Digital Commons Network^™

De Novo Variants In Cdkl1 And Cdkl2 Are Associated With Neurodevelopmental Symptoms, Ali H Bereshneh, Jonathan C Andrews, Daniel F Eberl, Guney Bademci, Nicholas A Borja, Stephanie Bivona, Wendy K Chung, Shinya Yamamoto, Michael F Wangler, Shane Mckee, Mustafa Tekin, Hugo J Bellen, Oguz Kanca

Duncan NRI Faculty and Staff Publications

The CDKL (cyclin-dependent kinase-like) family consists of five members in humans, CDKL1-5, that encode serine-threonine kinases. The only member that has been associated with a Mendelian disorder is CDKL5, and variants in CDKL5 cause developmental and epileptic encephalopathy type 2 (DEE2). Here, we study four de novo variants in CDKL2 identified in five individuals, including three unrelated probands and monozygotic twins. These individuals present with overlapping symptoms, including global developmental delay, intellectual disability, childhood-onset epilepsy, dyspraxia, and speech deficits. We also identified two individuals with de novo missense variants in CDKL1 in the published Deciphering Developmental Disorders (DDD) and GeneDx …

Open Access Dataset And Common Data Model For Pulse Oximeter Performance Data, Nicholas Fong, Michael S Lipnick, Ella Behnke, Yu Chou, Seif Elmankabadi, Lily Ortiz, Christopher S Almond, Isabella Auchus, Garrett W Burnett, Ronald Bisegerwa, Desireé R Conrad, Carolyn M Hendrickson, Shubhada Hooli, Robert Kopotic, Gregory Leeb, Daniel Martin, Eric D Mccollum, Ellis P Monk, Kelvin L Moore, Leonid Shmuylovich, J Brady Scott, An-Kwok Ian Wong, Tianyue Zhou, Romain Pirracchio, Philip E Bickler, John Feiner, Tyler J Law

Faculty, Staff and Students Publications

The OpenOximetry Dataset stores clinical and lab pulse oximetry data. It supports measurements of arterial oxygen saturation (SaO2) by arterial blood gas co-oximetry and pulse oximetry (SpO2), alongside processed and unprocessed photoplethysmography (PPG) data and other metadata. This includes skin color measurements, finger diameter, vital signs (e.g., arterial blood pressure, end-tidal carbon dioxide), and arterial blood gas parameters (e.g., acid-base balance, hemoglobin concentration). All data, from desaturation studies to clinical trials, are collected prospectively to ensure accuracy. A common data model and standardized protocols for consistent archival and interpretation ensure consistent data archival and interpretation. The dataset aims to facilitate …

Clinical Validation Of Rna Sequencing For Mendelian Disorder Diagnostics, Sen Zhao, Kristina Macakova, Jefferson C Sinson, Hongzheng Dai, Jill Rosenfeld, Gladys E Zapata, Shenglan Li, Patricia A Ward, Christiana Wang, Chunjing Qu, Becky Maywald, Brendan Lee, Christine Eng, Pengfei Liu

Faculty, Staff and Students Publications

Despite rapid advancements in clinical sequencing, over half of diagnostic evaluations still lack definitive results. RNA sequencing (RNA-seq) has shown promise in research settings for bridging this gap by providing essential functional data for accurate interpretation of diagnostic sequencing results. However, despite advanced research pipelines, clinical translation of diagnostic RNA-seq has not yet been realized. We have developed and validated a clinical diagnostic RNA-seq test for individuals with suspected genetic disorders who have existing or concurrent comprehensive DNA diagnostic testing. This diagnostic RNA-seq test processes RNA samples from fibroblasts or blood and derives clinical interpretations based on the analytical detection …

Biochemical Profiling And Structural Basis Of Adar1-Mediated Rna Editing, Xiangyu Deng, Lina Sun, Min Zhang, Rashmi Basavaraj, Jin Wang, Yi-Lan Weng, Yang Gao

Faculty, Staff and Students Publications

ADAR1 regulates RNA-induced immune responses by converting adenosine to inosine in double-stranded RNA. Mutations in ADAR1 are associated with human autoimmune disease, and targeting ADAR1 has been proposed for cancer immunotherapy. However, the molecular mechanisms underlying ADAR1-mediated editing remain unclear. Here, we provide detailed biochemical and structural characterizations of human ADAR1. Our biochemical profiling reveals that ADAR1 editing is both sequence and RNA-duplex-length dependent but can well tolerate mismatches near the editing site. High-resolution ADAR1-RNA complex structures, combined with mutagenesis, elucidate RNA binding, substrate selection, dimerization, and the essential role of RNA-binding domain 3. The ADAR1 structures also help explain …

Methylome-Wide Association Analyses Of Lipids And Modifying Effects Of Behavioral Factors In Diverse Race And Ethnicity Participants, Yao Hu, Jeff Haessler, Jessica I Lundin, Burcu F Darst, Eric A Whitsel, Megan Grove, Weihua Guan, Rui Xia, Mindy Szeto, Laura M Raffield, Scott Ratliff, Yuxuan Wang, Xuzhi Wang, Alison E Fohner, Megan T Lynch, Yesha M Patel, S Lani Park, Huichun Xu, Braxton D Mitchell, Joshua C Bis, Nona Sotoodehnia, Jennifer A Brody, Bruce M Psaty, Gina M Peloso, Michael Y Tsai, Stephen S Rich, Jerome I Rotter, Jennifer A Smith, Sharon L R Kardia, Alex P Reiner, Leslie Lange, Myriam Fornage, James S Pankow, Mariaelisa Graff, Kari E North, Charles Kooperberg, Ulrike Peters

Faculty, Staff and Student Publications

Circulating lipid concentrations are clinically associated with cardiometabolic diseases. The phenotypic variance explained by identified genetic variants remains limited, highlighting the importance of searching for additional factors beyond genetic sequence variants. DNA methylation has been linked to lipid concentrations in previous studies, although most of the studies harbored moderate sample sizes and exhibited underrepresentation of non-European ancestry populations. In addition, knowledge of nongenetic factors on lipid profiles is extremely limited. In the Population Architecture Using Genomics and Epidemiology (PAGE) Study, we performed methylome-wide association analysis on 9,561 participants from diverse race and ethnicity backgrounds for HDL-c, LDL-c, TC, and TG …

The Microbiome-Restorative Potential Of Ibezapolstat For The Treatment Of Clostridioides Difficile Infection Is Predicted Through Variant Polc-Type Dna Polymerase Iii In Lachnospiraceae And Oscillospiraceae, Jacob K Mcpherson, Julian G Hurdle, Matthew L Baker, Tahir Hussain, Ashok Kumar, Kevin W Garey

Faculty, Staff and Student Publications

Ibezapolstat (IBZ), a first-in-class antibiotic targeting the PolC-type DNA polymerase III alpha-subunit (PolC) in low G + C bacteria, is in clinical development for the treatment of Clostridioides difficile infection (CDI). In the phase 2 trials, IBZ had potent activity against C. difficile while sparing or causing regrowth of Lachnospiraceae, Oscillospiraceae, and Erysipelotrichales, common commensal low G + C bacteria. The purpose of this study was to utilize in silico approaches to better interpret the narrower than expected IBZ spectrum of activity. IBZ susceptibility to human commensal microbiota was predicted using genomic analysis and PolC phylogenetic tree construction in relation …

Chronic Viral Mimicry Induction Following P53 Loss Promotes Immune Evasion, Charles A Ishak, Sajid A Marhon, Naïri Tchrakian, Anjelica Hodgson, Helen Loo Yau, Isabela M Gonzaga, Melanie Peralta, Ilinca M Lungu, Stephanie Gomez, Sheng-Ben Liang, Shu Yi Shen, Raymond Chen, Jocelyn Chen, Biji Chatterjee, Kevin N Wanniarachchi, Junwoo Lee, Nicholas Zehrbach, Amir Hosseini, Parinaz Mehdipour, Siyu Sun, Alexander Solovyov, Ilias Ettayebi, Kyle E Francis, Aobo He, Taiyi Wu, Shengrui Feng, Tiago Da Silva Medina, Felipe Campos De Almeida, Jane Bayani, Jason Li, Spencer Macdonald, Yadong Wang, Sarah S Garcia, Elisa Arthofer, Noor Diab, Aneil Srivastava, Paul Tran Austin, Peter J B Sabatini, Benjamin D Greenbaum, Catherine A O'Brien, Trevor G Shepherd, Ming Sound Tsao, Katherine B Chiappinelli, Amit M Oza, Blaise A Clarke, Robert Rottapel, Stephanie Lheureux, Daniel D De Carvalho

Faculty, Staff and Student Publications

Epigenetic therapies facilitate transcription of immunogenic repetitive elements that cull cancer cells through ‘viral mimicry’ responses. Paradoxically, cancer-initiating events also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood. In this report, we characterize premalignant lesions of the fallopian tube along with syngeneic epithelial ovarian cancer models to explore the earliest events of tumorigenesis following loss of the p53 tumor suppressor protein. We report that p53 loss permits transcription of immunogenic repetitive elements and chronic viral mimicry activation …

Computational Sensitivity Evaluation Of Ultrasound Neuromodulation Resolution To Brain Tissue Sound Speed With Robust Beamforming, Boqiang Fan, Wayne Goodman, Sameer A Sheth, Richard R Bouchard, Behnaam Aazhang

Faculty, Staff and Student Publications

Low-intensity focused ultrasound (LIFU) neuromodulation requires precise targeting and high resolution enabled by phased array transducers and beamforming. However, focusing optimization usually relies on phantom measurements or simulations with inaccurate acoustic properties to degrade neuromodulation resolution. Therefore, this work analyzes the sensitivity of neuromodulation resolution, measured by off-target activation area (OTAA), to brain tissue sound speed. A Robust Optimal Resolution (ROR) beamforming method is proposed to minimize the worst-case OTAA with restricted sound speed inaccuracy and propagation information estimated with deviated sound speed. The propagation estimation model utilizes equivalent source method (ESM) to map sound field between different acoustic parameter …

Identifiability And Model Selection Frameworks For Models Of High-Grade Glioma Response To Chemoradiation, Khushi C Hiremath, Kenan Atakishi, Ernesto A B F Lima, Maguy Farhat, Bikash Panthi, Holly Langshaw, Mihir D Shanker, Wasif Talpur, Sara Thrower, Jodi Goldman, Caroline Chung, Thomas E Yankeelov, David A Hormuth Ii

Faculty, Staff and Student Publications

We have developed a family of biology-based mathematical models of high-grade glioma (HGG), capturing the key features of tumour growth and response to chemoradiation. We now seek to quantify the accuracy of parameter estimation and determine, when given a virtual patient cohort, which model was used to generate the tumours. In this way, we systematically test both the parameter and model identifiability. Virtual patients are generated from unique growth parameters whose growth dynamics are determined by the model family. We then assessed the ability to recover model parameters and select the model used to generate the tumour. We then evaluated …

Bone-Induced Her2 Promotes Secondary Metastasis In Hr+/Her2- Breast Cancer, Rahat Alam, Anna Reva, David G Edwards, Bree M Lege, Laura S Munoz-Arcos, Carolina Reduzzi, Swarnima Singh, Xiaoxin Hao, Yi-Hsuan Wu, Zeru Tian, Laura M Natalee, Gargi Damle, Deniz Demircioglu, Yixian Wang, Ling Wu, Elisabetta Molteni, Dan Hasson, Bora Lim, Zbigniew Gugala, Jerry E Chipuk, Julie E Lang, Joseph A Sparano, Chonghui Cheng, Massimo Cristofanilli, Han Xiao, Xiang H-F Zhang, Igor L Bado

Faculty, Staff and Students Publications

Bone metastases can disseminate to secondary sites and promote breast cancer progression creating additional clinical challenges. The mechanisms contributing to secondary metastasis are barely understood. Here, we evaluate the prediction power of Her2-expressing (Her2E) circulating tumor cells (CTCs) after analyzing over 13,000 CTCs from a cohort of 137 metastatic breast cancer (MBC) patients with initial HR+/Her2− status and employ preclinical models of bone metastasis (BM) to validate the role of Her2E CTCs in multi-organ metastases. While Her2 expression was higher in patients with bone metastasis, experimental analyses revealed that Her2E CTCs derived from bone lesions were more dependent on Her2 …

Deciphering Genotype-Phenotype Connections: Leveraging Pangenomes And Comprehensive Genome Variation, Flavia Villani

Alternative Theses and Dissertations (AETDs)

My thesis explores the application of advanced techniques for discovery of genetic variation and pangenomic approaches to enhance our understanding of genetic variation and genotype-phenotype relationships in two key model organisms: the HXB/BXH recombinant inbred rat family and the BXD mouse family. Through deep sequencing and innovative computational methods, I constructed com- prehensive pangenome graphs that captured genetic diversity beyond what is accessible through conventional single-reference approaches. In the HXB rat family, I identified approximately 200 million base pairs of sequence absent from the reference genome and discovered novel variants associated with glucose metabolism and chromogranin expression through phenome-wide association …

Dean's Update, April 2025, Neil W. Schluger

SOM Dean's Research Newsletter

No abstract provided.

The Relationship Between Physical Activity And Telomere Length In Women: A Systematic Review, Jeni Page, Catherine Stephens, Melissa Richard, Elizabeth Lyons, Elizabeth Baumler, M Terese Verklan, Elizabeth Lorenzo

Faculty, Staff and Student Publications

Telomere length (TL) is a biomarker of cellular aging with variations observed by sex, age, race, and ethnicity. Prior studies have suggested that physical activity (PA) may positively impact TL by potentially elongating telomeres and slowing cellular aging. However, research examining the optimal type and intensity of PA needed to elicit these changes specific to women remains limited. This systematic review aimed to investigate variations in TL in response to PA among women, exploring how these effects differ by age, race, or ethnicity. Following PRISMA guidelines, searches across five databases identified 17 relevant studies published from 2008 to 2022. A …

The Illusion Of Brain Health Across A Plastic Canvas, Thomas J. Kelly Jr, Lauren Gaspar, Jaime Ross Phd, Guiseppe Coppotelli Phd

Senior Honors Projects

In recent years, there has been increasing concern for the role that plastic waste, and more specifically micro- and nanoplastics, play in our environment and their potential health risks. Microplastics are particles less than 5 mm in size and nanoplastics are considered to be less than 1000 nm in size. Microplastics can either purposely be produced or can sludge off larger pieces of plastic. Microplastics have not only been detected within soil, air, and water, but have also recently been found to accumulate within the human body. The mosaic artwork that is presented in this project, entitled “Our Cerebral Plastic …

Aging-Related Hearing Decline And Resting State Networks, Cassidy S. T. Ellsworth

College of Education and Human Sciences: Dissertations, Theses, and Student Research

This study investigated the effects of age-related hearing decline on functional networks using resting-state functional magnetic resonance imaging (rs-fMRI). The main objective of the present study was to examine resting-state functional connectivity (rsFC) and graph theory-based network efficiency metrics in forty-nine adults categorized by age and hearing thresholds to identify the neural mechanisms of age-related hearing decline. RsFC within key brain networks and auditory-related brain regions, including the default mode network, salience network, dorsal attention network, and primary auditory cortices, was assessed using region-of-interest (ROI)-based and graph theory approaches. Functional metrics, such as rsFC strength and global and local efficiency, …

Clinical Case Study: The Effects Of Saltatory Pneumotactile Stimulation Of Glabrous Hand And Perioral Face On Cerebral Oxygenation, Cognitive Performance, And Sensorimotor Function In An Adult Following Left Hemorrhagic Stroke, Tara L. Hull

College of Education and Human Sciences: Dissertations, Theses, and Student Research

Stroke remains a leading cause of adult disability and a significant global health concern. Effective rehabilitation strategies for cognitive and communicative impairments following stroke are limited (Kuhn & Sharman, 2023). One emerging approach involves repetitive somatosensory stimulation to drive cerebral hemodynamic changes, potentially offering a novel rehabilitative method. Functional Near-Infrared Spectroscopy (fNIRS) is a non-invasive, accessible tool for monitoring these changes during stroke recovery. Prior studies suggest tactile stimulation rapidly affects brain hemodynamics (Custead et al., 2015; Oh et al., 2017). This clinical single-case study explored the use of GALILEO saltatory pneumotactile stimulation applied to the face and hand in …

Associations Between B Vitamin Interactions With Polyunsaturated Fatty Acids And Cognitive Function Among Cognitively Healthy Older People As Modified By Amyloid Status And Sex, Chuliang Zhao, Karen A. Abbott, Chinedu Momoh, Geraint Price, Oliver J. K. Robinson, Sujin Kang, Celeste A. De Jager Loots

Brain and Mind Institute

Background/Objectives: Nutrients such as vitamin B12, folate (B9), and polyunsaturated fatty acids (PUFAs) may independently influence cognitive health, but their combined effects and interactions remain unclear. This study aims to investigate the effects of B12, folate, and PUFAs, including their interactions, on cognitive function in cognitively healthy older adults, considering effect modification by sex and amyloid-beta status.

Methods: A cross-sectional analysis was conducted using data from 321 participants aged 60–85 y enrolled in the UK CHARIOT–PRO SubStudy. Dietary intake was assessed using the Scottish Collaborative Group Food Frequency Questionnaire, and cognitive performance was measured via the Repeatable Battery …

Sox18 Unleashed: Exploring The Transcriptomic Landscape – Differential Gene Expression Analysis Via Rna Seq In Overexpressed Sox18, Van Nguyen, Terry Shackleford, Lori Boies

Posters - 2025

Cancer remains a leading cause of death worldwide, and childhood sarcomas such as Rhabdomyosarcoma (RMS) and Ewing Sarcoma (ES) are particularly aggressive with limited targeted treatment options. Despite advancements in cancer therapies, metastatic sarcomas still have a survival rate below 30%, emphasizing the need for new therapeutic targets. SOX18, a transcription factor has played a role in vascular development and endothelial differentiation, functioning as a key driver of angiogenesis. In cancer, increased SOX18 expression has been linked to dysregulated cell migration, invasion, and therapy resistance mechanisms. However, the extent to which SOX18 influences RMS and ES at the transcriptional level …

Role For Astrocytes In Complex Cognition: An Evolutionary, Behavioral And Computational Perspective, Gregory Simandl

Dissertations (1934 -)

The human brain has more computational power than modern supercomputers by utilizing only a few signaling systems, rendering it the most efficient computational device ever created. Evolution, though not prospective, has iteratively constructed neural networks of increasing complexity that have ultimately endowed humans with extraordinary cognitive abilities. Through an evolutionary lens, there is a clear correlation between organismal sophistication and network signaling complexity Astrocytes, a non-neuronal cell that makes up approximately half the cells in the human brain, show dramatic increases in morphological and signaling complexity in higher-order species. This co-evolution is likely not coincidental but rather represents the development …

Short-Course Subcutaneous Alemtuzumab Induces Clinical Responses In Relapsed T-Cell Large Granular Leukemia, Miguel Ruiz, Zachary Braunstein, Eric Mclaughlin, Anjali Mishra, Pierluigi Porcu, Jonathan E. Brammer

Department of Medical Oncology Faculty Papers

No abstract provided.

Ibuprofen, Flurbiprofen Or Naproxen Sodium Minimally Influences Musculoskeletal Adaptations To Treadmill Exercise In Rats, Brandon Roberts, Alyssa Geddis, Alexandra Ciuciu, Marinaliz Reynoso, Nikhil Mehta, Alyssa Varanoske, Alyssa Kelley, Maximus Leiss, Alexander Kolb, Julie Hughes, Marshall Naimo, Ryan Tomlinson, Jeffery Staab

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) may influence musculoskeletal health. The purpose of this study was to compare the effects of three different NSAIDS: naproxen sodium, ibuprofen, flurbiprofen or a placebo on musculoskeletal adaptations in rodents with or without 6 weeks of aerobic exercise.

METHODS: Nine-week-old male Wistar rats (n = 80) were randomized to either exercise (EX) or no-exercise control (CON) conditions and treated with naproxen, ibuprofen (IBU), flurbiprofen (FLU) or placebo (PLA). For exercise, rats ran 5 days per week for 6 weeks at a 5% incline on a motorized treadmill for 30 min. Three-point bending (3 PB) and …

Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes

Open Access Theses & Dissertations

C-C chemokine receptor 7 (CCR7) is critical in guiding T cell migration within the thymus and peripheral lymphoid tissues, shaping the adaptive immune response by promoting central tolerance and regulating immune homeostasis. Although its role in lymphocyte trafficking is well established, the molecular mechanisms by which CCR7 influences thymocyte development and T cell receptor (TCR) repertoire formation remain less understood. This study examines how CCR7 deficiency impacts thymic selection, TCR diversity, and the signaling events that shape repertoire restriction. Using a homozygously deleted CCR7 murine model, we found that the absence of CCR7 results in a less restricted TCR repertoire …

Demographic Variations In Long Qt Syndrome: Analyzing The Impact Of Gender, Ethnicity, And Environmental Factors On Prevalence And Risk, Heidi Bosch

Senior Honors Theses

Long QT syndrome (LQTS) is an arrhythmic condition characterized by delayed repolarization of cardiomyocytes, identified by prolonged QT interval on an electrocardiogram (ECG). LQTS can be caused by congenital mutations of ion channels or acquired through conditions, medications, and environmental factors. Prolongation of the QT interval can trigger deadly arrhythmia including torsade de pointes (TdP). LQTS has been named the top cause of sudden cardiac death (SCD) for young individuals with anatomically normal hearts. The incidence of LQTS has been reported to be between 1:2000 and 1:2500. The demographic differences in LQTS prevalence have not been thoroughly researched. The incidence …

Rhythm Is Essential: Unraveling The Relation Between The Circadian Clock And Cancer, Olajumoke Ogunlusi, Abantika Ghosh, Mrinmoy Sarkar, Kayla Carter, Harshini Davuluri, Mahul Chakraborty, Kristin Eckel-Mahan, Alex Keene, Jerome S Menet, Deborah Bell-Pedersen, Tapasree Roy Sarkar

The Brown Foundation: Institute of Molecular Medicine

Physiological processes such as the sleep-wake cycle, metabolism, hormone secretion, neurotransmitter release, sensory capabilities, and a variety of behaviors, including sleep, are controlled by a circadian rhythm adapted to 24-hour day-night periodicity. Disruption of circadian rhythm may lead to the risks of numerous diseases, including cancers. Several epidemiological and clinical data reveal a connection between the disruption of circadian rhythms and cancer. On the contrary, oncogenic processes may suppress the homeostatic balance imposed by the circadian clock. The integration of circadian biology into cancer research offers new options for making cancer treatment more effective, and the pharmacological modulation of core …

Epigenome-Wide Association Study Of Incident Type 2 Diabetes In Black And White Participants From The Atherosclerosis Risk In Communities Study, Sowmya Venkataraghavan, James S Pankow, Eric Boerwinkle, Myriam Fornage, Elizabeth Selvin, Debashree Ray

The Brown Foundation: Institute of Molecular Medicine

Aims/hypothesis: DNA methylation studies of incident type 2 diabetes in US populations are limited and to our knowledge none include individuals of African descent. We aimed to fill this gap by identifying methylation sites (CpG sites) and regions likely influencing the development of type 2 diabetes using data from Black and White individuals from the USA.

Methods: We prospectively followed 2091 Black and 1029 White individuals without type 2 diabetes from the Atherosclerosis Risk in Communities study over a median follow-up period of 17 years, and performed an epigenome-wide association analysis of blood-based methylation levels with incident type 2 diabetes …

From Relapse To Restoration: Insights Into The Immunopathology Of Bacterial Vaginosis (Bv) In Women Of Reproductive Age, Nhi To, Ms

Student Papers, Posters & Projects

Bacterial vaginosis (BV) has been a subject of study for decades, yet its complex pathogenesis remains poorly understood. BV affects most women of reproductive age, with significant associations to gynecological and obstetric complications. A deeper understanding of the complicated host-microbiota dynamic is crucial for advancing treatment options, as BV continues to pose challenges in effective management. This review aims to explore the current research on vaginal microbiota as well as potential mechanisms of BV-associated bacteria (BVAB) and their interaction with the host immune system, altogether sheds light on the complex interplay within the human reproductive tract. While Lactobacillus-dominant communities support …

Immunotherapy Targeting A Leader Sequence Cathepsin G-Derived Peptide, Chunhua Shi, Ze Tian, Jun Yan, Mao Zhang, Pariya Sukhumalchandra, Edward Chang, Guojun Yang, Junping You, Meng Cui, Qing Shi, Celine Kerros, Anne Philips, Na Qiao, Hiroki Torikai, Sathvik Patchametla, Anna Sergeeva, Lisa St John, Helen He, Dmitri Wiederschain, Benjamin H Lee, Geraldine L C Paulus, Dongxing Zha, Jeffrey Molldrem, Gheath Alatrash

Faculty, Staff and Student Publications

Myeloid azurophil granules provide a rich source of intracellular leukemia antigens. Cathepsin G (CG) is a serine protease that has higher expression in acute myeloid leukemia (AML) blasts in comparison to normal myeloid progenitors. Based on the unique biology of HLA-A*0201 (HLA-A2), in which presentation of leader sequence (LS)-derived peptides is favored, we focused on the LS-CG-derived peptide CG1 (FLLPTGAEA). We previously detected CG1/HLA-A2 complexes on the surface of primary HLA-A2+ AML blasts and cell lines, and immunity targeting CG1/HLA-A2 in leukemia patients. T cell receptor (TCR)-mimic (m) antibodies are immunotherapeutic antibodies that target peptide-HLA (pHLA) complexes. Here we report …

Staged Screening Identifies People With Biomarkers Related To Neuronal Alpha-Synuclein Disease, Ethan G Brown, Lana M Chahine, Andrew Siderowf, Caroline Gochanour, Ryan Kurth, Micah J Marshall, Chelsea Caspell-Garcia, Michael C Brumm, Craig E Stanley, Monica Korell, Bridget Mcmahon, Maggie Kuhl, Kimberly Fabrizio, Laura Heathers, Luis Concha-Marambio, Claudio Soto, Sohini Chowdhury, Christopher S Coffey, Tatiana M Foroud, Tanya Simuni, Kenneth Marek, Caroline M Tanner

Faculty, Staff and Student Publications

Objective: Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.

Methods: The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis. Participants were invited to complete a University of Pennsylvania Smell Identification Test (UPSIT) independently through an online portal. Hyposmic participants were invited to complete DAT-SPECT, which determined eligibility for enrollment in …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …