Digital Commons Network^™

Kinetic Control Of Nuclear-Encoded Mitochondrial Mrna Localization And Local Translation, Surbhi Sharma, Xuemei Wang, Steven Nguyen, Madeline E Rasband, Trinh T Tat, Prabha Chupal, Jen-Yun Chang, Eric L Van Nostrand, Daniel L Kiss, Aidan I Brown, Furqan M Fazal

Faculty, Staff and Students Publications

Most biological processes are dynamic, yet experimental methods predominantly rely on steady-state measurements to investigate their underlying mechanisms. RNA localization is a fundamental aspect of eukaryotic cell organization and is dynamically regulated by cells. While extensively studied in specialized cell types for a limited number of candidate RNAs, the general principles governing dynamic RNA localization at a transcriptome-wide scale remain largely unexplored. Existing transcriptome-wide studies provide only a static snapshot of RNAs residing in specific cellular locales, in part due to the limited availability of tools for probing cellular spatial organization at biologically relevant scales. Here, we leverage the high …

Exploring Protein-Protein Interactions: A Promising Avenue For Biomarker And Anti-Tb Drug Development, Rajwa Dwifauza Suryanto, Maritsa Widati Aqila Rumawan, Imam Adi Wicaksono

Pharmacology and Clinical Pharmacy Research

In 2023, tuberculosis (TB) reached its highest incidence with 8.2 million new cases reported by the World Health Organization (WHO). The virulence of Mycobacterium tuberculosis (MTB) is strongly governed by protein-protein interactions (PPIs) that regulate essential processes such as cell wall biosynthesis, immune evasion, and persistence. This study aims to map and analyze the mechanisms of key PPIs in MTB using a scoping review approach. Data was retrieved from PubChem and related literature with the keyword ``PPIs Network TB''. Our findings highlight crucial PPI-driven mechanisms, including the role of DprE1/DprE2 in arabinogalactan synthesis, VapB4/VapC4 in stress response and self-toxicity, ESX-1 …

Versatile Smad2 And Smad3 Epitope-Tagged Mouse Models For Genomic Profiling Of Tgfβ Signaling: Uncovering Gdf9-Smad2/3 Targets, Zian Liao, Qian Zhang, Keisuke Shimada, Kaori Nozawa, Suni Tang, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Transforming growth factor β (TGFβ) signaling pathways are integral for a plethora of biological processes. SMAD2 and SMAD3 are the principal transcriptional effectors of TGFβ superfamily ligands, yet quantitative, genome-wide mapping of their DNA-associated complexes under physiological contexts has remained limited due to the lack of specific, robust models. Here, we generated two versatile epitope-tagged mouse models in which endogenous SMAD2 and SMAD3 proteins are globally tagged with hemagglutinin (HA) and podoplanin (PA) sequences, respectively, enabling high-fidelity profiling of SMAD2 and SMAD3 binding across tissues. To demonstrate the broad application of our models, we exemplified the usage of our lines …

Efficient In Vivo Pharmacological Inhibition Of Δfosb, An Ap-1 Transcription Factor, In The Brain, Sean Mcneme, Anil Kumar, Yun Young Yim, Brandon W Hughes, Corey St Romain, Yi Li, Ashwani Kumar, Qichao Bao, Molly Estill, Shanghua Fan, Nadeen Takatka, Earnest P Chen, Matthew Rivera, Haiying Chen, Alfred J Robison, Mischa Machius, Stephen J Haggarty, Jeannie Chin, Eric J Nestler, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, an unusually stable member of the AP-1 family of transcription factors, mediates long-term maladaptations that play a key role in the pathogenesis of drug addiction, cognitive decline, dyskinesia, and several other chronic neurological and psychiatric conditions. We have recently identified that 2-phenoxybenzenesulfonic acid-containing compounds disrupt the binding of ΔFOSB to DNA in vitro in cell-based assays, and one such compound, JPC0661, disrupts ΔFOSB binding to genomic DNA in vivo in the mouse brain with partial efficiency. JPC0661 binds to a groove outside of the DNA-binding cleft of the ΔFOSB/JUND bZIP heterodimer in a cocrystal structure. Here, we generated a …

High-Throughput Multi-Organ Proteomics Workflow For Drug Efficacy And Toxicity Analysis, Yun Xiong, Lin Tan, Wai-Kin Chan, Dandan Zhu, Huimin Zhang, Eric S Yin, Sri Ramya Donepudi, Jibin Ding, Bo Wei, Bao Tran, Sara Martinez, Iqbal Mahmud, Faiza Hanif Waghu, Hamish I Stewart, Daniel J Hermanson, Rehan Akbani, John N Weinstein, Junjie Chen, Philip L Lorenzi

Faculty, Staff and Student Publications

Rapid and comprehensive analysis of complex proteomes across large sample sets is vital for unlocking the potential of systems biology. We present a high-throughput mass spectrometry (MS) proteomics method that integrates narrow-window data-independent acquisition (nDIA) with short-gradient micro-flow chromatography, enabling profiling of >240 samples per day. This optimized MS approach identifies 6,201 and 7,466 human proteins with 1- and 2-min gradients, respectively. As a practical application, we analyzed 507 samples composed of 13 different tissues from mice treated with the enzyme-drug L-asparaginase (ASNase) or its glutaminase-free Q59L mutant, generating a quantitative profile of 11,472 proteins following drug treatment. The MS …

Characterization Of Inflammatory Pseudotumors In A Large Animal Model Of Liver Cancer, Erik N K Cressman, Samantha Hicks, Natalie W Fowlkes, Danielle L Stolley, Maria Sophia Stenkamp

Faculty, Staff and Student Publications

Background: The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease. Transgenic approaches hold promise in addressing this complex problem. One such model, the Oncopig, has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation. However, the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.

Methods: Herein, we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and replaced …

Poly(A) Probe Hcr Rna-Fish Specifically Marks Pyriform Nurse Cells In The Brown Anole Lizard Ovary, Zoe B Griffin, Bonnie K Kircher, Richard R Behringer

Faculty, Staff and Student Publications

Hybridization chain reaction RNA-fluorescent in situ hybridization (HCR RNA-FISH) is a powerful and increasingly used method for visualizing gene expression in cells and tissues. A probe set against polyadenylated RNA (poly(A)) is often used as a positive control for RNA integrity and staining quality. While optimizing this technique in the ovary of the brown anole lizard (Anolis sagrei), we found that the poly(A) probe produced a strikingly specific and intense signal in pyriform cells, a specialized lizard-specific nurse cell type. This staining pattern was found in both whole-mount samples and paraffin sections, suggesting that poly(A) signal intensity can serve as …

G2pdeep-V2: A Web-Based Deep-Learning Framework For Phenotype Prediction And Biomarker Discovery For All Organisms Using Multi-Omics Data, Shuai Zeng, Trinath Adusumilli, Sania Zafar Awan, Manish Sridhar Immadi, Dong Xu, Trupti Joshi

Biomedical Sciences

Multi-omics data offers rich insights into complex traits across organisms, yet integrating and analyzing these datasets for phenotype prediction and marker discovery remains challenging. Researchers need accessible tools that combine deep learning, hyperparameter optimization, visualization, and downstream analysis in a unified web platform. To address this, we developed G2PDeep-v2, a web-based platform powered by deep learning for phenotype prediction and marker discovery from multi-omics data across a wide range of organisms, including humans and plants. The server provides multiple services for researchers to create deep-learning models through an interactive interface and train these models using an automated hyperparameter tuning algorithm …

Developing Optogenetic Approaches To Study Ca2+ Signaling Processes, Tatsuki Nonomura, Xiaoxuan Liu, Megan Chiu, Zhi Tan, Tien-Hung Lan, Yubin Zhou

Faculty, Staff and Students Publications

Calcium ions (Ca2+) are essential second messengers intimately implicated in a variety of biological processes, ranging from short-term events such as muscle contraction to long-term effects like gene expression. Dysregulated Ca2+ signaling can disrupt cellular function and contribute to the development of various human diseases, including developmental, neurological, immunoinflammatory, metabolic, and cardiovascular disorders. To study the mechanisms and biological consequences of Ca2+ signaling, optogenetic approaches have proven invaluable, as they offer exceptional spatiotemporal resolution compared to traditional methods. Recent progress in non-opsin-based optogenetics, particularly those engineered from Ca2+ release–activated Ca2+ (CRAC) channels, has substantially advanced our understanding of Ca2+ signaling …

Depression Polygenicity And Disease Activity And Disability Worsening In Multiple Sclerosis, Ali Manouchehrinia, Kathryn C Fitzgerald, Amber Salter, Ruth Ann Marrie, Lars Alfredsson, Charles N Bernstein, James M Bolton, Gary Cutter, John D Fisk, Lesley A Graff, Carol A Hitchon, Jan Hillert, Ingrid Kockum, Yi Lu, Fred D Lublin, Kyla Mckay, Tomas Olsson, Scott Patten, Amit Patki, Hayley Riel, Klementy Shchetynsky, Pernilla Stridh, Hemant K Tiwari, Jerry S Wolinsky, Kaarina Kowalec

Faculty, Staff and Student Publications

Objective: A better understanding of factors associated with multiple sclerosis (MS) disease activity and disability is needed. Given the strong link between comorbid depression and MS disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with MS disease activity and disability worsening.

Methods: In this cohort study, we used samples from neurologist-defined adult people with MS (PwMS) followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes. We computed the depression polygenic score (PGS) and …

Adaptive Filters At The First Olfactory Synapse, Elizabeth H Moss, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

The olfactory system is able to filter odor representations based on attention and learning. Two PLoS Biology studies reveal how short axon cells in the olfactory bulb integrate cholinergic input from the basal forebrain to dynamically regulate olfactory input.

Established And Emerging Asthma Biomarkers With A Focus On Biologic Trials: A Narrative Review, Philip F Lavere, Kaitlin M Phillips, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

Chronic airway inflammation with variable airflow obstruction is clinical asthma, and it arises from distinct molecular and pathological mechanisms called endotypes. Biomarkers allow for precise endotype characterization and have been used in clinical trials to design, monitor, and evaluate outcomes for asthma biologic therapies. This review will highlight the central and evolving role of biomarkers for past, present, and future asthma, with a focus on regulatory-approved biologic therapies and emerging biomarkers. Established biomarkers, including serum immunoglobulin E (IgE), blood eosinophils, the fraction of exhaled nitric oxide (FeNO), and serum periostin, helped elucidate the complex pathophysiology of the eosinophilic type 2 …

The Psychiatric Genomics Consortium: Discoveries And Directions, Arpana Agrawal, Cynthia M Bulik, Dawit Shawel Abebe, Ole A Andreassen, Elizabeth G Atkinson, Karmel W Choi, Aiden Corvin, Helena L Davies, Lea K Davis, Anna R Docherty, Howard J Edenberg, Barbara Franke, Joel Gelernter, Paola Giusti-Rodríguez, John M Hettema, Jens Hjerling-Leffler, Hailiang Huang, Emma C Johnson, Cathryn M Lewis, Yi Lu, Mary-Ellen Lynall, Joanna Martin, Andrew M Mcintosh, Janitza L Montalvo-Ortiz, Niamh Mullins, Caroline M Nievergelt, Kevin S O'Connell, Michael C O'Donovan, Adeniran Okewole, Roseann E Peterson, Danielle Posthuma, Jonathan Sebat, Jordan W Smoller, Reeteka Sud, Biju Viswanath, James T R Walters, Hyejung Won, Naomi R Wray, Patrick F Sullivan, Coordinating Committee Of The Psychiatric Genomics Consortium

Faculty, Staff and Students Publications

The Psychiatric Genomics Consortium (PGC) has fueled discoveries of common and rare genetic variation contributing to liability to many psychiatric and neurodevelopmental conditions. This narrative review reflects on major findings from the past half decade of research by this international group of investigators in five priority areas: discovery of common variants using GWAS; rare variation and its interplay with polygenic risk; leveraging genetics to go beyond diagnostic boundaries; ascribing functional attributes to genomic discoveries; and developing and implementing processes for data sharing, outreach to various communities, and training. The insights gained in these domains frame the agenda for the next …

Treatment With Allogenic Mesenchymal Stromal Cells For Moderate To Severe Acute Respiratory Distress Syndrome: A Double-Blind, Placebo-Controlled, Multi-Center, Phase 2b Clinical Trial (Stat), Michael A Matthay, Hanjing Zhou, Aartik Sarma, Narges Alipanah-Lechner, Carolyn Hendrickson, Lucy Z Kornblith, Martin Schreiber, David Zonies, Akram Khan, Bryce Robinson, Nicholas J Johnson, Lorraine B Ware, Oscar Guillamondegui, Jonathan Casey, Laura Moore, Bela Patel, Lillian Kao, Charles E Wade, Erin Fox, Charles Cox, Farrakh Khawanja, Robier Aguillon Prada, Sami Hossri, Rachael Callcut, Timothy Albertson, Kevin L Delucchi, Melanie Mcmillan, Charles R Langelier, Shibani Pati, David H Mckenna, Carolyn Leroux, Carolyn S Calfee, Kathleen D Liu

Faculty, Staff and Student Publications

Background: Prior clinical trials established the safety, but not the efficacy of bone marrow-derived mesenchymal stromal cells (MSCs) in the acute respiratory distress syndrome (ARDS).

Methods: We conducted a prospective, double-blind, multi-center randomized phase 2b clinical trial of one dose of intravenous MSCs (10 x 106/kg predicted body weight) versus placebo in 120 ventilated patients with ARDS (PaO2/FiO2 < 250 mmHg). The primary endpoint was change in oxygenation index (OI) over 36 hours from baseline.

Findings: Enrollment began in January 2020. Due to the Coronavirus 2019 (COVID-19) pandemic, the majority of subjects (101/120, 84%) developed ARDS from COVID-19. There were no significant baseline differences in severity of illness between patients treated with MSCs and those who received …

Functional Assays In Drosophila Facilitate Classification Of Variants Of Uncertain Significance Associated With Rare Diseases, Jung-Wan Mok, Shelley B Gibson, Haley A Dostalik, Shinya Yamamoto

Faculty, Staff and Students Publications

Individuals living with rare diseases often undergo a frustrating and expensive diagnostic odyssey. Clinical geneticists who analyze exome or genome sequencing data from rare disease patients often encounter a list of variants of uncertain significance (VUS) in known disease-causing genes or rare variants in genes of uncertain significance (GUS) that are difficult to interpret, even with the integration of the latest bioinformatic tools. In this Perspective, we review how studies using the fruit fly Drosophila melanogaster have facilitated rare disease diagnosis by uncovering the clinical relevance of GUS and classifying rare variants into specific allelic categories (loss-of-function or gain-of-function, Muller's …

Bibliometric Analysis Of Colchicine In Cardiovascular Health: Trends, Key Contributors, And Global Collaborations, Meltem Sertbaş, Özlem Özaydin, Habi̇p Yilmaz, Abdullah Emre Güner, Özden Güdük, Nalan Okuroğlu, Ali̇ Özdemir, Yaşar Sertbaş

Turkish Journal of Medical Sciences

Background/aim: The study aims to systematically analyze the body of literature concerning the effects of colchicine on the cardiovascular system, providing a comprehensive evaluation of the current knowledge and highlighting the clinical and scientific relevance of colchicine in this field.

Materials and methods: Data were obtained from the Web of Science Core Collection database on November 17, 2024. The search terms included “Colchicine” AND "Cardiovascular effects" OR "Cardiovascular diseases" OR "Heart diseases" OR "Coronary artery disease" OR "Myocarditis" OR "Pericarditis" OR "Atherosclerosis" OR "Heart failure" OR "Myocardial infarction." No restrictions were applied regarding publication date or language, ensuring the comprehensive …

The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna

Faculty, Staff and Student Publications

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, …

Development Of Lineal Energy Spectrum-Based Biological Effects Models For Protons, Joseph M. Decunha, Fada Guan, David Grosshans, Zhongxing Liao, Dragan Mirkovic, Oleg Vassiliev, Radhe Mohan

Dissertations and Theses (Open Access)

In this dissertation, methods are developed and described to allow for the rapid calculation of microdosimetric spectra (specifically, lineal energy) for protons. SuperTrack, a GPU-accelerated tool for calculation of microdosimetric spectra was developed and is capable of computing lineal energy spectra up to 5000x faster than using Geant4 directly. Proton lineal energy spectra generated by SuperTrack are indistinguishable from those generated by Geant4. With SuperTrack, large libraries of lineal energy spectra for monoenergetic protons spanning 0-300 MeV have been developed. The proton lineal energy spectra calculated by SuperTrack have been compared to experimental measurements made by a tissue equivalent proportional …

Gene Promoters Are Genomically Encoded To Facilitate Histone Exchange/Incorporation, Blaine Bartholomew

Faculty, Staff and Student Publications

Gene promoters are intrinsically hardwired not only to facilitate transcription preinitiation complex formation but also the release of paused RNA polymerase by H2A.Z. A new PLOS Biology study reveals poly (dA) tracts at promoters positively stimulate H2A.Z incorporation by the SWR complex in yeast.

Idh Status Dictates Ohsv Mediated Metabolic Reprogramming Affecting Anti-Tumor Immunity, Upasana Sahu, Matthew P Mullarkey, Sara A Murphy, Joshua C Anderson, Vasanta Putluri, Abu Hena Mostafa Kamal, Jun Hyoung Park, Tae Jin Lee, Alexander L Ling, Benny A Kaipparettu, Ashok Sharma, Nagireddy Putluri, Pamela L Wenzel, Christopher D Willey, E Antonio Chiocca, James M Markert, Balveen Kaur

Faculty, Staff and Student Publications

Identification of isocitrate dehydrogenase (IDH) mutations has uncovered the crucial role of metabolism in gliomagenesis. Oncolytic herpes virus (oHSV) initiates direct tumor debulking by tumor lysis and activates anti-tumor immunity, however, little is known about the role of glioma metabolism in determining oHSV efficacy. Here we identify that oHSV rewires central carbon metabolism increasing glucose utilization towards oxidative phosphorylation and shuttling glutamine towards reductive carboxylation in IDH wildtype glioma. The switch in metabolism results in increased lipid synthesis and cellular ROS. PKC induces ACSL4 in oHSV treated cells leading to lipid peroxidation and ferroptosis. Ferroptosis is critical to launch an …

Connectome-Based Predictive Modeling Of Ptsd Development Among Recent Trauma Survivors, Ziv Ben-Zion, Alexander J Simon, Matthew Rosenblatt, Nachshon Korem, Or Duek, Israel Liberzon, Arieh Y Shalev, Talma Hendler, Ifat Levy, Ilan Harpaz-Rotem, Dustin Scheinost

Staff and Researcher Publications

Importance: The weak link between subjective symptom-based diagnostics for posttraumatic psychopathology and objective neurobiological indices hinders the development of effective personalized treatments.

Objective: To identify early neural networks associated with posttraumatic stress disorder (PTSD) development among recent trauma survivors.

Design, setting, and participants: This prognostic study used data from the Neurobehavioral Moderators of Posttraumatic Disease Trajectories (NMPTDT) large-scale longitudinal neuroimaging dataset of recent trauma survivors. The NMPTDT study was conducted from January 20, 2015, to March 11, 2020, and included adult civilians who were admitted to a general hospital emergency department in Israel and screened for early PTSD symptoms indicative …

Investigating The Role Of Prostasin In Angiogenesis: A Chorioallantoic Membrane Model Approach, Zaima Aline

Honors Undergraduate Theses

Prostasin, also known as PRSS8 or CAP1, is a glycosylphosphatidylinositol (GPI)-anchored extracellular serine protease involved in various physiological and pathophysiological processes. Prostasin expression is observed during key phases of trophoblast invasion and placental development, critical steps in embryo implantation in Rhesus monkeys. This suggests a role for prostasin in extracellular matrix remodeling and tissue invasion, both essential for a healthy pregnancy. Moreover, prostasin appears vital for development as studies in mice show that a germline knockout of the gene leads to significant placental defects and eventual embryonic death, highlighting its importance in vascular and structural development within the placenta.

Building …

Decoding Tattoo And Permanent Makeup Pigments: Linking Physicochemical Properties To Absorption, Distribution, Metabolism, And Elimination Profiles Using Quantitative Structure-Activity Relationship (Qsar)-Based New Approach Methodologies (Nams), Girija Bansod, Ajay Vikram Singh, Preeti Bhardwaj, Tulika Rai, Sweta Vijay Nakhale, Amruta Shelar, Rajendra Patil, Peter Laux, Andreas Luch, Christopher J. Osgood, Michael W. Stacey

Biological Sciences Faculty Publications

The safety and quality of tattoo and permanent makeup (PMU) pigments are subject to increased scrutiny due to their potential to cause adverse effects like anaphylaxis, photoallergic responses, and long-term toxicity. These undesirable reactions governed by their chemical structure possess varied physicochemical properties and absorption, distribution, metabolism, and elimination (ADME) characteristics. These properties control the pigment behavior during application, stability, and interaction with human tissue. The correlation between these physicochemical characteristics and ADME parameters of tattoo/PMU pigments remain under-explored despite the current advances in toxicology. Our study aims to address and bridge the gap by leveraging open-access QSAR computational toxicology …

Establishing A Conventional Linac-Based Electron Flash Beam, Justin Defrancisco

Theses and Dissertations

Problems: A rediscovered radiotherapy technique, FLASH, involves increasing the dose rate to >40 Gy/s. For a given dose, FLASH is shown to decrease the normal tissue complication probability without affecting the tumor control probability. More preclinical studies are necessary to confirm and enable these desirable properties on humans. Current preclinical investigations have diverse constraints, requiring FLASH apparatuses with flexible parameters and accurate control. However, there are limited FLASH platforms available, the existing ones are costly. Our institution is not in possession of any such infrastructure. Even if available, dosimetry and beam control in FLASH are extremely lacking. There is …

Defining Dysphoric Milk Ejection Reflex: Using Premenstrual Dysphoric Disorder As A Framework For Proposing Preliminary Diagnostic Criteria, Megan Howard, Teni Davoudian, Nicole H Cirino

Faculty, Staff and Students Publications

Dysphoric Milk Ejection Reflex (D-MER) is a distinct neurobiological condition characterized by negative alterations in mental state in response to milk letdown during lactation. Symptoms vary by patient and can include feelings of sadness, anxiety or agitation. Importantly, the symptoms are brief, typically lasting no more than 5 minutes. Prevalence has been found between 6 and 27% of lactating women, but studies show heterogeneity, due in part to inconsistent definition. D-MER is not currently classified in the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the International Classification of Diseases (ICD), which presents a challenge for researchers of the …

Mapping The Functional Network Of Human Cancer Through Machine Learning And Pan-Cancer Proteogenomics, Zhiao Shi, Jonathan T Lei, John M Elizarraras, Bing Zhang

Faculty, Staff and Students Publications

Large-scale omics profiling has uncovered a vast array of somatic mutations and cancer-associated proteins, posing substantial challenges for their functional interpretation. Here we present a network-based approach centered on FunMap, a pan-cancer functional network constructed using supervised machine learning on extensive proteomics and RNA sequencing data from 1,194 individuals spanning 11 cancer types. Comprising 10,525 protein-coding genes, FunMap connects functionally associated genes with unprecedented precision, surpassing traditional protein-protein interaction maps. Network analysis identifies functional protein modules, reveals a hierarchical structure linked to cancer hallmarks and clinical phenotypes, provides deeper insights into established cancer drivers and predicts functions for understudied cancer-associated …

Targeted Degradation Of Oncogenic Krasg12v Triggers Antitumor Immunity In Lung Cancer Models, Dezhi Li, Ke Geng, Yuan Hao, Jiajia Gu, Saurav Kumar, Annabel T Olson, Christina C Kuismi, Hye Mi Kim, Yuanwang Pan, Fiona Sherman, Asia M Williams, Yiting Li, Fei Li, Ting Chen, Cassandra Thakurdin, Michela Ranieri, Mary Meynardie, Daniel S Levin, Janaye Stephens, Alison Chafitz, Joy Chen, Mia S Donald-Paladino, Jaylen M Powell, Ze-Yan Zhang, Wei Chen, Magdalena Ploszaj, Han Han, Shengqing Stan Gu, Tinghu Zhang, Baoli Hu, Benjamin A Nacev, Medard Ernest Kaiza, Alice H Berger, Xuerui Wang, Jing Li, Xuejiao Sun, Yang Liu, Xiaoyang Zhang, Tullia C Bruno, Nathanael S Gray, Behnam Nabet, Kwok-Kin Wong, Hua Zhang

Faculty, Staff and Student Publications

Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most frequently mutated oncogene in lung adenocarcinoma, with G12C and G12V being the most predominant forms. Recent breakthroughs in KRASG12C inhibitors have transformed the clinical management of patients with the G12C mutation and advanced our understanding of the function of this mutation. However, little is known about the targeted disruption of KRASG12V, partly due to a lack of specific inhibitors. Here, we leverage the degradation tag (dTAG) system to develop a KRASG12V-transgenic mouse model. We explored the therapeutic potential of KRASG12V degradation and characterized its effect on the tumor microenvironment (TME). …

Π-Hub: The Proteomic Navigator Of The Human Body, Fuchu He, Ruedi Aebersold, Mark S Baker, Xiuwu Bian, Xiaochen Bo, Daniel W Chan, Cheng Chang, Luonan Chen, Xiangmei Chen, Yu-Ju Chen, Heping Cheng, Ben C Collins, Fernando Corrales, Jürgen Cox, Weinan E, Jennifer E Van Eyk, Jia Fan, Pouya Faridi, Daniel Figeys, George Fu Gao, Wen Gao, Zu-Hua Gao, Keisuke Goda, Wilson Wen Bin Goh, Dongfeng Gu, Changjiang Guo, Tiannan Guo, Yuezhong He, Albert J R Heck, Henning Hermjakob, Tony Hunter, Narayanan Gopalakrishna Iyer, Ying Jiang, Connie R Jimenez, Lokesh Joshi, Neil L Kelleher, Ming Li, Yang Li, Qingsong Lin, Cui Hua Liu, Fan Liu, Guang-Hui Liu, Yansheng Liu, Zhihua Liu, Teck Yew Low, Ben Lu, Matthias Mann, Anming Meng, Robert L Moritz, Edouard Nice, Guang Ning, Gilbert S Omenn, Christopher M Overall, Giuseppe Palmisano, Yaojin Peng, Charles Pineau, Terence Chuen Wai Poon, Anthony W Purcell, Jie Qiao, Roger R Reddel, Phillip J Robinson, Paola Roncada, Chris Sander, Jiahao Sha, Erwei Song, Sanjeeva Srivastava, Aihua Sun, Siu Kwan Sze, Chao Tang, Liujun Tang, Ruijun Tian, Juan Antonio Vizcaíno, Chanjuan Wang, Chen Wang, Xiaowen Wang, Xinxing Wang, Yan Wang, Tobias Weiss, Mathias Wilhelm, Robert Winkler, Bernd Wollscheid, Limsoon Wong, Linhai Xie, Wei Xie, Tao Xu, Tianhao Xu, Liying Yan, Jing Yang, Xiao Yang, John Yates, Tao Yun, Qiwei Zhai, Bing Zhang, Hui Zhang, Lihua Zhang, Lingqiang Zhang, Pingwen Zhang, Yukui Zhang, Yu Zi Zheng, Qing Zhong, Yunping Zhu, Π-Hub Consortium

Faculty, Staff and Students Publications

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies. Recent advances in proteomic technology and computational sciences now provide opportunities to investigate the intricate biology of the human body …

Mimicking Large Spot-Scanning Radiation Fields For Proton Flash Preclinical Studies With A Robotic Motion Platform, Fada Guan, Dadi Jiang, Xiaochun Wang, Ming Yang, Kiminori Iga, Yuting Li, Lawrence Bronk, Julianna Bronk, Liang Wang, Youming Guo, Narayan Sahoo, David R Grosshans, Albert C Koong, Xiaorong R Zhu, Radhe Mohan

Faculty, Staff and Student Publications

Previously, a synchrotron-based horizontal proton beamline (87.2 MeV) was successfully commissioned to deliver radiation doses in FLASH and conventional dose rate modes to small fields and volumes. In this study, we developed a strategy to increase the effective radiation field size using a custom robotic motion platform to automatically shift the positions of biological samples. The beam was first broadened with a thin tungsten scatterer and shaped by customized brass collimators for irradiating cell/organoid cultures in 96-well plates (a 7-mm-diameter circle) or for irradiating mice (1-cm

Modulation Of Energetic And Lipid Pathways By Curcumin As A Potential Chemopreventive Strategy In Human Prostate Cancer Cells, Michele Pellegrino, Maria Antonietta Occhiuzzi, Fedora Grande, Ilaria Stefania Pagani, Stefano Aquaro, Paola Tucci

Staff and Researcher Publications

In Western industrialized countries, prostate cancer (PCa) is the second most common malignant disease and prevalent cause of death for men. Epidemiological studies have shown that curcumin (CUR) either prevents PCa initiation or delays its progression to a more aggressive and treatment-refractory form, thus reducing related mortality. Our previous studies have proven the anticancer, antioxidant, and anti-inflammatory properties of CUR on PCa cells. However, there are few reports of the effect of CUR on energy and lipid pathways in PCa. Herein, we show that CUR can modulate the two metabolic energy pathways, increasing glycolytic reserve and reducing oxidative phosphorylation. Moreover, …