About
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Introduction
Current institution
Current position
- Join appointment with Icahn Institute for Genomics and Multiscale Biology
Additional affiliations
April 2015 - February 2017
Position
- Join appointment with Icahn Institute for Genomics and Multiscale Biology
February 2011 - April 2015
June 2010 - present
Center for Clinical and Translational Science (CCTS)
Position
- Co-Director, Biostatistics/Epidemiology/Research Design
Education
September 2003 - January 2007
February 1999 - February 2003
Publications
Publications (487)
Background
Major Adverse Kidney Events within 30 days (MAKE30) is an important patient-centered outcome for assessing the impact of acute kidney injury (AKI). Existing prediction models for MAKE30 are static and overlook dynamic changes in clinical status. We introduce ORAKLE, a novel deep-learning model that utilizes evolving time-series data to p...
Background and Aims
Patients with inflammatory bowel disease (IBD) exhibit distinct shifts in circulating metabolite levels linked to disease activity and phenotype, but associations with disease progression remain unexplored. Our aim was to investigate relationships between circulating metabolites and metabolic pathways with disease progression ri...
Study Objectives
To evaluate whether a foundational transformer using 8-hour, multichannel polysomnogram (PSG) data can effectively encode signals and classify sleep stages with state-of-the-art performance.
Methods
The Sleep Heart Health Study, Wisconsin Sleep Cohort, and Osteoporotic Fractures in Men (MrOS) Study Visit 1 were used for training,...
Induction of intestinal immune responses occurs in gut-associated lymphoid tissues (GALT). After priming in GALT, lymphocytes upregulate integrin α4β7, which drives their homing back to intestinal effector sites through engagement of MADCAM1. Tertiary lymphoid structures (TLS) such as ILF increase in inflamed intestines but their role in the pathog...
The gut microbiota enhances systemic immunoglobulin G (IgG) responses to vaccines, but it is unknown whether this effect involves IgA, which coats intestinal microbes. That IgA may amplify postimmune IgG production is suggested by the impaired IgG response to pneumococcal vaccines in some IgA-deficient patients. Here, we found that antipneumococcal...
Background:
Approved therapeutics for peanut allergy are not designed for the many patients with allergic reactions to more than one peanut.
Methods:
We randomly assigned (1:1) participants 4 to 14 years of age reacting to a challenge of between 443 mg and 5043 mg of peanut protein to peanut oral immunotherapy (P-OIT) using home-measured peanut...
Background
Acute kidney injury (AKI) is common in SARS-CoV-2 infection and COVID-19, often leading to long-term kidney dysfunction. However, the transcriptomic features of AKI severity and its long-term effects are underexplored.
Methods
We performed bulk RNA sequencing on peripheral blood mononuclear cells (PBMCs) from hospitalized SARS-CoV-2 pat...
Background
Antiangiogenics combined with immune checkpoint blockade have become standard of care for recurrent endometrial cancer after standard platinum-based chemotherapy. To dissect mechanisms and define biomarkers associated with clinical outcomes to these combinations, we applied multidimensional immune monitoring to peripheral blood specimens...
Background
Identification of immune signatures in pre-clinical IBD provides a unique window of therapeutic intervention with disease-modifying potential. This study aimed to define the antigen specificities, breadth, longitudinal stability, and predictive ability of pre-clinical serum antibody repertoires using a novel, high-throughput phage-displa...
Background
Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are present in up to 90% of ulcerative colitis (UC) patients and predate disease development, but there is a paucity of data regarding anti-αvβ6 in Crohn’s disease (CD). We hypothesized that anti-αvβ6 would be present in colonic CD given the shared biological characteristics with UC.
Methods...
Background
Around 20-30% of patients with Crohn's disease (CD) experience a mild disease course. However, identifying patients likely to maintain a mild course is challenging. This study aimed to identify molecular features of mild CD by exploring biological datasets from two large patient cohorts.
Methods
Patients with mild CD were analysed from...
Background
The kynurenine pathway is upregulated in inflammatory bowel disease (IBD) in a disease-activity induced manner. This route of tryptophan (Trp) degradation leads to a variety of bioactive compounds, including several with anti-inflammatory (e.g., kynurenic acid (Kyna), xanthurenic acid (Xana)) or cytotoxic (quinolinic acid (Quin)) effects...
Background
Major Adverse Kidney Events within 30 days (MAKE30) is an important patient-centered outcome for assessing the impact of acute kidney injury (AKI). The existing prediction models for MAKE30 are static and overlook dynamic changes in clinical status. In this study, we introduce ORAKLE, a novel deep-learning model that utilizes evolving ti...
Purpose
We designed a study investigating the cardioprotective role of sleep apnea (SA) in patients with acute myocardial infarction (AMI), focusing on its association with infarct size and coronary collateral circulation.
Methods
We recruited adults with AMI, who underwent Level-III SA testing during hospitalization. Delayed-enhancement cardiac m...
Achieving adequate enteral nutrition among mechanically ventilated patients is challenging, yet critical. We developed NutriSighT, a transformer model using learnable positional coding to predict which patients would achieve hypocaloric nutrition between days 3 to 7 of mechanical ventilation. Using retrospective data from two large ICU databases (3...
Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high-resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic...
Study Objectives
To investigate whether a foundational transformer model using 8-hour, multi-channel data from polysomnograms can outperform existing artificial intelligence (AI) methods for sleep stage classification.
Methods
We utilized the Sleep Heart Health Study (SHHS) visits 1 and 2 for training and validation and the Multi-Ethnic Study of A...
Background
Despite studies confirming that patients with inflammatory bowel disease (IBD) present with dyslipidaemia, the associations between IBD and the serum lipid profile have not been determined. The present study aimed to investigate the causal relationship between the serum lipid profile and IBD risk and elucidate the nature of the interacti...
Gastrointestinal (GI) B cells and plasma cells (PCs), critical to mucosal homeostasis, play an important role in the host response to HIV-1 infection. Here, high resolution mapping of human B cells and PCs from colon and ileum during both viremic and suppressed HIV-1 infection identified a significant reduction in germinal center (GC) B cells and F...
Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7 ⁺ ) plasmablast...
Obstructive sleep apnea (OSA) affects almost a billion people worldwide and is associated with a myriad of adverse health outcomes. Among the most prevalent and morbid are cardiovascular diseases (CVDs). Nonetheless, randomized controlled trials (RCTs) of OSA treatment have failed to show improvements in CVD outcomes. A major limitation in our fiel...
Rationale:
Randomized controlled trials of continuous positive airway pressure (CPAP) therapy for cardiovascular disease (CVD) prevention among patients with obstructive sleep apnea (OSA) have been largely neutral. However, given OSA is a heterogeneous disease, there may be unidentified subgroups demonstrating differential treatment effects.
Obje...
The role of long noncoding RNAs (lncRNAs) in disease is incompletely understood, but their regulation of inflammation is increasingly appreciated. We addressed the extent of lncRNA involvement in inflammatory bowel disease (IBD) using biopsy-derived RNA-sequencing data from a large cohort of deeply phenotyped patients with IBD. Weighted gene correl...
Background
Approximately 20-30% of patients with Crohn's disease (CD) experience a mild disease course following initial diagnosis. Balancing the effectiveness and safety of medical treatments is crucial in the management of mild CD. However, the main clinical challenge currently lies in identifying patients likely to maintain this mild disease cou...
Background
Patients with inflammatory bowel diseases (IBD) exhibit distinct shifts in circulating metabolite levels that have been associated with clinical disease activity and disease phenotype. However, there are limited data on the impact of metabolomic changes on disease progression in IBD. We aimed to understand the association of circulating...
Background
Vedolizumab (VDZ) targets the gut-homing receptor α4β7. Despite its widespread use as a frontline therapy for ulcerative colitis (UC), its mode of action (MOA) remains unclear. Previously, we documented that response to VDZ is associated with size loss of gut-associated lymphoid tissues (GALT). To further understand drug MOA, here we aim...
Background
Secukinumab, an anti-IL-17A monoclonal antibody, induces histological and molecular resolution of psoriatic plaques by 12 weeks. However, the long-term effects of secukinumab on molecular resolution of psoriatic inflammation remain unknown.
Objective
To investigate the molecular resolution of psoriasis following 52-weeks of secukinumab...
The severity of aortic stenosis (AS) is associated with acquired von Willebrand syndrome (AVWS) and gastrointestinal bleeding, leading to anemia (Heyde's syndrome). We investigated how anemia is linked with AS and AVWS using the LA100 mouse model and patients with AS. Induction of anemia in LA100 mice increased transforming growth factor (TGF)-β1 a...
Background.
Acute kidney injury (AKI) is common in hospitalized patients with SARS-CoV2 infection despite vaccination and leads to long-term kidney dysfunction. However, peripheral blood molecular signatures in AKI from COVID-19 and their association with long-term kidney dysfunction are yet unexplored.
Methods.
In patients hospitalized with SARS-C...
Background
Secukinumab is effective against a range of psoriatic manifestations. Investigating psoriasis (PsO) relapse following secukinumab discontinuation could provide insights into long-term PsO remission.
Objective
To examine PsO relapse rates upon treatment discontinuation following one year of secukinumab treatment.
Methods
This study (NCT...
Background:
Substantial effort has been directed toward demonstrating uses of predictive models in health care. However, implementation of these models into clinical practice may influence patient outcomes, which in turn are captured in electronic health record data. As a result, deployed models may affect the predictive ability of current and fut...
Background
Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms.
Methods
Using measurements of ~4000 plasma proteins in two cohorts of patient...
Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with sharply rising global prevalence. Dysfunctional epithelial compartment (EC) dynamics are implicated in UC pathogenesis although EC-specific studies are sparse. Applying orthogonal high-dimensional EC profiling to a Primary Cohort (PC; n=222), we detail major epi...
Objective
To assess whether an individual’s degree of psychological resilience can be determined from physiological metrics passively collected from a wearable device.
Materials and Methods
Data were analyzed in this secondary analysis of the Warrior Watch Study dataset, a prospective cohort of healthcare workers enrolled across 7 hospitals in New...
Background:
Histological response to treatment is an important outcome in patients with ulcerative colitis (UC). The accuracy of biopsy-based measurements of inflammation may be limited by error imposed by natural microscopic heterogeneity on the scale of individual biopsies. We determined the magnitude of this error, its histological correlates,...
Background:
Oral immunotherapy (OIT) is limited by adverse events, and most patients require continued treatment to maintain their increased threshold. Adjunctive treatments have been explored to increase the safety and efficacy of OIT.
Objective:
This study aimed to determine the safety and efficacy of E-B-FAHF-2 for inducing remission in subje...
Purpose:
Hippocampal dysfunction plays a key role in the pathology of psychosis. Given hippocampal sensitivity to changes in cerebral perfusion, decreased baroreflex function could contribute to psychosis pathogenesis. This study had two aims: (1) To compare baroreflex sensitivity in participants with psychosis to two control groups: participants...
Rationale:
Studies have shown elevated inflammatory biomarkers in OSA, but data following CPAP treatment are inconsistent.
Objectives:
We used the Olink® proteomics panel to identify unique OSA clusters based on inflammatory protein expression, and assess the impact of CPAP therapy.
Methods:
Adults with newly-diagnosed OSA had blood drawn at b...
Background
While the majority of Ulcerative Colitis (UC)-related mucosal studies have focused on whole intestinal tissues or the lamina propria (LP), epithelial compartment (EC)-specific studies are largely lacking. Here, we have defined EC-associated molecular and cellular dynamics during inflammation and studied their response to anti-tumor necro...
BACKGROUND
Inflammatory bowel disease (IBD) flares are common and unpredictable. Disease monitoring relies on symptom reporting or single timepoint assessments of stool, blood, imaging, or endoscopy—these are inconvenient and invasive and do not always reflect the patient perspective. Advances in wearable technology allow for passive, continuous an...
Targeting the α4β7-MAdCAM-1 axis with vedolizumab (VDZ) is a front-line therapeutic paradigm in ulcerative colitis (UC). However, mechanism(s) of action (MOA) of VDZ remain relatively undefined. Here, we examined three distinct cohorts of patients with UC (n=83, n=60, and n=21), to determine the effect of VDZ on the mucosal and peripheral immune sy...
Background
Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms.
Methods
Using measurements of ~4000 plasma proteins in two cohorts of patients...
Background:
Currently, there is no laboratory test that can accurately identify children at risk of developing peanut allergy. Utilizing a subset of children randomized to the peanut avoidance arm of the LEAP trial, we monitored the development of epitope-specific (ses-)IgE and ses-IgG4 from 4-11 months to 5 years of age.
Objective:
The aim of t...
Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is lacking. We integrated transcriptional data of over 3,000 samples, from 820 adults across 28 studies of 13 vaccines and analyzed vaccination-induced signatures of antibody responses. Most...
Vaccines are among the most cost-effective public health interventions for preventing infection-induced morbidity and mortality, yet much remains to be learned regarding the mechanisms by which vaccines protect. Systems immunology combines traditional immunology with modern ‘omic profiling techniques and computational modeling to promote rapid and...
Several studies have shown that the pre-vaccination immune state is associated with the antibody response to vaccination. However, the generalizability and mechanisms that underlie this association remain poorly defined. Here, we sought to identify a common pre-vaccination signature and mechanisms that could predict the immune response across 13 di...
Objective
IBD therapies and treatments are evolving to deeper levels of remission. Molecular measures of disease may augment current endpoints including the potential for less invasive assessments.
Design
Transcriptome analysis on 712 endoscopically defined inflamed (Inf) and 1778 non-inflamed (Non-Inf) intestinal biopsies (n=498 Crohn’s disease,...
Objective
To determine whether a machine learning model can detect SARS-CoV-2 infection from physiological metrics collected from wearable devices.
Materials and Methods
Health care workers from 7 hospitals were enrolled and prospectively followed in a multicenter observational study. Subjects downloaded a custom smart phone app and wore Apple Wat...
Understanding the immune response to dengue virus (DENV) is essential for developing a dengue vaccine that is protective against all four DENV serotypes. We evaluated the immune response post-vaccination (live attenuated tetravalent dengue vaccine TV005 or trivalent admixture) and post-challenge with DEN2Δ30 (Tonga/74) to better understand the impo...
There is a need for better classification and understanding of tumor-infiltrating lymphocytes (TILs). Here, we applied advanced functional genomics to interrogate 9,000 human tumors and multiple single-cell sequencing sets using benchmarked T cell states, comprehensive T cell differentiation trajectories, human and mouse vaccine responses, and othe...
Systems biology approaches have been used to define molecular signatures and mechanisms of immunity to vaccination. However, most such studies have been done with single vaccines, and comparative analysis of the response to different vaccines is lacking. We integrated temporal transcriptional data of over 3,000 samples, obtained from 820 healthy ad...
B cells, which are critical for intestinal homeostasis, remain understudied in ulcerative colitis (UC). In this study, we recruited three cohorts of patients with UC (primary cohort, n = 145; validation cohort 1, n = 664; and validation cohort 2, n = 143) to comprehensively define the landscape of B cells during UC-associated intestinal inflammatio...
Background
Wearable devices enable monitoring and measurement of physiological parameters over a 24-h period, and some of which exhibit circadian rhythm characteristics. However, the currently available R package cosinor could only analyze daily cross-sectional data and compare the parameters between groups with two levels. To evaluate longitudinal...
Vaccines are among the most cost-effective public health interventions for preventing infection-induced morbidity and mortality, yet much remains to be learned regarding the mechanisms by which vaccines protect. Systems immunology combines traditional immunology with modern 'omic profiling techniques and computational modeling to promote rapid and...
Importance: Passive and non-invasive identification of SARS-CoV-2 infection remains a challenge. Widespread use of wearable devices represents an opportunity to leverage physiological metrics and fill this knowledge gap.
Objective: To determine whether a machine learning model can detect SARS-CoV-2 infection from physiological metrics collected fro...
Background
Polygenic and environmental factors are underlying causes of inflammatory bowel disease (IBD). We hypothesized that integration of the genetic loci controlling a metabolite’s abundance, with known IBD genetic susceptibility loci, may help resolve metabolic drivers of IBD.
Methods
We measured the levels of 1300 metabolites in the serum o...
Many factors determine whether an individual responding to vaccination will generate an immune response that can lead to protection. Several studies have shown that the pre-vaccination immune state associate with the antibody response to vaccines. However, the generalizability and mechanisms that underlie this association remain poorly defined. Her...
Background
Disease extent varies in ulcerative colitis (UC) from proctitis to left-sided colitis to pancolitis and is a major prognostic factor. When the extent of UC is limited there is often a sharp demarcation between macroscopically involved and uninvolved areas and what defines this or subsequent extension, is unknown. We characterized the dem...
An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful predict...
Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection1,2, yet the host response at the lung tissue-level is poorly understood. Here, we performed single-nucleus RNA-sequencing of ~116,000 nuclei of lungs from 19 COVID-19 decedents who underwent rapid autopsy and 7 control lungs. Integrated analyses revealed...
Background
The COVID-19 pandemic has resulted in a high degree of psychological distress among health care workers (HCWs). There is a need to characterize which HCWs are at an increased risk of developing psychological effects from the pandemic. Given the differences in the response of individuals to stress, an analysis of both the perceived and ph...
BACKGROUND
The COVID-19 pandemic has resulted in a high degree of psychological distress among health care workers (HCWs). There is a need to characterize which HCWs are at an increased risk of developing psychological effects from the pandemic. Given the differences in the response of individuals to stress, an analysis of both the perceived and ph...
Background
Accurate diagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood test using the peanut bead‐based epitope assay (“peanut BBEA”) was developed utilizing the LEAP cohort and then validated using two independent cohorts.
Methods
The development of the peanut BBEA diagnostic test followed the National...
Patients with a disorder of mitochondrial long-chain fatty acid β-oxidation (FAO) have reduced fasting tolerance and may present with hypoketotic hypoglycemia, hepatomegaly, (cardio)myopathy and rhabdomyolysis. Patients should avoid a catabolic state because it increases reliance on FAO as energy source. It is currently unclear whether weight loss...
With the fast evolution of high-throughput technology, longitudinal gene expression experiments have become affordable and increasingly common in biomedical fields. Generalized estimating equation (GEE) approach is a widely used statistical method for the analysis of longitudinal data. Feature selection is imperative in longitudinal omics data anal...
An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of ulcerative colitis (UC) patients require colectomy within five years of diagnosis, but polygenic risk scores (PRS) utilizing findings from GWAS are unable to provide meaningful prediction of this adverse status. By contrast,...
Background
Inflammatory bowel disease (IBD) is a complex disease with variable presentation, progression and response to therapies. Current disease classification is based on subjective clinical phenotypes. The peripheral blood immunophenome can reflect local inflammation, thus we measured 39 circulating immune cell types in a large cohort of IBD a...
Questions
Question (1)
A postdoctoral position in Machine Learning is available at the Mount Sinai School of Medicine. The successful candidate will join ongoing efforts in the Precise MD program, an innovative initiative that leverages our computational pathology infrastructure to integrate machine vision and machine learning algorithms for diagnostic and prognostic assay development. Specifically, the candidate will be working on building prognosis models in prostate and breast cancer, based on the integration of clinical endpoints and quantitative biomarker characteristics derived by an advanced machine vision platform. Successful candidates will have earned a doctoral degree or foreign equivalent in an interdisciplinary, data-driven field, with educational emphasis in machine learning /statistics/data science preferred; experience in image analysis is a plus. Special consideration will be given to candidates with experience in survival analysis. Additional qualifications include: a superior academic performance, proficiency in Matlab, R, Python etc and an ability to be self-directed with broadly-defined limits on assignments; excellent communication skills, both oral and written; and a demonstrated ability to interact efficiently with diverse people in a highly multidisciplinary environment. This is a full-time, two-year postdoctoral position. The postdoc may not have more than five years of postdoctoral experience including that from other institutions. Review of applications will begin immediately with the position to be filled as soon as possible. We encourage applications from individuals of diverse backgrounds. Interested individuals should send a CV and the names of three references to Dr. Suarez-Farinas (mayte.suarezfarinas@mssm.edu) with a subject line “postdoc position”).
