Leukemia & lymphoma Silva, O., Charu, V., Ewalt, M. D., Metcalf, R. A., Zhao, S., Castellanos, E. M., Orellana, E., Natkunam, Y., Luna-Fineman, S. 2021: 1–13


    Classic Hodgkin lymphoma (cHL) in young children (ages 0-6) is rare in high income countries (HICs) but is more prevalent in low- and middle-income countries (LMICs) like Guatemala. Given that the majority of cHL studies have evaluated adolescent/adults, and the immune system changes with age, we sought to characterize Epstein-Barr virus (EBV) expression, immune regulatory pathway markers and the tumor microenvironment in 42 children ages 0-6 with cHL from Guatemala. We found a very high frequency of EBV expression (97.5%). Hodgkin cells showed increased expression of PD1 ligands and CD137, indicative of shared immune regulatory mechanisms with adult cHL. Pediatric cHL also showed an increase in CD8+ tumor infiltrating lymphocytes and tumor associated macrophages within the tumor microenvironment. Despite 25 having high risk disease, only 4 patients died from progressive disease, relapse or infection.

    View details for DOI 10.1080/10428194.2021.1885666

    View details for PubMedID 33627023

  • Nonleukemic T/B mixed phenotype acute leukemia with PHF6 and NOTCH1 mutations. Blood Silva, O., Kurzer, J. 2021; 138 (9): 818

    View details for DOI 10.1182/blood.2021012538

    View details for PubMedID 34473233

  • Increased double-negative αβ+ T-cells reveal adult-onset autoimmune lymphoproliferative syndrome in a patient with IgG4-related disease. Haematologica Brar, N., Spinner, M. A., Baker, M. C., Advani, R. H., Natkunam, Y., Lewis, D. B., Silva, O. 2021


    Not available.

    View details for DOI 10.3324/haematol.2021.278772

    View details for PubMedID 34474549

  • Chronic lymphoproliferative disorder of NK cells with TNFAIP3 and DNMT3A mutations. Blood Bulterys, P. L., Silva, O. 2021; 137 (24): 3460

    View details for DOI 10.1182/blood.2021011812

    View details for PubMedID 34137843

  • Additional considerations related to the elusive boundaries of EBV-associated T/NK-cell lymphoproliferative disorders. Haematologica Fernandez-Pol, S., Silva, O., Natkunam, Y. 2019; 104 (3): e125–e126

    View details for PubMedID 30819837

  • Defining the elusive boundaries of chronic active Epstein-Barr virus infection. Haematologica Fernandez-Pol, S., Silva, O., Natkunam, Y. 2018; 103 (6): 924–27

    View details for PubMedID 29866887

  • A Feedback-Based Training Module Improves Tumor Cellularity Estimation for Molecular Testing Weiel, J. J., Silva, O., Mooney, K. L., Lin, C., Kunder, C. A. NATURE PUBLISHING GROUP. 2017: 144A
  • Discs Large Homolog 1 Splice Variants Regulate p38-Dependent and -Independent Effector Functions in CD8+T Cells PLOS ONE Silva, O., Crocetti, J., Humphries, L. A., Burkhardt, J. K., Miceli, M. C. 2015; 10 (7)


    Functionally diverse CD8+ T cells develop in response to antigenic stimulation with differing capacities to couple TCR engagement to downstream signals and functions. However, mechanisms of diversifying TCR signaling are largely uncharacterized. Here we identified two alternative splice variants of scaffold protein Dlg1, Dlg1AB and Dlg1B, that diversify signaling to regulate p38-dependent and -independent effector functions in CD8+ T cells. Dlg1AB, but not Dlg1B associated with Lck, coupling TCR stimulation to p38 activation and proinflammatory cytokine production. Conversely, both Dlg1AB and Dlg1B mediated p38-independent degranulation. Degranulation depended on a Dlg1 fragment containing an intact Dlg1SH3-domain and required the SH3-ligand WASp. Further, Dlg1 controlled WASp activation by promoting TCR-triggered conformational opening of WASp. Collectively, our data support a model where Dlg1 regulates p38-dependent proinflammatory cytokine production and p38-independent cytotoxic granule release through the utilization of alternative splice variants, providing a mechanism whereby TCR engagement couples downstream signals to unique effector functions in CD8+ T cells.

    View details for DOI 10.1371/journal.pone.0133353

    View details for Web of Science ID 000358198700128

    View details for PubMedID 26186728

  • Selective Phosphorylation of the Dlg1AB Variant Is Critical for TCR-Induced p38 Activation and Induction of Proinflammatory Cytokines in CD8(+) T Cells JOURNAL OF IMMUNOLOGY Crocetti, J., Silva, O., Humphries, L. A., Tibbs, M. D., Miceli, M. C. 2014; 193 (6): 2651-2660


    CD8(+) T cells respond to TCR stimulation by producing proinflammatory cytokines, and destroying infected or malignant cells through the production and release of cytotoxic granules. Scaffold protein Discs large homolog 1 (Dlg1) specifies TCR-dependent functions by channeling proximal signals toward the activation of p38-dependent proinflammatory cytokine gene expression and/or p38-independent cytotoxic granule release. Two Dlg1 variants are expressed in CD8(+) T cells via alternative splicing, Dlg1AB and Dlg1B, which have differing abilities coordinate TCR-dependent functions. Although both variants facilitate p38-independent cytotoxicity, only Dlg1AB coordinates p38-dependent proinflammatory cytokine expression. In this study, we identify TCR-induced Dlg1 tyrosine phosphorylation as a key regulatory step required for Dlg1AB-mediated p38-dependent functions, including proinflammatory cytokine expression. We find that Dlg1AB but not Dlg1B is tyrosine phosphorylated by proximal tyrosine kinase Lck in response to TCR stimulation. Furthermore, we identify Dlg1 tyrosine 222 (Y222) as a major site of Dlg1 phosphorylation required for TCR-triggered p38 activation and NFAT-dependent expression of proinflammatory cytokines, but not for p38-independent cytotoxicity. Taken together, our data support a model where TCR-induced phosphorylation of Dlg1 Y222 is a key point of control that endows Dlg1AB with the ability to coordinate p38 activation and proinflammatory cytokine production. We propose blocking Dlg1AB phosphorylation as a novel therapeutic target to specifically block proinflammatory cytokine production but not cytotoxicity.

    View details for DOI 10.4049/jimmunol.1401196

    View details for Web of Science ID 000341859700005

    View details for PubMedID 25098293

  • Dantrolene Enhances Antisense-Mediated Exon Skipping in Human and Mouse Models of Duchenne Muscular Dystrophy SCIENCE TRANSLATIONAL MEDICINE Kendall, G. C., Mokhonova, E. I., Moran, M., Sejbuk, N. E., Wang, D. W., Silva, O., Wang, R. T., Martinez, L., Lu, Q. L., Damoiseaux, R., Spencer, M. J., Nelson, S. F., Miceli, M. C. 2012; 4 (164)


    Duchenne muscular dystrophy (DMD) causes profound and progressive muscle weakness and loss, resulting in early death. DMD is usually caused by frameshifting deletions in the gene DMD, which leads to absence of dystrophin protein. Dystrophin binds to F-actin and components of the dystrophin-associated glycoprotein complex and protects the sarcolemma from contraction-induced injury. Antisense oligonucleotide-mediated exon skipping is a promising therapeutic approach aimed at restoring the DMD reading frame and allowing expression of an intact dystrophin glycoprotein complex. To date, low levels of dystrophin protein have been produced in humans by this method. We performed a small-molecule screen to identify existing drugs that enhance antisense-directed exon skipping. We found that dantrolene, currently used to treat malignant hyperthermia, potentiates antisense oligomer-guided exon skipping to increase exon skipping to restore the mRNA reading frame, the sarcolemmal dystrophin protein, and the dystrophin glycoprotein complex in skeletal muscles of mdx mice when delivered intramuscularly or intravenously. Further, dantrolene synergized with multiple weekly injections of antisense to increase muscle strength and reduce serum creatine kinase in mdx mice. Dantrolene similarly promoted antisense-mediated exon skipping in reprogrammed myotubes from DMD patients. Ryanodine and Rycal S107, which, like dantrolene, targets the ryanodine receptor, also promoted antisense-driven exon skipping, implicating the ryanodine receptor as the critical molecular target.

    View details for DOI 10.1126/scitranslmed.3005054

    View details for Web of Science ID 000312393900004

    View details for PubMedID 23241744

  • Characterization of In Vivo Dlg1 Deletion on T Cell Development and Function PLOS ONE Humphries, L. A., Shaffer, M. H., Sacirbegovic, F., Tomassian, T., McMahon, K., Humbert, P. O., Silva, O., Round, J. L., Takamiya, K., Huganir, R. L., Burkhardt, J. K., Russell, S. M., Miceli, M. C. 2012; 7 (9)


    The polarized reorganization of the T cell membrane and intracellular signaling molecules in response to T cell receptor (TCR) engagement has been implicated in the modulation of T cell development and effector responses. In siRNA-based studies Dlg1, a MAGUK scaffold protein and member of the Scribble polarity complex, has been shown to play a role in T cell polarity and TCR signal specificity, however the role of Dlg1 in T cell development and function in vivo remains unclear.Here we present the combined data from three independently-derived dlg1-knockout mouse models; two germline deficient knockouts and one conditional knockout. While defects were not observed in T cell development, TCR-induced early phospho-signaling, actin-mediated events, or proliferation in any of the models, the acute knockdown of Dlg1 in Jurkat T cells diminished accumulation of actin at the IS. Further, while Th1-type cytokine production appeared unaffected in T cells derived from mice with a dlg1 germline-deficiency, altered production of TCR-dependent Th1 and Th2-type cytokines was observed in T cells derived from mice with a conditional loss of dlg1 expression and T cells with acute Dlg1 suppression, suggesting a differential requirement for Dlg1 activity in signaling events leading to Th1 versus Th2 cytokine induction. The observed inconsistencies between these and other knockout models and siRNA strategies suggest that 1) compensatory upregulation of alternate gene(s) may be masking a role for dlg1 in controlling TCR-mediated events in dlg1 deficient mice and 2) the developmental stage during which dlg1 ablation begins may control the degree to which compensatory events occur.These findings provide a potential explanation for the discrepancies observed in various studies using different dlg1-deficient T cell models and underscore the importance of acute dlg1 ablation to avoid the upregulation of compensatory mechanisms for future functional studies of the Dlg1 protein.

    View details for DOI 10.1371/journal.pone.0045276

    View details for Web of Science ID 000311313900112

    View details for PubMedID 23028902

  • Caveolin-1 Orchestrates TCR Synaptic Polarity, Signal Specificity, and Function in CD8 T Cells JOURNAL OF IMMUNOLOGY Tomassian, T., Humphries, L. A., Liu, S. D., Silva, O., Brooks, D. G., Miceli, M. C. 2011; 187 (6): 2993-3002


    TCR engagement triggers the polarized recruitment of membrane, actin, and transducer assemblies within the T cell-APC contact that amplify and specify signaling cascades and T effector activity. We report that caveolin-1, a scaffold that regulates polarity and signaling in nonlymphoid cells, is required for optimal TCR-induced actin polymerization, synaptic membrane raft polarity, and function in CD8, but not CD4, T cells. In CD8(+) T cells, caveolin-1 ablation selectively impaired TCR-induced NFAT-dependent NFATc1 and cytokine gene expression, whereas caveolin-1 re-expression promoted NFATc1 gene expression. Alternatively, caveolin-1 ablation did not affect TCR-induced NF-κB-dependent Iκbα expression. Cav-1(-/-) mice did not efficiently promote CD8 immunity to lymphocytic choriomeningitis virus, nor did cav-1(-/-) OT-1(+) CD8(+) T cells efficiently respond to Listeria monocytogenes-OVA after transfer into wild-type hosts. Therefore, caveolin-1 is a T cell-intrinsic orchestrator of TCR-mediated membrane polarity and signal specificity selectively employed by CD8 T cells to customize TCR responsiveness.

    View details for DOI 10.4049/jimmunol.1101447

    View details for Web of Science ID 000295034200018

    View details for PubMedID 21849673