Towia Libermann

Beth Israel Deaconess Medical Center | BIDMC · Division of Interdisciplinary Medicine and Biotechnology

Background Reliable, noninvasive tools to diagnose at-risk metabolic dysfunction–associated steatohepatitis (MASH) are urgently needed to improve management. We developed a risk stratification score incorporating proteomics-derived serum markers with clinical variables to identify high-risk patients with MASH (NAFLD activity score >4 and fibrosis s...

Background Although the pathogenesis of delirium is poorly understood, increasing evidence supports a role for inflammation. Previously, individual inflammatory biomarkers have been associated with delirium. Aggregating biomarkers into an index may provide more information than individual biomarkers in predicting certain health outcomes (e.g., mort...

BACKGROUND Delirium after cardiac surgery is common, morbid, and costly, but may be prevented with risk stratification and targeted intervention. In this study, we aimed to identify protein biomarkers and develop a predictive model for postoperative delirium in older patients undergoing cardiac surgery. METHODS SomaScan analysis of 1305 proteins i...

Postoperative Delirium (POD) is the most common complication following surgery among older adults, and has been consistently associated with increased mortality and morbidity, cognitive decline, and loss of independence, as well as markedly increased health-care costs. The development of new tools to identify individuals at high risk for POD could...

Preoperative risk biomarkers for delirium may aid in identifying high-risk patients and developing intervention therapies, which would minimize the health and economic burden of postoperative delirium. Previous studies have typically used single omics approaches to identify such biomarkers. Preoperative cerebrospinal fluid (CSF) from the Healthier...

Previous studies suggest a role for inflammation in hepatocarcinogenesis. However, no study has comprehensively evaluated associations between circulating inflammatory proteins and risk of hepatocellular carcinoma (HCC) among the general population. We conducted a nested case–control study in the Nurses' Health Study (NHS) and the Health Profession...

Objective Proteomics may discover pathophysiological changes related to hepatocellular carcinoma (HCC), an aggressive and lethal type of cancer with low sensitivity for early-stage diagnosis. Design We measured 1,305 pre-diagnostic (median 12.7 years) SOMAscan proteins from 54 pairs of healthy individuals who subsequently developed HCC and matched...

Background Identifying minimally invasive diagnostic biomarkers that predict and monitor response to TNF inhibitors would enable treatment to be personalized and increase knowledge of the biological pathways associated with response or lack thereof. Methods Children and adolescents with Crohn’s disease who started treatment with infliximab (IFX) w...

Background While the two main inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), share various clinical features, they differ in clinical, endoscopic and histological features, and may have different underlying etiopathological mechanisms, resulting in different treatment options. Consequently, the development of r...

Background The Successful Aging after Elective Surgery (SAGES) II Study was designed to examine the relationship between delirium and Alzheimer's disease and related dementias (AD/ADRD), by capturing novel fluid biomarkers, neuroimaging markers, and neurophysiological measurements. The goal of this paper is to provide the first complete description...

Delirium, an acute change in cognition, is common, morbid, and costly, particularly among hospitalized older adults. Despite growing knowledge of its epidemiology, far less is known about delirium pathophysiology. Initial work understanding delirium pathogenesis has focused on assaying single or a limited subset of molecules or genetic loci. Recent...

Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to a lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover a...

Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) is an E3 ligase for the neddylation, a post-translational process similar to and occurring in parallel to ubiquitin proteasome pathway. Although established as an oncogene in a variety of squamous cell carcinomas, the precise role of DCUN1D1 in prostate cancer (PCa) has not been previo...

Background Identifying factors that confer resilience to developing delirium is critical given the negative impact of delirium on clinical care and risk for mortality. Here, we investigated a cohort of cognitively normal older adults undergoing elective surgery and examined the role of pre‐operative memory function and cortical thickness in the inc...

Background: Delirium following cardiac surgery is common, morbid, and costly, but may be prevented with risk stratification and targeted intervention. Preoperative protein signatures may identify patients at increased risk for worse postoperative outcomes, including delirium. In this study, we aimed to identify plasma protein biomarkers and develop...

Study question: What are the similarities and differences in the systemic proteomic profiles by endometriosis-associated pain subtypes among adolescents and young adults with endometriosis? Summary answer: Endometriosis-associated pain subtypes exhibited distinct plasma proteomic profiles. What is known already: Endometriosis patients, especia...

Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype, accounts for ~15% of all breast cancers and is associated with a poor prognosis and high rates of recurrence and distant metastases. Patients diagnosed with TNBC have limited treatment options and are often restricted to chemotherapy-based regimens, in stark contrast to pati...

Simple Summary Oral cancer is a life-threatening disease and among the ten most common cancer types. Specific protein biomarkers in the blood of these patients may allow early tumor detection, earlier intervention and help to individualize therapy resulting in improved patient survival. This exploratory study analyzed the serum proteome with a high...

Background: Diet modulates inflammation and insulin response and may be an important modifiable factor in the primary prevention of hepatocellular carcinoma (HCC) and chronic liver disease (CLD). We developed the empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores to assess the inflammatory...

Background A major unmet need for Systemic Sclerosis (SSc) clinical management is the lack of biomarkers for the early diagnosis of patients with Raynaud’s Phenomenon at high risk of evolving into SSc. Objective To identify proteins contained within serum exosomes employing an aptamer proteomic analysis that may serve to reveal patients with Rayna...

Background: Post-surgical delirium is associated with increased morbidity, lasting cognitive decline, and loss of functional independence. Within a conceptual framework that delirium is triggered by stressors when vulnerabilities exist in cerebral connectivity and plasticity, we previously suggested that neurophysiologic measures might identify in...

Background: The Successful Aging after Elective Surgery (SAGES) II study was designed to increase knowledge of the pathophysiology and linkages between delirium and dementia. We examine novel biomarkers potentially associated with delirium, including inflammation, Alzheimer's disease (AD) pathology and neurodegeneration, neuroimaging markers, and...

Due to cost and participant burden, neuroimaging studies are often performed in relatively small samples of voluntary participants. This may lead to selection bias. It is important to identify factors associated with participation in neuroimaging studies and understand their effect on outcome measures. We investigated the effect of postoperative de...

Study question: What are the systemic molecular profiles of endometriosis diagnosed in adolescents and young adults? Summary answer: Significant enrichment and increased activation of proteins related to angiogenesis and cell migration pathways were observed in endometriosis cases compared to controls (P-value < 2.4 × 10-8). What is known alrea...

Fanconi anemia (FA), a genetic disorder affecting DNA repair, is characterized by bone marrow failure and cancer susceptibility. In FA mouse models the biguanide metabolic agent metformin improves blood counts and delays tumor development. We conducted a single institution pilot study of metformin in non-diabetic patients with FA to assess feasibil...

Limited data exist on the performance of high‐throughput proteomics profiling in epidemiological settings, including the impact of specimen collection and within‐person variability over time. Thus, the Olink (972 proteins) and SOMAscan7Kv4.1 (7,322 proteoforms of 6,596 proteins) assays were utilized to measure protein concentrations in archived pla...

Atelectasis is a frequent clinical condition, yet knowledge is limited and controversial on its biological contribution towards lung injury. We assessed the regional proteomics of atelectatic versus normally-aerated lung tissue to test the hypothesis that immune and alveolar-capillary barrier functions are compromised by purely atelectasis and dysr...

Background: The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF....

Background & Aims Collagenous gastritis (CG) is a rare disorder characterized by increased subepithelial collagen deposition and inflammatory infiltrates. The mechanisms involved in CG pathogenesis are poorly understood and no CG-associated biomarkers have been identified. This proteomics study identified serum biomarkers and pathogenic pathways to...

Fanconi anemia (FA), a genetic disorder affecting DNA repair, is characterized by bone marrow failure and cancer susceptibility. In FA mouse models, metformin (N,N-dimethylguanide) a biguanide metabolic agent, improves blood counts and delays tumor development. Given these findings, we conducted a single institution pilot study of metformin in non-...

[This corrects the article DOI: 10.3389/fimmu.2021.624821.].

Background Men with African ancestry are more likely to develop aggressive prostate cancer (PCa) and to die from this disease. The study of PCa in the South African population represents an opportunity for biomedical research due to the high prevalence of aggressive PCa. While inflammation is known to play a significant role in PCa progression, its...

Background: Men with African ancestry are more likely to develop aggressive prostate cancer (PCa) and to die from this disease. The study of PCa in the South African population represents an opportunity for biomedical research due to the high prevalence of aggressive PCa. While inflammation is known to play a significant role in PCa progression, it...

Diabetic kidney disease (DKD) and its major clinical manifestation, progressive renal decline that leads to end-stage renal disease (ESRD), are a major health burden for individuals with diabetes. The disease process that underlies progressive renal decline comprises factors that increase risk as well as factors that protect against this outcome. U...

Kidney disease affects 10% of the world population and is associated with increased mortality. Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children, often failing standard immunosuppression. Here, we report the results of a prospective study to investigate the immunological impact and safety of a gl...

( Am J Obstet Gynecol . 2020;223:433.e1–14) Placenta accreta spectrum (PAS), which includes placenta accreta, placenta increta and placenta percreta, often leads to hysterectomy and large-volume maternal hemorrhage and is a major cause of maternal mortality and morbidity. While maternal outcomes can be improved with planning after an accurate diagn...

Background: Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surge...

Introduction: The interaction between delirium and dementia is complex. We examined if Alzheimer's disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity. Methods: Participants (n = 59) were free...

Left Ventricular Outflow Tract (LVOT) obstruction occurs in approximately 70% of Hypertrophic Cardiomyopathy (HCM) patients and currently requires imaging or invasive testing for diagnosis, sometimes in conjunction with provocative physiological or pharmaceutical stimuli. To identify potential biomarkers of LVOT obstruction, we performed proteomics...

Background: Delirium (an acute change in cognition) is a common, morbid, and costly syndrome seen primarily in aging adults. Despite increasing knowledge of its epidemiology, delirium remains a clinical diagnosis with no established biomarkers to guide diagnosis or management. Advances in proteomics now provide opportunities to identify novel mark...

Left Ventricular Outflow Tract (LVOT) obstruction occurs in approximately 70% of Hypertrophic Cardiomyopathy (HCM) patients and currently requires imaging or invasive testing for diagnosis, sometimes in conjunction with provocative physiological or pharmaceutical stimuli. To identify potential biomarkers of LVOT obstruction, we performed proteomics...

Postoperative delirium is the most common complication among older adults undergoing major surgery. The pathophysiology of delirium is poorly understood, and no blood-based, predictive markers are available. We characterized the plasma metabolome of 52 delirium cases and 52 matched controls from the Successful Aging after Elective Surgery (SAGES) c...

Blood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to...

Apolipoprotein E (APOE) ɛ4 does not confer increased risk of delirium in older surgical patients; however, ɛ4 status modifies the relationship of C-reactive protein (CRP) with delirium: increased risk for delirium in ɛ4 carriers with high CRP. We examine whether APOE genotype modifies the established association between inflammatory marker chitinas...

Background: Men with African ancestry are more likely to develop aggressive prostate cancer (PCa) and to die from this disease. A distinct genomic landscape associated with specific ethnic groups may lead to different metabolic adaptations and inflammatory responses that permit tumor cells to proliferate and to grow. We hypothesize that a higher ri...

Background Delirium and Alzheimer’s disease (AD) are common causes of late‐life cognitive impairment with clear epidemiologic links; however, the pathophysiology underlying these links remains unclear. Our recent work suggests that Apolipoprotein E (APOE) ɛ4, the strongest genetic risk marker for AD, does not confer significantly increased risk of...

Background Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery...

Introduction: Few proteomics studies have included non-white individuals, and none have explored the influence of resiliency resources on the association between proteins and cardiovascular disease (CVD). Religious and spiritual beliefs and practices are understudied resiliency resources that may attenuate the influence of proteins associated with...

Background: Our objective was to assess the performance of machine learning methods to predict post-operative delirium using a prospective clinical cohort. Methods: We analyzed data from an observational cohort study of 560 older adults (≥ 70 years) without dementia undergoing major elective non-cardiac surgery. Post-operative delirium was deter...

Objective: To examine the association of the plasma neuroaxonal injury markers neurofilament light (NfL), total tau, glial fibrillary acid protein, and ubiquitin carboxyl-terminal hydrolase L1 with delirium, delirium severity, and cognitive performance. Methods: Delirium case-no delirium control (n = 108) pairs were matched by age, sex, surgery...

Major surgery is associated with a systemic inflammatory cascade that is thought, in some cases, to contribute to transient and/or sustained cognitive decline, possibly through neuroinflammatory mechanisms. However, the relationship between surgery, peripheral and central nervous system inflammation, and post-operative cognitive outcomes remains un...

Breast cancer brain metastasis is a major clinical challenge and is associated with a dismal prognosis. Understanding the mechanisms underlying the early stages of brain metastasis can provide opportunities to develop efficient diagnostics and therapeutics for this significant clinical challenge. We have previously reported that breast cancer-deriv...

Shwachman–Diamond syndrome (SDS) is an autosomal recessive multisystem disorder characterized by exocrine pancreatic dysfunction, bone marrow failure, and leukemia predisposition. Approximately 90% of cases are due to biallelic mutations in the Shwachman–Bodian–Diamond (SBDS) gene. Additional phenotypic features variably associated with SDS include...

Introduction Many cases of placenta accreta spectrum (PAS) are not diagnosed antenatally, despite identified risk factors and improved imaging methods. Identification of plasma protein biomarkers could further improve antenatal diagnosis of PAS. Objective The purpose of this study was to determine if women with PAS have a distinct plasma protein p...

Background: Oral steroids, traditionally thought of as immunosuppressive agents that are broad in their immunomodulatory effects, are a mainstay of treatment to reduce disease burden in chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of this study was to determine how differentially expressed proteins in CRSwNP are affected by oral...

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with epithelial expansion and polyp survival. However, the molecular mechanism of this aberrant proliferation is unclear. The purpose of this study was to interrogate derangements of the pappalysin-A/insulin-like growth factor binding protein/insulin-like growth factor-1 (...

Face transplantation is a promising solution for patients with devastating facial injuries who lack other satisfactory treatment options. At the same time, this type of transplantation is accompanied with high risks of acute transplant rejection. The limitations of traditional skin biopsy and the need to frequently monitor the condition of face tra...

Introduction: The Role of Inflammation after Surgery for Elders study correlates novel inflammatory markers measured in blood, cerebrospinal fluid (CSF) assays, and [11C]-PBR28 positron-emission tomography imaging. Methods: This study involved a prospective cohort design with patients who underwent elective hip and knee arthroplasty under spinal...

Delirium is a common, morbid, and costly geriatric syndrome, yet its pathophysiology remains poorly understood. In a nested matched case-control study within the Successful Aging after Elective Surgery (SAGES) study, a cohort of adults age ≥70 without dementia undergoing major non-cardiac surgery, we previously identified inflammatory proteins to b...

Postoperative delirium complicates 15-50% of major surgery in older adults, resulting in poor patient outcomes and increased healthcare costs. Basic mechanisms of delirium are largely unknown. In this study we implemented a protocol that uses high-throughput metabolomics to explore potential biological mechanisms of delirium. We profiled the plasma...

Introduction: Apolipoprotein E (APOE) status may modify the risk of postoperative delirium conferred by inflammation. Methods: We tested whether APOE modifies the established association between C-reactive protein (CRP) and delirium incidence, severity, and duration in 553 noncardiac surgical patients aged 70 and older. High postoperative plasma...

Systemic capillary leak syndrome (SCLS; Clarkson disease) is a rare orphan disorder characterized by transient yet recurrent episodes of hypotension and peripheral oedema due to diffuse vascular leakage of fluids and proteins into soft tissues. Humoral mediators, cellular responses and genetic features accounting for the clinical phenotype of SCLS...

Shwachman-Diamond Syndrome (SDS) is a rare and clinically-heterogeneous bone marrow (BM) failure syndrome caused by mutations in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. Although SDS was described over 50 years ago, the molecular pathogenesis is poorly understood due, in part, to the rarity and heterogeneity of the affected hematopoietic...