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Biomarkers

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Full-Text Articles in Life Sciences

Synthesis Of Neoglycoproteins As Potential Biomarkers For Chagas Disease And Cutaneous Leishmaniasis Caused By Leishmania (Viannia) Braziliensis, Eileni Rodriguez Gil May 2024

Synthesis Of Neoglycoproteins As Potential Biomarkers For Chagas Disease And Cutaneous Leishmaniasis Caused By Leishmania (Viannia) Braziliensis, Eileni Rodriguez Gil

Open Access Theses & Dissertations

Protozoan parasites are responsible for causing numerous diseases in humans and mammals worldwide. Among them are Chagas disease (CD), caused by the parasite Trypanosoma cruzi (T. cruzi), and tegumentary leishmaniasis (TL), caused by the parasite Leishmania (Viannia). Both diseases coexist in many regions of Latin America, and current hurdles to differentially diagnose them and determine chemotherapy success need to be overcome. CD can be diagnosed by traditional serological tests and polymerase chain reaction (PCR), but disadvantages of these methods are that they may produce false negatives because the antigens used in commercial CD kits are not conserved across all T.cruzi …


Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester Apr 2024

Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester

Department of Medical Oncology Faculty Papers

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10-15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10-15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of …


Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman Mar 2024

Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. …


The Dose-Response Effect Of Aerobic Exercise On Inflammation In Colon Cancer Survivors, Justin C. Brown, Stephanie L.E. Compton, Jeffrey A. Meyerhardt, Guillaume Spielmann, Shengping Yang Dec 2023

The Dose-Response Effect Of Aerobic Exercise On Inflammation In Colon Cancer Survivors, Justin C. Brown, Stephanie L.E. Compton, Jeffrey A. Meyerhardt, Guillaume Spielmann, Shengping Yang

School of Medicine Faculty Publications

Background; Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. Methods; In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1;1;1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor …


Identification Of Circulating Proteins Associated With General Cognitive Function Among Middle-Aged And Older Adults, Adrienne Tin, Alison E Fohner, Qiong Yang, Jennifer A Brody, Gail Davies, Jie Yao, Dan Liu, Ilana Caro, Joni V Lindbohm, Michael R Duggan, Osorio Meirelles, Sarah E Harris, Valborg Gudmundsdottir, Adele M Taylor, Albert Henry, Alexa S Beiser, Ali Shojaie, Annabell Coors, Annette L Fitzpatrick, Claudia Langenberg, Claudia L Satizabal, Colleen M Sitlani, Eleanor Wheeler, Elliot M Tucker-Drob, Jan Bressler, Josef Coresh, Joshua C Bis, Julián Candia, Lori L Jennings, Maik Pietzner, Mark Lathrop, Oscar L Lopez, Paul Redmond, Robert E Gerszten, Stephen S Rich, Susan R Heckbert, Thomas R Austin, Timothy M Hughes, Toshiko Tanaka, Valur Emilsson, Ramachandran S Vasan, Xiuqing Guo, Yineng Zhu, Christophe Tzourio, Jerome I Rotter, Keenan A Walker, Luigi Ferrucci, Mika Kivimäki, Monique M B Breteler, Simon R Cox, Stephanie Debette, Thomas H Mosley, Vilmundur G Gudnason, Lenore J Launer, Bruce M Psaty, Sudha Seshadri, Myriam Fornage Nov 2023

Identification Of Circulating Proteins Associated With General Cognitive Function Among Middle-Aged And Older Adults, Adrienne Tin, Alison E Fohner, Qiong Yang, Jennifer A Brody, Gail Davies, Jie Yao, Dan Liu, Ilana Caro, Joni V Lindbohm, Michael R Duggan, Osorio Meirelles, Sarah E Harris, Valborg Gudmundsdottir, Adele M Taylor, Albert Henry, Alexa S Beiser, Ali Shojaie, Annabell Coors, Annette L Fitzpatrick, Claudia Langenberg, Claudia L Satizabal, Colleen M Sitlani, Eleanor Wheeler, Elliot M Tucker-Drob, Jan Bressler, Josef Coresh, Joshua C Bis, Julián Candia, Lori L Jennings, Maik Pietzner, Mark Lathrop, Oscar L Lopez, Paul Redmond, Robert E Gerszten, Stephen S Rich, Susan R Heckbert, Thomas R Austin, Timothy M Hughes, Toshiko Tanaka, Valur Emilsson, Ramachandran S Vasan, Xiuqing Guo, Yineng Zhu, Christophe Tzourio, Jerome I Rotter, Keenan A Walker, Luigi Ferrucci, Mika Kivimäki, Monique M B Breteler, Simon R Cox, Stephanie Debette, Thomas H Mosley, Vilmundur G Gudnason, Lenore J Launer, Bruce M Psaty, Sudha Seshadri, Myriam Fornage

Journal Articles

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.


Mutational And Expression Analysis Of Fbxw7 Gene In Colorectal Cancer Patients Among North Indian Population, Laraib Uroog Sep 2023

Mutational And Expression Analysis Of Fbxw7 Gene In Colorectal Cancer Patients Among North Indian Population, Laraib Uroog

Research Symposium

Background: Colorectal cancer is the third most common cancer worldwide with the incidence rate of 1.8 million (10.2%) (GOBOCON-2018). CRC is endemic to Kashmir Valley due to both, kangri use and non-veg food habit. The current study was designed to explore the possible correlation between that FBXW7 and colorectal cancer progression.

Methods: FBXW7 gene mutations and expression was analyzed in 173 colorectal carcinoma tissues along with the adjacent non-cancerous matched tissues using polymerase chain reaction-single stranded confirmation polymorphism assay. Gene expression analysis was conducted using qRT-PCR, western blot and IHC.

Results: In total, six mutations were found …


The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle Sep 2023

The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle

International Undergraduate Journal of Health Sciences

Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …


Ancestral Diversity In Lipoprotein(A) Studies Helps Address Evidence Gaps, Moa P Lee, Sofia F Dimos, Laura M Raffield, Zhe Wang, Anna F Ballou, Carolina G Downie, Christopher H Arehart, Adolfo Correa, Paul S De Vries, Zhaohui Du, Christopher R Gignoux, Penny Gordon-Larsen, Xiuqing Guo, Jeffrey Haessler, Annie Green Howard, Yao Hu, Helina Kassahun, Shia T Kent, J Antonio G Lopez, Keri L Monda, Kari E North, Ulrike Peters, Michael H Preuss, Stephen S Rich, Shannon L Rhodes, Jie Yao, Rina Yarosh, Michael Y Tsai, Jerome I Rotter, Charles L Kooperberg, Ruth J F Loos, Christie Ballantyne, Christy L Avery, Mariaelisa Graff Aug 2023

Ancestral Diversity In Lipoprotein(A) Studies Helps Address Evidence Gaps, Moa P Lee, Sofia F Dimos, Laura M Raffield, Zhe Wang, Anna F Ballou, Carolina G Downie, Christopher H Arehart, Adolfo Correa, Paul S De Vries, Zhaohui Du, Christopher R Gignoux, Penny Gordon-Larsen, Xiuqing Guo, Jeffrey Haessler, Annie Green Howard, Yao Hu, Helina Kassahun, Shia T Kent, J Antonio G Lopez, Keri L Monda, Kari E North, Ulrike Peters, Michael H Preuss, Stephen S Rich, Shannon L Rhodes, Jie Yao, Rina Yarosh, Michael Y Tsai, Jerome I Rotter, Charles L Kooperberg, Ruth J F Loos, Christie Ballantyne, Christy L Avery, Mariaelisa Graff

Journal Articles

INTRODUCTION: The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations.

METHODS: Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations.

RESULTS: Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R

CONCLUSIONS: …


Detectable Ctdna At The Time Of Treatment Cessation Of Ipilimumab And Nivolumab For Toxicity Predicts Disease Progression In Advanced Melanoma Patients, Lydia Warburton, Anna Reid, Benhur Amanuel, Leslie Calapre, Michael Millward, Elin Gray Jan 2023

Detectable Ctdna At The Time Of Treatment Cessation Of Ipilimumab And Nivolumab For Toxicity Predicts Disease Progression In Advanced Melanoma Patients, Lydia Warburton, Anna Reid, Benhur Amanuel, Leslie Calapre, Michael Millward, Elin Gray

Research outputs 2022 to 2026

Background: Immune checkpoint inhibition (ICI) has led to unprecedented outcomes for melanoma patients but is associated with toxicity. ICI resumption after high grade irAEs poses a significant challenge in the clinical management of melanoma patients and there are no biomarkers that can help identify patients that might benefit from resuming treatment. This study aims to determine if circulating tumor DNA (ctDNA) levels at the time of treatment-limiting irAE could guide treatment decisions in this clinical context. Methods: This is a retrospective exploratory biomarker study from 34 patients treated with combination ICI for stage IV melanoma. Patients had a treatment-limiting toxicity …


Integrated Dna Copy Number And Expression Profiling Identifies Igf1r As A Prognostic Biomarker In Pediatric Osteosarcoma., Aaron M Taylor, Jiayi M Sun, Alexander Yu, Horatiu Voicu, Jianhe Shen, Donald A Barkauskas, Timothy J Triche, Julie M Gastier-Foster, Tsz-Kwong Man, Ching C Lau Jul 2022

Integrated Dna Copy Number And Expression Profiling Identifies Igf1r As A Prognostic Biomarker In Pediatric Osteosarcoma., Aaron M Taylor, Jiayi M Sun, Alexander Yu, Horatiu Voicu, Jianhe Shen, Donald A Barkauskas, Timothy J Triche, Julie M Gastier-Foster, Tsz-Kwong Man, Ching C Lau

Faculty Research 2022

Osteosarcoma is a primary malignant bone tumor arising from bone-forming mesenchymal cells in children and adolescents. Despite efforts to understand the biology of the disease and identify novel therapeutics, the survival of osteosarcoma patients remains dismal. We have concurrently profiled the copy number and gene expression of 226 osteosarcoma samples as part of the Strategic Partnering to Evaluate Cancer Signatures (SPECS) initiative. Our results demonstrate the heterogeneous landscape of osteosarcoma in younger populations by showing the presence of genome-wide copy number abnormalities occurring both recurrently among samples and in a high frequency. Insulin growth factor receptor 1 (IGF1R) is a …


Integrative Analysis Of Clinical And Epigenetic Biomarkers Of Mortality, Tianxiao Huan, Steve Nguyen, Elena Colicino, Carolina Ochoa-Rosales, W David Hill, Jennifer A Brody, Mette Soerensen, Yan Zhang, Antoine Baldassari, Mohamed Ahmed Elhadad, Tanaka Toshiko, Yinan Zheng, Arce Domingo-Relloso, Dong Heon Lee, Jiantao Ma, Chen Yao, Chunyu Liu, Shih-Jen Hwang, Roby Joehanes, Myriam Fornage, Jan Bressler, Joyce B J Van Meurs, Birgit Debrabant, Jonas Mengel-From, Jacob Hjelmborg, Kaare Christensen, Pantel Vokonas, Joel Schwartz, Sina A Gahrib, Nona Sotoodehnia, Colleen M Sitlani, Sonja Kunze, Christian Gieger, Annette Peters, Melanie Waldenberger, Ian J Deary, Luigi Ferrucci, Yishu Qu, Philip Greenland, Donald M Lloyd-Jones, Lifang Hou, Stefania Bandinelli, Trudy Voortman, Brenner Hermann, Andrea Baccarelli, Eric Whitsel, James S Pankow, Daniel Levy Jun 2022

Integrative Analysis Of Clinical And Epigenetic Biomarkers Of Mortality, Tianxiao Huan, Steve Nguyen, Elena Colicino, Carolina Ochoa-Rosales, W David Hill, Jennifer A Brody, Mette Soerensen, Yan Zhang, Antoine Baldassari, Mohamed Ahmed Elhadad, Tanaka Toshiko, Yinan Zheng, Arce Domingo-Relloso, Dong Heon Lee, Jiantao Ma, Chen Yao, Chunyu Liu, Shih-Jen Hwang, Roby Joehanes, Myriam Fornage, Jan Bressler, Joyce B J Van Meurs, Birgit Debrabant, Jonas Mengel-From, Jacob Hjelmborg, Kaare Christensen, Pantel Vokonas, Joel Schwartz, Sina A Gahrib, Nona Sotoodehnia, Colleen M Sitlani, Sonja Kunze, Christian Gieger, Annette Peters, Melanie Waldenberger, Ian J Deary, Luigi Ferrucci, Yishu Qu, Philip Greenland, Donald M Lloyd-Jones, Lifang Hou, Stefania Bandinelli, Trudy Voortman, Brenner Hermann, Andrea Baccarelli, Eric Whitsel, James S Pankow, Daniel Levy

Journal Articles

DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10


Liquid Biopsies For Type 2 Diabetes Mellitus: Biomarkers For Disease Risk And Diagnosis, Stephanie Chidester Apr 2022

Liquid Biopsies For Type 2 Diabetes Mellitus: Biomarkers For Disease Risk And Diagnosis, Stephanie Chidester

Dissertations

Background: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in the United States. There is a critical need for earlier and more effective screening and diagnostic tools. Innovative liquid biopsy technologies may play a key role in meeting this need. Liquid biopsies are a non-invasive, adjunctive tool for determining diagnosis, prognosis, and therapeutic response. This dissertation focuses on two potential applications of liquid biopsy technologies to T2DM: (1) epigenome-wide association studies to identify epigenetic markers of risk for T2DM, and (2) extracellular vesicle (EV)-based biomarker studies to identify and detect markers associated with T2DM development and progression. Dissertation studies: …


Spatiotemporal Dynamics Of Clonal Selection And Diversification In Normal Endometrial Epithelium., Manako Yamaguchi, Hirofumi Nakaoka, Kazuaki Suda, Kosuke Yoshihara, Tatsuya Ishiguro, Nozomi Yachida, Kyota Saito, Haruka Ueda, Kentaro Sugino, Yutaro Mori, Kaoru Yamawaki, Ryo Tamura, Sundaramoorthy Revathidevi, Teiichi Motoyama, Kazuki Tainaka, Roel G W Verhaak, Ituro Inoue, Takayuki Enomoto Feb 2022

Spatiotemporal Dynamics Of Clonal Selection And Diversification In Normal Endometrial Epithelium., Manako Yamaguchi, Hirofumi Nakaoka, Kazuaki Suda, Kosuke Yoshihara, Tatsuya Ishiguro, Nozomi Yachida, Kyota Saito, Haruka Ueda, Kentaro Sugino, Yutaro Mori, Kaoru Yamawaki, Ryo Tamura, Sundaramoorthy Revathidevi, Teiichi Motoyama, Kazuki Tainaka, Roel G W Verhaak, Ituro Inoue, Takayuki Enomoto

Faculty Research 2022

It has become evident that somatic mutations in cancer-associated genes accumulate in the normal endometrium, but spatiotemporal understanding of the evolution and expansion of mutant clones is limited. To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we sequence 1311 endometrial glands from 37 women. By collecting endometrial glands from different parts of the endometrium, we show that multiple glands with the same somatic mutations occupy substantial areas of the endometrium. We demonstrate that "rhizome structures", in which the basal glands run horizontally along the muscular layer and multiple …


The Aassociation Between Rest-Activity Rhythms And Glycemic Markers: The Us National Health And Nutrition Examination Survey, 2011-2014, Qian Xiao, Charles E Matthews, Mary Playdon, Cici Bauer Feb 2022

The Aassociation Between Rest-Activity Rhythms And Glycemic Markers: The Us National Health And Nutrition Examination Survey, 2011-2014, Qian Xiao, Charles E Matthews, Mary Playdon, Cici Bauer

Journal Articles

OBJECTIVES: Previous studies conducted in mostly homogeneous sociodemographic samples have reported a relationship between weakened and/or disrupted rest-activity patterns and metabolic dysfunction. This study aims to examine rest-activity rhythm characteristics in relation to glycemic markers in a large nationally representative and diverse sample of American adults.

METHODS: This study used data from the National Health and Nutrition Examination Survey 2011-2014. Rest-activity characteristics were derived from extended cosine models using 24-hour actigraphy. We used multinomial logistic regression and multiple linear regression models to assess the associations with multiple glycemic markers (i.e., glycated hemoglobin, fasting glucose and insulin, homeostatic model assessment of …


An Artifact In Intracellular Cytokine Staining For Studying T Cell Responses And Its Alleviation., Zheng Gong, Qing Li, Jiayuan Shi, Guangwen Ren Jan 2022

An Artifact In Intracellular Cytokine Staining For Studying T Cell Responses And Its Alleviation., Zheng Gong, Qing Li, Jiayuan Shi, Guangwen Ren

Faculty Research 2022

Intracellular cytokine staining (ICS) is a widely employed ex vivo method for quantitative determination of the activation status of immune cells, most often applied to T cells. ICS test samples are commonly prepared from animal or human tissues as unpurified cell mixtures, and cell-specific cytokine signals are subsequently discriminated by gating strategies using flow cytometry. Here, we show that when ICS samples contain Ly6G+ neutrophils, neutrophils are ex vivo activated by an ICS reagent - phorbol myristate acetate (PMA) - which leads to hydrogen peroxide (H2O2) release and death of cytokine-expressing T cells. This artifact …


Examining The Effects Of Exercise-Induced, Physical Stress Overtraining On Stress Biomarkers In Adolescent, C57bl/6 Mice, Curtis Scotty Davis Jan 2022

Examining The Effects Of Exercise-Induced, Physical Stress Overtraining On Stress Biomarkers In Adolescent, C57bl/6 Mice, Curtis Scotty Davis

Theses, Dissertations and Capstones

Exercise has long been established as a therapeutic modality to improve health and related physical fitness, sports performance, and injury/risk reduction in both adults and adolescents (Haff & Triplett, 2015; Kaminsky, 2010). Nonetheless, there is a lack of research investigating the negative effects of exercise overstress (i.e., overtraining syndrome) in these populations, particularly adolescents (Brenner & American Academy of Pediatrics Council on Sports Medicine and Fitness, 2007; Matos & Winsley, 2007). The objective of this study was to examine hormone biochemical markers, anthropometric markers, and behavioral traits, which are associated with overtraining syndrome, in adolescent C57BL/6 mice. A total of …


Antioxidant Biomarkers And Nutraceutical Therapeutics In Neurodegeneration And Neurotrauma, Lilia A. Koza Jan 2022

Antioxidant Biomarkers And Nutraceutical Therapeutics In Neurodegeneration And Neurotrauma, Lilia A. Koza

Electronic Theses and Dissertations

Mild traumatic brain injury (mTBI), yielding a Glascow Coma Scale of 13-15, is the most commonly occurring severity of TBI. Pathology from mTBI consists of blood brain barrier disruption, neuroinflammation, oxidative stress, excitotoxicity, mitochondrial dysfunction, protein aggregation, axonal degeneration, and resulting neuronal death. These processes deplete the body’s endogenous antioxidant system. We report a retrospective analysis of antioxidant blood biomarkers in patients with a history of mTBI from a local sports medicine clinic, Resilience Code. We found persistent sex-specific antioxidant depletions in mTBI patients associated with worsened symptomology.

Certain populations, such as athletes, are at high risk for repetitive mTBI …


Novel Biomarkers Of Ciliary Extracellular Vesicles Interact With Ciliopathy And Alzheimer’S Associated Proteins, Ashraf M. Mohieldin, Amal Alachkar, John R. Yates Iii, Surya M. Nauli Dec 2021

Novel Biomarkers Of Ciliary Extracellular Vesicles Interact With Ciliopathy And Alzheimer’S Associated Proteins, Ashraf M. Mohieldin, Amal Alachkar, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Ciliary extracellular vesicles (ciEVs), released from primary cilia, contain functional proteins that play an important role in cilia structure and functions. We have recently shown that ciEVs and cytosolic extracellular vesicles (cyEVs) have unique and distinct biomarkers. While ciEV biomarkers have shown some interactions with known ciliary proteins, little is known about the interaction of ciEV proteins with proteins involved in ciliopathy and neurodegenerative disorders. Here, we reveal for the first time the protein-protein interaction (PPI) between the top five ciEVs biomarkers with ciliopathy and Alzheimer disease (AD) proteins. These results support the growing evidence of the critical physiological roles …


Bile Acid Profiling Reveals Distinct Signatures In Undernourished Children With Environmental Enteric Dysfunction, Xueheng Zhao, Kenneth D R. Setchell, Rong Huang, Indika Mallawaarachchi, Lubaina Ehsan, Edward Dobrzykowski Iii, Junfang Zhao, Sana Syed, Najeeha Talat Iqbal, Junaid Iqbal, Kamran Sadiq, Sheraz Ahmed, Syed Asad Ali Dec 2021

Bile Acid Profiling Reveals Distinct Signatures In Undernourished Children With Environmental Enteric Dysfunction, Xueheng Zhao, Kenneth D R. Setchell, Rong Huang, Indika Mallawaarachchi, Lubaina Ehsan, Edward Dobrzykowski Iii, Junfang Zhao, Sana Syed, Najeeha Talat Iqbal, Junaid Iqbal, Kamran Sadiq, Sheraz Ahmed, Syed Asad Ali

Department of Paediatrics and Child Health

Background: Intestinal inflammation and malabsorption in environmental enteric dysfunction (EED) are associated with early childhood growth faltering in impoverished settings worldwide.
Objectives: The goal of this study was to identify candidate biomarkers associated with inflammation, EED histology, and as predictors of later growth outcomes by focusing on the liver-gut axis by investigating the bile acid metabolome.
Methods: Undernourished rural Pakistani infants (n = 365) with weight-for-height Z score (WHZ) < -2 were followed up to the age of 24 mo and monitored for growth, infections, and EED. Well-nourished local children (n = 51) were controls, based on consistent WHZ > 0 and height-for-age Z score (HAZ) > -1 on 2 consecutive visits at 3 and 6 mo. Serum bile acid (sBA) profiles were measured by tandem MS at the ages of 3-6 …


Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach Dec 2021

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …


Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Jeffrey Cummings, Numerous Authors, See Full List Below Aug 2021

Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Jeffrey Cummings, Numerous Authors, See Full List Below

School of Medicine Faculty Publications

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the “Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project.” The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine …


Predictive Biomarkers For 5-Fluorouracil And Oxaliplatin-Based Chemotherapy In Gastric Cancers Via Profiling Of Patient-Derived Xenografts., Deukchae Na, Jeesoo Chae, Sung-Yup Cho, Wonyoung Kang, Ahra Lee, Seoyeon Min, Jinjoo Kang, Min Jung Kim, Jaeyong Choi, Woochan Lee, Dongjin Shin, Ahrum Min, Yu-Jin Kim, Kyung-Hun Lee, Tae-Yong Kim, Yun-Suhk Suh, Seong-Ho Kong, Hyuk-Joon Lee, Woo-Ho Kim, Hansoo Park, Seock-Ah Im, Han-Kwang Yang, Charles Lee, Jong-Il Kim Aug 2021

Predictive Biomarkers For 5-Fluorouracil And Oxaliplatin-Based Chemotherapy In Gastric Cancers Via Profiling Of Patient-Derived Xenografts., Deukchae Na, Jeesoo Chae, Sung-Yup Cho, Wonyoung Kang, Ahra Lee, Seoyeon Min, Jinjoo Kang, Min Jung Kim, Jaeyong Choi, Woochan Lee, Dongjin Shin, Ahrum Min, Yu-Jin Kim, Kyung-Hun Lee, Tae-Yong Kim, Yun-Suhk Suh, Seong-Ho Kong, Hyuk-Joon Lee, Woo-Ho Kim, Hansoo Park, Seock-Ah Im, Han-Kwang Yang, Charles Lee, Jong-Il Kim

Faculty Research 2021

Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both …


Associations Between Physiological Biomarkers And Psychosocial Measures Of Pregnancy-Specific Anxiety And Depression With Support Intervention, Karen L Weis, Tony T Yuan, Katherine C Walker, Thomas F Gibbons, Wenyaw Chan Jul 2021

Associations Between Physiological Biomarkers And Psychosocial Measures Of Pregnancy-Specific Anxiety And Depression With Support Intervention, Karen L Weis, Tony T Yuan, Katherine C Walker, Thomas F Gibbons, Wenyaw Chan

Journal Articles

Stress and anxiety significantly impact the hypothalamic-pituitary axis, and in pregnancy, the subsequent maternal-fetal response can lead to poor outcomes. The objective of this study was to assess the association between psychosocial measures of pregnancy-specific anxiety and physiologic inflammatory responses. Specifically, to determine the effectiveness of the Mentors Offering Maternal Support (M-O-M-S


Long Non-Coding Rnas And Their Targets As Potential Biomarkers In Breast Cancer., Maryam Khalid, Rehan Zafar Paracha, Maryum Nisar, Sumaira Malik, Salma Tariq, Iqra Arshad, Amnah Siddiqa, Zamir Hussain, Jamil Ahmad, Amjad Ali Jul 2021

Long Non-Coding Rnas And Their Targets As Potential Biomarkers In Breast Cancer., Maryam Khalid, Rehan Zafar Paracha, Maryum Nisar, Sumaira Malik, Salma Tariq, Iqra Arshad, Amnah Siddiqa, Zamir Hussain, Jamil Ahmad, Amjad Ali

Faculty Research 2021

Breast cancer is among the lethal types of cancer with a high mortality rate, globally. Its high prevalence can be controlled through improved analysis and identification of disease-specific biomarkers. Recently, long non-coding RNAs (lncRNAs) have been reported as key contributors of carcinogenesis and regulate various cellular pathways through post-transcriptional regulatory mechanisms. The specific aim of this study was to identify the novel interactions of aberrantly expressed genetic components in breast cancer by applying integrative analysis of publicly available expression profiles of both lncRNAs and mRNAs. Differential expression patterns were identified by comparing the breast cancer expression profiles of samples with …


The Context-Dependent Impact Of Integrin-Associated Cd151 And Other Tetraspanins On Cancer Development And Progression: A Class Of Versatile Mediators Of Cellular Function And Signaling, Tumorigenesis And Metastasis, Sonia F. Erfani, Hui Hua, Yueyin Pan, Binhua P. Zhou, Xiuwei H. Yang Apr 2021

The Context-Dependent Impact Of Integrin-Associated Cd151 And Other Tetraspanins On Cancer Development And Progression: A Class Of Versatile Mediators Of Cellular Function And Signaling, Tumorigenesis And Metastasis, Sonia F. Erfani, Hui Hua, Yueyin Pan, Binhua P. Zhou, Xiuwei H. Yang

Molecular and Cellular Biochemistry Faculty Publications

As a family of integral membrane proteins, tetraspanins have been functionally linked to a wide spectrum of human cancers, ranging from breast, colon, lung, ovarian, prostate, and skin carcinomas to glioblastoma. CD151 is one such prominent member of the tetraspanin family recently suggested to mediate tumor development, growth, and progression in oncogenic context- and cell lineage-dependent manners. In the current review, we summarize recent advances in mechanistic understanding of the function and signaling of integrin-associated CD151 and other tetraspanins in multiple cancer types. We also highlight emerging genetic and epigenetic evidence on the intrinsic links between tetraspanins, the epithelial-mesenchymal transition …


Corneal Nonmyelinating Schwann Cells Illuminated By Single-Cell Transcriptomics And Visualized By Protein Biomarkers., Paola Bargagna-Mohan, Gwendolyn Schultz, Bruce Rheaume, Ephraim F Trakhtenberg, Paul Robson, Sonali Pal-Ghosh, Mary Ann Stepp, Katherine S Given, Wendy B Macklin, Royce Mohan Mar 2021

Corneal Nonmyelinating Schwann Cells Illuminated By Single-Cell Transcriptomics And Visualized By Protein Biomarkers., Paola Bargagna-Mohan, Gwendolyn Schultz, Bruce Rheaume, Ephraim F Trakhtenberg, Paul Robson, Sonali Pal-Ghosh, Mary Ann Stepp, Katherine S Given, Wendy B Macklin, Royce Mohan

Anatomy and Regenerative Biology Faculty Publications

No abstract provided.


Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan Feb 2021

Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan

Biostatistics Faculty Publications

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure …


Role Of Vascular Endothelial Growth Factor Receptor 2 Pathway Due To Preeclampsia: A Review, Firdous Ali Jan 2021

Role Of Vascular Endothelial Growth Factor Receptor 2 Pathway Due To Preeclampsia: A Review, Firdous Ali

Williams Honors College, Honors Research Projects

Preeclampsia is a pregnancy complication that is characterized mainly by hypertension in the mother. The exact pathogenesis of preeclampsia is unknown, although the disease is attributed to a number of factors such as angiogenic factor levels and endothelial dysfunction. Presently, the control program for the disease involves the delivery of the fetus and the placenta. There is a need to develop novel therapies that would control preeclampsia from the moment it is diagnosed to minimize the effects on the mother and child. VEGF is a protein involved in the pathogenesis of the condition. The defect in one of its receptors, …


Chronic Inflammation Was A Major Predictor And Determinant Factor Of Anemia In Lactating Women In Sidama Zone Southern Ethiopia: A Cross-Sectional Study, Tafere Gebreegziabher Belay, Taylor Roice, Barbara J. Stoecker Oct 2020

Chronic Inflammation Was A Major Predictor And Determinant Factor Of Anemia In Lactating Women In Sidama Zone Southern Ethiopia: A Cross-Sectional Study, Tafere Gebreegziabher Belay, Taylor Roice, Barbara J. Stoecker

All Faculty Scholarship for the College of the Sciences

Anemia in women of reproductive age is highly prevalent globally and remains a public health problem. In Ethiopia, despite efforts to minimize the burden of anemia, it is still a moderate public health problem. Anemia has various etiologies including nutritional deficiency, parasitic infection, and inflammation. The aim of this study was to examine contributing factors to anemia in lactating women. Following ethical approval, and six months after delivery, all lactating women (n = 150) were recruited to participate in this study from eight randomly selected rural villages. Anthropometric and socio-economic factors were assessed. From each, a blood sample was collected …


Personalized Medicine: The Use Of Biomarkers And Molecularly Targeted Therapies For Patient Care And Cancer Intervention, Wafa Asad, Emily Schmitt Lavin Sep 2020

Personalized Medicine: The Use Of Biomarkers And Molecularly Targeted Therapies For Patient Care And Cancer Intervention, Wafa Asad, Emily Schmitt Lavin

Mako: NSU Undergraduate Student Journal

Personalized medicine and targeted therapy have been emerging fields of study for the remediation and inhibition of cancer. Personalized medicine in the treatment of cancer involves using genetic, immune, and proteomic profiling to provide therapeutic options as well as prognostic background for every patient and their tumor’s genetic mutations. Targeted therapies allow researchers and medical personnel alike to determine the appropriate treatment for a patient based on the molecular basis and mechanistic actions of a cancerous tumor. The overall significance of this study was to express how these treatments use biomarkers to pinpoint the location, and severity of the cancer, …