Medical Biochemistry Commons^™

Titanium Dioxide: An Inquiry Into The Mechanisms And Implications Of Exposure In Gut Dysbiosis And Metabolic Disorders, Meghan Gardiner

Senior Honors Theses

Titanium dioxide (TiO₂) is one of the most prevalent food additives utilized in commercial products in the United States. While TiO₂ was originally hailed as a nontoxic and cost-effective additive, studies are beginning to reveal that TiO₂ is not as safe as it once seemed. TiO₂ may contribute to the development of insulin resistance and metabolic disorders through direct and indirect mechanisms. The compound induces gut dysbiosis, leading to alterations in bacterial metabolites and pro-inflammatory cytokines, which results in the selective resistance of glucocorticoid receptors. Additionally, TiO₂ itself can translocate from the gut to …

Slc22a3/Oct3 Drives Serotonin-Mediated Stemness In Pancreatic Cancer, Nivedeta Krishna Kumar, Venkatesh Varadharaj, Neelanjana Gayen, Annant Bir Kaur, Kirtana Arikath, Ashu Shah, Poompozhil Mathivanan, Palanisamy Nallasamy, Zahraa Wajih Alsafwani, Bhuvaneshwari Seshadri, Pratima Raut, Sanchita Rauth, Jimmie Persinger, Sandipan Brahma, Micah Schott, Rebecca E. Oberley-Deegan, Geoffrey A. Talmon, Jesse L. Cox, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) is a highly aggressive malignancy, with cancer stem cells (CSCs) playing a critical role in metastasis, therapy resistance, and recurrence, thereby presenting significant treatment challenges. Emerging evidence suggests that normal embryonic and adult progenitor stem cells share common gene signatures with CSCs. However, the early pluripotency-associated factors and stemness programs that become aberrantly reactivated during oncogenic transformation remain poorly defined. Here, we identify SLC22A3/OCT3 (Solute Carrier Family 22 Member 3) as a reactivated embryonic-associated signature that regulates PC stemness. SLC22A3 is markedly upregulated in CSC-enriched populations, and its silencing in PC cells grown in both 2D cultures …

Unlocking The Power Of Cxcr2 Inhibition To Overcome Gemcitabine Resistance In Pancreatic Cancer, Caitlin Molczyk, Reegan Sturgeon, Sugandha Saxena, Esther Johnson, Rakesh Bhatia, Namita Bhyravbhatla, Sushil Kumar, Surinder K. Batra, Rakesh K. Singh

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality, characterized by intrinsic resistance to conventional therapies and limited effective treatment options. In this study, we investigated the role of the CXCR2 axis in PDAC therapy resistance. CXCR2, a chemokine receptor, is actively involved in inflammation, tumor angiogenesis, and metastasis. Our working hypothesis is that CXCR2 contributes to PDAC chemotherapy resistance. To test this, we generated gemcitabine-resistant (GemR) lines using T3M4 and CD18/HPAF (CD18) cell lines. Baseline expression of CXCL1, CXCL5, and CXCL8 ligands was higher in GemR cells compared to parental cells. Upon gemcitabine treatment, parental cells …

Midkine (Mdk) As A Central Regulator Of The Tumor Microenvironment: From Developmental Cytokine To Therapeutic Target, Hareesh B. Nair, Ajay Nair, Ya-Guang Liu, Dileep K. Vijayan, Ramadevi Subramani, Rajkumar Lakshmanaswamy, Suryavathi Viswanadhapalli, Gangadhara R. Sareddy, Surinder K. Batra, Ratna K. Vadlamudi

Journal Articles: Biochemistry & Molecular Biology

Midkine (MDK) is an oncofetal, heparin-binding cytokine that is re-expressed across diverse cancers and correlates with aggressive disease and treatment resistance. This review synthesizes current evidence on MDK as a coordinator of tumor-intrinsic signaling and microenvironmental remodeling. We summarize MDK structural features, extracellular matrix interactions, and receptor systems that mediate MDK signaling, highlighting LRP1 and PTPRZ1 with context-dependent participation of ALK, nucleolin and integrins. Downstream, MDK engages MAPK, PI3K-AKT, STAT3 and NF-κB pathways to promote tumor cell survival, epithelial-mesenchymal plasticity, and therapeutic stress tolerance. We then focus on tumor microenvironment (TME) programs shaped by MDK, including angiogenesis, fibroblast activation and …

Mucin 5ac Modulates Cancer-Associated Fibroblast Heterogeneity Through Epigenetic Reprogramming Of Precursor Cells, Rachel J. Kehrberg, Namita Bhyravbhatla, Zahraa Wajih Alsafwani, Xiaoqi Li, Gopalakrishnan Natarajan, Imran Khan, Randall E. Brand, Maneesh Jain, Surinder K. Batra, Sushil Kumar

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) is characterized by extensive desmoplasia, with heterogeneous cancer-associated fibroblasts (CAFs) as a major component. However, the contribution of distinct precursor cells to CAF heterogeneity remains poorly defined. This study investigated the role of Muc5ac in modulating CAF heterogeneity by maturing precursor cells, including adipose-derived mesenchymal stem cells (AD-MSCs), bone marrow-derived MSCs (BM-MSCs), and pancreatic stellate cells (PSCs), into different CAF subsets. RNA sequencing of precursor cells treated with conditioned media from Muc5ac-proficient or -deficient cancer cells revealed distinct transcriptional profiles. Muc5ac significantly modulated the expression of Dnmts and Tets in AD-MSCs, promoting the acquisition of extracellular matrix …

Extracellular Vesicles In Prostate Cancer: Current Understanding And Future Perspectives, Balaji Perumalsamy, Parthasarathy Seshacharyulu, Raghupathy Vengoji, Nicole Shonka, Benjamin A. Teply, Surinder K. Batra, Sakthivel Muniyan

Journal Articles: Biochemistry & Molecular Biology

Exosomes are nanoscale, lipid bilayer extracellular vesicles (EVs) actively secreted by cells under both physiological and pathological conditions. As key mediators of intercellular communication, exosomes carry a diverse array of molecular cargo, including nucleic acids, proteins, lipids, and metabolites, which can influence the function of recipient cells. Based on evidence from 2016–2025 across PubMed, Embase, the Cochrane Library, and clinicaltrials.org, this review consolidates current understanding of exosome biology in prostate cancer (PCa). We discuss exosome biogenesis, molecular cargo composition, and their functional roles in tumor progression, angiogenesis, immune evasion, metastasis, and therapy resistance of PCa. We emphasize the biomarker potential …

The Underexplored Complexity Of Pancreatic Cancer: Early Dissemination And Quiescence, Nivedeta Krishna Kumar, Annant Bir Kaur, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer has been renowned for its aggressive nature and occasionally manifests periods of dormancy, presenting a perplexing challenge in studying disease progression. Despite surgery, many patients relapse due to dormancy and chemoresistance, resulting in recurrence and death within a few years. Studies also suggest that pancreatic cancer disseminates early on, spreading to secondary organs with no evidence of disease. The lingering question is: how, where, and when does pancreatic cancer recur and spread? Herein, we explore evidence for clinically dormant pancreatic cancer cells, examining the roles of quiescence and stemness populations and their interactions with the tumor microenvironment. Understanding …

Pancreatic Cancer Detection Consortium Biomarker Bakeoff: A Phase Ii Blinded Biomarker Validation And Panel Discovery Study, Ann L. Oberg, William R. Bamlet, Grant Izmirlian, Seetharaman Balasenthil, Surinder K. Batra, Masataka Hayashi, Daniel S. Herman, Michael A. Hollingsworth, Maneesh Jain, Ann M. Killary, Brianna M. Krusen, Suyu Liu, Shounak Majumder, Gopalakrishnan Natarajan, Subrata Sen, Lynette M. Smith, Sudhir Srivastava, Brian M. Wolpin, Kenneth S. Zaret, Michael G. Goggins

Journal Articles: Biochemistry & Molecular Biology

PURPOSE: The Pancreatic Cancer Detection Consortium (PCDC) performed a blinded Early Detection Research Network-defined phase II biomarker bakeoff study of blood-based biomarker panels. The aims were to evaluate panel performance, to compare the panels' performance with that of cancer antigen 19-9 (CA19-9) alone, and to evaluate the performance of new combinations of the individual biomarkers.

EXPERIMENTAL DESIGN: Ten biomarkers representing eight biomarker panels and CA19-9 were evaluated using plasma, serum, and germline DNA from 140 stage I to IV pancreatic ductal adenocarcinoma (PDAC) cases and 140 controls from three tertiary care institutions, with controls frequency matched to cases on age …

Rac1 Gtpase Regulates The Scfβtrcp-Mediated Degradation Of Claspin And The Cellular Response Of Pancreatic Cancer Cells To Gamma Rays, Neha Chaudhary, Tabbatha N. Somers, Surinder K. Batra, Ying Yan, Michel M. Ouellette

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinomas (PDACs) are lethal tumors exhibiting resistance to most cancer therapeutics, particularly DNA-damaging agents. The

METHODS: Western blot analyses were used to assess the impacts of Rac1 inhibition on the components of the ATR/Chk1 cascade.

RESULTS: Here, we show that Rac1 inhibition disrupts ATR/Chk1 signaling by promoting degradation of Claspin, a key component of the fork protection complex needed for the Ser345-phosphorylation of Chk1 by ATR. In PDACs and normal pancreatic ductal cells, Rac1 inhibition (via inhibitors or siRNA) decreased Claspin protein levels without affecting its mRNA, reflecting a >3-fold reduction in Claspin's half-life. Claspin contains a …

Overcoming Radiation Resistance: Ferroptosis Induction To Sensitize Solid Tumors To Radiation Therapy, Joseph Carmicheal, Caden M. Fritson, Alexandra Seas, Heidi M. Vieira, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Radiation therapy (RT) is a mainstay of treatment for a myriad of cancers, often utilized for tumors that are unable to be resected, as well as an adjunct to surgery and chemotherapy. Unfortunately, many cancers are resistant to RT-induced damage and subsequent cell death. This has spurred the pursuit of novel radiation sensitizers that could potentiate the effects of this widely used and important treatment modality. Since its discovery as a regulated cell death mechanism in 2012, ferroptosis has been studied for its connection to cancer and other known oxidative pathways. With this, the interplay between RT and ferroptosis in …

Distinct Glycosyltransferase Expression Governs Organ-Specific Survival In Pancreatic Cancer Metastasis, Venkatesh Varadharaj, Frank Leon, Nivedeta Krishna Kumar, Palanisamy Nallasamy, Pratima Raut, Annant Bir Kaur, Kirtana Arikath, Wyatt Petersen, Sanchita Rauth, Neelanjana Gayen, Zahraa Wajih Alsafwani, Poompozhil Mathivanan, Saravanakumar Marimuthu, Kavita Mallya, Madhu Bommideni, Jesse L. Cox, G. Talmon, Paul M. Grandgenett, Michael A. Hollingsworth, Dominick J. Dimaio, Jean L. Grem, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, with over 83% of patients presenting metastases to vital organs such as the liver, lungs, and peritoneum. Although glycosylation has been established as a critical factor in PDAC development, little is known about the molecular underpinnings of organ-specific metastasis. In this study, we investigated the role of glycosyltransferases (GTs) in mediating PDAC metastatic organotropism. Through an unbiased transcriptomic screen, we identified distinct GT expression patterns in liver- and lung-tropic PDAC cells. Notably, GCNT3 and B3GNT3 were selectively upregulated in liver and lung-tropic cells, respectively. These mutually exclusive expression patterns were …

Isg15 Dysregulates Endoplasmic Reticulum-Mitochondrial Contacts And Calcium Homeostasis In Ataxia Telangiectasia, Oygul Mirzalieva, Ryan E. Reed, Arthur L. Haas, Meredith A. Juncker, Patrick Logarbo, Jennifer M. Klein, David Worthylake, Shyamal D. Desai

School of Graduate Studies Faculty Publications

Dysregulation of endoplasmic reticulum and mitochondrial (ER:Mit) contacts and mitochondrial calcium (mitCa2+) homeostasis are found in several neurodegenerative disorders, including Ataxia Telangiectasia (A-T). However, the cellular basis of these defects remains unclear. Previously, we demonstrated that the aberrantly elevated Interferon-Stimulated Gene 15 (ISG15) pathway inhibits protein polyubiquitylation, its dependent protein turnover, and mitophagy pathways in A-T. Literature indicates that silencing of mitochondrial ubiquitin ligase 1 (MUL1) stabilizes mitofusin2 (MFN2) and attenuates mitCa2+ uptake from ER to Mit (mitCa2+influx) in primary neurons. We have replicated these findings in apparently healthy fibroblasts. We hypothesized that elevated ISG15 may inhibit ubiquitin-dependent MUL1-mediated degradation …

Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan

School of Graduate Studies Faculty Publications

Neuroblastoma (NB), a pediatric cancer of sympatho-adrenal (SA) lineage, is marked by disrupted differentiation and cellular heterogeneity. INSM1, a zinc-finger transcription factor, is highly expressed in NB and developing SA tissues, where it regulates neuroendocrine differentiation, especially in chromaffin cells. We investigated INSM1's role in maintaining an undifferentiated, progenitor-like state in NB and its regulation via metabolic and epigenetic mechanisms. Transcriptomic profiling, promoter assays, and metabolic flux analysis revealed that INSM1 expression correlates with methionine cycle activity, particularly the S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio. Disruption of SAM/SAH balance altered INSM1 promoter activity and histone methylation, implicating epigenetic control in NB cell …

Influence And Excess: A Study Of Alcohol’S Governmental, Societal, Biochemical, And Enzymatic Impact In The U.S And Other Countries Around The World, Thomas W. Snider

Senior Honors Theses

The conduct of the thesis is to explore the intricacies of alcohol consumption. The thesis will outline the history of alcohol and the societal pressures and conduct of drinking with relation to the government. After the history of alcohol has been defined, the thesis will move into the chemistry portion, delineating the absorption, digestion, metabolism, and excretion of alcohol. This is the portion of the thesis that will contain the quantitative data and source material as much research has already been conducted regarding these components of alcohol consumption. The condition of the research is that the data will be collected …

Disruption Of The Placenta–Brain Axis In Transgenic Mice Lacking Serotonin Transporter (Sert) In Trophoblast Cells, David T. Ellenberger, Zhen Lyu, Rosalind T. B. Herrington, Jessica A. Kinkade, Gustavo W. Leone, Ji Ying Sze, Nathan J. Bivens, R. Frank Baker, R. Michael Roberts, Trupti Joshi, Cheryl S. Rosenfeld

Biomedical Sciences

Serotonin reuptake inhibitors (SSRIs) are commonly prescribed to pregnant women experiencing depression. Such drugs, however, might adversely affect placenta and fetal brain development. Parietal trophoblast giant cells (pTGCs) in the mouse placenta are postulated to internalize maternal serotonin (5-HT) via transport through SERT, encoded by Slc6a4, and to provide the initial source of 5-HT to the emerging brain via the placental–brain axis. Genetic deletion of Slc6a4 in pTGCs has been hypothesized to impact placental and fetal brain development. A transgenic mouse line with high-affinity SERT, encoded by Slc6a4, was selectively deleted by pairing mice with Cre recombinase linked …

The Non-Coding Rna Journal Club: Highlights On Recent Papers-14, El Cheima Mhamedi, Florent Hubé, Suresh K. Alahari, Francisco J. Enguita, Barbara Pardini, Mark W. Feinberg, Laura Poliseno, Beshoy Armanios, Jing Jin, Xiao-Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, Gaetano Santulli, Stanislovas S. Jankauskas, Will S. Plewa, Simon J. Conn, Ling Yang, Patrick K. Shiu, Abhishek Kaushik, Alexander Serganov, Gentile, Giuseppe Viglietto, Nicola Amodio, Tijana Mitić, Andrea Caporali

School of Graduate Studies Faculty Publications

The field of non-coding RNA research is advancing at a breathtaking pace, continually uncovering new layers of regulatory complexity and functional diversity [...].

Proteomic Analysis Of Central Amygdala Systems Regulated By Mifepristone In The Context Of Alcohol Dependence, Stephanie S. Lee, Laura Monteagudo Romero, John W. Lammons, Jennifer M. Klein, Kimberly N. Edwards, Jessie J. Guidry, Scott Edwards

School of Graduate Studies Faculty Publications

Alcohol use disorder (AUD) is a psychiatric disorder characterized by escalated alcohol use and the emergence of negative affective symptoms. Studies have described a dysregulation of glucocorticoid receptor (GR) signaling in the context of AUD at the levels of the hypothalamic-pituitary-adrenal (HPA) axis and central amygdala (CeA). A functional increase in CeA GR activity occurs during alcohol withdrawal in alcohol-dependent animal models, and the GR antagonist mifepristone reduces alcohol-seeking and drinking behaviors in both rodents and humans. The aims of this study were to determine differential CeA protein expression in alcohol-dependent rats and examine the effects of mifepristone treatment in …

Synthesis, Pharmacokinetic Studies, And Metabolite Analysis Of Meridianin C In Rats Using A Validated Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry Method, Liangyu Xu, Zhaogen Wu, Karna Ramachandraiah, Guihun Jiang, Guozhe Zhang

School of Graduate Studies Faculty Publications

Introduction: Meridianin C (MC) is a marine-derived indole alkaloid that has demonstrated kinase inhibitory and anti-tumor activities. Despite its diverse biological properties, no previous reports have systematically evaluated the in vivo quantitative analysis of MC and its metabolites. Methods: In this study, MC was synthesized following a previously reported procedure with slight modifications. A sensitive, accurate, and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method was developed to simultaneously detect MC and its five major metabolites (MC-1-N-O-GluA, MC-1-N-O-SO3H, MC-2′-N-O-GluA, MC-2′-N-O-SO3H, and MC-O-GluA-didehydration) in rat plasma. Rats received a single oral dose of MC (100 mg/kg), and pharmacokinetic analysis was …

Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari

School of Medicine Faculty Publications

The novel (nua) kinases 1 and 2 are two of 12 AMP-activated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate …

Polymorphic Α-Glucans As Structural Scaffolds In Cryptococcus Cell Walls For Chitin, Capsule, And Melanin: Insights From 13c And 1h Solid-State Nmr, Ankur Ankur, Jayasubba Reddy Yarava, Isha Gautam, Faith J. Scott, Frederic Mentink-Vigier, Christine Chrissian, Li Xie, Dibakar Roy, Ruth E. Stark, Tamara L. Doering, Ping Wang, Tuo Wang

School of Graduate Studies Faculty Publications

Cryptococcus species are major fungal pathogens responsible for life-threatening infections in approximately a million individuals globally each year, with alarmingly high mortality rates. These fungi are distinguished by a distinctive cell wall architecture further reinforced by two virulence-associated layers, melanin and capsule, rendering them insensitive to antifungal agents targeting the cell wall, such as echinocandins. The molecular interplay between these three biomolecular layers remains poorly understood. Here we employ solid-state NMR spectroscopy to examine intact cells of both wild-type and capsule-deficient strains of C. neoformans, along with melanized cells. High-resolution 13C and 1H data revealed five distinct structural forms of …

Biocomputing Approach To Modeling And Modulating Calcium Signaling, Sehee Sun

School of Computing: Dissertations, Theses, and Student Research

Biocomputing is an emerging field that seeks to perform computational tasks using biological substrates and processes. Unlike conventional computing systems based on silicon hardware, biocomputing leverages the parallelism, energy efficiency, and complex dynamics of living systems. Among various cellular mechanisms, calcium (Ca2+) signaling stands out as a central regulator of diverse biological functions, offering a promising basis for programmable logic and control in living cells.

This thesis introduces a novel framework for modeling and modulating Ca2+ dynamics using biologically inspired Boolean logic circuits. Specifically, we propose the Ca2+ Boolean Logic (CaBL) model, in which Ca2+ fluxes and interactions are abstracted …

Factors Affecting Production Of Scopulariopsis Brevicaulis Spores For Use In Self-Healing Concrete, Lu-Kwang Ju, Ahsanul Kabir Sumon

University Research

Concrete durability is compromised by its susceptibility to cracking, necessitating innovative solutions like self-healing concrete (SHC). Scopulariopsis brevicaulis is capable of biomineralization and its spores were found to hold high potential for use in SHC. Realizing this potential requires clean and effective production of S. brevicaulis spores, which remains unexplored. Here the factors and processes conducive to high productivity of S. brevicaulis spores were investigated. Suitability of cheap, renewable soy-based substrates: soy molasses (SM), soy hull (SH), and soy flour (SF) were first evaluated, and SH was found suitable. The comparison of SH-based solid-state fermentation (SSF) with submerged fermentation (SmF) …

Mucin4 (Muc4) Antibody Labeled With An Nir Dye Brightly Targets Pancreatic Cancer Liver Metastases And Peritoneal Carcinomatosis, Sunidhi Jaiswal, Siamak Amirfakhri, Javier Bravo, Keita Kobayashi, Abhijit Aithal, Sumbal Talib, Kavita Mallya, Maneesh Jain, Aaron M. Mohs, Robert M. Hoffman, Surinder K. Batra, Michael Bouvet

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND/OBJECTIVES: Pancreatic cancer is the fourth leading cause of deaths related to cancer. It is a highly aggressive malignancy and often metastasizes quickly to other parts of the body and organs. The most effective cure is surgical resection, which also is limited by tumor identification and clear tumor margin visualization. Previously, we used MUC4 antibodies labeled with IRDye800CW (anti-MUC4-IR800) to target primary human pancreatic cancer in orthotopic cell line mouse models.

METHODS: In the present study, we established a pancreatic cancer liver metastasis mouse model by implanting a tumor fragment in the liver and a peritoneal carcinomatosis mouse model by …

Extracellular Matrix Repair And Organization Of Chronic Infected Diabetic Wounds Treated With Methacrylated Chitosan-Based Hydrogels, Nic D. Leipzig, Shahrzad Abri, Hannah A. Durr, Samuel D. Salinas

University Research

Diabetic foot ulcers (DFUs) are a multifactorial medical problem that require multifaceted approaches for effective healing. Most research on DFU healing has concentrated on promoting wound closure, with less emphasis on the quality of repaired tissue. This is problematic, however, since quality of the repaired tissues can have potential to improve wound healing outcomes and limit re-ulceration. If more functionally active dermis replaces the lost tissue, this can effectively maximize strength, organization, and overall structure of the plantar surface. Additionally, DFUs commonly show multi-strain infection, which further exacerbates the non-healing status of these wounds. Treatment of chronic wounds can be …

Knowledge Discovery In Databases Of Proteomics By Systems Modeling In Translational Research On Pancreatic Cancer, Mathilde Resell, Elisabeth Pimpisa Graarud, Hanne-Line Rabben, Animesh Sharma, Lars Hagen, Linh Hoang, Nan T. Skogaker, Anne Aarvik, Magnus K. Svensson, Manoj Amrutkar, Caroline S. Verbeke, Surinder K. Batra, Gunnar Qvigstad, Timothy C. Wang, Anil Rustgi, Duan Chen, Chun-Mei Zhao

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Knowledge discovery in databases (KDD) can contribute to translational research, also known as translational medicine, by bridging the gap between

METHODS: This framework includes the data collection of a composition model (various research models), processing model (proteomics) and analytical model (bioinformatics, artificial intelligence/machine leaning and pattern evaluation), knowledge presentation, and feedback loops for hypothesis generation and validation. We applied this workflow to study pancreatic ductal adenocarcinoma (PDAC).

RESULTS: We identified the common proteins between human PDAC and various research models

CONCLUSIONS: This systems modeling workflow can be a valuable method for KDD, facilitating knowledge discovery in translational targets in …

Steps Toward Clinical Validation Of Exhaled Volatile Organic Compound Biomarkers For Hypoglycemia In Persons With Type 1 Diabetes., Mark Woollam, Paula Angarita-Rivera, Sanskar Thakur, Ali Daneshkhah, Amanda P Siegel, Dana S Hardin, Mangilal Agarwal

Ambulatory and Primary Care Articles

Persons with type 1 diabetes (T1D) must track/control their blood glucose (BG) levels to avoid hypoglycemic events (BG <  70 mg/dL), which in the most severe cases can lead to seizures or even death. Canines may lead the way toward innovative testing solutions, as they can be trained to identify hypoglycemia simply and noninvasively by smelling exhaled volatile organic compounds (VOCs). To identify breath-based biomarkers of hypoglycemia, samples were collected during two consecutive summers at a diabetes camp (Cohort 1 and Cohort 2), and VOCs were analyzed by gas chromatography-mass spectrometry. Conserved VOCs between the two cohorts were identified, but individual VOCs alone had low accuracies for detection. Therefore, supervised multivariate statistical analysis was undertaken to identify a biosignature in the training data set (Cohort 1) that could detect hypoglycemia with higher accuracy (sensitivity = 94.8%/specificity = 95.0%). When this model was blindly tested on Cohort 2, hypoglycemia was classified with sensitivity = 90.0%/specificity = 89.9%. Ultimately, this study makes strides toward clinical validation through verifying biomarkers of hypoglycemia in hundreds of breath samples. These results may be translated to design a sensor array that could be integrated into a portable breathalyzer to increase glycemic control in persons with T1D.

Implementation Of A Health Care Transition Pathway For Children And Adults With Inborn Errors Of Metabolism: A Pilot Project, Brittany M. Murray

Doctor of Nursing Practice Scholarly Projects

Background: Children with medically complex diseases require highly specialized care by a highly specialized team. Those with rare disease, including inborn errors of metabolism (IEMs), are a medically complex population and face significant challenges undergoing the health care transition from a child/family-centered model to an adult/patient-centered model of care. The project site follows patients with IEMs in the Metabolism Program, but previously did not have a coordinated process and had insufficient resources for patients/families for the health care transition.

Methods: The Plan-Do-Study-Act (PDSA) method was utilized as the model for improvement. Due to the complexity of the population and time …

Antifreezing Hydrogels From Mechanisms, Strategies, To Applications, Jie Zheng, Dong Zhang, Hong Cheng, Yanxian Zhang

University Research

Antifreezing hydrogels have emerged as an innovative solution for maintaining functional performance and mechanical integrity in subzero environments, offering a robust alternative to traditional water-free antifreezing materials that often fail under wet and cold conditions. These water-rich hydrogels leverage their porous, crosslinked, polymeric networks, which serve as the structural basis for implementing two parallel strategies: the incorporation of antifreezing additives (peptides/proteins, salts, ionic liquids, and organics) and the meticulous engineering of polymer systems and network structures for manipulating the water–ice phase equilibrium to significantly enhance antifreezing properties. This review synthesizes recent findings to provide a fundamental overview of the important …

Ion-Dna Interactions As A Key Determinant Of Uracil Dna Glycosylase Activity., Sharon N Greenwood, Alexis N Dispensa, Matthew Wang, Justin R Bauer, Timothy D Vaden, Zhiwei Liu, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Because of their ubiquitous presence, ions interact with numerous macromolecules in the cell and affect critical biological processes. Here, we discuss how cations including Mg²⁺ alter the enzymatic activity of a DNA glycosylase by tuning its affinity for DNA. The response of uracil DNA glycosylase (UNG2) to Mg²⁺ ions in solution is biphasic and paradoxical, where low concentrations of the ion stimulate the enzyme, but high concentrations inhibit the enzyme. We analyzed this phenomenon by modeling experimental data with a statistical framework that we empirically derived to understand molecular systems that display biphasic behaviors. Parameters from our statistical …

St6galnac-I Regulates Tumor Cell Sialylation Via Nectin2/Muc5ac-Mediated Immunosuppression And Angiogenesis In Non-Small Cell Lung Cancer, Muthamil Iniyan Appadurai, Sanjib Chaudhary, Ashu Shah, Gopalakrishnan Natarajan, Zahraa W. Alsafwani, Parvez Khan, Dhananjay D. Shinde, Subodh M. Lele, Lynette M. Smith, Mohd W. Nasser, Surinder K. Batra, Apar Kishor Ganti, Imayavaramban Lakshmanan

Journal Articles: Biochemistry & Molecular Biology

Glycosylation controls immune evasion, tumor progression, and metastasis. However, how tumor cell sialylation regulates immune evasion remains poorly characterized. ST6GalNAc-I, a sialyltransferase that conjugates sialic acid to the glycans in glycoproteins, was overexpressed in an aggressive-type KPA (KrasG12D/+ Trp53R172H/+ Ad-Cre) lung adenocarcinoma (LUAD) model and patient samples. Proteomic and biochemical analysis indicated that ST6GalNAc-I mediated NECTIN2 sialylation in LUAD cells. ST6GalNAc-I-deficient tumor cells cocultured with T cells were more susceptible to T cell-mediated tumor cell killing, indicating a key role for NECTIN2 in T cell dysfunction. Mice injected with St6galnac-I-knockdown syngeneic cells showed reduced lung tumor incidence and Nectin2/Tigit-associated immunosuppression. …