Life Sciences Commons^™

Predicting The Response Of Triple Negative Breast Cancer To Neoadjuvant Systemic Therapy Via Biology-Based Modeling And Habitat Analysis, Casey E Stowers, Chengyue Wu, Clinton Yam, Jingfei Ma, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite being the standard-of-care treatment, neoadjuvant therapy (NAT) attains a complete response only in approximately half of the patients with triple negative breast cancer. Thus, methods to predict and optimize patient response to NAT are needed. Previously, we employed patient-specific MRI data to calibrate a biology-based mathematical model that describes cell movement, proliferation, and death due to drug at the tumor level and cell proliferation at an image voxel level. We now extend our approach by using MRI data to group voxels into "habitats" whereby tumor cells of a habitat share the same proliferation. With this approach, we now calibrate …

Shp2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy To Cancer Treatment And Vascular Risk, Silvia Fernanda López Moreno, Stefania Assunto Lenz, Bernardo Casso-Chapa, Angelica Paniagua-Bojorges, Jung Hyun Kim, Nicolas L Palaskas, Kevin T Nead, Venkata S K Samanthapudi, Gilbert Mejia, Oanh Hoang, Jonghae Lee, Steven H Lin, Joerg Herrmann, Guangyu Wang, Syed Wamique Yusuf, Cezar A Iliescu, Noah I Beinart, Charlotte Manisty, Masuko Ushio-Fukai, Tohru Fukai, Pietro Ameri, Roza I Nurieva, Michelle A T Hildebrandt, Keri Schadler, Efstratios Koutroumpakis, Sivareddy Kotla, Nhat-Tu Le, Jun-Ichi Abe

Faculty, Staff and Student Publications

Src homology 2-domain containing protein tyrosine phosphatase 2 (SHP2), encoded by the Ptpn11 gene (Tyrosine-protein phosphatase non-receptor type 11), is a key downstream effector of PD-1/PD-L1 signaling and is likely important, in addition to immune modulation, in tumor development and vascular homeostasis. SHP2 conveys PD-1 mediated inhibitory signaling in T cells, and is emerging as a therapeutic target. Importantly, there is an association between immune checkpoint inhibitors (ICIs), immune-related adverse events (irAEs), and cardiovascular complications, underscoring the need to understand SHP2’s role in these processes. This review aims to summarize current knowledge on SHP2/PTPN11 biology, its role in immune …

Navigating Structure, Function, And Stability: Bridging Immunotherapy And Protein Engineering In The Era Of Machine Learning, Christopher J. Haynie

Theses and Dissertations

The immune system is a remarkably adaptive network, yet it often fails to function optimally due to evasion strategies of pathogens or mutated cells. Many of these evasion strategies involve alterations in protein expression and function. Protein design is an area of computational biology with potential applications in improving protein function and therapeutic protein engineering. This thesis explores methods to enhance immune function and protein design across multiple scales, from molecular engineering of antibody fragments and chimeric antigen receptors (CARs) to cellular immune responses, and computational approaches for protein structure optimization. We characterize Thymidine Kinase 1-specific single-chain antibodies, highlighting both …

Conjunctival Melanoma Genomic Analysis Reveals Intermediate Tumor Mutation Burden And Genomic Overlap With Cutaneous Melanoma, Florentia Dimitriou, Xiaogang Wu, Priyadharsini Nagarajan, Isabella C Glitza, Li Zhao, Jing Ning, Sapna P Patel, Jennifer A Wargo, Andrew Futreal, Scott Woodman, Jennifer L Mcquade, Bita Esmaeli

Faculty, Staff and Student Publications

Conjunctival melanoma (CJM) is a rare and aggressive malignancy. Mainly attributed to its rarity, the genomic features of CJM have not been well characterized. In the present study, we sequenced the exomes of primary and metastatic CJM tumors with the aim to unravel their genomic landscape. The results of the study suggest that CJM is a molecularly distinct melanoma subtype with mixed genotype and targetable mutations. Notably, there were features overlapping with both mucosal, and mainly cutaneous melanoma. Of note, some genetic alterations were found in association with specific subsets of CJM, such as bulbar anatomical localization. CJM tumors had …

Proteomic Perspectives On Kras-Driven Cancers And Emerging Therapeutic Approaches, Ramesh Karki, Ru Chen, Sheng Pan

Faculty, Staff and Student Publications

KRAS mutations are implicated in approximately 23% of all human malignancies, with particularly high prevalence in pancreatic ductal adenocarcinoma (PDAC) (~92%), colorectal cancer (CRC) (~49%), and non-small cell lung cancer (NSCLC) (~35%). The recent approval of the KRASG12C-specific inhibitors for NSCLC represents a pivotal advancement in KRAS-targeted therapy. Nevertheless, the emergence of intrinsic and acquired resistance to KRAS-targeted therapies poses a significant clinical obstacle to targeting KRAS, which necessitates a deeper understanding of the resistance mechanisms. Recent progress in proteomic studies has enabled comprehensive profiling of the proteomic alterations driven by KRAS mutations, offering valuable insights into the disrupted KRAS …

Protocol For Isolating Patient-Derived Ascites Cells And Extracellular Vesicles From Gastric Cancer Peritoneal Metastases, Yibo Fan, Jody V Vykoukal, Shumei Song, Melissa Pool Pizzi, Gengyi Zou, Katsuhiro Yoshimura, Jiankang Jin, Hiroyuki Katayama, George A Calin, Rebecca E Waters, Qiong Gan, Linghua Wang, Samir Hanash, Shilpa S Dhar, Jaffer A Ajani

Faculty, Staff and Student Publications

Peritoneal carcinomatosis (PC) cells and extracellular vesicles (EVs) from gastric cancer ascites are valuable for studying tumor-stroma interactions. Here, we present a protocol for isolating PC cells and EVs from patient ascites. We describe steps for PC cell culture, iodixanol-based EV purification, electron microscopy, nanoparticle tracking analysis, flow cytometry, and proteomic profiling. This protocol also includes TD-139 loading into exosomes for functional assays to evaluate their role in modulating the tumor microenvironment. For complete details on the use and execution of this protocol, please refer to Fan et al.

Introducing Mcodegpt As A Zero-Shot Information Extraction From Clinical Free Text Data Tool For Cancer Research, Kai Zhang, Tongtong Huang, Bradley A Malin, Travis Osterman, Qi Long, Xiaoqian Jiang

Faculty, Staff and Student Publications

Background: The vast amount of natural language clinical notes about patients with cancer presents a challenge for efficient information extraction, standardization, and structuring. Traditional NLP methods require extensive annotation by domain experts for each type of named entity and necessitate model training, highlighting the need for an efficient and accurate extraction method.

Methods: This study introduces a tool based on the Large Language Model (LLM) for zero-shot information extraction from cancer-related clinical notes into structured data aligned with the minimal Common Oncology Data Elements (mCODE™) structure. We utilize the zero-shot learning capabilities of LLMs for information extraction, eliminating the need …

Preclinical Models Of Melanoma Leptomeningeal Disease To Assess Intrathecal Checkpoint Blockade, Renato A Guerrieri, Grant M Fischer, Jacob R Cortez, Barbara G Knighton, Debora A Ledesma, Courtney W Hudgens, Yimmy F Delcid, Qianghua Hu, Christian Y B Onana, Fernando C L Carapeto, Michael T Tezlaff, Jason T Huse, Patrick Hwu, Elizabeth M Burton, Isabella C Glitza Oliva, Michael A Davies, Sherise D Ferguson

Faculty, Staff and Student Publications

Leptomeningeal disease (LMD) is a subtype of central nervous system metastatic disease that is associated with poor patient outcomes and limited treatment options. There is an unmet need to develop preclinical models of LMD to expedite and improve the development of new therapeutics. Here, we describe the development of multiple orthotopic immunocompetent murine models of melanoma LMD, including their use to assess the efficacy of systemic and/or intrathecal immunotherapy. LMD was established by direct intrathecal injection of murine cell lines (B16-F10, BP, D4M, D4M-UV2, MC38-gp100, RMS, YUMM3.1, and YUMMER1.7) into the cisterna magna of C57BL/6 mice. Tumor take rate, distribution, …

(Si15-107) Mathematical Modeling Of Cancer Dynamics Stability Analysis Of Post Therapy Protection, Rajendran Swetha, Tharmalingam Gunasekar, Kamalendra Kumar, Krishnasamy Sakthivel

Applications and Applied Mathematics: An International Journal (AAM)

The study of PSITPS mathematical model is developed to analyze cancer dynamics, focusing on post-therapy protection. The model’s solution is rigorously examined for boundedness and positivity of solutions. Equilibrium points are identified, and numerical methods are employed to study stability. Simulations using accurate cancer data demonstrate the effectiveness of post-treatment protection in controlling cancer spread and minimizing recurrence. Stability analysis confirms the model’s predictive capability, offering valuable insights into long-term patient outcomes. The results highlight the importance of continuous post-treatment care in improving survival rates and reducing disease prevalence. This study provides a framework for optimizing cancer treatment strategies by …

Decorin Evokes A Pro-Lysosomal Pathway In Lymphatic Endothelial Cells, Gabriel J. Pascal, Dipon K. Mondal, Sadie Kim, Christopher Xie, Devanarayanan Siva Sankar, Jörn Dengjel, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The lymphatic system is critical to the body's immune and circulatory system, and lymphangiogenesis, the development of new lymphatic vessels from pre-existing ones, is a significant process capitalized upon by cancer during tumorigenesis. Decorin is a small leucine-rich proteoglycan which we have previously shown to be anti-tumorigenic and a suppressor of lymphangiogenesis. We have also shown that decorin exercises its anticancer properties through its ability to evoke autophagy. Through a comprehensive and unbiased proteomic analysis, we explored the implications of decorin exposure on protein expression within mouse lymphatic endothelial cells. We discovered that decorin enriches several protein pathways, notably proteasomal …

Multiscale Modelling Of Eg5: Structural Insights Into Microtubule Interactions, Atp Hydrolysis, And Allosteric Inhibition Mechanisms, Soundarya Priya Alexandar Ms

Theses and Dissertations

The mitotic kinesin EG5 is essential for spindle bipolarity and accurate chromosome segregation during cell division, making it a validated anti-cancer target. Unlike conventional microtubule-targeting agents, EG5 inhibitors offer mitosis-specific action, reducing neurotoxicity. Although inhibitors targeting EG5’s allosteric site-I have been extensively studied, mechanistic insights into inhibition at site-II, and their combined effects, remain underexplored. This thesis systematically investigates the structural and dynamic mechanisms underlying EG5 function and its inhibition using an integrative computational approach.

Conformational analysis, coarse-grained dynamics, all-atom molecular dynamics simulations, and protein network analysis were performed on EG5 motor domain structures and EG5-microtubule complexes. Results show that …

Human Cerebral Organoids Model Tumor Initiation And Infiltration In An Autologous Astrocyte-Supported Setting, Esther Schickel, Tamara Bender, Leon Kaysan, Simone Hufgard, Margot Mayer, David R Grosshans, Christiane Thielemann, Insa S Schroeder

Faculty, Staff and Student Publications

Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing

Low-Cost Cutaneous Protoporphyrin Ix (Ppix) Detection (Cpd) Device For Follow-Up Monitoring Of Patients After Photodynamic Therapy, Md Asaduzzaman Rasel

Graduate Masters Theses

Background: Photodynamic Therapy (PDT) utilizes specific wavelengths of light to activate photosensitizing chemical compounds, known as photosensitizers, which induce the generation of cytotoxic reactive oxygen species (ROS) for the targeted destruction of cancer cells. Among various photosensitizers for PDT, Protoporphyrin IX (PpIX) is widely employed in oncology and dermatology due to its natural in situ generation via the metabolic conversion of 5- aminolevulinic acid (ALA), a non-phototoxic prodrug. Systemic administration of ALA after 3-6 hr drug delay leads to peak PpIX accumulation in tissues, facilitating therapeutic and diagnostic applications. However, PpIX can persist in the skin for 24–48 hours post-treatment, …

Reproducibility Of Statistically Significant Phase Iii Oncology Trials: An In Silico Meta-Epidemiological Analysis, Alexander D Sherry, Pavlos Msaouel, Avital M Miller, Timothy A Lin, Joseph Abi Jaoude, Ramez Kouzy, Adina H Passy, Tomer Meirson, Nikolaos Ignatiadis, Zachary R Mccaw, Erik Van Zwet, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: The conventional assumption that P values ≤ 0.05 imply reproducible effects has come under recent criticism. This concern is particularly relevant in oncology, as phase III oncology trials, which directly inform practice, are usually not repeated. Using advanced modeling techniques, we investigated the relationship between P values and reproducibility in oncology.

Methods: We obtained the signal-to-noise ratio distribution in phase III oncology using outcomes from 632 two-arm superiority trials enrolling 496,219 patients. With this distribution, we estimated successful replication probability as the probability that a replicate trial, having the same design, effect size, and standard error, would have a …

In Silico Investigation Of The Anticancer Activity Of Natural Isoquinoline Alkaloids Targeting The Monoamine Oxidase A Enzyme, Reham A. Al-Anssari, Anwar H. Ali, Ola Adel Al-Saad, Shaker A.N. Al-Jadaan

AUIQ Complementary Biological System

Monoamine oxidase A (MAO-A) has recently been identified as a candidate for cancer therapy due to its roles in tumor development and growth. Conventional approaches for the discovery of MAO-A inhibitors are both costly and time-consuming. The objective of this work was to apply in silico methods to predict natural isoquinoline alkaloids capable of acting as potent MAO-A inhibitors, and to establish this class of compounds as potential sources of a cost-effective anticancer therapy. Twenty-one natural isoquinoline alkaloids were subjected to a multistep computer-aided drug discovery protocol. The compounds were initially screened for pharmacokinetic (ADME), toxicity, and drug-likeliness properties by …

Role Of Immunosuppressive Jnk Pathway In The Tumor Microenvironment Among Tnbc Subtypes In Ibcsg Trial 22–00, Andrea Joaquin Garcia, Takashi Semba, Mattia Rediti, Daniel J Mcgrail, Xuemei Xie, Xiaoping Wang, Dileep R Rampa, David Venet, Laurence Buisseret, Samira Majjaj, Roswitha Kammler, Marco Colleoni, Sherene Loi, Giuseppe Viale, Meredith M Regan, Françoise Rothé, Christos Sotiriou, Naoto T Ueno

Faculty, Staff and Student Publications

Phosphorylation of the JNK (pJNK) protein promotes an immunosuppressive tumor microenvironment (TME), enhancing aggressiveness in inflammatory triple-negative breast cancer (TNBC). This study evaluated the role of JNK signaling using a gene signature. RNA sequencing was performed on 347 TNBC tumors from the phase 3 International Breast Cancer Study Group (IBCSG) 22-00 trial, which evaluated adjuvant low-dose cyclophosphamide and methotrexate (CM). Immune-related tumors were identified by TNBC subtype or tumor-infiltrating lymphocytes (TILs). Associations between JNK and outcomes were analyzed using Cox models. Low pJNK levels were associated with better disease-free survival (DFS) in immune-related tumors. These tumors also had lower Treg …

Phosphorylation Deficient Inducible Camp Early Repressor (Icer) Modulates Tumorigenesis And Survival In A Transgenic Zebrafish (Danio Rerio) Model Of Melanoma, Justin Wheelan, Melissa Rose Spigelman, Angelo Cirinelli, James Reilly, Carlos A. Molina

Department of Biology Faculty Scholarship and Creative Works

Melanoma, the most lethal form of skin cancer, is commonly associated with mutations in the BRAF gene, particularly BRAF^V600E, which drives tumor proliferation via the ERK1/2 signaling cascade. While BRAF inhibitors initially demonstrate efficacy, therapeutic resistance remains a significant challenge. Emerging evidence implicates the cAMP signaling pathway, particularly the cAMP response element-binding protein (CREB) and its repressor, inducible cAMP early repressor (ICER), in melanoma progression and drug resistance. ICER, a transcriptional repressor regulated via Ras/MAPK-mediated phosphorylation and ubiquitination, is degraded in melanoma, undermining its tumor-suppressive role. In a braf^V600E; p53 (loss of function) transgenic zebrafish ( …

Exploring Factors Affecting The Adoption And Use Of Digital Health Technologies Among Older Adults With Cancer: A Qualitative Study, Misun Hwang, Youmin Cho, Katie Gahn, Heidi Mason, Milisa Manojlovich, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Purpose: Although digital health technologies (DHTs) are promising to improve health outcomes in older adults with cancer, the low adoption and limited use remain significant gaps in their effective digital health care. Little is known about their concerns about adopting and using DHTs in routine life, particularly in the continued use phase. This study aims to explore factors affecting the initial adoption and continued use of DHTs among older adults with cancer.

Methods: A secondary analysis of qualitative data was conducted based on interviews with 21 older adults (≥ 65 years) with breast, prostate, lung, or colorectal cancer. The transcripts …

Investigating The Role Of The Lysine-Specific Demethylase 4c In Pancreatic Ductal Adenocarcinoma, Mennatallah Shaheen

Dissertations and Theses (Open Access)

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell-like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared to non-neoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomics analyses revealed that loss of KDM4C in both human …

Bifunctional Fusion Protein Pdl1sfv/Micae For Cancer Immunothearpy, Junyi Li

All Dissertations

Cancer immunotherapy has highlighted the importance of immune checkpoint blockade and innate immune cell engagement in battling tumor-mediated immune suppression in the past few decades. However, with cancer development, advanced tumors are often found to develop resistance towards single-target immunotherapy due to the complexity of the immunosuppressive mechanisms within the tumor microenvironment (TME). To address this, we developed a novel bifunctional fusion protein, PDL1sFv/MICAe, which combines the tumor-targeting capability of an anti-PDL1 single-chain variable fragment (sFv) with the NK cells immunostimulatory properties of the MICA extracellular domain.

In vitro functional assays revealed that PDL1sFv/MICAe significantly enhanced cytotoxicity towards natural killer …

Effects Of Flavonoids On Reducing Colon Cancer Risk Via Macrophage Polarization, Gracien Jules

Graduate Theses and Dissertations

Colorectal cancer is one of the most fatal diseases in the United States. Chronic tissue inflammation can cause cell proliferation, which leads to tumor formation and cancer development. Macrophages are responsible for maintaining tissue homeostasis and for inflammatory responses. M1 macrophages exhibit proinflammatory responses while M2 macrophages exhibit anti-inflammatory responses. Imbalance between M1 and M2 macrophages is closely related to inflammation-associated disease development. The anti-inflammatory effects of apiaceous vegetable constituents, specifically flavonoids, have been studied for their preventative effects towards reducing disease risk. However, sufficient evidence is lacking on the mechanisms by which flavonoids impact M1/M2 macrophage polarization. RAW 264.7 …

Early Treatment Engagement And Long-Term Smoking Abstinence Among Women With Cervical Intraepithelial Neoplasia Or Cervical Cancer, Charles E Hoogland, Steven K Sutton, Bethany Shorey Fennell, Vani N Simmons, Christine Vinci, Issam El Naqa, Ramzi G Salloum, Sanjay S Shete, Timothy Hembree, Damon J Vidrine, Jennifer I Vidrine

Faculty, Staff and Student Publications

Introduction: Cancer survivors who quit smoking have improved treatment response and decreased mortality. Although data indicate that greater tobacco cessation treatment engagement leads to better cessation outcomes in cancer survivors, little is known about how different tobacco treatment engagement patterns influence long-term cessation success. To help address this issue, this study examined how tobacco treatment engagement patterns predict cessation outcomes through 18 months and identified baseline participant characteristics predictive of treatment engagement patterns.

Methods: Data from a smoking-cessation RCT among women with a history of cervical intraepithelial neoplasia or cervical cancer comparing a 12-month, 6-session motivation and problem solving phone …

Optimization Of Mhealth Behavioral Interventions For Patients With Chronic Lymphocytic Leukemia: The Health4cll Study, Che Young Lee, Max J Gordon, Melissa M Markofski, Emily C Lavoy, Susan K Peterson, Liang Li, Sara Fares, Miranda Baum, Margaret Pace, Danielle Walsh, Alessandra Ferrajoli, Karen Basen-Engquist

Faculty, Staff and Student Publications

Purpose: This pilot study of a diet and physical activity intervention (HEALTH4CLL) was conducted to reduce fatigue and improve physical function (PF) in patients with chronic lymphocytic leukemia (CLL).

Methods: The HEALTH4CLL study used a randomized factorial design based on the multiphase optimization strategy (MOST). Patients received diet, exercise, and body weight management instructional materials plus a Fitbit and were randomized to undergo one of 16 combinations of 4 evidence-based mHealth intervention strategies over 16 weeks. Patients' fatigue, PF, health-related quality of life, behavior changes, and program satisfaction and retention were assessed. Paired t-tests were used to examine changes in …

Mitophagy’S Impacts On Cancer And Neurodegenerative Diseases: Implications For Future Therapies, Jason Huang, Vincent Truong Pham, Shaozi Fu, Gang Huang, Ya-Guang Liu, Lei Zheng

Faculty, Staff and Student Publications

Substantial evidence supports an inverse relationship between cancer and neurodegenerative diseases (NDDs), but few studies investigate the biological mechanisms underlying this phenomenon. While previous explanations-such as inflammation, reactive oxygen species (ROS), genetic mutations, and cell death-remain significant, they ultimately converge on mitophagy. This review identifies mitophagy as a pivotal factor in the development of both cancer and NDDs, while also evaluating specific mechanisms and processes to clarify how mitophagy connects these opposing disease trajectories. By examining these factors, we aim to uncover the underlying mechanisms that explain the inverse relationship between cancer and NDDs, which will help develop therapeutic strategies …

Regulation Of Icer Degradation And Its Role In Melanoma, Justin Wheelan

Theses, Dissertations and Culminating Projects

Melanoma is the deadliest form of skin cancer, with 100,640 new cases and 8,290 deaths estimated in the United States in 2024. While targeted therapies and immunotherapy have improved patient outcomes, resistance remains a major challenge, necessitating new therapeutic approaches. Approximately 50% of melanomas harbor BRAFⱽ⁶⁰⁰ᴱ mutations, leading to constitutive MAPK pathway activation. Targeted small molecule therapies such as BRAF and MEK inhibitors are available and initially reduce tumor burden, however resistance frequently occurs, likely through many pathways including compensatory activation of cAMP signaling. ICER (Inducible cAMP Early Repressor), a transcriptional repressor of CREB-mediated gene expression, is absent in melanoma …

Pan-Cancer Immune And Stromal Deconvolution Predicts Clinical Outcomes And Mutation Profiles, Bhavneet Bhinder, Verena Friedl, Sunantha Sethuraman, Davide Risso, Kami E Chiotti, R Jay Mashl, Kyle P Ellrott, Jordan A Lee, Christopher K Wong, Kofi Gyan, Aditya Deshpande, Marcin Imielinski, Rohan Bareja, Josh Stuart, Myron Peto, Katherine A Hoadley, Alexander J Lazar, Andrew D Cherniack, Jingchun Zhu, Shaolong Cao, Mark Rubin, Wenyi Wang, Oliver F Bathe, Nicolas Robine, Li Ding, Peter W Laird, Wanding Zhou, Hui Shen, Vésteinn Thorsson, Jen Jen Yeh, Matthew H Bailey, Daniel Cui Zhou, Xianlu L Peng, Mary Goldman, Yongsheng Li, Anil Korkut, Nidhi Sahni, D Neil Hayes, Michael K A Mensah, Ina Felau, Anab Kemal, Samantha Caesar-Johnson, John A Demchok, Liming Yang, Martin L Ferguson, Roy Tarnuzzer, Zhining Wang, Jean C Zenklusen, Paul Spellman, Olivier Elemento

Faculty, Staff and Student Publications

Traditional gene expression deconvolution methods assess a limited number of cell types, therefore do not capture the full complexity of the tumor microenvironment (TME). Here, we integrate nine deconvolution tools to assess 79 TME cell types in 10,592 tumors across 33 different cancer types, creating the most comprehensive analysis of the TME. In total, we found 41 patterns of immune infiltration and stroma profiles, identifying heterogeneous yet unique TME portraits for each cancer and several new findings. Our findings indicate that leukocytes play a major role in distinguishing various tumor types, and that a shared immune-rich TME cluster predicts better …

Foxo Factors’ Ability In Binding To And Inducing Tcf7 In Glioblastoma Cells, Stephanie Oyervides

Theses and Dissertations

Glioblastoma Multiforme (GBM) is an aggressive astrocytoma tumor type with a poor prognosis and limited immunotherapeutic options for those inflicted. Stem gene expression of this cancer indicates a direct relationship with the transcription factors, Forkhead box subfamily O (FOXO-1, -3 and - 4). These transcription factors are evolutionarily conserved, partially redundant. They are involved in diverse and fundamental biological processes such as cell survival, stem cell homeostasis, cell fate determination, cell cycle maintenance, metabolism, and apoptosis. Increasing evidence suggests interconnectivity between the WNT Pathway and FOXO transcription factors; however, the mechanism and full extent to which these interactions play a …

A Follow-Up Study On The Novel Use Of Contrast-Enhanced Susceptibility-Weighted Imaging For Extremity Desmoid Fibromatosis Response Assessment, Raul F Valenzuela, Elvis Duran-Sierra, Mathew Antony, Behrang Amini, Sam Lo, Keila E Torres, Ken-Pin Hwang, Jingfei Ma, R Jasson Stafford, Ravin Ratan, John E Madewell, Dejka Araujo, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Desmoid tumors are rare mesenchymal neoplasms characterized by a clonal proliferation of fibroblasts and myofibroblasts. Using the novel contrast-enhanced susceptibility-weighted imaging (CE-SWI) for characterizing desmoid tumors can enhance the separation between fibrous T2-hypointense and cellular T1-enhancing components. We aim to evaluate the effectiveness of the CE-SWI signal, volumetric, and radiomics-derived features in assessing desmoid treatment response. This IRB-approved study included 17 single-lesion extremity desmoid fibromatosis patients who underwent standard-of-care MRI, including CE-SWI, from March 2021 to February 2024. Measurements of maximum diameter, volume, and the modified Choi (m-Choi: tumor/muscle T2 ratio) were computed based on CE-SWI and T2-STIR volumetric tumor …

The Long-Term Effects Of Chemotherapy On Normal Blood Cells, Emily Mitchell, My H Pham, Anna Clay, Rashesh Sanghvi, Nicholas Williams, Sandra Pietsch, Joanne I Hsu, Nina Friesgaard Øbro, Hyunchul Jung, Aditi Vedi, Sarah Moody, Jingwei Wang, Daniel Leonganmornlert, Michael Spencer Chapman, Ellie Dunstone, Anna Santarsieri, Alex Cagan, Heather E Machado, E Joanna Baxter, George Follows, Daniel J Hodson, Ultan Mcdermott, Gary J Doherty, Inigo Martincorena, Laura Humphreys, Krishnaa Mahbubani, Kourosh Saeb Parsy, Koichi Takahashi, Margaret A Goodell, David Kent, Elisa Laurenti, Peter J Campbell, Raheleh Rahbari, Jyoti Nangalia, Michael R Stratton

Faculty, Staff and Student Publications

Several chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage in normal tissues. To investigate the impact of chemotherapy on mutation burdens and the cell population structure of normal tissue, we sequenced blood cell genomes from 23 individuals aged 3-80 years who were treated with a range of chemotherapy regimens. Substantial additional somatic mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but the effects were dependent on the drug and blood cell types. Chemotherapy induced premature changes …

Protocol For Assessing Mobilization Of Peritoneal B Cells To The Pre-Metastatic Omentum In An Orthotopic Mouse Model Of Ovarian Cancer, Wonjae Lee, Hironari Akasaka, Honami Naora

Faculty, Staff and Student Publications

The omentum is a visceral adipose tissue that undergoes dynamic immunological changes prior to and following metastasis. Here, we present a protocol for assessing the mobilization of peritoneal B cells to the pre-metastatic omentum in a mouse ovarian cancer model. We describe steps for isolation and adoptive transfer of peritoneal donor B cells and their detection in the omentum of recipient mice. This protocol could be utilized to study the mobilization of peritoneal B cells to the omentum in other pathological contexts. For complete details on the use and execution of this protocol, please refer to Lee et al.