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A Study Of Machine Learning Techniques In Solving Biochemical And Chemical Problems, Kenneth Micheal Plackowski

Chemistry and Chemical Biology ETDs

Data-driven approaches to solving problems in biology and chemistry require utilization of reliable techniques and machine learning algorithms are the modern reliable approach. This work presents three problems that involve use of supervised learning techniques when classification is the goal and unsupervised learning techniques when global data representation is the goal.

In the first problem, we demonstrate the use of unsupervised clustering techniques, self-organizing maps and K-means, to ascertain analyte detection capabilities of carbon nitride dots. In the second problem, we add scalability features to a functional group classification model applied to infrared data and evaluate its ability to inform …

Nanoporous Gold Nanoparticles And Model Membrane Systems Applied To The Study Of Lipopolysaccharide (Lps), Dhanbir Lingden

Dissertations

Lipopolysaccharide (LPS), a key structural component of Gram-negative bacteria, is a major trigger of sepsis and septic shock, the systemic inflammatory conditions responsible for millions of deaths annually. Even at concentrations as low as 1 ng/mL, LPS can activate the immune system and initiate inflammatory cascades. According to the Global Burden of Disease Study 2017, sepsis accounted for 48.9 million cases globally, with 11 million deaths, emphasizing the urgent need for improved diagnostic and therapeutic strategies.

Accurate and rapid detection of LPS is vital for early intervention and improved clinical outcomes. While traditional detection methods are still widely used, modern …

Screen Foundations: How Pediatric Nurse Practitioners Can Implement ‘Family Media Use Plans’ In Primary Care To Reduce Pediatric Behavior Concerns, Katie Anderson

Dissertations

Abstract for:

Screen Foundations: How Pediatric Nurse Practitioners Can Implement ‘Family Media Use Plans’ in Primary Care to Reduce Pediatric Behavior Concerns

Problem: Parents of children 2-5 years-old increasingly reach out to PCPs for escalating behavior concerns, including when the child doesn’t listen well, is inattentive, having tantrums, meltdowns, hitting, yelling, etc. Referrals to psychiatry and/or play therapy result in long waits, or referrals not accepted. Coincidingly, toddler and preschool aged children continue to exceed daily screen time recommendations. This results in a gap of care for families with young children and externalizing behavior.

Methods: This quality improvement project addressed …

Research Progress In Thermo-Reversible Polysaccharide Gels, Dongxin Zhou, Ziao Zhang, Su Chen, Weimin Yang, Jiajun Sun, Shengzu Han, Anning Xie, Xiaoxiao Li, Yuxiang Bai

Journal of Food Science and Biotechnology

Thermo-reversible gels are widely applied in the processing of baking,meat,and snack products including cakes,candies,jelly,aspic,and steamed custard buns.Currently,the most effective thermo-reversible gel is gelatin,which can combine with water to form a transparent gel that melts when it is close to the temperature of the human oral cavity.However,gelatin is expensive.Therefore,researchers have turned their attention to polysaccharide gels,hoping to obtain more thermo-reversible food raw materials with different properties.The author reviews thermo-reversible polysaccharide gels from natural sources such as plants,algae,and microorganisms and those modified by physical,chemical,and enzymatic methods and summarizes the sources,structures,gelatinization mechanisms,and product applications of polysaccharide gels.It is expected to provide a reference …

Mechanisms Of Antioxidant Activity Of Lactic Acid Bacteria And Its Application In Oxidative Stress-Related Diseases, Yixiao Shao, Chuang Huang, Chenjian Liu, Xiaoran Li

Journal of Food Science and Biotechnology

The antioxidant properties of lactic acid bacteria are related to various probiotic activities,which can prevent and alleviate a variety of chronic diseases caused by oxidation in the host.The antioxidant mechanisms of lactic acid bacteria,including the action mechanisms of antioxidant enzymes and non-enzymatic antioxidants and regulation of host signaling pathways,were expounded.Furthermore,the application status of antioxidant properties of lactic acid bacteria in diseases of the nervous system,digestive system,and skin system were summarized.The aim is to explore how to enhance the antioxidant activity of lactic acid bacteria in oxidative stress-related diseases and give new insights into the development of related treatment strategies.

Reconstruction And Analysis Of Genome-Scale Metabolic Model Of Aspergillus Oryzae Fmme-S- 38, Cong Gao, Weijia Yuan, Chao Ye, Jia Liu, Liming Liu

Journal of Food Science and Biotechnology

[Objective ] A genome-scale metabolic model (GSMM ) of the high L-malic acid-producing strain Aspergillus oryzae (A.oryzae ) FMME-S- 38 was constructed and analyzed.[Method ] The new GSMM iJW1333 was established for A.oryzae FMME-S- 38 through a two-step process of draft reconstruction and model refinement.[Result ] The model integrated 1 723 biochemical reactions,1 723 metabolites,and 1 333 functional genes,achieving the prediction accuracy of 94.6% for substrate metabolism and 92.0% for cell growth.Comparative genomic analysis revealed that mutations in the genes involved in the hexose monophosphate pathway (HMP ) and oxidative phosphorylation underpinned the enhanced L-malic acid production of A.oryzae FMME-S- …

Effects Of Extraction Methods On The Composition And Immunological Activities Of Yeast Mannoproteins, Haibo Zhang, Yongjun Xia, Guangqiang Wang, Ning Peng, Zhixian Chen, Lianzhong Ai

Journal of Food Science and Biotechnology

[Objective ] The extraction efficiency of different methods and the effects of these methods on the composition of mannoproteins extracted from yeast cell walls were compared.Furthermore,the anti-inflammatory activities of the extracted mannoprotein were evaluated.[Method ] Three yeast mannoproteins (MP-W,MP-B,and MP-E ) were extracted via high-temperature water,alkali,and enzyme-assisted extraction methods and purified via ethanol precipitation.The identification of monosaccharide composition and amino acid composition,distribution of relative molecular mass,and Fourier transform infrared spectroscopy were employed to analyze the composition and chemical structures of yeast mannoproteins.A cell experiment was carried out to examine the anti-inflammatory activity.[Result ] The yields of yeast mannoproteins extracted by …

In Vitro Antioxidant And Anti-Inflammatory Activities Of Tea Flower Extract And Its Inhibitory Effect On Cell Aging, Shishuai Yu, Yining Hao, Bo Peng, Youyun Liu, Liping Qu

Journal of Food Science and Biotechnology

[Objective ] This study aims to investigate the in vitro antioxidant and anti-inflammatory activities of Yunnan tea flower extract (TFE ) and its Inhibitory effect on cell aging.[Method ] The main active components in TFE were determined by ultraviolet (UV)-visible spectrophotometry and high performance liquid chromatography (HPLC ).The antioxidant and anti-inflammatory activities of TFE were determined by the free radical scavenging assay and UV-induced photoaging model of human keratinocytes (HaCaT ),respectively.After the aging model of fibroblasts was established,the aging level of cells was assessed by the β-galactosidase (β-gal) staining assay,and the expression of matrix metalloproteinase- 1 (MMP- 1),matrix metalloproteinase- 3 …

Synthesis Of N-Acetyl- Trans -4-Hydroxyproline Catalyzed By Acyltransferase, Chuanxiang Wei, Keru Chen, Yun Hu, Chao Sun, Rukang Xue, Fubao Sun, Jingfang Cheng

Journal of Food Science and Biotechnology

[Objective ] This study aims to establish the biosynthesis process of N-acetyl- trans -4-hydroxyproline (N-ATHOP ).[Method ] Escherichia coli (E.coli ) BL21 (DE3) was selected as the host to heterologously express the acyltransferase (MsAcT ) derived from Mycobacterium smegmatis.A semi-rational design was employed to construct the mutant MsAcT (S11C) capable of catalyzing the synthesis of N-ATHOP.[Result ] The catalytic reaction conditions of the mutant MsAcT (S11C) were optimized as pH 6.9,reaction temperature 49 ℃,initial trans -4-hydroxyproline (THOP ) concentration of 315.5 mmol/L,and vinyl acetate volume fraction of 10%.Under the optimized conditions,the yield of N-ATHOP synthesized under the catalysis of MsAcT …

Identification And Spoilage Capacity Analysis Of Main Spoilage Bacteria In Pickles, Li Zhu, Huimin Li, Liejiang Yuan, Cancan Peng, Bo Zhou, Sheng Song, Haizhi Wu, Mingyang Zhu, Fangmei Wang, Yu Liu, Yuqian Hu, Ge Li, Yiqing Sun, Yi Zhou

Journal of Food Science and Biotechnology

[Objective ] This study aims to identify the main spoilage bacteria and evaluate their spoilage capacity in the spoilage process of pickles.[Method ] High-throughput sequencing was employed to analyze the microbial community dynamics in the samples of pickles at the early,middle,and late stages of spoilage.The key spoilage bacteria were isolated,purified,and then identified through a combination of colony morphology observation,biochemical analysis,and 16S rDNA/ITS sequencing.Re-inoculation experiments were carried out for further validation of the primary spoilage bacteria in pickles.[Result ] Acinetobacter and Bacillus were the dominant spoilage bacterial genera across the three spoilage stages.Notably,Bacillus exhibited rapid growth over time,with the relative abundance …

Design & Development Of Efficient Biometric Authentication And Key Agreement Schemes For Wireless Body Area Network, Aarthi S

Theses and Dissertations

Wireless Body Area Networks (WBANs) play a vital role in continuous health monitoring, where sensitive biometric and physiological data must be protected from privacy breaches and emerging quantum-based threats. Conventional security mechanisms are often inadequate due to resource constraints, scalability issues, and vulnerability to advanced attacks. To address these challenges, this research proposes a lightweight, scalable, and future-proof security framework tailored for WBAN applications, focusing on secure communication, privacy preservation, and quantum resilience.

An anonymous Certificate-Based Signcryption–Mutual Authentication and Key Agreement (CBS-MAKE) protocol is introduced to secure extra-body communications while ensuring patient anonymity. The protocol integrates Elliptic Curve Cryptography with …

How Multi-Scale Modeling Can Help Examine Social Determinants Of Health And Resulting Disparities, Kyoko Yoshida, Elsje Pienaar, Shalanda A. Bynum, Naomi Chesler, Mitchel J. Colebank, Jessie Heneghan, Nadra Tyus, Jasmine Miller-Kleinhenz, Bruce Y. Lee

Faculty Publications

Social determinants of health (SDOH) are the conditions in which people live, work, and play, and the wider set of factors (e.g., social and economic systems and policies) that shape a person’s daily life. SDOH can differ significantly across communities and populations, having positive impacts for some and negative impacts for others. Ultimately, this results in differences in health and disease distribution, that are known as health disparities. Despite the known impacts of SDOH and calls to characterize, address, reduce, and eliminate health disparities, they persist and, in some cases, have worsened. To address this challenge, a session at the …

Current Trends In Clinical Trials For Merkel Cell Carcinoma (Mcc), Tilak Patel, Rachel Butz, Brian Boulmay, Vilija Vaitaitis

School of Medicine Faculty Publications

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine cutaneous malignancy with high rates of recurrence and metastasis. The treatment of MCC has historically involved surgery, radiation, and chemotherapy; however, current clinical trials are investigating immunotherapies, intratumoral injections, and combination therapies to improve outcomes. This review explores the current trends in clinical trials for MCC, highlighting recent advances in management.

Age, Gender, And Length Of Stay For Copd Patients In Florida Community Hospitals For 2019, Dr. Carol-Ann Miller

Walden Dissertations and Doctoral Studies

Hospital administrators have been challenged due to length of stay (LOS) among patients suffering with chronic obstructive pulmonary disease (COPD). The purpose of this quantitative study was to examine whether there was a relationship between age, gender, and length of stay for COPD patients in Florida during the year 2019. The dependent variable was COPD length of stay, and independent variables were age and gender in Florida community hospitals during 2019. The Donabedian model was selected as the theoretical framework for this study to address structure, process, and outcomes associated with COPD readmissions. Secondary data was obtained from the Healthcare …

Predictors Of Final Visual Outcome In Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy, Robert C Sergott, Valerio Carelli, Nancy Newman, Valérie Biousse, Patrick Yu-Wai-Man, Catherine Vignal-Clermont, Constant Josse, Magali Taiel, José-Alain Sahel, Piero Barboni

Wills Eye Hospital Papers

PURPOSE: This exploratory analysis aimed to identify predictive factors of final best-corrected visual acuity (BCVA) in patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A mutation who received lenadogene nolparvovec gene therapy.

METHODS: The following covariates were individually evaluated as possible factors associated with improved final BCVA: age, gender, timing of treatment, baseline BCVA value, and baseline optical coherence tomography (OCT) parameters. Univariate analyses were performed from three phase 3 studies (RESCUE, REVERSE, and REFLECT), using BCVA at 1.5 years post-treatment as the dependent variable.

RESULTS: In 113 eyes treated at least 6 months after disease onset, the …

The International Soft Tissue Sarcoma Consortium, Gianni Bisogno, Monika Sparber-Sauer, David Rodeberg, Johannes H.M. Merks, Ewa Koscielniak, Suzanne L. Wolden, Gian Luca De Salvo, Paola Del Bianco, Wei Xue, Martin Ebinger, Christian Vokuhl, Rajkumar Venkatramani, Samuel L. Volchenboum, Brian Furner, Veronique Minard Colin, Douglas S. Hawkins

Surgery Faculty Publications

Background: The International Soft Tissue Sarcoma Consortium (INSTRuCT) was established in 2017 to enhance international collaboration. This study describes the characteristics of rhabdomyosarcoma (RMS) patients in the INSTRuCT database and examines differences across contributing groups. Methods: INSTRuCT includes data Children’s Oncology Group (COG), Cooperative Weichteilsarkom Studiengruppe (CWS), and European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) along with prior studies from Malignant Mesenchymal Tumour Committee (MMT) and Italian Soft Tissue Sarcoma Committee (STSC). Data standardization was supported by the University of Chicago’s Pediatric Cancer Data Commons. Pseudonymized patient-level data from clinical trials were harmonized. Differences across groups were assessed using …

A Qualitative Case Study On Mental Health Stigma Within Rastafarian Culture, Alecia Douglas

Walden Dissertations and Doctoral Studies

Cultural and social factors, such as ethnic and racial backgrounds, religion, and supernatural beliefs, influence mental health utilization among African Americans. Past studies show that Rastafarians underutilize mental health services due to the stigma associated with mental health. However, there remains a gap in the literature regarding the incorporation of culturally sensitive and inclusive approaches in mental illness treatment. Per the biopsychosocial (BPS) pathways framework, biological, psychological, and social factors interact to provide a holistic architype of mental illness. The framework can be applied to understand how mental health stigma is influenced by personal beliefs, experiences, values, cultural, and societal …

Technology Roadmap Of Micro/Nanorobots, Xiaohui Ju, Chuanrui Chen, Cagatay M Oral, Semih Sevim, Ramin Golestanian, Mengmeng Sun, Negin Bouzari, Xiankun Lin, Mario Urso, Jong Seok Nam, Yujang Cho, Xia Peng, Fabian C Landers, Shihao Yang, Azin Adibi, Nahid Taz, Raphael Wittkowski, Daniel Ahmed, Wei Wang, Veronika Magdanz, Mariana Medina-Sánchez, Maria Guix, Naimat Bari, Bahareh Behkam, Raymond Kapral, Yaxin Huang, Jinyao Tang, Ben Wang, Konstantin Morozov, Alexander Leshansky, Sarmad Ahmad Abbasi, Hongsoo Choi, Subhadip Ghosh, Bárbara Borges Fernandes, Giuseppe Battaglia, Peer Fischer, Ambarish Ghosh, Beatriz Jurado Sánchez, Alberto Escarpa, Quentin Martinet, Jérémie Palacci, Eric Lauga, Jeffrey Moran, Miguel A Ramos-Docampo, Brigitte Städler, Ramón Santiago Herrera Restrepo, Gilad Yossifon, James D Nicholas, Jordi Ignés-Mullol, Josep Puigmartí-Luis, Yutong Liu, Lauren D Zarzar, C Wyatt Shields, Longqiu Li, Shanshan Li, Xing Ma, David H Gracias, Orlin Velev, Samuel Sánchez, Maria Jose Esplandiu, Juliane Simmchen, Antonio Lobosco, Sarthak Misra, Zhiguang Wu, Jinxing Li, Alexander Kuhn, Amir Nourhani, Tijana Maric, Ze Xiong, Amirreza Aghakhani, Yongfeng Mei, Yingfeng Tu, Fei Peng, Eric Diller, Mahmut Selman Sakar, Ayusman Sen, Junhui Law, Yu Sun, Abdon Pena-Francesch, Katherine Villa, Huaizhi Li, Donglei Emma Fan, Kang Liang, Tony Jun Huang, Xiang-Zhong Chen, Songsong Tang, Xueji Zhang, Jizhai Cui, Hong Wang, Wei Gao, Vineeth Kumar Bandari, Oliver G Schmidt, Xianghua Wu, Jianguo Guan, Metin Sitti, Bradley J Nelson, Salvador Pané, Li Zhang, Hamed Shahsavan, Qiang He, Il-Doo Kim, Joseph Wang, Martin Pumera

Faculty, Staff and Student Publications

Inspired by Richard Feynman’s 1959 lecture and the 1966 film Fantastic Voyage, the field of micro/nanorobots has evolved from science fiction to reality, with significant advancements in biomedical and environmental applications. Despite the rapid progress, the deployment of functional micro/nanorobots remains limited. This review of the technology roadmap identifies key challenges hindering their widespread use, focusing on propulsion mechanisms, fundamental theoretical aspects, collective behavior, material design, and embodied intelligence. We explore the current state of micro/nanorobot technology, with an emphasis on applications in biomedicine, environmental remediation, analytical sensing, and other industrial technological aspects. Additionally, we analyze issues related to …

Synergistic Activity Of Combined Flt3-Itd And Mdm2 Inhibition With Quizartinib And Milademetan In Flt3-Itd Mutant/Tp53 Wild-Type Acute Myeloid Leukemias, Weiguo Zhang, Li Li, Muharrem Muftuoglu, Mahesh Basyal, Noriko Togashi, Koichi Iwanaga, Fumie Tanzawa, Masashi Numata, Dale L Bixby, Harry P Erba, Nikolai Podoltsev, Gary J Schiller, Prasanna Kumar, Arnaud Lesegretain, Takeshi Isoyama, Takahiko Seki, Naval Daver, Michael Andreeff

Faculty, Staff and Student Publications

Purpose: Acute myeloid leukemia (AML) is characterized by frequent mutations in FMS-like tyrosine kinase 3 (FLT3), overexpression of murine double minute 2 (MDM2), and TP53 wild-type (WT). Monotherapies targeting FLT3 frequently result in the development of resistant disease. In this study, we investigated the antileukemic efficacy of co-targeting FLT3 and MDM2 with quizartinib and milademetan (Q/M) in FLT3 internal tandem duplication (FLT3-ITD) AML cell lines, xenograft and patient-derived xenograft (PDX) models, and a phase I clinical trial.

Experimental design: Preclinical studies used human and murine cell lines carrying FLT3-ITD and/or tyrosine kinase domain mutations, TP53 WT/knockdown, leukemia cell xenograft models, …

Fgfr3-Induced Y158 Parp1 Phosphorylation Promotes Parp Inhibitor Resistance Via Brg1/Mre11-Mediated Dna Repair In Breast Cancer Models, Mei-Kuang Chen, Hirohito Yamaguchi, Yuan Gao, Weiya Xia, Jeffrey T Chang, Yu-Chun Hsiao, Tewodros W Shegute, Zong-Shin Lin, Chen-Shiou Wu, Yu-Han Wang, Jennifer K Litton, Qingqing Ding, Yongkun Wei, Yu-Yi Chu, Funda Meric-Bernstam, Helen Piwnica-Worms, Banu Arun, Jordi Rodon Ahnert, Jinsong Liu, Jun Yao, Wei-Chao Chang, Hung-Ling Wang, Coya Tapia, Constance T Albarracin, Khandan Keyomarsi, Shao-Chun Wang, Ying-Nai Wang, Gabriel N Hortobagyi, Chunru Lin, Liuqing Yang, Dihua Yu, Mien-Chie Hung

Faculty, Staff and Student Publications

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are used to treat BRCA-mutated (BRCAm) cancer patients; however, resistance has been observed. Therefore, biomarkers to indicate PARPi resistance and combination therapy to overcome that are urgently needed. We identified a high prevalence of activated FGF receptor 3 (FGFR3) in BRCAm triple-negative breast cancer (TNBC) cells with intrinsic and acquired PARPi resistance. FGFR3 phosphorylated PARP1 at tyrosine 158 (Y158) to recruit BRG1 and prolong chromatin-loaded MRE11, thus promoting homologous recombination (HR) to enhance PARPi resistance. FGFR inhibition prolonged PARP trapping and synergized with PARPi in vitro and in vivo. High-level PARP1 Y158 phosphorylation (p-Y158) positively …

Antitumor Efficacy Of Intermittent Low-Dose Erlotinib Plus Sulindac Via Mhc Upregulation And Remodeling Of The Immune Cell Niche, Chakrapani Tripathi, Jorge E Tovar Perez, Sabeeta Kapoor, Ahmed Muhsin, Wan Mohaiza Dashwood, Yunus Demirhan, Melek Demirhan, Alessandro Shapiro, Altaf Mohammed, Shizuko Sei, Jacklyn Thompson, Mahira Zaheer, Krishna M Sinha, Powel H Brown, Michelle I Savage, Eduardo Vilar, Praveen Rajendran, Roderick H Dashwood

Faculty, Staff and Student Publications

A previously reported clinical trial in familial adenomatous polyposis (FAP) patients treated with erlotinib plus sulindac (ERL + SUL) highlighted immune response/interferon-γ signaling as a key pathway. In this study, we combine intermittent low-dose ERL ± SUL treatment in the polyposis in rat colon (Pirc) model with mechanistic studies on tumor-associated immune modulation. At clinically relevant doses, short-term (16 weeks) and long-term (46 weeks) ERL ± SUL administration results in near-complete tumor suppression in Pirc colon and duodenum (p < 0.0001). We identify a low-dose threshold for significant antitumor activity in Pirc rats given SUL at 125 ppm in the diet plus ERL at 5 mg/kg body weight via twice-weekly oral gavage (SUL125 + ERL5 × 2). Longitudinal analyses show diminished expression of MHC class I and II genes in polyps larger than Grade 5, a novel finding in the Pirc model. Treatment with ERL ± SUL upregulates the corresponding MHC and immune-associated factors in a subset of Pirc colon polyps, Pirc tumor cell lines, murine colon carcinoma cells, and FAP patient-derived organoids, with Nlrc5 playing a critical role in this effect. Imaging mass cytometry reveals that SUL125 + ERL5 × 2 increases tumor-associated Cd4+ T cells by ~2.6-fold (p < 0.05), with no apparent effect on Cd8+ T cells. The treatment also increases tumor-associated Cd68+ cells (p < 0.05) and decreases Foxp3+ (p < 0.01) and Arg1+ (p < 0.05) cells. Thus, intermittent low-dose ERL + SUL treatment enhances tumor-associated MHC expression and remodels the immune cell niche toward a more permissive "helper" immune microenvironment. We conclude that early immune-interception strategies targeting interferon-γ signaling may benefit FAP patients at drug doses below the clinical standard of care.

Targeting The Cd40 Costimulatory Receptor To Improve Virotherapy Efficacy In Diffuse Midline Gliomas, Sara Labiano, Javier Marco-Sanz, Iker Ausejo-Mauleon, Virginia Laspidea, Reyes Hernández-Osuna, Marc Garcia-Moure, Daniel De La Nava, Sara Nuin, Marisol Gonzalez-Huarriz, Timothy N Phoenix, Ibon Tamayo, Marta Zalacain, Andrea Lacalle, Lucía Marrodan, Montserrat Puigdelloses, Irati Hervás-Corpión, Maria C Ochoa, Noelia Casares, Oren J Becher, Candelaria Gomez-Manzano, Juan Fueyo, Jaime Gallego Perez-Larraya, Ana Patiño-Garcia, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse midline glioma (DMG) is a devastating pediatric brain tumor. The oncolytic adenovirus Delta-24-RGD has shown promising efficacy and safety in DMG patients but is not yet curative. Thus, we hypothesized that activating dendritic cells (DCs) through the CD40 costimulatory receptor could increase antigen presentation and enhance the anti-tumor effect of the virus, resulting in long-term responses. This study shows that the intratumoral co-administration of Delta-24-RGD and a CD40 agonistic antibody is well tolerated and induces long-term anti-tumor immunity, including complete responses (up to 40%) in DMG preclinical models. Mechanistic studies revealed that this therapy increased tumor-proliferating T lymphocytes and …

Ctdna Analysis In Erbb2-Amplified Colorectal Cancer: Biomarker Analysis Of The Mypathway Trial, Funda Meric-Bernstam, Kanwal Pratap Singh Raghav, Christopher J Sweeney, Charles Swanton, David R Spigel, Ron Bose, Howard A Burris, Claire F Friedman, Carin R Espenschied, Jessica M Grindheim, Julia Malato, Katja Schulze, Richard Price, Razelle Kurzrock

Faculty, Staff and Student Publications

Purpose: A combination of two HER2-directed antibodies, pertuzumab and trastuzumab (P + T), has antitumor activity in HER2-positive colorectal cancer. Although liquid biopsies are increasingly being used in clinical oncology, the association between tumor and ctDNA ERBB2 status and ctDNA monitoring for early response and resistance are unknown.

Patients and methods: Eighty-five patients with ERBB2-amplified and/or -overexpressed colorectal cancer were treated with P + T in the MyPathway trial; 42 had ctDNA testing at cycle (C) 1 day (D) 1, and 38 had longitudinal plasma tested for ctDNA. We analyzed the ctDNA versus tissue ERBB2 concordance, genomic co-alterations, and ctDNA …

Facts And Hopes: Toward The Next Quantum Leap In Melanoma, Keith T Flaherty, Andrew E Aplin, Michael A Davies, Nir Hacohen, Meenhard Herlyn, Dave Hoon, Patrick Hwu, Michal Lotem, James Mulé, Jennifer A Wargo, David E Fisher

Faculty, Staff and Student Publications

Outcomes from advanced melanoma, the deadliest of the skin cancers arising from melanocytes and capable of widely metastasizing, have greatly improved, with death rates decreasing for patients with American Joint Committee on Cancer stage 4 melanoma by 3% to 5% annually over the past 10 years. This improvement is a result of advances in both targeted therapy and immunotherapy. BRAF and MEK inhibitors for advanced melanoma have led the way for targeted cancer strategies and first-in-class approvals for immune checkpoint blockers targeting CTLA4, PD-1, and LAG3; T-cell engager therapy targeting the antigen gp100; and tumor-infiltrating lymphocyte therapy. All of these …

Sensory Neuron-Expressed Fgf13 Controls Nociceptive Signaling In Diabetic Neuropathy Models, Aditya K Singh, Matteo Bernabucci, Nolan M Dvorak, Zahra Haghighijoo, Jessica Di Re, Nana A Goode, Feni K Kadakia, Laura A Maile, Olumarotimi O Folorunso, Paul A Wadsworth, Cynthia M Tapia, Pingyuan Wang, Jigong Wang, Haiying Chen, Yu Xue, Jully Singh, Kali Hankerd, Isaac J Gamez, Makenna Kager, Vincent Truong, Patrick Walsh, Stephanie I Shiers, Nishka Kuttanna, Hanyue Liao, Margherita Marchi, Erika Salvi, Ilaria D'Amato, Daniela D'Amico, Parsa Arman, Catharina G Faber, Rayaz A Malik, Marina De Tommaso, Dan Ziegler, Krishna Rajarathnam, Thomas A Green, Peter M Grace, Matthew R Sapio, Michael J Iadarola, Gregory D Cuny, Diana S Chow, Giuseppe Lauria Pinter, Steve Davidson, Dustin P Green, Jun-Ho La, Jin Mo Chung, Jia Zhou, Theodore J Price, Elizabeth Salisbury, Subo Yuan, Fernanda Laezza

Faculty, Staff and Student Publications

Nociception involves complex signaling, yet intrinsic mechanisms bidirectionally regulating this process remain unexplored. Here, we show that the fibroblast growth factor 13 (FGF13)/Nav1.7 protein-protein interaction (PPI) complex bidirectionally modulates nociception, and that the FGF13/Nav1.7 ratio is upregulated in type 2 diabetic neuropathy (T2DN). PW164, an FGF13/Nav1.7 channel C-terminal tail domain (CTD) PPI interface inhibitor, which reduces complex assembly, selectively suppressed Na+ currents sensitized by capsaicin-induced activation of TRPV1 channels in human induced pluripotent stem cell-derived (hIPSC-derived) sensory neurons and inhibited mechanical and thermal hyperalgesia in mice. FGF13 silencing mimics PW164 activity in culture and in vivo. Conversely, ZL192, an FGF13 …

Met Pathway Inhibition Increases Chemo-Immunotherapy Efficacy In Small Cell Lung Cancer, Raúl Del Rey-Vergara, Miguel Alejandro Galindo-Campos, Pedro Rocha, Marina Carpes, Carlos Martínez, Laura Masfarré, Silvia Menéndez, Fabricio Quimis, Adrià Rossell, Albert Iñañez, Sandra Pérez-Buira, Federico Rojo, Ramon Gimeno, Dolores Isla, Jon Zugazagoitia, Cristina Martí Blanco, Rosario García-Campelo, Alberto Moreno-Vega, Luis León-Mateos, Ángel Callejo Mellén, Kwon-Sik Park, Simon Heeke, John V Heymach, Álvaro Taus, Luis Paz-Ares, Ana Rovira, Edurne Arriola

Faculty, Staff and Student Publications

The introduction of immunotherapy as a first-line treatment for advanced small cell lung cancer (SCLC) represents significant progress, yet there remains an opportunity to further improve patient outcomes. Hepatocyte growth factor (HGF) receptor (MET) pathway activation promotes epithelial-mesenchymal transition, driving chemoresistance and potentially impairing the efficacy of immunotherapy. In SCLC mouse models, adding MET inhibition to chemo-immunotherapy (anti-PD-L1) reduces tumor growth, extends survival, and reshapes the tumor microenvironment by decreasing suppressive myeloid cell infiltration and enhancing the immune response. Analysis of pretreatment human SCLC tumor samples reveals that myeloid-enriched immune infiltrates may contribute to chemo-immunotherapy resistance. Elevated serum HGF levels …

The Integrated Stress Response Pathway Coordinates Translational Control Of Multiple Immune Checkpoints In Lung Cancer, Shayna Thomas-Jardin, Shruthy Suresh, Ariana Arce, Nicole Novaresi, Qing Deng, Emily Stein, Lisa Thomas, Cheryl Lewis, Chul Ahn, Bret M Evers, Esra A Akbay, Maria E Salvatierra, Wei Lu, Khaja Khan, Luisa M Solis Soto, Ignacio I Wistuba, John D Minna, Kathryn A O'Donnell

Faculty, Staff and Student Publications

The integrated stress response (ISR) is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. ISR activation potently induces PD-L1, leading to suppression of antitumor immunity. In this study, we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. The ISR coordinately induced cluster of differentiation 155 (CD155) and PD-L1, enhancing translation of both immune checkpoint proteins through bypass of inhibitory upstream open reading frames in their 5' untranslated regions. Analysis of primary human lung tumors identified a significant correlation between expression of PD-L1 and …

Cancer Vaccination And Immune-Based Approaches In Pancreatic Cancer, Matthew D. Bloom, Ali Raza Shaikh, Zhengyang Sun, Babar Bashir, Adam E. Snook

Department of Medical Oncology Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high recurrence rates even after curative resection and adjuvant chemotherapy. Although immunotherapeutic approaches, such as immune checkpoint blockade (ICB), have revolutionized the treatment of some solid tumor malignancies, this has not been the case for PDAC. Several characteristics of PDAC, including its distinctive desmoplastic tumor microenvironment (TME), intratumor heterogeneity, and poor antigenicity and immune cell infiltration, contribute to its dismal immunotherapeutic landscape. Cancer vaccines offer one approach to overcoming these barriers, particularly in the resectable or borderline resectable settings, where tumor burden is low and immunosuppression is less pronounced. Various vaccination …

Theoretical And Experimental Investigation Of Liquid-Liquid Phase Separation: Characterizing Elastin-Like-Polypeptides, Adam D. Quintana

Chemical and Biological Engineering ETDs

This dissertation develops and validates a semi-empirical Flory–Huggins-based interaction model, combined with Cahn–Hilliard simulations, for predicting multi-component liquid–liquid phase separation (LLPS) in elastin-like polypeptide (ELP) systems. Equilibrium droplet compositions, measured using a PDMS-based microfluidic device, enabled direct parameterization of interaction coefficients. The model was applied to generate phase diagrams and assess composition dependence in ternary mixtures. Cahn–Hilliard simulations were conducted to explore potential phase morphologies under different interfacial conditions. Multi-component Lattice Boltzmann simulations were implemented to model droplet morphology evolution under varying interfacial and diffusive parameters, reproducing experimentally relevant morphologies. A three-phase wetting study revealed conditions for selective wetting and …

Epha4 Signaling Dysregulation Links Abnormal Locomotion And The Development Of Idiopathic Scoliosis, Lianlei Wang, Xinyu Yang, Sen Zhao, Pengfei Zheng, Wen Wen, Kexin Xu, Xi Cheng, Qing Li, Anas M Khanshour, Yoshinao Koike, Junjun Liu, Xin Fan, Nao Otomo, Zefu Chen, Yaqi Li, Lulu Li, Haibo Xie, Panpan Zhu, Xiaoxin Li, Yuchen Niu, Shengru Wang, Sen Liu, Suomao Yuan, Chikashi Terao, Ziquan Li, Shaoke Chen, Xiuli Zhao, Pengfei Liu, Jennifer E Posey, Zhihong Wu, Guixing Qiu, Disco Study Group (Deciphering Disorders Involving Scoliosis & Comorbidities), Shiro Ikegawa, James R Lupski, Jonathan J Rios, Carol A Wise, Jianguo T Zhang, Chengtian Zhao, Nan Wu

Faculty, Staff and Students Publications

Idiopathic scoliosis (IS) is the most common form of spinal deformity with unclear pathogenesis. In this study, we first reanalyzed the loci associated with IS, drawing upon previous studies. Subsequently, we mapped these loci to candidate genes using either location-based or function-based strategies. To further substantiate our findings, we verified the enrichment of variants within these candidate genes across several large IS cohorts encompassing Chinese, East Asian, and European populations. Consequently, we identified variants in the EPHA4 gene as compelling candidates for IS. To confirm their pathogenicity, we generated zebrafish mutants of epha4a. Remarkably, the zebrafish epha4a mutants exhibited …