Medicine and Health Sciences Commons^™

Molecular Modification Of Queen Bee Acid And 10-Hydroxydecanoic Acid With Specific Tripeptides: Rational Design, Organic Synthesis, And Assessment For Prohealing And Antimicrobial Hydrogel Properties, Song Hong, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Weilie Zhou

School of Medicine Faculty Publications

Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. …

Enhancing Immunotherapy Efficacy With Synergistic Low-Dose Radiation In Metastatic Melanoma: Current Insights And Prospects, Zahid Rafiq, Mingyo Kang, Hampartsoum B Barsoumian, Gohar S Manzar, Yun Hu, Carola Leuschner, Ailing Huang, Fatemeh Masrorpour, Weiqin Lu, Nahum Puebla-Osorio, James W Welsh

Faculty, Staff and Student Publications

Recent advances in oncology research have highlighted the promising synergy between low-dose radiation therapy (LDRT) and immunotherapies, with growing evidence highlighting the unique benefits of the combination. LDRT has emerged as a potent tool for stimulating the immune system, triggering systemic antitumor effects by remodeling the tumor microenvironment. Notably, LDRT demonstrates remarkable efficacy even in challenging metastatic sites such as the liver (uveal) and brain (cutaneous), particularly in advanced melanoma stages. The increasing interest in utilizing LDRT for secondary metastatic sites of uveal, mucosal, or cutaneous melanomas underscores its potential efficacy in combination with various immunotherapies. This comprehensive review traverses …

Diverse Roles Of Antibodies In Antibody-Drug Conjugates, Aiko Yamaguchi, H Charles Manning

Faculty, Staff and Student Publications

The emergence of antibody-drug conjugates (ADCs) has transformed the treatment landscape of a variety of cancers. ADCs typically consist of three main components: monoclonal antibody, chemical linker, and cytotoxic payload. These integrated therapeutic modalities harness the benefits of each component to provide a therapeutic response that cannot be achieved by conventional chemotherapy. Antibodies play roles in determining tumor specificity through target-mediated uptake, prolonging the circulation half-life of cytotoxic payloads, and providing additional mechanisms of action inherent to the original antibody, thus significantly contributing to the overall performance of ADCs. However, ADCs have unique safety concerns, such as drug-induced adverse events …

Local Tissue Damage Treatment Of Snake Venom, Suchitra Khunsap

The Thai Journal of Veterinary Medicine

Local tissue damage caused by snake envenomation was a medical problem that caused morbidity and mortality for more than a decade, with no defined treatment guidelines. Nowadays, antivenom is the primary treatment for snakebite, which substantially reduces systemic venom but not significantly reducing local symptoms. We compiled a list of local damage therapies, including antivenom medication, surgery and skin grafting, small molecule medicines, and alternative therapies. Although each was not approved as a standard treatment, it may be a treatment option for tissue damage caused by snake venom. However, antivenoms and most resistant compounds may not be the best strategy …

Ai-Integrated Cross-Disciplinary Liberal Arts Colloquium, Diana S. Perdue, Niloofar Gholamrezaei, Jennifer Krusinger, Shannon Hogan

Teaching Repository of AI-Infused Learning

What began organically as an AI-focused collaboration between faculty in different disciplines along with researchers in the college’s Center for Instructional Innovation, has evolved into college-wide pedagogical workshops and the development of a studio model that affects courses, programs, and paradigms for faculty scholarship.

Lessons from these collaborations inform understandings of how key features of liberal arts education can be supported through intentional AI-integration within a Cross-Disciplinary Liberal Arts Colloquium. More specifically, this colloquium offers recommendations on adapting a collaborative, interdisciplinary, and reflective studio model to in-person, online, and hybrid educational environments facilitated through a Technological Pedagogical Content Knowledge (TPACK) …

Cultural Capital Skill Development In Undergraduate Kinesiology Curriculum, Jenica Alvarez, Sabrina R. Fordham, Elizabeth M. Harrison, Blake Podsen, Jason C. Casey, Rich Pruett

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 6: Issue 1, Article 2, 2025. Specialization within Kinesiology and related fields over the past 20 years has led to the prioritization of technical skill development. This specialization leaves limited availability of resources for the development of Cultural Capital (CC) skills in undergraduate kinesiology and kinesiology-related curricula. The purpose of this study was to examine how seven Experiential Learning Activities (ELAs) influence CC skill development in an undergraduate kinesiology practicum course. An interpretive qualitative action research design was applied to investigate five senior undergraduate kinesiology students’ experiences. The study concluded: (a) six of …

Metabolic Effects Of R-1,3-Butanediol (Ketone-Iq) During Aerobic And Anaerobic Exercise Bouts, Mathew C. Soto, Andrew J. Jakiel, Latt Mansor, Jenica D. Alvarez, Ashley M. Bruce, Blake Podsen, Sabrina R. Fordham, Parker N. Hyde

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 6: Issue 1, Article 1, 2025. BACKGROUND: Current evidence demonstrates the efficacy of low carbohydrate/high fat ketogenic diets as it related to exercise. Exogenous ketone supplements have made it possible to ingest ketone molecules, elevating blood b-hydroxybutyrate (BHB) despite consuming carbohydrates (CHO). The purpose of this investigation was to determine both metabolic and performance effects of R-1,3-butanediol (BDO). METHODS: A randomized repeated measures placebo-controlled design was used to compare BDO and placebo (PLA). Each phase of testing utilized two primary testing days: 1) a dose exposure day designed to determine blood metabolite changes …

A Linear Periodized Resistance Training Program Is Effective At Reducing Depressive Symptoms But Not Anxiety In Females: A Pilot, Jason Sawyer, Matthew Mcpherson, Meghan Reuter, Paul A. Cacolice

Biological and Biomedical Sciences Department Faculty Journal Articles

The purpose of this study was to determine whether a periodized resistance training program would influence self-reported depression and anxiety scores in college-aged females. Methods: Eight participants participated in a six-week periodized resistance training program. The participants completed a 3–5 repetition maximum (3–5 RM) for the sumo deadlift (SDL), bench press (BP), barbell back squat (BBS), and standing shoulder press (SSP). These data were used to estimate the 1 repetition maximum (1RM), which in turn was used to develop the periodization program. Following baseline testing, participants participated in two full-body workouts per week for six weeks. Each individual was retested …

Overcoming Cd226-Related Immune Evasion In Acute Myeloid Leukemia With Cd38 Car-Engineered Nk Cells, Luciana Melo Garcia, Achintyan Gangadharan, Pinaki Banerjee, Ye Li, Andy G X Zeng, Hind Rafei, Paul Lin, Bijender Kumar, Sunil Acharya, May Daher, Luis Muniz-Feliciano, Gary M Deyter, Gabriel Dominguez, Jeong Min Park, Francia Reyes Silva, Ana Karen Nunez Cortes, Rafet Basar, Nadima Uprety, Mayra Shanley, Mecit Kaplan, Enli Liu, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226. CRISPR-Cas9 deletion of CD226 led to reduced LFA-1 recruitment, poor synapse formation, and decreased NK cell anti-leukemic activity. Engineering NK cells to express a chimeric antigen receptor targeting the AML antigen CD38 (CAR38) could overcome the need for CD226 to establish strong immune synapses. LFA-1 …

A Morphometric Signature To Identify Ductal Carcinoma In Situ With A Low Risk Of Progression, Marcelo Sobral-Leite, Simon P Castillo, Shiva Vonk, Hendrik A Messal, Xenia Melillo, Noomie Lam, Brandi De Bruijn, Yeman B Hagos, Myrna Van Den Bos, Joyce Sanders, Mathilde Almekinders, Lindy L Visser, Emma J Groen, Petra Kristel, Caner Ercan, Leyla Azarang, Jacco Van Rheenen, E Shelley Hwang, Yinyin Yuan, Renee Menezes, Esther H Lips, Jelle Wesseling

Faculty, Staff and Student Publications

Ductal carcinoma in situ (DCIS) may progress to ipsilateral invasive breast cancer (iIBC), but often never will. Because DCIS is treated as early breast cancer, many women with harmless DCIS face overtreatment. To identify features associated with progression, we developed an artificial intelligence-based DCIS morphometric analysis pipeline (AIDmap) on hematoxylin-eosin-stained (H&E) tissue sections. We analyzed 689 digitized H&Es of pure primary DCIS of which 226 were diagnosed with subsequent iIBC and 463 were not. The distribution of 15 duct morphological measurements was summarized in 55 morphometric variables. A ridge regression classifier with cross validation predicted 5-years-free of iIBC with an …

Optimal Size And Peg Coating Of Gold Nanoparticles For Prolonged Blood Circulation: A Statistical Analysis Of Published Data, Dmitry Nevozhay, Ronald Rauch, Zhongya Wang, Konstantin V Sokolov

Faculty, Staff and Student Publications

This study presents a statistical analysis of how gold nanoparticle (GNP) size and polyethylene glycol (PEG) coating molecular weight (MW) affect the circulation of nanoparticles in blood. We showed a non-linear relationship with interaction between GNP size and PEG MW. The findings revealed a threshold effect, and recommendations for GNP coating are discussed.

Erk Activation Dynamics In Maturing Oocyte Controls Embryonic Nuclear Divisions In Caenorhabditis Elegans, Han Bit Baek, Debabrata Das, Shin-Yu Chen, Hongyuan Li, Swathi Arur

Faculty, Staff and Student Publications

ERK activity oscillates between sustained activation during oocyte formation and transient inactivation during oocyte maturation, fertilization, and early embryogenesis. Consequences of ectopic ERK activity upon oocyte maturation and in early embryogenesis are unknown. We show, in Caenorhabditis elegans, that ectopic ERK activity upon oocyte maturation (metaphase I oocytes) results in embryos with abnormalities in nuclear divisions leading to embryonic death. We uncover that ERK directly phosphorylates Polo-like kinase I (PLK-1), on Serine 404, to inhibit nuclear envelope breakdown (NEBD) in early embryogenesis. The RAS/ERK/PLK-1 pathway poisons zygotic NEBD and inhibits the merging of parental genomes, underlining the importance of turning …

Screening Young Adult Cancer Patients For Vocational Rehabilitation Services: A Vocational Rehabilitation Readiness Screening Tool, Rhonda Robert, Clark R Andersen, Kathleen M Murphy, Sandra Medina-George, Melissa Scardaville, Sha-Ron Conley, David Farris, Michael Roth, Vinh Nguyen, Lex Frieden

Faculty, Staff and Student Publications

Purpose: We aimed to develop an online vocational rehabilitation (VR) readiness screening (VRRS) tool for young adults diagnosed with cancer. VR readiness was defined as being physically and cognitively ready to enter or return to work or school.

Methods: We developed an initial VRRS tool informed by previous studies, a scoping review to determine such a tool had not already been developed, and consultation with subject matter experts. We iteratively refined the tool on the basis of four rounds of interviews with young adults with cancer. The refined VRRS was then administered online to patients before they attended scheduled clinic …

Trmt1l-Catalyzed M22g27 On Tyrosine Trna Is Required For Efficient Mrna Translation And Cell Survival Under Oxidative Stress, Sseu-Pei Hwang, Han Liao, Katherine Barondeau, Xinyi Han, Cassandra Herbert, Hunter Mcconie, Amirtha Shekar, Dimitri G Pestov, Patrick A Limbach, Jeffrey T Chang, Catherine Denicourt

Faculty, Staff and Student Publications

tRNA modifications are critical for several aspects of their functions, including decoding, folding, and stability. Using a multifaceted approach encompassing eCLIP-seq and nanopore tRNA-seq, we show that the human tRNA methyltransferase TRMT1L interacts with the component of the Rix1 ribosome biogenesis complex and binds to the 28S rRNA as well as to a subset of tRNAs. Mechanistically, we demonstrate that TRMT1L is responsible for catalyzing N2,N2-dimethylguanosine (m22G) solely at position 27 of tRNA-Tyr-GUA. Surprisingly, TRMT1L depletion also impaired the deposition of 3-(3-amino-3-carboxypropyl) uridine (acp3U) and dihydrouridine on tRNA-Tyr-GUA, Cys-GCA, and Ala-CGC. TRMT1L knockout cells have a marked decrease in tRNA-Tyr-GUA …

Sex-Specific Astrocyte Regulation Of Spinal Motor Circuits By Nkx61, Navish A Bosquez Huerta, Zhung-Fu Lee, Eun-Ah Christine Song, Junsung Woo, Yi-Ting Cheng, Debosmita Sardar, Ozlem Sert, Ehson Maleki, Kwanha Yu, Ekin Su Akdemir, Kaitlyn Sanchez, Juyeon Jo, Matthew N Rasband, Hyun Kyoung Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes exhibit diverse cellular and molecular properties across the central nervous system (CNS). Recent studies identified region-specific transcription factors (TF) that oversee these diverse properties; how sex differences intersect with region-specific transcriptional programs to regulate astrocyte function is unknown. Here, we show that the TF Nkx6.1 is specifically expressed in ventral astrocytes of the spinal cord and that its deletion results in sex-specific effects on astrocyte morphology. Astrocytes from males exhibit enhanced morphological complexity, accompanied by increased motor function and cholinergic synapses. In contrast, female astrocytes exhibit reduced complexity and no changes in motor function. Mechanistically, we found that Nkx6.1 …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M Kusminski, Terry D Hinds, Philipp E Scherer

Faculty, Staff and Students Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

Challenges And Opportunities In The Dissemination Of Scientific Content: Insights From Media Professionals In Jordan, Ruba Mustafa Mohammad Dr, Mahmoud Ahmad Al-Rajabi Dr, Hala Nabil Amr

Middle East Journal of Communication Studies

This study explored the challenges and opportunities in disseminating scientific content from the perspective of media experts in Jordan. Using a descriptive methodology and a questionnaire, the research aimed to understand the landscape better. The sample included 343 media experts holding master's degrees or higher in various media fields, along with several journalists actively working in the sector. The study revealed several key findings. Chief among them are the numerous obstacles hindering the dissemination of scientific content in Jordanian media. These include a lack of training for journalists on accessing new scientific information, a general absence of critical thinking skills …

The Degree Of Dependence Of The Jordanian Public On Social Media In Health Awareness Of Obesity Diseases (Survey Study), Jumana Irshiedat Dr, Kamel Khurshid Murad Prof

Middle East Journal of Communication Studies

The article aimed to reveal the dependency of social media platforms in educating the Jordanian public about obesity diseases and explore the cognitive, emotional, and behavioral effects on the Jordanian public. The survey method was adopted; an approach used in descriptive studies, and the questionnaire tool was used to a sample (357) of the Jordanian public in Amman. The study-produced results including the platform most used by the Jordanian public to receive knowledge about health awareness is WhatsApp in the first place, followed by Instagram and then Facebook. The results also showed that the health topics of most interest to …

The Energy Transition In The Jordanian Media, Hanan Al-Shiekh Dr

Middle East Journal of Communication Studies

The study aimed to clarify the role of scientific journalism towards stimulating investment in environmentally friendly renewable energy sources, which is one of the necessary challenges facing the Kingdom of Jordan for economic growth and social development, due to its heavy dependence on energy imports, which reflects negatively on the Jordanian economy. This study is one of the descriptive studies that focuses on describing a specific topic, as it is in the current reality, in terms of its general and detailed characteristics, including variables, elements, relationships, and influences, which are among the most prominent features of scientific journalism in terms …

The Role Of Television In Increasing Knowledge About Health Issues Among Jordanian Citizens, Izzat Mohammad Hijab Prof, Ahmad Oreqat Dr, Hani Al-Badri Dr

Middle East Journal of Communication Studies

This study explores the role of TV health programs in increasing the knowledge of Jordanian citizens about health issues. The study was based on the social survey methodology through a questionnaire distributed to a sample of 200 people from the city of Amman watching Jordan Television (JTV) health programs. The researcher concluded the following; a high watching for health programs, and that the Jordanians watch health programs with their family at home. The study also confirmed that the Jordanian benefits from health programs provided by JTV, and these programs are important and essential in educating citizens in health issues. Finally, …

Chemotherapy In Synergy With Innate Immune Agonists Enhances T Cell Priming For Checkpoint Inhibitor Treatment In Pancreatic Cancer, Nan Niu, Keyu Li, Junke Wang, Vanessa Funes, Birginia Espinoza, Pan Li, Jianxin Wang, Melissa Lyman, Mengni He, Brian Herbst, Michael Wichroski, Ruslan Novosiadly, Sami Shoucair, Yiping Mou, Lei Zheng

Faculty, Staff and Student Publications

Background: The combination of conventional chemotherapy and immune checkpoint inhibitors (ICIs) has been unsuccessful for pancreatic ductal adenocarcinoma (PDAC). Administration of maximum tolerated dose of chemotherapy drugs may have immunosuppressive effects.

Methods: We thus tested, by using the preclinical model of PDACs including the genetically engineered mouse KPC spontaneous pancreatic tumor model and the pancreatic KPC tumor orthotopic implant model, the combinations of synthetic innate immune agonists including STING and NLRP3 agonist, respectively, and ICIs with or without chemotherapy.

Results: We found that innate agonists potentiate the role of chemotherapy in inducing effector T cells and subsequently to prime the …

01.27.2025 Ored Connect, Liz Williamson

ORED Newsletter

Data Science for Addiction Research

UM research and related activities as a new presidential administration transition occurs

Development And Validation Of Natural Language Processing Algorithms In The Enact National Electronic Health Record Research Network, Yanshan Wang, Jordan Hilsman, Chenyu Li, Michele Morris, Paul M Heider, Sunyang Fu, Min Ji Kwak, Andrew Wen, Joseph R Applegate, Liwei Wang, Elmer Bernstam, Hongfang Liu, Jack Chang, Daniel R Harris, Alexandria Corbeau, Darren Henderson, John D Osborne, Richard E Kennedy, Nelly-Estefanie Garduno-Rapp, Justin F Rousseau, Chao Yan, You Chen, Mayur B Patel, Tyler J Murphy, Bradley A Malin, Chan Mi Park, Jungwei W Fan, Sunghwan Sohn, Sandeep Pagali, Yifan Peng, Aman Pathak, Yonghui Wu, Zongqi Xia, Salvatore Loguercio, Steven E Reis, Shyam Visweswaran

Faculty, Staff and Student Publications

Electronic health record (EHR) data are a rich and invaluable source of real-world clinical information, enabling detailed insights into patient populations, treatment outcomes, and healthcare practices. The availability of large volumes of EHR data are critical for advancing translational research and developing innovative technologies such as artificial intelligence. The Evolve to Next-Gen Accrual to Clinical Trials (ENACT) network, established in 2015 with funding from the National Center for Advancing Translational Sciences (NCATS), aims to accelerate translational research by democratizing access to EHR data for all Clinical and Translational Science Awards (CTSA) hub investigators. The present ENACT network provides access to …

Immuno-Bioinformatics Study Of Secondary Metabolites From Watercress Nasturtium Officinale As Immunostimulant In Whiteleg Shrimp Litopenaeus Vannamei By Targeting Peroxinectin And Scavenger Receptor Class B, Qurrota A’Yunin, Muhaimin Rifa’I, Maftuch Maftuch, Yoga Dwi Jatmiko, Muhammad Hermawan Widyananda, Triyanto Triyanto, Muhammad Tegar Handrianto

Karbala International Journal of Modern Science

The viral disease affects the whiteleg shrimp (Litopenaeus vannamei) and causes losses. Immunostimulants are recognized as a more environmentally friendly approach to disease management and antimicrobial properties of aquatic organisms. Watercress (Nasturtium officinale) is an aquatic plant species that contains antioxidant properties that can protect the organism from disease and boost the immune system. Shrimp rely heavily on innate immunity to combat infectious agents due to their absence of adaptive immunity. Peroxinectin and scavenger receptor class B (SRB) play essential roles in the shrimp defense system. This research employs a bioinformatic to assess the immunostimulatory potential …

Sigma1 Inhibitor Suppression Of Adaptive Immune Resistance Mechanisms Mediated By Cancer Cell Derived Extracellular Vesicles, Paola A. Castagnino, Derick A. Haas, Luca Musante, Nathalia A. Tancler, Bach V. Tran, Rhonda Kean, Alexandra R. Steck, Luis A. Martinez, Elahe A. Mostaghel, D. Craig Hooper, Felix J. Kim

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER. Sigma1 is a unique ligand-regulated integral membrane scaffolding protein enriched in the ER of cancer cells. PD-L1 is an integral membrane glycoprotein that is translated into the ER and processed through the cellular secretory pathway. At the cell surface, PD-L1 is an immune …

Statistical Identification Of Cell Type-Specific Spatially Variable Genes In Spatial Transcriptomics, Lulu Shang, Peijun Wu, Xiang Zhou

Faculty, Staff and Student Publications

An essential task in spatial transcriptomics is identifying spatially variable genes (SVGs). Here, we present Celina, a statistical method for systematically detecting cell type-specific SVGs (ct-SVGs)-a subset of SVGs exhibiting distinct spatial expression patterns within specific cell types. Celina utilizes a spatially varying coefficient model to accurately capture each gene's spatial expression pattern in relation to the distribution of cell types across tissue locations, ensuring effective type I error control and high power. Celina proves powerful compared to existing methods in single-cell resolution spatial transcriptomics and stands as the only effective solution for spot-resolution spatial transcriptomics. Applied to five real …

Genome-Wide Profiling Of Trna Modifications By Induro-Trnaseq Reveals Coordinated Changes, Yuko Nakano, Howard Gamper, Henri Mcguigan, Sunita Maharjan, Jiatong Li, Zhiyi Sun, Erbay Yigit, Sebastian Grünberg, Keerthana Krishnan, Nan-Sheng Li, Joseph Piccirilli, Ralph Kleiner, Nicole Nichols, Brian Gregory, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro-a new group-II intron-encoded RT-to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and …

Phase I Trial Of Hydroxychloroquine To Enhance Palbociclib And Letrozole Efficacy In Er+/Her2- Breast Cancer, Akshara Singareeka Raghavendra, Nicole M Kettner, Danielle Kwiatkowski, Senthil Damodaran, Yan Wang, David Ramirez, Dan S Gombos, Kelly K Hunt, Yu Shen, Khandan Keyomarsi, Debu Tripathy

Faculty, Staff and Student Publications

Endocrine therapy with CDK4/6 inhibitors is standard for estrogen receptor-positive, HER2-negative metastatic breast cancer (ER+/HER2- MBC), yet clinical resistance develops. Previously, we demonstrated that low doses of palbociclib activate autophagy, reversing initial G1 cell cycle arrest, while high concentrations induce off-target senescence. The autophagy inhibitor hydroxychloroquine (HCQ) induced on-target senescence at lower palbociclib doses. We conducted a phase I trial (NCT03774472 registered in ClinicalTrials.gov on 8/20/2018) of HCQ (400, 600, 800 mg/day) with palbociclib (75 mg/day continuous) and letrozole, using a 3 + 3 design. Primary objectives included safety, tolerability, and determining the recommended phase 2 dose (RP2D) of HCQ. …

Development And Characterization Of Cd44-Targeted X-Aptamers With Enhanced Binding Affinity For Cancer Therapeutics, Hongyu Wang, Weiguo He, Miguel-Angel Elizondo-Riojas, Xiaobo Zhou, Tae Jin Lee, David G Gorenstein

Faculty, Staff and Student Publications

CD44, a pivotal cell surface molecule, plays a crucial role in many cellular functions, including cell-cell interactions, adhesion, and migration. It serves as a receptor for hyaluronic acid and is involved in lymphocyte activation, recirculation, homing, and hematopoiesis. Moreover, CD44 is a commonly used cancer stem cell marker associated with tumor progression and metastasis. The development of CD44 aptamers that specifically target CD44 can be utilized to target CD44-positive cells, including cancer stem cells, and for drug delivery. Building on the primary sequences of our previously selected thioaptamers (TAs) and observed variations, we developed a bead-based X-aptamer (XA) library by …

Urine Proteomics Defines An Immune Checkpoint-Associated Nephritis Signature, James P Long, Shailbala Singh, Yanlan Dong, Cassian Yee, Jamie S Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients. Delayed or incorrect diagnosis of ICI-AIN is particularly detrimental, as over 50% of patients are at risk of permanent renal damage. Thus, there is an urgent need for non-invasive biomarkers that can rapidly and accurately distinguish …