cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
AI based discovery of novel T cell therapies for diverse immunogenetic backgrounds
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: The pursuit of novel T cell targets that unleash potent anti-cancer immune responses is hindered by the lack of scalability of traditional wet lab techniques –– imposing burdensome costs and inefficiencies on immunotherapy target discovery. While T cell therapies have brought about a transformative impact on cancer treatment, their effectiveness is limited to a few cancer types, and has struggled to be applicable to individuals with diverse immunogenetic profiles. There is an urgent need to shift our focus towards automated target discovery, with the aim of reaching a broader patient population. The overall goal of this project is to propel the discovery of targets for novel T-cell therapies and expand their use in patients with diverse immunogenetic backgrounds by deploying AI-driven tools to analyze high throughput RNA sequencing data. My lab has recently developed an AI-driven framework and two pivotal datasets, containing 2 million publicly available single T cell transcriptomes, with matching T cell receptor data, and experimentally validated T cell antigen specificity data, extracted from 265 cancer patients, across 30 cancer types. This framework aims to accelerate the discovery of novel T cell therapies for cancer, promising faster and more cost effective development, with broader accessibility to diverse patient populations. Notably, ours is the only known methodology capable of automating the design of T cell therapies using data from an individual's adaptive immune system, without knowledge of their cancer genome. We harnessed our AI-driven framework and database to discover a novel T cell therapy that can target two key cancer antigens: insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2), prevalent in multiple cancer types, and associated with poorer patient survival, and well known target, melanoma antigen recognized by T-cells 1, (MART1). In collaboration with Dr. Powell at the UPenn, we are testing this newly discovered immunotherapy for clinical translation. We propose to leverage our framework for the discovery of: 1) multispecific T cell therapies simultaneously targeting multiple cancer antigen(s) and 2) T cell therapies applicable to populations with diverse immunogenetic backgrounds. The CRCC funding will allow us to discover and gather preliminary data on additional targets that will be leveraged to obtain NIH funding.
Additional file 1 of A novel method for identifying fine-scale bottom-use in a benthic-foraging pinniped
Creators: name: Angelakis, Nathan
name: Goldsworthy, Simon D.
name: Connell, Sean D.
name: Durante, Leonardo M.
Publisher: name: figshare
Year: 2024
Subjects: subject: Ecology
subject: FOS: Biological sciences

description: Supplementary Material 1
Evaluation of Hepatocellular Carcinoma care capacity in Tanzania
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in sub-Saharan Africa (SSA). Pathogenesis is driven by high rates of viral hepatitis, untreated cirrhosis, and limited access to HCC screening and treatment. Globally, 2.5% of patients with cirrhosis will develop HCC each year. With adequate resources around 40% of diagnosed HCC patients will receive curative surgical resection, local ablation, or transplant, however in SSA less than 1% of patients receive such treatment. In Tanzania, there is a national effort to improve early diagnosis and treatment of HCC. Despite this, the multidisciplinary liver tumor board (MDTB) at the Muhimbili National Hospital (MNH) notes that treatment rates for localized HCC are less than 25% of expected. Access to treatment and resources are limited outside of the largest hospitals and care recommendations vary by location, resulting in delayed, disjointed, and uncoordinated care. The landscape for HCC care in Tanzania is unknown. We hypothesize that lack of established referral pathways and treatment guidelines contribute to deficient treatment rates. To address the current absence of HCC data and facilitate treatment, we aim to perform the following: 1) Perform a national assessment of HCC diagnostic and treatment resources, including screening infrastructure, surgical and locoregional capacity, systemic treatment availability, and access to supportive care, 2) Implement a national virtual liver cancer tumor board to strengthen multidisciplinary care and coordination, and 3) Develop contextualized and resource-specific treatment guidelines for liver cancer in Tanzania with assessment of impact using a retrospective patient cohort. Nation liver cancer care capacity assessments will be performed at all major public medical centers to identify available physical and human resources. The virtual tumor board will be distributed nationwide for optimal provider engagement, with implementation success measured by participation and effect on care recommendations. Resource-specific treatment guidelines for liver cancer in Tanzania will be developed on expert consensus. This proposal is part of a larger effort to improve cancer care in SSA and will provide valuable baseline data leading to future capacity building and intervention-driven research.
Targeting Cancer Cells with Carborane Salts for Photodynamic Therapy
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: In collaboration with professors Richard and Sophia Lunt at Michigan State, we have identified an extraordinary class of chemical entities that allow for highly selective and non-toxic breast cancer cell targeting system that has potential for infrared activated photodynamic therapy. The preliminary discovery was serendipitous but the PI is trying to acquire funding to pursue this important finding. Photodynamic therapy (PDT) has emerged as a promising targeted treatment for cancer. However, current PDT is limited by low tissue penetration, insufficient phototoxicity (toxicity with light irradiation), and undesirable cytotoxicity (toxicity without light irradiation). Recently, Sophia and Richard Lunt introduced a novel platform for tuning the toxicity of near-infrared (NIR) light activated photosensitizers (PSs) through counterion pairing in organic salts, achieving greater tissue penetration, improved phototoxicity, and minimal cytotoxicity. It turns out that using this approach, but with special molecules called carborane anions developed in Lavallo's lab, unprecedented higher potency and efficacy against primary breast tumors as well as metastatic breast cancer cells has been observed. Sophia Lunt has characterized their cellular uptake, organelle localization, generation of reactive oxygen species (ROS), suppression of pro-metastatic pathways, and activation of apoptotic pathways using metastatic breast cancer cell lines. Further she has shown that Lavallo's molecules have the ability to create PSs that stop tumor growth in vivo using an orthotopic mouse model of breast cancer to an unprecedented level. The newly developed lead PS formulation introduces a potent therapeutic approach against aggressive breast cancer cells while decreasing side effects in healthy cells. This seed grant funding will be used by Lavallo's group to create libraries of commercially unavailable carborane salts and provide them to the Lunt groups for elaboration and exploration of structure activity/toxicity relationships of the therapeutics. Lavallo's lab is traditionally a synthetic/fundamental/battery inorganic group that has never participated in cancer research previously.
Targeting Bladder Cancer with Intravesical and Systemic NECTIN4-directed Therapies
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Bladder cancer (BC) is the 2nd most common genitourinary malignancy and 6th most common cancer in the US, leading to an estimated 16,000 deaths in the US per year. Unfortunately, patients who develop metastatic BC (mBC) have a poor 5-year survival of ~15%. Recently, an antibody-drug conjugate (ADC) targeting the surface protein NECTIN4 (enfortumab vedotin, EV) was approved, validating NECTIN4 as an important target in mBC. Although EV monotherapy has a response rate of 44%, resistance invariably develops to the ADC. Interestingly, our preliminary and unpublished data demonstrates that NECTIN4 expression is retained on the surface of EV-resistant cells (that we generated in the lab) as well as in patient biopsy samples post-EV resistance (measured by immunohistochemistry). Therefore, we hypothesize that additional strategies to target NECTIN4 using CAR T and radioimmunotherapies (RIT) are rapidly needed, and will be efficacious both in EV-naïve and EV-resistant settings. However, to date, neither of these therapeutic modalities have been approved for bladder cancer patients. In this proposal, we will develop these two approaches and perform rigorous preclinical evaluation using 3 in vivo model systems: 1) an orthotopic bladder tumor model; 2) a subcutaneous patient-derived xenograft (PDX) model; and 3) a lung metastasis model. Our study will also use unique PDX’s developed at UCSF from minority patients (an important understudied population) and models of EV resistance that we created in our lab. If our results are positive, we plan to translate our findings into an investigator-initiated clinical trial, and will have two non-overlapping opportunities to do so – one with the CAR T and the other with the RIT. As a translational genitourinary medical oncologist and lab-based investigator, I have extensive experience leading pre-clinical studies of novel agents in the lab and running investigated-initiated clinical trials at UCSF. I am also fortunate to work with a fantastic team, so that we can translate findings from the bench to the bedside and back again. Overall, this application represents an important step in developing novel NECTIN4-targeting strategies, with implications that may extend beyond bladder cancer to other NECTIN4-positive tumor types such as breast, ovarian, lung and pancreatic cancers.
Enhancing CAR-T Therapy by Targeting PP2A in Glioblastoma
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Glioblastoma (GBM) is one of the most aggressive cancers without cure. Chimeric antigen receptor (CAR)-T cell therapy is a powerful strategy for cancer treatment that offers new opportunities for patients with malignant gliomas. However, there are several barriers that possibly dampen the efficacy of CAR-T cell therapy for glioma, including the intrinsic nonimmunogenic phenotype of glioma cells and their immunosuppressive tumor microenvironment (TME). To solve this problem, we have established murine orthotopic GBM models for optimizing IL13Rα2 CAR-T cell therapeutic parameters for clinical translation through collaboration. The immunocompetent syngeneic mouse models of GBM, and murine-CAR-T cells more precisely recapitulate patient glioma tumors and will provide essential information regarding the effect of therapies on the TME. For effective CAR-T therapy against GBM, it has been shown that activation of endogenous T cells and anti-tumor TME is required. Protein Phosphatase 2A is heterotrimeric, consisting of scaffolding (A), regulatory (B), and catalytic (C) subunits that interact to form a functional holoenzyme. We were the first to demonstrate that inhibiting PP2A enhanced immunogenicity of glioma cells to induce sensitivity to tumor specific T cells mediated killing and reprogrammed the TME toward anti tumor. We demonstrated that LB-100, small molecule inhibitor of the conserved catalytic subunit of PP2A (PP2Ac), synergizes with PD1 blockade in multiple in vivo tumor models including GBM7,8. These results led to a phase I/II clinical trial testing LB100 in patients with recurrent GBM (NCT03027388) and a combination trial with anti-PD-1 in ovarian clear cell carcinoma (NCT06065462). Elucidating the role of PP2Ac within different cell types of the TME in regulating tumor sensitivity to CAR-T therapy is critical to inform rational combination in future clinical trials. We hypothesize that inhibition of PP2Ac will overcome the barriers for CAR-T cell therapy in glioma TME, and combination of IL13Rα2 CAR-T cell therapy and PP2A inhibitor will be a potential novel combination treatment for brain tumors. Successful completion of this project will provide preclinical insights to initiate novel clinical trials of combining PP2A inhibitor with IL13Rα2 CAR-T therapy.
Additional file 1 of Metabolomics-guided identification of compounds with antibacterial and antioxidant activities from Polygonatum sibiricum-derived endophytic fungi
Creators: name: Zhao, Lingyun
name: Liu, Yu
name: Sun, Huiru
name: Li, Yu
name: Pachaiyappan, Saravana Kumar
name: Fang, Xinyue
name: Ran, Yalan
name: Qin, Yang
name: Luo, Kai
name: He, Meijun
Publisher: name: figshare
Year: 2024
Subjects: subject: Biochemistry
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: Biological Sciences not elsewhere classified
subject: Plant Biology
subject: Virology

description: Additional file 1. Supplementary tables and figures.
Supplemental Material, Chao_19040064_toSage_SuppTbls - A Systematic Review of Taste Differences Among People With Eating Disorders
Creators: name: Chao, Ariana M.
name: Abhrarup Roy
name: Franks, Alexis T.
name: Joseph, Paule V.
Publisher: name: SAGE Journals
Year: 2019
Subjects: subject: 111099 Nursing not elsewhere classified
subject: FOS: Health sciences

description: Supplemental Material, Chao_19040064_toSage_SuppTbls for A Systematic Review of Taste Differences Among People With Eating Disorders by Ariana M. Chao, Abhrarup Roy, Alexis T. Franks and Paule V. Joseph in Biological Research For Nursing
Identifying distinct lymphvascular drivers of tumor initiation and evolution
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: All forms of cancer begin with genetic alterations in otherwise healthy cells. Yet, these alone are insufficient to predict an individual’s disease onset and risks, indicating that nongenetic events within the tumor ecosystem (‘niches’) play a role in unleashing tumorigenesis. Stem cells are the origin of many life-threatening malignancies and are notorious for their tight dependency on the surrounding microenvironment. Despite undisputed importance, our understanding of how the ecosystems that stem cells inhabit direct oncogenic fate flexibility is limited. Equally, it remains a mystery whether early-stage tumor initiation through advanced disease progression is supported by overlapping or distinct niches. These gaps in knowledge can largely be attributed to a dearth of tools and models that capture the oncogenic stem cell identity landscape in intact tissues. The lymphatic vascular network is an emerging, previously unrecognized niche entity for epithelial stem cells, yet much of the mystery of the lymphatic niches in directing tumorigenesis remains untapped. The goal of our proposed work is to determine how distinct vascular cues drive oncogenic flexibility and tumorigenesis in rare pre-cancer stem cells. Using deep imaging and sequencing approaches in skin squamous cell carcinoma, we discovered that lymphatic vascular insufficiency predisposes to malignant transformation. Detailed temporal volumetric imaging revealed that oncogenic plasticity propelling the transition from benign to metastatic carcinoma is preceded by dynamic lymphatic remodeling. These results raise the intriguing possibility that lymphatic niches evolve during disease progression, directing oncogenic tolerance in tumor-initiating cells while becoming a significant barrier to cancer treatments. To fill these knowledge gaps, we aim to determine how vascular circuits shape oncogenic tolerance in mutated yet untransformed cells in concert with their evolving niches, and to identify non-mutational drivers that build the pro-metastatic niche using our newly developed enhancer-based proximity sensor technology. Our innovative approach will define how vascular circuits shape the stem cell oncogenic landscape. A successful outcome of these studies holds promise for the development of therapeutics that block early cancer progression and pave the way to combat advanced metastatic disease.
5-012-LinearSystemConjecture-TechniqueNarrative
Creators: name: Winkel, Brian
Publisher: name: QUBES Educational Resources
Year: 2022

description: Students go from the solution for y'(t) = k*y(t) to a natural extension to the solution conjecture of a system of two constant coefficient, homogeneous, linear differential equations introducing eigenvalues and eigenvectors through student discovery.
Controlling tumor metastasis via the gut microbiota
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Metastasis requires cancer cells to evade the immune system while circulating and colonizing distal sites. Therefore, the basal activation level of the immune system may determine the rate of successful metastases in individual patients and could be a viable therapeutic target to slow cancer progression. Our recent work has suggested that the gut microbiota is a potent source for immune stimulatory molecules and that an individual’s microbiota can correlate with their responsiveness to cancer immunotherapies. Thus, we hypothesize that the microbiota’s capacity to generate specific, immune active metabolites may more broadly affect cancer progression including the successful formation of new metastatic sites. This one-year, pilot project will focus on two aims. First, we will examine whether increasing the processing of bacterial cell wall in the gut can control the metastatic progression of melanoma. This will be accomplished using our previous model to orally supplement the gut microbiota with specific microbes or enzymes and will be applied to the established murine model of melanoma metastasis using intravenous injection of B16-F10 cells. Second, we will define host factors caused by increased enzymatic activity in the gut that may function as both biomarkers and causal agents for immune activity against circulating and newly colonizing tumor cells. Here, we will use targeted mass spectrometry to quantify muramic acid in murine blood samples after supplementation as a proxy readout for circulating cell wall fragments. We will also use flow cytometry and single-cell RNA sequencing to quantify and characterize a population of bacterial cell wall-responsive CX3CR1+Ly6Clo patrolling monocytes as a cellular biomarker and a potential effector cell population for reduced metastasis. These studies align with our laboratory’s broader goals (1) to define the mechanisms of immune activation by the gut microbiota during cancer progression and treatment and (2) to develop enzyme- and probiotic-based methods to selectively augment host immune responses as single agents or in combination with other cancer therapies. If successful, this work will provide direct evidence that modulation of enzymatic capacity in the gut – that is, the overall ability to selectively produce metabolites – can alter immune-mediated protection against metastasis.
sj-pdf-1-neu-10.1177_1971400920924799 - Supplemental material for Diffuse large B-cell lymphoma relapse presenting as extensive neurolymphomatosis
Creators: name: Nepal, Pankaj
name: Batchala, Prem P
name: Rehm, Patrice K
name: Fadul, Camilo E
Publisher: name: SAGE Journals
Year: 2020
Subjects: subject: 110904 Neurology and Neuromuscular Diseases
subject: FOS: Clinical medicine
subject: Neuroscience

description: Supplemental material, sj-pdf-1-neu-10.1177_1971400920924799 for Diffuse large B-cell lymphoma relapse presenting as extensive neurolymphomatosis by Pankaj Nepal, Prem P Batchala, Patrice K Rehm and Camilo E Fadul in The Neuroradiology Journal
Additional file 3 of Implementation of Nanopore sequencing as a pragmatic workflow for copy number variant confirmation in the clinic
Creators: name: Greer, Stephanie U.
name: Botello, Jacquelin
name: Hongo, Donna
name: Levy, Brynn
name: Shah, Premal
name: Rabinowitz, Matthew
name: Miller, Danny E.
name: Im, Kate
name: Kumar, Akash
Publisher: name: figshare
Year: 2024
Subjects: subject: Genetics
subject: FOS: Biological sciences

description: Additional file 3. Additional methods.
Genome-wide maps of c-Myc dependent genetic interactions
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Overexpression of the c-Myc cancer gene drives growth >70% of malignant tumors, including breast, brain and lung. The c-Myc oncogene encodes a transcription factor and thus regulates many other genes. However, transcription factors are difficult targets for which to design drugs. As exemplified by c-Myc, genetic interactions are at the root of normal and malignant cell growth. Interactions between gene pairs have been cataloged in mammalian cells by combining knockouts created using CRISPR/Cas9 or siRNA and observing the changes in cell growth. However, these piecemeal approaches are laborious and expensive and do not address the >200 million genetic interactions that potentially occur. An approach that can affordably map the entire array of genetic interactions in normal and diseased cells is urgently needed. We have developed a technology using radiation hybrid (RH) cells that is capable of elucidating with high sensitivity and specificity genes that interact even though they are located at a distance within in the genome. Our approach yields high-resolution, comprehensive maps of interacting gene pairs. RH panels are constructed by lethally irradiating cells so that the DNA shatters. The fragments are then introduced into living cells so that a random assortment, ~25%, of genes are triploid rather than diploid. Statistically significant patterns of co-inherited triploid genes point to the cell's survival mechanism. Most importantly, the fragments are so small that the technique often provides single-gene resolution, revealing with specificity the multiple roles one gene plays within a cell. Our preliminary data shows that low pass genome sequencing of nascent human RH clones (RH-Seq) is an economical approach to constructing interaction maps. The network showed significant overlap with a previous network obtained by us that established the groundwork for the RH approach and showed that coinheritance of distant genes is an important mechanism for cell viability. Our goal is to map genetic interactions for the entire genome in normal cells and cells that overexpress c-Myc. The result will be a high resolution map of the genetic interactions that drive cell growth in the context of aberrant c-Myc expression, providing new, highly relevant targets for treatment.
Additional file 1 of Carbon dioxide fixation via production of succinic acid from glycerol in engineered Saccharomyces cerevisiae
Creators: name: Malubhoy, Zahabiya
name: Bahia, Frederico Mendonça
name: de Valk, Sophie Claire
name: de Hulster, Erik
name: Rendulić, Toni
name: Ortiz, Juan Paulo Ragas
name: Xiberras, Joeline
name: Klein, Mathias
name: Mans, Robert
name: Nevoigt, Elke
Publisher: name: figshare
Year: 2022
Subjects: subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Pharmacology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: Science Policy

description: Additional file 1: Figure S1. History of constructing the 2nd-generation SA producers. Figure S3. Figure S2. Comparison of the DHA pathway (baseline) strains used in the study of Xiberras et al. [17] and in the current work. Specific and volumetric glycerol consumption rates of 2nd-generation SA producers in ordinary shake flask cultures. Figure S4. Time courses of medium pH for the shake flask cultivations supplemented with 30 g L−1 CaCO3.
sj-pdf-1-eso-10.1177_2396987320923447 - Supplemental material for Effect of atrial fibrillation on endovascular thrombectomy for acute ischemic stroke. A meta-analysis of individual patient data from six randomised trials: Results from the HERMES collaboration
Creators: name: JA Smaal
name: IR De Ridder
name: A Heshmatollah
name: WH Van Zwam
name: DWJ Dippel
name: CB Majoie
name: S Brown
name: M Goyal
name: BCV Campbell
name: KW Muir
name: AM Demchuck
name: A Davalos
name: TG Jovin
name: PJ Mitchell
name: P White
name: JL Saver
name: MD Hill
name: YB Roos
name: A Van Der Lugt
name: RJ Van Oostenbrugge
Publisher: name: SAGE Journals
Year: 2020
Subjects: subject: Cardiology
subject: Medicine
subject: 110904 Neurology and Neuromuscular Diseases
subject: FOS: Clinical medicine

description: Supplemental material, sj-pdf-1-eso-10.1177_2396987320923447 for Effect of atrial fibrillation on endovascular thrombectomy for acute ischemic stroke. A meta-analysis of individual patient data from six randomised trials: Results from the HERMES collaboration by JA Smaal, IR de Ridder, A Heshmatollah, WH van Zwam, DWJ Dippel, CB Majoie, S Brown, M Goyal, BCV Campbell, KW Muir, AM Demchuck, A Davalos, TG Jovin, PJ Mitchell, P White, JL Saver, MD Hill, YB Roos, A van der Lugt, RJ van Oostenbrugge and For the HERMES collaboration in European Stroke Journal
Determining mechanisms of anti-tumor synergy elicited by innate immune agonist cancer therapies.
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Therapeutically activating innate immunity in tumors can elicit profound anti-cancer responses in a variety of indications. Drugs that target the innate immune protein STING elicit potent anti-cancer responses in mice, and >15 STING agonists entered clinical trials in the past 10 years. However, in 2023 the first trial results showed a lack of efficacy. The emerging challenges in the field are now to increase efficacy of innate immune agonists while maintaining tumor-specific T cell responses. We recently discovered that STING agonist efficacy is dramatically enhanced when used in combination with agonists of Toll-like receptors (TLRs), another class of innate immune receptors. We found that a single combination dose can elicit complete responses in >80% of mice bearing established B16-F10 melanomas, as compared to 25% with monotherapy. Mice that cleared primary tumors developed resistance to tumor cell rechallenge. This demonstrates that the challenges of efficacy and T cell priming can be overcome through STING+TLR agonist combination therapy. However, key questions regarding the mechanisms of synergy are unanswered, including: what cytokines and cell types are required for the anti-tumor synergy elicited by STING+TLR agonists? Understanding this mechanism will aid future clinical studies on innate immune agonist therapies for cancer. We propose in Aim 1 to determine the role for immune cells in the anti-tumor response to combination therapy. We will use flow cytometry to measure T cell activation and the abundance of immune cell types including neutrophils, macrophages, and dendritic cells. To determine the requirement for these cells in the anti-tumor synergy, we will deplete CD8, CD4, and NK cells and measure tumor volume after therapy. This will determine the cellular mechanisms of anti-tumor synergy. Then in Aim 2, we will identify the cytokines required for eliciting synergistic anti-tumor responses to STING+TLR combination therapy in vivo. IL-12 and TNF-a are upregulated in response to STING+TLR agonist co-administration, but their necessity is unknown. We will neutralize these cytokines and measure tumor volume after therapy. Together, this work will determine the cytokines and cell types required for STING+TLR agonist synergy, advancing the field and paving the way for clinical trials with combinations of innate immune agonists.
Small Molecule Inhibition of GNAS; Creating the First Targeted Treatments for Appendix Cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: The Gα protein GNAS, which encodes for the heterotrimeric G protein Gαs, is the second most frequently mutated gene in mucinous appendiceal adenocarcinoma (AA) (~50% of tumors) and Pseudomyxoma Peritonei (PMP, ~75% of tumors) and third most common in non-mucinous AA (~25% of tumors), making it a promising drug target in this orphan disease. Although classically druggable, no commercially available inhibitors of Gαs exist. Here, we propose an innovative approach to develop and characterize chemical inhibitors of Gαs. Given prior in vitro and in vivo data demonstrating that GNAS knockout is lethal to GNASR201 tumors, there is a high likelihood that chemical inhibition of Gαs will be an effective therapeutic strategy for GNASR201 mutant tumors. New Treatments are Needed for Appendiceal Cancer, Currently an Orphan Disease. Appendiceal tumors encompass a rare and diverse group of neoplasms; AA is the most common histologic subtype. Epidemiologic studies based on Surveillance, Epidemiology, and End Results (SEER) data have shown a steady increase in incidence from approximately 0.2 cases per 100,000 in the 1970s, to current estimates of just over 1 per 100,000. In comparison, this is 40-fold less common than colon cancer, which in the US has an incidence of approximately 40 per 100,000. Cases of early-onset AA, defined as diagnosis before age 50, have increased by 24% between 2011 to 2016, and in 2016 represented 40% of all appendiceal cancer. In contrast, the increase in early-onset colorectal cancer (CRC) was only 2.2% for that same time period. Historically, appendiceal tumors have been grouped together with CRCs, and as of 2021 the National Comprehensive Cancer Network (NCCN) guidelines still suggested that appendiceal tumors be treated with chemotherapy similarly to colon tumors. The rarity of AA has made it difficult to conduct clinical trials, and in the absence of trial data, the NCCN guidelines assume biological similarity due to anatomic vicinity, common embryological origin, and common expression of the transcription factor CDX2. However, there is a growing consensus that AA is a clinically and molecularly distinct entity from CRC, and that AA specific therapies (none exist currently) need to be developed. We have discovered two druggable sites on GNAS and have developed small molecule inhibitors targeting the site next to the point of mutation.
Supplemental Material, brancatilucardi-2018-democracy-protests-jcr_appendix - What We (Do Not) Know about the Diffusion of Democracy Protests
Creators: name: Brancati, Dawn
name: Lucardi, Adrián
Publisher: name: SAGE Journals
Year: 2019
Subjects: subject: 220104 Human Rights and Justice Issues
subject: FOS: Philosophy, ethics and religion
subject: 160607 International Relations
subject: FOS: Political science

description: Supplemental Material, brancatilucardi-2018-democracy-protests-jcr_appendix for What We (Do Not) Know about the Diffusion of Democracy Protests by Dawn Brancati and Adrián Lucardi in Journal of Conflict Resolution
Additional file 1 of Supported self-management for all with musculoskeletal pain: an inclusive approach to intervention development: the EASIER study
Creators: name: Healey, Emma L.
name: Lewis, Martyn
name: Corp, Nadia
name: Shivji, Noureen A.
name: van der Windt, Danielle A.
name: Babatunde, Opeyemi O.
name: Simkins, Joanna
name: Bartlam, Bernadette
name: Rowlands, Gill
name: Protheroe, Joanne
Publisher: name: figshare
Year: 2024
Subjects: subject: Medicine
subject: Sociology
subject: FOS: Sociology
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Science Policy

description: Additional file 1. Details of datasets.
Role of post-viral lung damage in promoting metastatic outgrowth of cancer cells
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: The proposed research will explore a new direction in my lab investigating how post-viral lung damage and inflammation affect dormancy and metastatic outgrowth of cancer cells. Metastasis accounts for the majority of cancer related deaths and therapeutic strategies that can prevent or reduce metastatic burden are urgently needed. The lung is the most common site of metastasis in several cancers such as breast, lung, colon, melanoma, bladder, prostate and kidney. Recent studies have shown that cancer cells guide the creation of a pre-metastatic niche to exit cellular dormancy and proliferate to form metastatic lesions. Cancer cells achieve this by secretion of specific cytokines that promote an immune suppressive phenotype in the secondary organ. However, the role of the secondary organ in creating the metastatic niche is underappreciated. Moreover, it is unclear if and how previous injury through respiratory infections and pulmonary fibrosis can influence the growth of metastatic cancer cells in the lung. Among individuals hospitalized for severe respiratory viral infections, such as influenza and SARS-CoV-2, 25 - 50% of patients experience persistent respiratory symptoms due to chronic effects of lung tissue damage. Our research has demonstrated that these infections induce distinct fibroblast activation states that drive immunopathology during acute infection and promote pulmonary fibrosis following clearance of the infection. We have also developed a clinically relevant and well characterized influenza model in mice that allows us to study persistent inflammation and pulmonary fibrosis at chronic, post-viral stages of disease. Working in collaboration with the Sikandar lab at UC Santa Cruz, we have optimized this model to study breast cancer metastasis following viral infection. We are uniquely positioned to ask the following questions: 1. Does prior respiratory viral infection promote metastasis of breast tumor cells to the lung tissue? 2. Do inflammatory lung fibroblasts activated following severe viral infection promote metastatic niches for tumor cells? Using a combination of in vivo and in vitro assays we will test our working hypothesis that damage to the lung by viral infection resulting in persistent inflammation and fibrosis creates a metastatic niche promoting proliferation of breast tumor cells.
Additional file 7 of Supported self-management for all with musculoskeletal pain: an inclusive approach to intervention development: the EASIER study
Creators: name: Healey, Emma L.
name: Lewis, Martyn
name: Corp, Nadia
name: Shivji, Noureen A.
name: van der Windt, Danielle A.
name: Babatunde, Opeyemi O.
name: Simkins, Joanna
name: Bartlam, Bernadette
name: Rowlands, Gill
name: Protheroe, Joanne
Publisher: name: figshare
Year: 2024
Subjects: subject: Medicine
subject: Sociology
subject: FOS: Sociology
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Science Policy

description: Additional file 7. Mediation and moderation of mediation of the association between inadequate health literacy and poor pain and function at follow up.
The Warburg Effect is the result of faster ATP production by glycolysis than respiration
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Many prokaryotic and eukaryotic cells partially metabolize glucose to organism-specific byproducts instead of fully oxidizing it to carbon dioxide and water, even in the presence of oxygen. This phenomenon, often referred to as the Warburg Effect, was originally observed in tumor cells. The benefit of the Warburg Effect to a cell has been unclear, given that partial metabolism of glucose yields an order of magnitude less ATP per molecule of glucose than complete oxidation. In our recent theoretical study, we proposed that the Warburg Effect stems from the optimization of energy metabolism that allows cells to produce ATP at the highest rate in the presence of excess glucose independent of cell growth rate. By estimating the yield, specific activity, and proteome occupancy of the glycolysis and respiration pathways from published studies in bacteria, yeast, and mammals, we found that for each organism, the data is consistent with glycolysis producing ATP at a faster rate per gram of pathway protein than respiration. However, we could only find a limited number of published datasets for mammalian cells that contain measurements required for our calculations. Here, we propose to perform rigorous measurements of glycolysis and respiration pathway rates per gram of pathway protein in mammalian cancer cell lines to generate additional evidence to support or refute our hypothesis. Our lab has extensive experience performing metabolic flux and proteomics measurements in mammalian cells that will be required for this project, which will allow us to complete the proposed measurement within the 1-year duration of the Seed Grant. Taken together, our study will rigorously test the hypothesis that the Warburg Effect is an expected consequence of the optimization of cancer cell energy metabolism toward maximal energy production rates and might lead to the development of novel anticancer treatments specifically targeting the vulnerabilities of cancer cell bioenergetics.
DS_10.1369_0022155419871550 – Supplemental material for Elevated ATF4 Expression in Odontogenic Keratocysts Epithelia: Potential Involvement in Tissue Hypoxia and Stromal M2 Macrophage Infiltration
Creators: name: Zhong, Wen-Qun
name: Li, Zhi-Zheng
name: Jiang, Hao
name: Zou, Yan-Ping
name: Wang, Hai-Tao
name: Cai, Yu
name: Zhao, Yi
name: Zhao, Ji-Hong
Publisher: name: SAGE Journals
Year: 2019
Subjects: Cell Biology
Biological Sciences not elsewhere classified
Pharmacology and Pharmaceutical Sciences not elsewhere classified

description: Supplemental material, DS_10.1369_0022155419871550 for Elevated ATF4 Expression in Odontogenic Keratocysts Epithelia: Potential Involvement in Tissue Hypoxia and Stromal M2 Macrophage Infiltration by Wen-Qun Zhong, Zhi-Zheng Li, Hao Jiang, Yan-Ping Zou, Hai-Tao Wang, Yu Cai, Yi Zhao and Ji-Hong Zhao in Journal of Histochemistry & Cytochemistry
Elucidating the function of BET proteins in the G2-M cell cycle transition
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Fundamental cellular pathways are rewired in cancers to drive their inappropriate proliferation. This rewiring enhances cancer growth but can also generate vulnerabilities to therapeutic interventions. To enable cell proliferation, cancers frequently deregulate key transitions in the tightly-controlled cell division cycle. Prior work has focused on developing therapeutic agents that target uncontrolled entry into the DNA replication phase of the cell cycle in cancers (the G1-S transition). In this proposal, we will develop an unexpected observation that implicates BET (Bromodomain and ExtraTerminal domain) proteins in promoting entry into mitosis after completion of DNA replication (the G2-to-M transition). BET proteins harbor two domains that recognize acetylated lysine residues and are emerging targets for cancer therapy based on their involvement in numerous chromatin-related functions, including transcriptional regulation and protection from DNA damage. Employing a live imaging assay for quantitatively monitoring mitotic entry in single cells, we have observed a role for BET proteins in promoting the G2-to-M transition. BET inhibition delays mitotic entry in cancer-derived and non-transformed, immortalized cell lines. In a specific colorectal cancer-derived cell line, BET inhibition strongly synergizes with inhibition of the mitotic kinase PLK1 to block mitotic entry. The proposed work will investigate how BET proteins contribute to mitotic entry, testing specific hypotheses related to transcriptional regulation, DNA damage, and the mitotic entry circuit. The proposed effort represents an entirely new research area for the group, which has historically focused on chromosome segregation, centrosome function, spindle assembly, and checkpoint function during mitosis. Successful execution of the project has the potential to advance understanding of the cellular functions of BET proteins and of the control of mitotic entry in human cells, while also revealing whether there are opportunities for targeting the G2-M transition of the cell cycle, as has been done for the G1-S transition, in specific cancer contexts.
Identifying Disparities in Autologous HCT Utilization for DLBCL in California
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2025

description: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, which is fatal without treatment, but potentially curable with current therapies. The standard of care for patients who relapse or have refractory (R/R) DLBCL >12 months after initial treatment is an autologous, or in some instances, an allogeneic hematopoietic cell transplant (HCT). For patients who relapse <12 months after first-line therapy, HCT is still an option, with the addition of chimeric antigen T-cell therapy more recently becoming a standard of care treatment in this setting. Patients often receive second and further lines of chemo-immunotherapy for disease control for R/R DLBCL, but without HCT, all therapies are palliative in nature. The utilization of HCT in patients with DLBCL remains low for certain patients and can be impacted by multiple factors, such as access to a transplant center and insurance status. Prior studies have found racial/ethnic disparities in the utilization of autologous HCT in lymphoma patients, with Non-Hispanic Black patients undergoing HCT less often than their Non-Hispanic White counterparts and having inferior survival. To date, little is known about the influence of sociodemographic and clinical factors on HCT utilization for patients with lymphoma over time. In order to identify barriers to care in patients with DLBCL, we propose a retrospective cohort study of all DLBCL patients diagnosed in California from 1992 to 2016 using a novel data linkage from the Center for International Blood and Marrow Transplant Research (CIBMTR), California Cancer Registry (CCR), and statewide hospitalization data. A study in multiple myeloma patients from this linkage has identified that each of the three data sources independently capture HCT utilization, permitting the assessment of utilization of HCT at the population-level. These data sources also include sociodemographic factors (race/ethnicity, health insurance status, neighborhood socioeconomic status, sex, and age at diagnosis) and clinical factors (e.g., chemo-immunotherapy, disease stage, and comorbidities). This study will identify changes in sociodemographic and clinical associations with HCT over time and inform strategies to help to improve HCT rates, which is a curative therapy for patients with R/R DLBCL.
Additional file 1 of The effectiveness of interventions to reduce adverse outcomes among older adults following Emergency Department discharge: umbrella review
Creators: name: Conneely, Mairéad
name: Leahy, Siobhán
name: Dore, Liz
name: Trépel, Dominic
name: Robinson, Katie
name: Jordan, Fionnuala
name: Galvin, Rose
Publisher: name: figshare
Year: 2022
Subjects: subject: Medicine
subject: Pharmacology
subject: Biotechnology
subject: Developmental Biology
subject: Science Policy
subject: 110309 Infectious Diseases
subject: FOS: Health sciences

description: Additional file 1: Supplementary Information 1. Search Strategy.
Additional file 3 of Supported self-management for all with musculoskeletal pain: an inclusive approach to intervention development: the EASIER study
Creators: name: Healey, Emma L.
name: Lewis, Martyn
name: Corp, Nadia
name: Shivji, Noureen A.
name: van der Windt, Danielle A.
name: Babatunde, Opeyemi O.
name: Simkins, Joanna
name: Bartlam, Bernadette
name: Rowlands, Gill
name: Protheroe, Joanne
Publisher: name: figshare
Year: 2024
Subjects: subject: Medicine
subject: Sociology
subject: FOS: Sociology
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Science Policy

description: Additional file 3. Case Vignette.
Supplemental material for Normalization of reduced functional connectivity after revascularization of asymptomatic carotid stenosis
Creators: name: Quandt, Fanny
name: Fischer, Felix
name: Schröder, Julian
name: Heinze, Marlene
name: Kessner, Simon S
name: Malherbe, Caroline
name: Schulz, Robert
name: Cheng, Bastian
name: Fiehler, Jens
name: Gerloff, Christian
name: Thomalla, Götz
Publisher: name: SAGE Journals
Year: 2019
Subjects: subject: 110305 Emergency Medicine
subject: FOS: Clinical medicine
subject: 110306 Endocrinology
subject: Medicine
subject: 110904 Neurology and Neuromuscular Diseases
subject: 110320 Radiology and Organ Imaging
subject: Cell Biology
subject: Biochemistry
subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences
subject: Neuroscience

description: Supplemental Material for Normalization of reduced functional connectivity after revascularization of asymptomatic carotid stenosis by Fanny Quandt, Felix Fischer, Julian Schröder, Marlene Heinze, Simon S Kessner, Caroline Malherbe, Robert Schulz, Bastian Cheng, Jens Fiehler, Christian Gerloff and Götz Thomalla in Journal of Cerebral Blood Flow & Metabolism
Faulkenberry_AMPPSOpenPracticesDisclosure-v1.0-signedTJF – Supplemental material for Estimating Evidential Value From Analysis of Variance Summaries: A Comment on Ly et al. (2018)
Creators: name: Faulkenberry, Thomas J.
Publisher: name: SAGE Journals
Year: 2019
Subjects: subject: 170199 Psychology not elsewhere classified
subject: FOS: Psychology
subject: 110319 Psychiatry (incl. Psychotherapy)
subject: FOS: Clinical medicine

description: Supplemental material, Faulkenberry_AMPPSOpenPracticesDisclosure-v1.0-signedTJF for Estimating Evidential Value From Analysis of Variance Summaries: A Comment on Ly et al. (2018) by Thomas J. Faulkenberry in Advances in Methods and Practices in Psychological Science