About

My research program has two main goals: i) to make original and lasting contributions to the description and documentation of Indigenous languages of the Americas; and ii) to further our collective understanding of the nature of crosslinguistic and intralinguistic variation in phonology and morphology. My interest in crosslinguistic variation stems from my deep commitment to careful study of particular languages and the desire to bring data from lesser-studied languages to bear on topics in formal phonology and morphology, topics that tend to be addressed with data from an unrepresentative handful of better-known languages. My research interests in phonology and morphology extend to the psycholinguistic investigation of phonological and morphological processing in order to better understand patterns of morphophonological variation in morphologically complex languages.

Research topics

• Immunology
• Internal medicine
• Virology
• Medicine
• Biology
• Physiology

Selected publications

• HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer

  Current Oncology · 2025-07-04 · 3 citations

  articleOpen access

  Health outcomes for people with HIV (PWH) have improved significantly with combination antiretroviral therapy (ART), yet the risk of lung cancer remains elevated. While a single case cannot establish causality, we describe here an investigation of a 74-year-old male PWH with de novo high-grade neuroendocrine small cell lung carcinoma. To investigate the potential contribution of HIV to cancer development, we performed HIV integration site sequencing on blood, tumor, and non-tumor tissue samples from the patient. We analyzed integration site distribution, clonal expansion, and associated gene disruption. Phosphatase and Tensin Homolog (PTEN) expression was evaluated using immunofluorescence and microscopy. A total of 174 unique HIV integration sites were identified, with 29.9% (52/174) located in clonally expanded cells. The most frequent integration site in clonally expanded cells was within the PTEN gene, representing 4.2% to 16.7% of all HIV-infected cells across samples. PTEN expression was markedly reduced in tumor regions relative to non-tumor tissue. Areas positive for HIV p24 antigen showed minimal PTEN expression. These findings suggest that HIV integration into the PTEN gene, coupled with clonal expansion of HIV-infected cells, may impair anti-tumor immune responses and promote cancer progression in PWH.

  PublisherOA PDFDOI

• Impact of influenza and pneumococcal vaccines on HIV persistence and immune dynamics during suppressive antiretroviral therapy

  AIDS · 2024-03-22 · 1 citations

  articleOpen access

  OBJECTIVE: We sought to determine if standard influenza and pneumococcal vaccines can be used to stimulate HIV reservoirs during antiretroviral therapy (ART). DESIGN: A prospective, randomized, double-blinded, placebo-controlled, crossover trial of two clinically recommended vaccines (influenza and pneumococcal). METHODS: Persons with HIV on ART ( N = 54) were enrolled in the clinical trial. Blood was collected at baseline and days 2,4,7,14, and 30 postimmunizations. Levels of cellular HIV RNA and HIV DNA were measured by ddPCR. Expression of immunological markers on T cell subsets was measured by flow cytometry. Changes in unspliced cellular HIV RNA from baseline to day 7 postinjection between each vaccine and placebo was the primary outcome. RESULTS: Forty-seven participants completed at least one cycle and there were no serious adverse events related to the intervention. We observed no significant differences in the change in cellular HIV RNA after either vaccine compared with placebo at any timepoint. In secondary analyses, we observed a transient increase in total HIV DNA levels after influenza vaccine, as well as increased T cell activation and exhaustion on CD4 + T cells after pneumococcal vaccine. CONCLUSION: Clinically recommended vaccines were well tolerated but did not appear to stimulate the immune system strongly enough to elicit significantly noticeable HIV RNA transcription during ART.Clinicaltrials.gov identifier: NCT02707692.

  PublisherOA PDFDOI

• Viral and Immune Risk Factors of HIV Rebound After Interruption of Antiretroviral Therapy

  The Journal of Infectious Diseases · 2024-12-11 · 2 citations

  articleOpen access

  BACKGROUND: Identifying risk factors for human immunodeficiency virus (HIV) rebound after treatment interruption is crucial for designing effective remission strategies. METHODS: Peripheral blood mononuclear cells from participants in the Zurich HIV Primary Infection Cohort (ZPHI, n = 73) and ACTG study A5345 (n = 44) were analyzed before antiretroviral therapy (ART) interruption. We measured cell-associated HIV RNA, total HIV DNA, and proviral diversity (env gene). Immune phenotyping was conducted by flow cytometry. Cox proportional hazards (PH) models and penalized Cox PH models with an adaptive LASSO penalty identified risk factors for time to rebound (HIV RNA >1000 copies/mL). RESULTS: Late ART initiation was associated with higher rebound risk (shorter time to rebound) as compared to early ART. Higher pre-ART HIV RNA in plasma, total HIV DNA, and increased cellular HIV transcription at the time of ART interruption were associated with higher rebound risk. Higher proviral diversity was associated with higher rebound risk but only among male participants and those enrolled in the ZPHI cohort. Fewer CD4+ T cells at ART interruption, higher proportions of effector and terminally differentiated T cells, and more activated and exhausted T cells were associated with higher rebound risk, primarily in early-treated participants. No significant immunological risk factors were found in participants treated during chronic HIV. In the combined cohort, total HIV DNA and terminally differentiated CD8+ T cells appeared to be the most relevant risk factors for time to rebound, as indicated by variable selection in multivariable analysis. CONCLUSIONS: These findings underscore the importance of early ART initiation and suggest that tailored interventions based on virologic, immunologic, and demographic factors may help achieve sustained viral suppression. Clinical Trials Registration. NCT00537966 and NCT03001128.

  PublisherOA PDFDOI

• Supplementary Methods, Table 1, Figures 1-8 from A Pivotal Role for Heat Shock Protein 90 in Ewing Sarcoma Resistance to Anti-Insulin-like Growth Factor 1 Receptor Treatment: <i>In vitro</i> and <i>In vivo</i> Study

  2023-03-30

  preprintOpen access

  Supplementary Methods, Table 1, Figures 1-8 from A Pivotal Role for Heat Shock Protein 90 in Ewing Sarcoma Resistance to Anti-Insulin-like Growth Factor 1 Receptor Treatment: <i>In vitro</i> and <i>In vivo</i> Study

  PublisherDOI

• Identification of system-level features in HIV migration within a host

  PLoS ONE · 2023-09-26 · 3 citations

  articleOpen access

  OBJECTIVE: Identify system-level features in HIV migration within a host across body tissues. Evaluate heterogeneity in the presence and magnitude of these features across hosts. METHOD: Using HIV DNA deep sequencing data generated across multiple tissues from 8 people with HIV, we represent the complex dependencies of HIV migration among tissues as a network and model these networks using the family of exponential random graph models (ERGMs). ERGMs allow for the statistical assessment of whether network features occur more (or less) frequently in viral migration than might be expected by chance. The analysis investigates five potential features of the viral migration network: (1) bi-directional flow between tissues; (2) preferential migration among tissues in the same biological system; (3) heterogeneity in the level of viral migration related to HIV reservoir size; (4) hierarchical structure of migration; and (5) cyclical migration among several tissues. We calculate the Cohran's Q statistic to assess heterogeneity in the magnitude of the presence of these features across hosts. The analysis adjusts for missing data on body tissues. RESULTS: We observe strong evidence for bi-directional flow between tissues; migration among tissues in the same biological system; and hierarchical structure of the viral migration network. This analysis shows no evidence for differential level of viral migration with respect to the HIV reservoir size of a tissue. There is evidence that cyclical migration among three tissues occurs less frequent than expected given the amount of viral migration. The analysis also provides evidence for heterogeneity in the magnitude that these features are present across hosts. Adjusting for missing tissue data identifies system-level features within a host as well as heterogeneity in the presence of these features across hosts that are not detected when the analysis only considers the observed data. DISCUSSION: Identification of common features in viral migration may increase the efficiency of HIV cure efforts as it enables targeting specific processes.

  PublisherDOI

• Supplementary Methods, Table 1, Figures 1-8 from A Pivotal Role for Heat Shock Protein 90 in Ewing Sarcoma Resistance to Anti-Insulin-like Growth Factor 1 Receptor Treatment: <i>In vitro</i> and <i>In vivo</i> Study

  2023-03-30

  preprintOpen access

  Supplementary Methods, Table 1, Figures 1-8 from A Pivotal Role for Heat Shock Protein 90 in Ewing Sarcoma Resistance to Anti-Insulin-like Growth Factor 1 Receptor Treatment: <i>In vitro</i> and <i>In vivo</i> Study

  PublisherOA PDFDOI

• Data from A Pivotal Role for Heat Shock Protein 90 in Ewing Sarcoma Resistance to Anti-Insulin-like Growth Factor 1 Receptor Treatment: <i>In vitro</i> and <i>In vivo</i> Study

  2023-03-30

  preprintOpen access

  <div>Abstract<p>Ewing Sarcoma (ES) shows several deregulated autocrine loops mediating cell survival and proliferation. Therefore, their blockade is a promising therapeutic approach. We previously reported the <i>in vitro</i> effect of insulin-like growth factor 1 receptor (IGF1R)/KIT pathway blockade on ES cell lines, and we now extend our observations to changes induced by this treatment in interacting proteins/networks. A proteomic analysis revealed that Heat Shock Protein (HSP)90 was differentially expressed between ES cell lines sensitive and resistant to specific IGF1R/KIT inhibitors. We therefore inhibited HSP90 with 17-allylamino-17-demethoxygeldanamycin (17-AAG) and siRNA, and observed that ES cell line growth and survival were reduced, especially in the resistant cell lines. Conversely, HSP90 induced–expression conferred resistance to anti-IGF1R/KIT treatment in the sensitive cell lines. 17-AAG treatment induced HSP90 client protein degradation, including AKT, KIT, or IGF1R, by inhibiting their physical interaction with HSP90. Xenograft models developed with A673 ES cell line confirmed that HSP90 inhibition, alone or combined with IGF1R inhibition, significantly reduced tumor growth and expression of client proteins. Remarkably, using two independent clinical sample sets, we have found that nearly half of IGF1R-positive tumors also show HSP90 overexpression. This delineates a subset of patients that could benefit from combination of anti-HSP90 agents when considering IGF1R-targeting therapies. Importantly, sensitivity to drugs such as ADW/IMA depends not only on the levels of expression and basal activation of IGF1R/KIT, but also, and for the first time reported in ES, on the development of the stress response mechanism. Accordingly, HSP90 expression could be a predictive factor of response to IGF1R-targeting therapies. [Cancer Res 2008;68(15):6260–70]</p></div>

  PublisherDOI

• Data from A Pivotal Role for Heat Shock Protein 90 in Ewing Sarcoma Resistance to Anti-Insulin-like Growth Factor 1 Receptor Treatment: <i>In vitro</i> and <i>In vivo</i> Study

  2023-03-30

  preprintOpen access

  <div>Abstract<p>Ewing Sarcoma (ES) shows several deregulated autocrine loops mediating cell survival and proliferation. Therefore, their blockade is a promising therapeutic approach. We previously reported the <i>in vitro</i> effect of insulin-like growth factor 1 receptor (IGF1R)/KIT pathway blockade on ES cell lines, and we now extend our observations to changes induced by this treatment in interacting proteins/networks. A proteomic analysis revealed that Heat Shock Protein (HSP)90 was differentially expressed between ES cell lines sensitive and resistant to specific IGF1R/KIT inhibitors. We therefore inhibited HSP90 with 17-allylamino-17-demethoxygeldanamycin (17-AAG) and siRNA, and observed that ES cell line growth and survival were reduced, especially in the resistant cell lines. Conversely, HSP90 induced–expression conferred resistance to anti-IGF1R/KIT treatment in the sensitive cell lines. 17-AAG treatment induced HSP90 client protein degradation, including AKT, KIT, or IGF1R, by inhibiting their physical interaction with HSP90. Xenograft models developed with A673 ES cell line confirmed that HSP90 inhibition, alone or combined with IGF1R inhibition, significantly reduced tumor growth and expression of client proteins. Remarkably, using two independent clinical sample sets, we have found that nearly half of IGF1R-positive tumors also show HSP90 overexpression. This delineates a subset of patients that could benefit from combination of anti-HSP90 agents when considering IGF1R-targeting therapies. Importantly, sensitivity to drugs such as ADW/IMA depends not only on the levels of expression and basal activation of IGF1R/KIT, but also, and for the first time reported in ES, on the development of the stress response mechanism. Accordingly, HSP90 expression could be a predictive factor of response to IGF1R-targeting therapies. [Cancer Res 2008;68(15):6260–70]</p></div>

  PublisherDOI

• Sex Differences in Human Immunodeficiency Virus Persistence and Reservoir Size During Aging

  Clinical Infectious Diseases · 2021 · 54 citations

  • Medicine
  • Internal medicine
  • Physiology

  BACKGROUND: Sex differences in human immunodeficiency virus (HIV) reservoir dynamics remain underexplored. METHODS: Longitudinal samples from virally suppressed midlife women (n = 59, median age 45 years) and age-matched men (n = 31) were analyzed retrospectively. At each time point, we measured sex hormones (by means of enzyme-linked immunosorbent assay) and cellular HIV DNA and RNA (by means of digital droplet polymerase chain reaction). Number of inducible HIV RNA+ cells, which provides an upper estimate of the replication-competent reservoir, was quantified longitudinally in a different subset of 14 women, across well-defined reproductive stages. Mixed-effects models included normalized reservoir outcomes and sex, time since antiretroviral therapy (ART) initiation, and the sex-by-time interaction as predictors. RESULTS: At ART initiation, women and men had median (interquartile range [IQR]) CD4+ T-cell counts of 204/μL (83-306/μL) versus 238/μL (120-284/μL), respectively; median ages of 45 (42-48) versus 47 (43-51) years; and median follow-up times of 79.2/μL (60.5-121.1/μL) versus 66.2/μL (43.2-80.6/μL) months. We observed a significant decline of total HIV DNA over time in both men and women (P < .01). However, the rates of change differed significantly between the sexes (P < .01), with women having a significantly slower rate of decline than men, more pronounced with age. By contrast, the levels of inducible HIV RNA increased incrementally over time in women during reproductive aging (P < .01). CONCLUSIONS: In contrast to men, in whom the HIV reservoir steadily declines with aging, the HIV reservoir in women is more dynamic. Total HIV DNA (including intact and defective genomes) declines more slowly in women than in men, while the inducible HIV RNA+ reservoir, which is highly enriched in replication-competent virus, increases in women after menopause.

  PublisherOA PDFDOI

• Presence of asymptomatic cytomegalovirus and Epstein--Barr virus DNA in blood of persons with HIV starting antiretroviral therapy is associated with non-AIDS clinical events

  AIDS · 2020 · 34 citations

  • Virology
  • Medicine
  • Immunology

  BACKGROUND: Even with antiretroviral therapy (ART), persons with HIV (PWH) experience increased morbidity and mortality. Cytomegalovirus (CMV) and Epstein--Barr virus (EBV) co-infections likely exacerbate inflammatory-related diseases. OBJECTIVE: To determine if presence of detectable CMV or EBV DNA in peripheral blood mononuclear cells (PBMC) is associated with non-AIDS events among PWH receiving modern ART. DESIGN: We performed a case--control study of PWH starting ART and HIV-suppressed at year 1 and thereafter, 140 cases who experienced non-AIDS events and 305 matched controls. Events included myocardial infarction, stroke, malignancy, serious bacterial infection or death. METHODS: Blood samples were studied pre-ART, 1-year post-ART and pre-event. Controls had an event-free follow-up equal or greater than cases. CMV and EBV DNA levels were measured in PBMC. Conditional logistic regression analysis assessed associations and adjusted for relevant covariates; Spearman's correlations compared CMV and EBV DNA levels with other biomarkers. RESULTS: CMV DNA was detected in PBMC of 25% of participants, EBV DNA was detected in more than 90%. Higher EBV DNA levels were associated with increased risk of events at all time points (odds ratio (OR) per one IQR = 1.5-1.7, all P < 0.009). At year 1, detectable CMV DNA was associated with increased risk of events in most adjusted models (OR = 1.4-1.8, P values ranging 0.03-0.17). Higher levels of CMV and EBV DNA correlated with multiple inflammatory markers and lower CD4/CD8 ratio. CONCLUSION: In PWH starting ART, detection of CMV and EBV DNA in PBMC was associated with development of non-AIDS events. Clinical trials will be needed to understand causal mechanisms and ways to interrupt them.

  PublisherOA PDFDOI

Frequent coauthors

• Davey M. Smith

  30 shared

• Antoine Chaillon

  26 shared

• Douglas D. Richman

  University of California System

  23 shared

• Sergei L. Kosakovsky Pond

  Temple University

  16 shared

• Daniel Osuna

  14 shared

• Enrique de Álava

  Instituto de Biomedicina de Sevilla

  14 shared

• José Luis Ordóñez

  14 shared

• Carlos Mackintosh

  14 shared