Bradley E. Aouizerat

Faculty

Bradley E. Aouizerat headshot

Bradley E. Aouizerat

PhD

Professor, College of Dentistry

Bradley E. Aouizerat's additional information

BS, Microbiology/ Molecular Genetics - University of California at Los Angeles
PhD, Microbiology/ Molecular Genetics/lmmunology - University of California at Los Angeles
MAS, Master of Advance Science Research in Clinical - University of California at San Francisco

Oral-systemic health

American Heart Association
American Liver Foundation
American Pain Society
American Society for Human Genetics
International Association for the Study of Pain

Faculty Honors Awards

Excellence in Research Mentoring Faculty Teaching Award (2013)
Excellence in Research Mentoring Faculty Teaching Award (Nominee) (2012)
Excellence in Research Mentoring Faculty Teaching Award (Nominee) (2011)
Most Dedicated Mentor Award, PMCTR Fellowship Program (2009)
Early Career Investigator Award, Bayer Healthcare International (2006)
Multidisciplinary Clinical Research Scholar, Roadmap K12 (2006)
Early Career Faculty Award, Hellman Family (2005)
Faculty Mentorship Award Nominee (2005)
Young Investigator Award, National Hemophilia Foundation (2005)
National Liver Scholar Award, American Liver Foundation (2004)
Irvine H. Page Young Investigator Award (Finalist), American Heart Association (2004)
Faculty Mentorship Award Nominee (2004)
Sam and Rose Gilbert Fellowship, UCLA (1998)
Warsaw Fellowship (1998)

Publications

Gene Expression Profiling of Evening Fatigue in Women Undergoing Chemotherapy for Breast Cancer

Kober, K. M., Dunn, L., Mastick, J., Cooper, B., Langford, D., Melisko, M., Venook, A., Chen, L. M., Wright, F., Hammer, M., Schmidt, B. L., Levine, J., Miaskowski, C., & Aouizerat, B. E. (2016). Biological Research for Nursing, 18(4), 370-385. 10.1177/1099800416629209
Abstract
Abstract
Moderate-to-severe fatigue occurs in up to 94% of oncology patients undergoing active treatment. Current interventions for fatigue are not efficacious. A major impediment to the development of effective treatments is a lack of understanding of the fundamental mechanisms underlying fatigue. In the current study, differences in phenotypic characteristics and gene expression profiles were evaluated in a sample of breast cancer patients undergoing chemotherapy (CTX) who reported low (n = 19) and high (n = 25) levels of evening fatigue. Compared to the low group, patients in the high evening fatigue group reported lower functional status scores, higher comorbidity scores, and fewer prior cancer treatments. One gene was identified as upregulated and 11 as downregulated in the high evening fatigue group. Gene set analysis found 24 downregulated and 94 simultaneously up- and downregulated pathways between the two fatigue groups. Transcript origin analysis found that differential expression (DE) originated primarily from monocytes and dendritic cell types. Query of public data sources found 18 gene expression experiments with similar DE profiles. Our analyses revealed that inflammation, neurotransmitter regulation, and energy metabolism are likely mechanisms associated with evening fatigue severity; that CTX may contribute to fatigue seen in oncology patients; and that the patterns of gene expression may be shared with other models of fatigue (e.g., physical exercise and pathogen-induced sickness behavior). These results suggest that the mechanisms that underlie fatigue in oncology patients are multifactorial.

Human leucocyte antigen class I and II imputation in a multiracial population

Kuniholm, M. H., Xie, X., Anastos, K., Xue, X., Reimers, L., French, A. L., Gange, S. J., Kassaye, S. G., Kovacs, A., Wang, T., Aouizerat, B. E., & Strickler, H. D. (2016). International Journal of Immunogenetics, 43(6), 369-375. 10.1111/iji.12292
Abstract
Abstract
Human leucocyte antigen (HLA) genes play a central role in response to pathogens and in autoimmunity. Research to understand the effects of HLA genes on health has been limited because HLA genotyping protocols are labour intensive and expensive. Recently, algorithms to impute HLA genotype data using genome-wide association study (GWAS) data have been published. However, imputation accuracy for most of these algorithms was based primarily on training data sets of European ancestry individuals. We considered performance of two HLA-dedicated imputation algorithms – SNP2HLA and HIBAG – in a multiracial population of n = 1587 women with HLA genotyping data by gold standard methods. We first compared accuracy – defined as the percentage of correctly predicted alleles – of HLA-B and HLA-C imputation using SNP2HLA and HIBAG using a breakdown of the data set into an 80% training group and a 20% testing group. Estimates of accuracy for HIBAG were either the same or better than those for SNP2HLA. We then conducted a more thorough test of HIBAG imputation accuracy using five independent 10-fold cross-validation procedures with delineation of ancestry groups using ancestry informative markers. Overall accuracy for HIBAG was 89%. Accuracy by HLA gene was 93% for HLA-A, 84% for HLA-B, 94% for HLA-C, 83% for HLA-DQA1, 91% for HLA-DQB1 and 88% for HLA-DRB1. Accuracy was highest in the African ancestry group (the largest group) and lowest in the Hispanic group (the smallest group). Despite suboptimal imputation accuracy for some HLA gene/ancestry group combinations, the HIBAG algorithm has the advantage of providing posterior estimates of accuracy which enable the investigator to analyse subsets of the population with high predicted (e.g. >95%) imputation accuracy.

In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores

Schwimmer, J. B., Lavine, J. E., Wilson, L. A., Neuschwander-Tetri, B. A., Xanthakos, S. A., Kohli, R., Barlow, S. E., Vos, M. B., Karpen, S. J., Molleston, J. P., Whitington, P. F., Rosenthal, P., Jain, A. K., Murray, K. F., Brunt, E. M., Kleiner, D. E., Van Natta, M. L., Clark, J. M., Tonascia, J., … Yates, K. (2016). Gastroenterology, 151(6), 1141-1154.e9. 10.1053/j.gastro.2016.08.027
Abstract
Abstract
Background & Aims No treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD. Methods We performed a double-masked trial of 169 children with NAFLD activity scores of 4 or higher at 10 centers. From June 2012 to January 2014, the patients were assigned randomly to receive CBDR or placebo twice daily (300 mg for patients weighing ≤65 kg, 375 mg for patients weighing >65 to 80 kg, and 450 mg for patients weighing >80 kg) for 52 weeks. The primary outcome from the intention-to-treat analysis was improvement in liver histology over 52 weeks, defined as a decrease in the NAFLD activity score of 2 points or more without worsening fibrosis; patients without biopsy specimens from week 52 (17 in the CBDR group and 6 in the placebo group) were considered nonresponders. We calculated the relative risks (RR) of improvement using a stratified Cochran–Mantel–Haenszel analysis. Results There was no significant difference between groups in the primary outcome (28% of children in the CBDR group vs 22% in the placebo group; RR, 1.3; 95% confidence interval [CI], 0.8–2.1; P =.34). However, children receiving CBDR had significant changes in prespecified secondary outcomes: reduced mean levels of alanine aminotransferase (reduction, 53 ± 88 U/L vs 8 ± 77 U/L in the placebo group; P =.02) and aspartate aminotransferase (reduction, 31 ± 52 vs 4 ± 36 U/L in the placebo group; P =.008), and a larger proportion had reduced lobular inflammation (36% in the CBDR group vs 21% in the placebo group; RR, 1.8; 95% CI, 1.1–2.9; P =.03). In a post hoc analysis of children weighing 65 kg or less, those taking CBDR had a 4-fold better chance of histologic improvement (observed in 50% of children in the CBDR group vs 13% in the placebo group; RR, 4.0; 95% CI, 1.3–12.3; P =.005). Conclusions In a randomized trial, we found that 1 year of CBDR did not reduce overall histologic markers of NAFLD compared with placebo in children. Children receiving CBDR, however, had significant reductions in serum aminotransferase levels and lobular inflammation. ClinicalTrials.gov no: NCT01529268.

Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms

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Abstract
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). Aim: To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. Methods: A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. Results: The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with not only increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. Conclusions: These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression.

Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C

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Abstract
Abstract
Objective: Because HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to minimal hepatic encephalopathy in the absence of cirrhosis. Background: Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy. Minimal hepatic encephalopathy occurs in cirrhotic patients with or without HIV infection and may be associated with inflammation. Design/Methods: A cross-sectional investigation of liver fibrosis severity using the aspartate aminotransferase to platelet ratio index (APRI) and neuropsychological testing performance among women from the Women's Interagency HIV Study. A subset underwent liver transient elastography (FibroScan, n 303). Results: We evaluated 1479 women [mean (SD) age of 46 (9.3) years]: 770 (52%) only HIV infected, 73 (5%) only hepatitis C virus (HCV) infected, 235 (16%) HIV/HCV coinfected, and 401 (27%) uninfected. Of these, 1221 (83%) exhibited APRI ≤0.5 (no or only mild fibrosis), 206 (14%) exhibited APRI >0.5 and ≤1.5 (moderate fibrosis), and 52 (3%) exhibited APRI >1.5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with worse performance in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). The severity of fibrosis, measured by FibroScan, was associated with worse performance in attention, executive functioning, and fluency. Conclusions: Liver fibrosis had a contribution to cognitive performance independent of HCV and HIV; however, the pattern of neuropsychological deficit associated with fibrosis was not typical of minimal hepatic encephalopathy.

Phenotypic and molecular characteristics associated with various domains of quality of life in oncology patients and their family caregivers

Alexander, K. E., Cooper, B. A., Paul, S. M., Yates, P., Aouizerat, B. E., & Miaskowski, C. (2016). Quality of Life Research, 25(11), 2853-2868. 10.1007/s11136-016-1310-x
Abstract
Abstract
Purpose: Not all oncology patients and their family caregivers (FCs) experience the same quality of life (QOL). The purposes of this study were to identify latent classes of oncology patients (n = 168) and their FCs (n = 85) with distinct physical, psychological, social, and spiritual well-being trajectories from prior to through 4 months after the completion of radiation therapy and to evaluate for demographic, clinical, and genetic characteristics that distinguished between these latent classes. Methods: Using growth mixture modeling, two latent classes were found for three (i.e., physical, psychological, and social well-being) of the four QOL domains evaluated. Results: Across these three domains, the largest percentage of participants reported relatively high well-being scores across the 6 months of the study. Across these three QOL domains, patients and FCs who were younger, female, belonged to an ethnic minority group, had children at home, had multiple comorbid conditions, or had a lower functional status, were more likely to be classified in the lower QOL class. The social well-being domain was the only domain that had a polymorphism in nuclear factor kappa beta 2 (NFKB2) associated with latent class membership. Carrying one or two doses of the rare allele for rs7897947 was associated with a 54 % decrease in the odds of belonging to the lower social well-being class [OR (95 % CI) = .46 (.21,.99), p = .049]. Conclusions: These findings suggest that a number of phenotypic and molecular characteristics contribute to differences in QOL in oncology patients and their FCs.

Polymorphisms in Tumor Necrosis Factor-α Are Associated with Higher Anxiety Levels in Women after Breast Cancer Surgery

Miaskowski, C., Elboim, C., Paul, S. M., Mastick, J., Cooper, B. A., Levine, J. D., & Aouizerat, B. E. (2016). Clinical Breast Cancer, 16(1), 63-71.e3. 10.1016/j.clbc.2014.12.001
Abstract
Abstract
Introduction Before and after breast cancer surgery, women have reported varying anxiety levels. Recent evidence has suggested that anxiety has a genetic basis and is associated with inflammation. The purposes of the present study were to identify the subgroups of women with distinct anxiety trajectories; to evaluate for differences in the phenotypic characteristics between these subgroups; and to evaluate for associations between polymorphisms in cytokine genes and subgroup membership. Patients and Methods Patients with breast cancer (n = 398) were recruited before surgery and followed up for 6 months. The patients completed the Spielberger State Anxiety Inventory and provided a blood sample for genomic analyses. Growth mixture modeling was used to identify the subgroups of patients with distinct anxiety trajectories. Results Two distinct anxiety subgroups were identified. The women in the higher anxiety subgroup were younger and had a lower functional status score. Two single nucleotide polymorphisms in tumor necrosis factor-α (rs1799964, rs3093662) were associated with the higher anxiety subgroup. Conclusion The results of the present exploratory study suggest that polymorphisms in cytokine genes could partially explain the interindividual variability in anxiety. The determination of phenotypic and molecular markers associated with greater levels of anxiety can assist clinicians to identify high-risk patients and initiate appropriate interventions.

Predictors of altered upper extremity function during the first year after breast cancer treatment

Smoot, B., Paul, S. M., Aouizerat, B. E., Dunn, L., Elboim, C., Schmidt, B., Hamolsky, D., Levine, J. D., Abrams, G., Mastick, J., Topp, K., & Miaskowski, C. (2016). American Journal of Physical Medicine and Rehabilitation, 95(9), 639-655. 10.1097/PHM.0000000000000455
Abstract
Abstract
Objective The purpose of this study was to evaluate trajectories of and predictors for changes in upper extremity (UE) function in women (n = 396) during the first year after breast cancer treatment. Design Prospective, longitudinal assessments of shoulder range of motion (ROM), grip strength, and perceived interference of function were performed before and for 1 year after surgery. Demographic, clinical, and treatment characteristics were evaluated as predictors of postoperative function. Results Women had a mean (SD) age of 54.9 (11.6) years, and 64% were white. Small but statistically significant reductions in shoulder ROM were found on the affected side over 12 months (P < 0.001). Predictors of interindividual differences in ROM at the 1-month assessment were ethnicity, neoadjuvant chemotherapy, type of surgery, axillary lymph node dissection, and preoperative ROM. Predictors of interindividual differences in changes over time in postoperative ROM were living alone, type of surgery, axillary lymph node dissection, and adjuvant chemotherapy. Declines in mean grip strength from before through 1 month after surgery were small and not clinically meaningful. Women with greater preoperative breast pain interference scores had higher postoperative interference scores at all postoperative assessments. Conclusion Some of the modifiable risk factors identified in this study can be targeted for intervention to improve UE function in these women.

A Rasch Analysis of Assessments of Morning and Evening Fatigue in Oncology Patients Using the Lee Fatigue Scale

Lerdal, A., Kottorp, A., Gay, C., Aouizerat, B. E., Lee, K. A., & Miaskowski, C. (2016). Journal of Pain and Symptom Management, 51(6), 1002-1012. 10.1016/j.jpainsymman.2015.12.331
Abstract
Abstract
Context To accurately investigate diurnal variations in fatigue, a measure needs to be psychometrically sound and demonstrate stable item function in relationship to time of day. Rasch analysis is a modern psychometric approach that can be used to evaluate these characteristics. Objectives To evaluate, using Rasch analysis, the psychometric properties of the Lee Fatigue Scale (LFS) in a sample of oncology patients. Methods The sample comprised 587 patients (mean age 57.3 ± 11.9 years, 80% women) undergoing chemotherapy for breast, gastrointestinal, gynecological, or lung cancer. Patients completed the 13-item LFS within 30 minutes of awakening (i.e., morning fatigue) and before going to bed (i.e., evening fatigue). Rasch analysis was used to assess validity and reliability. Results In initial analyses of differential item function, eight of the 13 items functioned differently depending on whether the LFS was completed in the morning or in the evening. Subsequent analyses were conducted separately for the morning and evening fatigue assessments. Nine of the morning fatigue items and 10 of the evening fatigue items demonstrated acceptable goodness-of-fit to the Rasch model. Principal components analyses indicated that both morning and evening assessments demonstrated unidimensionality. Person-separation indices indicated that both morning and evening fatigue scales were able to distinguish four distinct strata of fatigue severity. Conclusion Excluding four items from the morning fatigue scale and three items from the evening fatigue scale improved the psychometric properties of the LFS for assessing diurnal variations in fatigue severity in oncology patients.

A review of the literature on multiple co-occurring symptoms in patients with colorectal cancer who received chemotherapy alone or chemotherapy with targeted therapies

Tantoy, I. Y., Cataldo, J. K., Aouizerat, B. E., Dhruva, A., & Miaskowski, C. (2016). Cancer Nursing, 39(6), 437-445. 10.1097/NCC.0000000000000343
Abstract
Abstract
Background: Patients with colorectal cancer (CRC) rarely experience a single symptom associated with their disease and its treatment. Objective: Purpose of this literature review was to summarize the current state of knowledge of multiple co-occurring symptoms in CRC patients who received chemotherapy (CTX) alone or CTX with targeted therapies. Methods: Comprehensive literature search was conducted from 1990 to 2014. These studies were evaluated in terms of the occurrence of multiple co-occurring symptoms in CRC patients who received CTX alone or CTX with targeted therapies; the most common symptom assessment and quality of life (QOL) instruments used; and the associations identified between select demographic and treatment characteristics, QOL, and multiple co-occurring symptoms. Results: Only 5 studies met this review's inclusion criteria. Two studies compared symptoms in patients who received CTX alone or CTX with targeted therapies, and only 1 study reported on symptom occurrence. Of the 5 studies identified, only 2 used the same instrument to assess symptoms, and only 2 studies evaluated for associations between demographic and treatment characteristics and symptom burden, as well as QOL outcomes. Conclusions: Given the larger number of patients with CRC, as well as the increased number of CRC patients who will receive targeted therapies with or without CTX, future studies need to describe the occurrence, severity, and distress of multiple co-occurring symptoms and their impact on CRC patients' QOL. Implications for Practice: To deliver effective symptom management interventions, the most common, severe, and distressing symptoms that CRC patients experience need to be identified.