Medical Molecular Biology Commons^™

Calcium Signaling And Postsynaptic Density Dynamics: The Roles Of Calmodulin In Synaptic Protein Regulation, Keyaa Dilip Shah, Yonghong Zhang

School of Integrative Biological & Chemical Sciences Faculty Publications

Calcium signaling in neuronal cells is the principal mechanism underlying learning and synaptic plasticity, whereas the postsynaptic density (PSD) is an important center where calcium-dependent processes are organized and regulated. This review explores the roles of calmodulin (CaM) in facilitating calcium-dependent modulation of the activities of synaptic proteins in the PSD. We focus on the molecular processes through which CaM interacts with calcium signals to regulate the function, localization, and interactions of central synaptic proteins, including calcium/calmodulin-dependent protein kinase II (CaMKII), membrane-associated guanylate kinases (MAGUKs), and N-methyl-D-aspartate (NMDA) receptors. We aim to summarize recent advances in structural, biochemical, and imaging …

Targeting Gliomas With Beta-Amyloid-Specific Dyes: A Novel Approach For In Vivo Staining And Potential Therapeutic Applications, Lilia Kucheryavykh, Jescelica Ortiz Rivera, Boris Ermolinsky, Vassiliy Tsytsarev, Lynnette Cary, Janaina Alves, Adriana Reyes, Noelis De La Cruz-Rivera, Kevin Rosa Gonzalez, Felix Narvaez Irizarry

School of Integrative Biological & Chemical Sciences Faculty Publications

Gliomas, the most common primary brain tumors, present significant diagnostic and treatment challenges due to their infiltrative nature and heterogeneity. Our previous research revealed that glioma tumors in both animals and humans accumulate beta-amyloid protein (Aβ), detectable through immunohistochemical methods or staining with amyloid-specific dyes. We hypothesize that beta-amyloid-specific dyes could serve as glioma markers, potentially enabling the delineation of glioma tumors or targeted therapeutics delivery. In this study, the specificity and blood-brain barrier permeability of two fluorescent beta-amyloid-specific dyes, Brilliant Blue G (BBG) and BODIPY-based Amyloid Probe-1 (BAP-1), were evaluated in C57Bl/6 mouse glioma implantation models using GL261 and …

Ybx1-Mediated Activation Of Srebp2 Drives Sorafenib Resistance Via Cholesterol Biosynthesis In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard, Ana Ayala Pazzi, Shaibir Hussain, Salique H. Shaham, Manish Tripathi

Research Colloquium

Background: Hepatocellular carcinoma (HCC) is an aggressive, largely chemo-resistant cancer with a poor prognosis and is the leading cause of cancer-related deaths worldwide. Currently, there is no effective systemic chemotherapy for HCC. Sorafenib is a multikinase inhibitor commonly used as the first-line treatment for advanced HCC. However, acquired drug resistance significantly limits its clinical effectiveness. The Y-box binding protein (YBX1) is an oncogenic RNA-binding protein found to be upregulated in sorafenib-resistant HCC cells and tissues.

Methods: HCC model SK Hep1, YBX1 overexpression, and knockdown cells were prepared by transient transfection with puromycin selection, and stable cell lines were established through …

Tc-Ptp Enhances Cordycepin-Induced Apoptosis In Human Pancreatic Cancer Cells, Olivia Samaie, Rodrigo Vidales, Lindsey Shim, Murali M. Yallapu, Subhash C. Chauhan, Mushfiq Hassan Shaikh, Dae Joon Kim

Research Colloquium

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy marked by early metastasis, dense desmoplastic stroma, and profound resistance to conventional therapies. Despite the development of combination regimens such as gemcitabine and FOLFIRINOX, outcomes remain dismal, with median survival under one year for metastatic cases. This underscores the urgent need for novel therapeutic approaches that target multiple pathways simultaneously. T-cell protein tyrosine phosphatase (TC-PTP) is one of nonreceptor PTPs that negatively regulates oncogenic signaling pathways, particularly STAT3 and AKT, both of which are constitutively active in many solid tumors. Cordycepin, a nucleoside analogue derived from Cordyceps militaris, has …

Novel Signaling Pathways Involved In Ybx1 Role In Hepatocellular Carcinoma, Yamile Abuchard Anaya, Ana Ayala Pazzi, Dennis Kwabiah, Veerababu Nagati, Ricardo Pequeno Bracho, Kyle Doxtater, Subhash C. Chauhan, Manish K. Tripathi

Research Symposium

Background: The most prevalent type of liver cancer is hepatocellular carcinoma (HCC), and socioeconomic and health disparities have a major impact on both its incidence and fatality rates. HCC rates are typically greater in areas with poor access to healthcare, high obesity rates, and a high frequency of infectious diseases. Because of risk factors include diabetes, non-alcoholic fatty liver disease (NAFLD), and Hepatitis B and C, HCC is particularly common in the Rio Grande Valley (RGV). The burden of HCC in this underprivileged area is made worse by McAllen, Texas, which regrettably holds the distinction of being the most obese …

Dysregulation Of Cholesterol Metabolism And Sorafenib Drug Resistance In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard Anaya, Ana Ayala Pazzi, Manish K. Tripathi

Research Symposium

Background: Hepatocellular carcinoma (HCC) is among the most prevalent cancers and a leading cause of cancer-related deaths worldwide. Sorafenib, a multikinase inhibitor, serves as a key first-line treatment for HCC when surgical intervention is not an option. However, primary and acquired resistance to sorafenib has significantly limited its effectiveness, reducing the disease control rate. Dysregulation of numerous genes that influence cancer cell proliferation, survival, and drug resistance contributes to this challenge. Identifying the molecular drivers of sorafenib resistance remains critical to improving treatment outcomes. Several factors, including activation of oncogenic pathways (e.g., Akt/mTOR), hypoxia, cholesterol metabolism, EMT, multidrug resistance, and …

Uca1 As A Key Regulator Of The Warburg Effect During Anoikis Resistance In Colorectal Cancer Metastasis, Ricardo Pequeno Bracho, Salique Hassan Shaham, Yamile Abuchard Anaya, Sophia Leslie, Kyle Doxtater, Subhash Chauhan, Bilal Hafeez, Tamer Oraby, Manish K. Tripathi

Research Symposium

Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality in the United States. While localized CRC has a 90% five-year survival rate, this drops sharply to 14% upon metastasis. Metastasis occurs in approximately 40–50% of CRC cases and requires cancer cells to acquire anoikis resistance—a critical adaptation allowing survival after detachment from the extracellular matrix, enabling migration and colonization of secondary sites. Understanding the molecular mechanisms driving anoikis resistance, particularly those linked to altered glucose metabolism, is essential for developing targeted therapies for metastatic CRC.

Cancer cells frequently exhibit the Warburg Effect, a metabolic adaptation favoring glycolysis over …

Comparison Of Deep Learning And Traditional Machine Learning Models For Predicting Mild Cognitive Impairment Using Plasma Proteomic Biomarkers, Kesheng Wang, Donald A. Adjeroh, Wei Fang, Suzy M. Walter, Danqing Xiao, Ubolrat Piamjariyakul, Chun Xu

Health & Biomedical Sciences Faculty Publications

Mild cognitive impairment (MCI) is a clinical condition characterized by a decline in cognitive ability and progression of cognitive impairment. It is often considered a transitional stage between normal aging and Alzheimer’s disease (AD). This study aimed to compare deep learning (DL) and traditional machine learning (ML) methods in predicting MCI using plasma proteomic biomarkers. A total of 239 adults were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort along with a pool of 146 plasma proteomic biomarkers. We evaluated seven traditional ML models (support vector machines (SVMs), logistic regression (LR), naïve Bayes (NB), random forest (RF), k-nearest neighbor …

The Role Of Molecular Profiling In De-Escalation Of Toxic Therapy In Breast Cancer, Sonia Y. Khan, Tonjeh Bah, Rakhshanda Layeequr Rahman

School of Medicine Publications

The prevalence and mortality associated with breast cancer have forced healthcare providers to leverage surgery, chemotherapy, radiation therapy, and immunotherapy to achieve a cure. Whereas mortality has significantly dropped over the decades, long-term toxicities and healthcare costs are prohibitive. Therefore, a better understanding of tumor biology through molecular profiling is being utilized for de-escalation of treatment where appropriate. As research evolves, there is growing evidence that less aggressive treatment regimens, when appropriately tailored, can be equally effective for certain patient populations. This approach not only enhances the quality of life for patients by reducing the financial, physical, and emotional burdens …

Gene-Environment Interactions In Non-Alcoholic Fatty Liver Disease: Insights From Mexican American Populations, Eron G. Manusov, Vincent P. Diego, Marcio Almeida, Jacob Galan, Auwal A. Bala, Marco Arriaga, Natasha Garcia-Rodriguez, Renee Hernandez, Satish Kumar, John Blangero, Sarah Williams-Blangero

School of Medicine Publications

Nonalcoholic Fatty Liver Disease (NAFLD) is a prevalent and complex condition influenced by both genetic and environmental factors. This chapter explores the genotype-by-environment interactions that contribute to the development and progression of NAFLD in the Mexican American population. Using advanced genetic epidemiology and bioinformatics approaches, we investigated how specific genetic variants interact with environmental factors such as depression, acculturation stress, and social determinants of health, to influence NAFLD risk and severity. Our findings reveal significant genotype-by-environment interactions for key NAFLD-related traits, including HbA1c, AST/ALT ratio, and steatosis-controlled attenuation parameter (CAP). We also discuss the application of cutting-edge proteomic and transcriptomic …

Unraveling Sorafenib Resistance In Hepatocellular Carcinoma: Exploring Key Facets, Dennis Kwabiah, Kyle Doxtater, Yamile Abuchard, Sophia Leslie, Ricardo Pequeno Bracho, Shaibir Hussain, Manish K. Tripathi

Research Symposium

Hepatocellular carcinoma (HCC) stands as the prevalent form of primary liver cancer worldwide, diagnosing over half a million new cases annually. Surgical interventions like hepatectomy and liver transplantation offer a potential cure for early-stage HCC. However, the prognosis for advanced stages remains grim due to drug resistance, particularly with high refractoriness rates. Sorafenib, a tyrosine kinase inhibitor, is an approved treatment for advanced HCC. Despite its use, the overall survival extension for these patients remains limited due to the drug's ineffectiveness, and the mechanism behind advanced HCC's resistance to sorafenib remains elusive. TCGA analysis of HCC patient cohorts reveals elevated …

Lncrna Impact On Regorafenib Resistance In Colorectal Cancer, Ricardo Pequeno Bracho, Kyle Doxtater, Dennis Kwabiah, Yamile Abuchard Anaya, Sophia Leslie, Mohammad Shabir Hussain, Manish Tripathi

Research Symposium

Cancer metastasis is one of the deadliest aspects of the disease, with about 90% of all cancer-related deaths due to its development at different sites within the body. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States, with 40-50% of all patients developing metastasis at some point during their fight with the disease. With the approval of Regorafenib for treating metastatic colorectal cancer, steps have been taken to combat metastasis in colorectal cancer. A vital aspect of the development of metastasis is the development of resistance to first-line chemotherapy. Regorafenib is an oral small-molecule …

Natural Remedies To Combat Aberrant Hallmark Signatures Including Altered Glycosylation In Oral Carcinoma, Kruti A. Mehta, Jayendra B. Patel, Prabhudas S. Patel

Research Symposium

Background: Tobacco associated oral cancers remain a major concern in India with higher incidence and mortality making it an Indian-centric burning issue. To combat this dreadful disease, we investigated effects of certain natural compounds on the hallmark signatures including glycosylation transcripts levels in oral carcinoma.

Methods: The tongue carcinoma cells- SAS cells were treated with tobacco compounds, natural compounds and Cisplatin. RNA was isolated from the cells and converted to cDNA. RT-qPCR was performed to evaluate expression levels of various genes.

Results: The treatment of tobacco compounds resulted in similar pattern of altered makers (ST3GAL1, NEU3, FUT5, FUT6, MMP2, BCL2) …

Palmitoylation As A Regulator Of Maguk Proteins Postsynaptic Localization, Rozena Shirvani-Arani, Santiago Balderas, Yonghong Zhang, Xioaqian Fang

Research Symposium

Synaptic plasticity is the ability of the brain to make changes and the changes occur at synapses. To achieve the complicated functions, a good number of proteins are present at synapse and are called synaptic proteins. To stabilize these proteins at synapses, proteins are modified through posttranslational modifications (PTMs). The most studied PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, palmitoylation, etc. Palmitoylation is a type of lipid modification and has received more attention recently for its contribution to protein trafficking, localization, and interaction in various synaptic plasticity. The membrane-associated guanylate kinase (MAGUK) family includes PSD-95, PSD-93 (also known as chapsyn-110), SAP102, …

Healthy Exosomes And Their Effects On Diabetic Cardiomyocytes, Miguel A. Garza, Genaro A. Ramírez-Correa, Maria Lourdes Garza-Rodríguez, Andres J. Medina

MEDI 9331 Scholarly Activities Clinical Years

Extracellular Vesicles, and more specifically, exosomes, are essential for effective cell-to-cell communication in a wide variety of tissues. In the last couple of decades, these nanovesicles have been proven to be active participants and regulators in many disease processes; therefore, their therapeutic effects have been widely studied and proven in various cardiovascular diseases both, in vitro and in vivo. Thus, this study aims at assessing the effects of running healthy mice exosomes on cardiomyocyte and cardiac tissue samples obtained from diabetic mice. Here, we successfully extract exosomes from mice plasma and detect their presence through the use of anti-CD9 and …

Further Decoding The Molecular Relationship Between Pancreatic Adenocarcinoma And Diabetes Mellitus, Russell H. Moreland Iii, Sheema Khan

MEDI 9331 Scholarly Activities Clinical Years

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy, especially as there are no current reliable methods of screening. Recently literature reports a significant relationship with pancreatic ductal adenocarcinoma and diabetes mellitus (DM). The pathologic molecular mechanism is not completely understood but it may hold insights into the development of novel screening and treatment options. In our study we compiled a list of 74 proteins involved in the PDAC and DM pathway, with 47 showing increased expression levels and 11 with decreased expression levels. These proteins are currently undergoing further computational analysis to identify their pathway interactions.