Life Sciences Commons^™

Government Agencies In The United States Are Obstructing Native Species Restoration, Creating Regulatory Pits For Wildlife, Jeremy T. Bruskotter, L. Mark Elbroch, John Vucetich

Michigan Tech Publications

No abstract provided.

Demographic Response Of Rana Uenoi To Land Use Near Breeding Sites: A Case Study From The Gayasan Region, South Korea, Hyun Kim, Hyun Tae Kim, Na Yeong Kim, Soo Dong Lee, Jared Wolfe

Michigan Tech Publications

Amphibians are highly sensitive to habitat disturbance because of their permeable skin and reliance on both aquatic and terrestrial environments. To evaluate how human-driven land-use change affects a forest-stream amphibian, we analysed long-term population dynamics of Rana uenoi in the Gayasan region of South Korea, with a focus on breeding habitats. Between 2007 and 2023, annual egg-mass surveys were conducted at 14 breeding sites, and land-use composition was extracted each year within a 500 m buffer from national geospatial databases. Land-use categories were reclassified into ecologically relevant groups (breeding, high-quality, low-quality and non-living/high-mortality habitats) and their areas were quantified for …

Predicting Oil Contamination In Water Using Machine Learning On Microbial Compositions, Tong Gao, Isaac Bigcraft, Stephen Techtmann, Issei Nakamura

Michigan Tech Publications

We present a compact and generative machine-learning framework that predicts oil contamination based on microbial community compositions from experimental samples. Our method combines dimensionality reduction with data augmentation and generative modeling to address high-dimensional, non-linear, and sparse microbial data. To reduce the 503-dimensional bacterial composition dataset, we compared three dimensionality reduction techniques: feature importance from random forest, principal component analysis (PCA), and t-distributed stochastic neighbor embedding (t-SNE). Feature importance outperformed PCA and t-SNE, improving predictive performance and identifying microbial species most strongly correlated with oil contamination. To mitigate data scarcity, we augmented the training data using an augmented data neural …

Crab And Lobster Shell Meal Taste Preferences Of Dairy Heifer Calves, Summer R. Pescinski, Peter S. Erickson

Honors Theses and Capstones

Objective: This preference study was conducted to evaluate the palatability of crab shell meal (CM) and lobster shell meal (LM) when added to calf starter for post-weaned dairy heifer calves.

Materials and methods: Six calves were used for a sequential elimination experiment to rank their taste preferences when offered control calf starter, calf starter mixed with 50 g of CM, and calf starter mixed with 50 g of LM.  The calves were kept on the study for a total of 5-d split into two feeding segments.  Preference was determined by calculating the total intake of each treatment …

Exploring The Effects Of Voluntary Wheel Running On Inhibitory Control, Ava Prieto

Honors Theses and Capstones

Inhibitory control, a central component of executive function, is the ability to suppress unwanted actions in response to a stimulus (Verbruggen et al., 2014; Verbruggen et al., 2019) and is one of the best indicators of executive task management as well as the ability to prevent unwanted prepotent responses. This capacity is essential for goal specific behavior and for responding flexibly to challenges. The present study examined the effects of voluntary wheel running on inhibitory control in two cohorts of Long-Evans rats using a rodent variant of the canonical stop-signal task. We found that rats with access to an active …

A Frog, A Toad, And A Salamander Walk Into A Forest: How Timber Harvest And Environmental Conditions Impact Amphibian Species Abundance In The White Mountain National Forest, William T. Brandenburg

Honors Theses and Capstones

Balancing the needs of humans and wildlife is one of the primary goals of conservation. Understanding how species respond to resource extraction is essential to achieve long-term population stability. This is especially relevant for amphibians, which are particularly sensitive to environmental disturbances due to habitat loss and degradation. As such they are often used as indicator species. This study leverages 20-years of amphibian abundance data from surveys in different silvicultural treatments to understand how American toads (Anaxyrus americanus), wood frogs (Lithobates sylvaticus), and red-backed salamanders (Plethodon cinereus) respond to changes in forest structure, weather, …

Effects Of Perching Behavior In Broilers On Welfare And Production Benefits, Natalie G. Bunn

Honors Theses and Capstones

Broiler chickens are bred for feed efficiency, rapid growth rate, and muscle development. Conventional broiler farms utilize fast-growing breeds that reach market weight rapidly and present welfare concerns. Primarily raised indoors with little enrichment, the genetics and husbandry practices of broilers encourage inactivity and perpetuate health problems such as skeletal deformities, lameness, and pododermatitis. Despite the commonness of these issues, there is little research on the reduction of such health complications through production management. This study investigated methods to promote perching behavior and the effects of riser perch and platform perch utilization in broilers. A mixed flock of slow-growing Gray …

Current And Historical Occurrences Of Rare Coastal Plants In The Hampton Falls Salt Marshes, Liliana T. Chirichella

Honors Theses and Capstones

A botanical survey of two sites in the Hampton Falls saltmarshes was conducted to document the occurrences of a list of eleven endangered and threatened coastal plants listed in the Natural Heritage Bureau’s NH Rare Plant List. This survey was conducted in fulfillment of the NH Native Plant Protection Act to highlight and identify target species in an area where restorative runneling is to be implemented in order to restore proper hydrology and prevent further expansion of mega-pools in the Little River and Depot Road salt marsh sites, which have been subject to historical ditching and are a part of …

Generating Concentrated Ring Polymers Through Supercoiled And Open Circle Pdna Isoform Separation, Kelsey E. Hodsdon

Honors Theses and Capstones

DNA can serve as a model polymer due to its high uniformity compared to synthetic polymers. Plasmid DNA (pDNA) in particular offers a well-defined, low-dispersity model for studying topologically uniform systems of a cyclic nature. pDNA has unique isoforms known as open circle (OC) and supercoiled (SC). Using fast protein liquid chromatography (FPLC), specifically anion exchange chromatography (AEX), these OC and SC isoforms can be separated in order to access their unique material properties. Our lab was able to yield the pure SC isoform. However, OC isoform separation has been more challenging. Various difficulties arose during this process, including imaging …

Fgf Signaling Is Necessary For Newt Lens Regeneration, Leo Alexander Napoleon

Honors Theses and Capstones

The Iberian ribbed newt Pleurodeles waltl can regenerate the lens by transdifferentiating iris pigmented epithelial (IPE) cells into lens epithelial cells (LECs), but the mechanism by which this occurs remains largely uncharacterized. We aim to mechanistically show an early and critical role for FGF signaling by using small molecules to inhibit FGF receptors and observe the histological and intracellular effects. Two inhibitors were found to completely stall lens regeneration. Cell cycle analysis revealed decreased DNA synthesis and uniformly low but unchanged entry to mitosis under signaling inhibition by staining for EdU incorporation and phospho-histone H3 (pH3), respectively. Western blot revealed …

Tmem116 Crispr-Mediated Knockout Prevents Proper Lens Regeneration In Iberian-Ribbed Newts, Damien T. Mann

Honors Theses and Capstones

Eye diseases like cataracts, age-related macular degeneration (AMD), and glaucoma are widespread and detrimental conditions affecting many people across the globe. While there are reliable and successful treatments for those with cataracts that can reverse vision impediments, others like glaucoma and AMD have limited treatment options. Additionally, eye damage resulting from these conditions is commonly irreversible, establishing a need for new treatment options. The Iberian-ribbed newt, Pleurodeles waltl, is a salamander species primarily studied for their amazing regenerative capabilities. Particularly, these newts are capable of de novo lens regeneration after a complete resection, providing a unique opportunity to study regeneration …

Effect Of Melatonin On Alleviating Chilling Injury In Cold-Stored ‘Kensington Pride’ Mangoes: A Comparative Evaluation Of Long Vs Short Dip Time, Mekhala Dinushi Kananke Vithana, Hafiz Muhammad Shoaib Shah, Mahmood Ul Hasan, Zora Singh

Research outputs 2022 to 2026

Mangoes (Mangifera indica L.) are notably susceptible to chilling injury (CI) when stored below 13 °C. This temperature threshold is too high for extended storage. Therefore, the influence of postharvest immersion in melatonin (MT) (50, 75, 100 µmol L^{− 1}) for 120 min on CI in ‘Kensington Pride’ mangoes kept at 5 ± 1 °C for 21 or 28 d was investigated. The most effective MT concentration was 75 µmol L^{− 1} causing 36.3% reduction in CI incidence compared to control. To facilitate adoptability in commercial practice, the influence of 120 min vs. 5- and 3-min immersions …

Miscellaneous Notes On Terrestrial Gastropods (Mollusca: Gastropoda) Of Seven Superfamilies Represented In Bhutan, With Two New Genera And Two New Species, Edmund Gittenberger, Sherub, Choki Gyeltshen, Nima Dorji, Kezang Tobgay

Research outputs 2022 to 2026

The species incorrectly referred to as Tropidophora spec. by Gittenberger et al. (2017, A field guide to the common molluscs of Bhutan: 42, fig. 27) is identified as Lagocheilus tomotrema (Benson, 1857). It is known from southern Bhutan, below 2000 m a.s.l. In fresh specimens the periostracum bears spiny or flattened, hitherto overlooked, stalked protrusions. Two species of Veronicellidae are reported as new for Bhutan. One of these was identified by a dna analysis as the pest species Laevicaulis alte. The second species could not be identified. Curvella sikkimensis is reported as new for Bhutan, where it was recorded in …

Detecting Habitat Use Of Three Endemic Freshwater Fish Of Far Southwestern Australia, Paige Rhiannon Wilson

Theses: Doctorates and Masters

The wetland ecosystems of far southwestern Australia face multiple threats including land clearing, historical cattle grazing, changed hydrology, extensive groundwater extraction, and changed fire regimes. Each is exacerbated by a drying climate, and together they provide a significant challenge to the on-going survival of the freshwater fish in this region particularly fish that are endemic, range restricted, and therefore, more likely to be more vulnerable. This study focuses on three such species: Galaxiella munda, Galaxiella nigrostriata and Lepidogalaxias salamandroides, the latter two of which are known to aestivate.

In order to make conservation decisions regarding management of wetlands for …

Case Report: Management Of A Challenging Case Presenting With Dysphagia After Thyroidectomy Requiring Administration Of Liquid 131i Via Mic-Key Low-Profile Tube—A Multidisciplinary Approach, Ahmed Ebada Salem, Sandra Ramirez, Brian R Weston, Akram Hussein, Simone Krebs

Faculty, Staff and Student Publications

Radioactive iodine (RAI) therapy with 131-iodine (131I) remains a cornerstone in the postoperative management of differentiated thyroid carcinoma (DTC). The standard route of administration is oral, typically in capsule form and less commonly as a liquid. However, in patients with severe dysphagia and compromised airway, traditional oral 131I delivery may be contraindicated due to the risk of aspiration and radioactivity contamination. These scenarios present unique clinical challenges that necessitate deviation from conventional protocols. While liquid 131I may be administered through the mouth or via nasogastric or percutaneous gastrostomy tubes, there is currently no standardized approach, and potential risks, such as …

Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz

Faculty, Staff and Student Publications

No abstract provided.

Integrative Multi-Omics Profiling Identifies Infiltrative Hepatocellular Carcinoma As An Immunotherapy-Resistant Subtype With Distinct Molecular Features, Won Suk Lee, Seonjeong Woo, Sung Hwan Lee, Gae Hoon Jo, Ilhwan Kim, Hyeyeong Kim, Chansik An, Sanghoon Jung, Gwangil Kim, Haeyoun Kang, Beodeul Kang, Jung Sun Kim, Ho Yeong Lim, Incheon Kang, Hannah Yang, So Jung Kong, Dahyeon Son, Dong Jun Shin, Woo Young Kwon, Da-Yeon Lee, Ju-Seog Lee, Junho Park, Youngsoo Kim, Sohyun Hwang, Chan Kim, Hong Jae Chon

Faculty, Staff and Student Publications

Background/aims: Hepatocellular carcinoma (HCC) exhibits substantial morphological and biological heterogeneity. Clinical and molecular relevance of the infiltrative subtype remains poorly defined in the context of cancer immunotherapy. We aimed to evaluate the prognostic impact and molecular features of infiltrative HCC in patients treated with first-line atezolizumab plus bevacizumab (Ate/Bev).

Methods: We included 307 patients with advanced HCC treated with Ate/Bev and classified them into four gross morphological types based on imaging. Multi-omics profiling was conducted on tumor samples. Type IV infiltrative signature was derived and externally validated using five independent HCC cohorts, including IMbrave150.

Results: Infiltrative morphology, encompassing pure and …

Evolving Molecular Subtypes Of Gastric Cancer: From Past Classifications To Present Consensus And Future Directions For Precision Therapy, Ju-Seog Lee

Faculty, Staff and Student Publications

Gastric cancer is a biologically heterogeneous disease. The advent of high-throughput multi-omic technologies has revolutionized our understanding of gastric cancer by deconstructing this heterogeneous entity into distinct and more homogeneous molecular subtypes. Early classifications based on gene expression, methylation, and histology have laid the groundwork for multi-omic frameworks proposed by The Cancer Genome Atlas and Asian Cancer Research Group, which established the foundation of modern molecular taxonomy. Subsequent integrative efforts, particularly the Consensus Genomic Subtypes (Super 6) model, have unified this collected information into clinically relevant subtypes that bridge prognostic stratification with treatment strategies. Established biomarkers such as human epidermal …

Bop2-Te: Bayesian Optimal Phase 2 Design For Jointly Monitoring Efficacy And Toxicity With Application To Dose Optimization, Kai Chen, Heng Zhou, J Jack Lee, Ying Yuan

Faculty, Staff and Student Publications

We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a Dirichlet-multinomial model to jointly model the distribution of toxicity and efficacy endpoints, making go/no-go decisions based on the posterior probability of toxicity and futility. In comparison to the original BOP2 and other existing designs, BOP2-TE offers the advantage of providing rigorous type I error control in cases where the treatment is toxic and futile, effective but toxic, or safe but futile, while optimizing …

A Combinatorial Approach To Synthetic Data Generation For Machine Learning, Krishna Khadka, Jaganmohan Chandrasekaran, Yu Lei, Raghu Kacker, D Richard Kuhn

Faculty, Staff and Student Publications

Datasets used in machine learning often contain sensitive information, including personally identifiable health and financial details. A common challenge faced by organizations and researchers is the risk of privacy breaches when using real-world data. Synthetic data can be used as an alternative to the real-world data. In existing synthetic data generation techniques, an encoder processes the real-world data to map it into a lower-dimensional latent space. Random sampling is then performed in this latent space. Subsequently, a decoder network is utilized to generate synthetic data from these sampled points in the latent space. Such approaches typically require generating a large …

Functional, Pharmacogenomic, And Immune Landscapes Of Long Non-Coding Rnas In Cancer, Runhao Wang, Mei Luo, Yuan Liu, Jingwen Yang, Yamei Chen, Chengxuan Chen, Lifei Ma, Stephanie Ding, James Wengler, Yong Zang, Bora Lim, Wenbo Li, Liuqing Yang, Chunru Lin, Lixia Diao, Leng Han

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) are emerging as key regulators in cancer, with significant potential as diagnostic, prognostic, and therapeutic targets. Here, this work systematically analyzes lncRNA associations with targeted therapies and immunotherapies across 33 cancer types using The Cancer Genome Atlas (TCGA) and real-world datasets. This work identifies 53,173 lncRNA-pathway associations, millions of lncRNA-drug response associations (via CancerRxTissue and VAEN), and extensive correlations with immune checkpoints and infiltration. This work further identifies 69 lncRNAs associated with immunotherapy response and 2,611 differentially expressed lncRNAs between low and high objective response rate (ORR) groups. Additionally, two lncRNAs are correlated with immune-related adverse …

Bop2-Comb: Bayesian Optimal Phase Ii Design For Optimizing Doses And Assessing Contribution Of Components In Drug Combinations, Xiaohan Chi, Ying Yuan, Ruitao Lin

Faculty, Staff and Student Publications

Background: Personalized cancer treatment using combination therapies offers substantial therapeutic benefits over single-agent treatments in most cancers. However, unmet clinical needs and increasing market competition pressure drug developers to quickly optimize combination doses and clearly demonstrate the contribution of each component when developing and evaluating new combination treatments.

Methods: We propose a Bayesian optimal phase II drug-combination (BOP2-Comb) design that optimizes the combination dose and evaluates the proof-of-concept as well as the contribution of each component in two seamless stages. Our optimal calibration scheme minimizes the total trial sample size while controlling incorrect decision rates at nominal levels. This calibration …

Peripheral Cd200r Signaling: A Critical Regulator Of Post-Stroke Inflammation In Aged Mice, Conelius Ngwa, Afzal Misrani, Yan Xu, Jingjing Wang, Rodney Ritzel, Fudong Liu

Faculty, Staff and Student Publications

The immune responses to ischemic stroke are subjected to endogenous inhibitory pathways that delimitate the post-stroke inflammation. Among them, the interaction between CD200 and its receptor (CD200R) is increasingly recognized for its role in regulating neuroinflammation across various central nervous system (CNS) disorders. In the present study, we have examined the role of central (brain) vs. peripheral CD200R signaling in acute ischemic stroke using aged bone marrow chimeric (BMC) mice (16-19 months old). These chimeras were generated by transplanting bone marrow from CD200R knockout (KO), green fluorescent protein (GFP), or wild-type (WT) donor mice into irradiated recipient mice, and then …

The Legacy Of A Gentleman Scientist: Pierre Hainaut, Christophe Arnoult, Laura D Attardi, Kerem Batsheva, Giovanni Blandino, Kathleen H Burns, Giannino Del Sal, David G Kirsch, David P Lane, Arnold J Levine, Guillermina Lozano, David Malkin, Gerry Melino, Moshe Oren, Carol Prives, Daniel Schramek

Faculty, Staff and Student Publications

No abstract provided.

Contemporary Opportunities And Potential Of Auger Electron-Emitting Theranostics, Seok-Yong Lee, H Charles Manning

Faculty, Staff and Student Publications

Recent breakthroughs in radiopharmaceutical (RP) therapy have emerged interest in employing Auger electron (AE)-emitting radionuclides as potential agents for precise theranostics. AE provides energy with exceptional localization due to their short tissue penetration range (TPR, < 10 nm), rendering them particularly effective for targeting nuclear DNA in tumor cells. In this context, AE-emitting radionuclide therapy (AE-emitting RLT) enables the targeted destruction of tumor cells while reducing harm to adjacent healthy tissue, a significant challenge in this field. Preclinical and early clinical investigations reveal the efficacy of AE-emitting RLTs in the theranostics of diverse malignancies, such as glioblastoma, prostate cancer, and neuroendocrine tumors. Notwithstanding these developments, challenges and limitations persist regarding dosimetry, delivery efficiency, and the treatment of radiotoxicity. A new paradigm is being developed to tackle the obstacles encountered by integrating molecular target markers (e.g., PARP) that function near the nucleus to improve the intranuclear delivery efficiency of AE-emitting radionuclides. Novel radiochemical methods such as these have facilitated the more stable and efficient labeling of biomolecules with AE-emitting radionuclides. Also, recent advances in DNA-molecular targeting, nanoparticles, nucleic acid/protein engineering, click- or bioorthogonal conjugation chemistry, and artificial intelligence (AI)-based structure modeling present concrete opportunities to overcome these limitations. Moreover, the integration of diagnostic imaging companion platforms employing theranostic radioisotope pairings facilitates real-time assessment of therapeutic efficacy and biodistribution, resulting in the formulation of enhanced treatment regimens. This review summarizes the prior development, recent advancements, barriers in clinical implementation, and future perspective of AE-emitting RLTs.

Nsd2 Inhibitors Rewire Chromatin To Treat Lung And Pancreatic Cancers, Jinho Jeong, Simone Hausmann, Hanyang Dong, Kacper Szczepski, Natasha M Flores, Andy Garcia Gonzalez, Liyang Shi, Xiaoyin Lu, Joanna Lempiäinen, Moritz Jakab, Liyong Zeng, Tourkian Chasan, Eric Bareke, Rui Dong, Emma Carlson, Reinnier Padilla, Dylan Husmann, Julia Thompson, Gerry A Shipman, Emily Zahn, Courtney A Barnes, Laiba F Khan, Liz Marie Albertorio-Sáez, Eva Brill, Vishnu Udayakumar Sunita Kumary, Matthew R Marunde, Danielle N Maryanski, Cheryl C Szany, Bryan J Venters, Carolina Lin Windham, Michal Eligiusz Nowakowski, Iwona Czaban, Mariusz Jaremko, Michael-Christopher Keogh, Kang Le, Michael J Soth, Benjamin A Garcia, Łukasz Jaremko, Jacek Majewski, Pawel K Mazur, Or Gozani

Faculty, Staff and Student Publications

NSD2 catalyses the epigenetic modification H3K36me2 (refs. 1,2) and is a candidate convergent downstream effector of oncogenic signalling in diverse malignancies3–5. However, it remains unclear whether the enzymatic activity of NSD2 is therapeutically targetable. Here we characterize a series of clinical-grade small-molecule catalytic NSD2 inhibitors (NSD2i) and show that the pharmacological targeting of NSD2 constitutes an epigenetic dependency with broad therapeutic efficacy in KRAS-driven preclinical cancer models. NSD2i inhibits NSD2 with single-digit nanomolar half-maximal inhibitory concentration potency and high selectivity over related methyltransferases. Structural analyses reveal that the specificity of NSD2i for NSD2 …

Respiratory Motion Effects And Plan Robustness For Lattice Radiation Therapy, Rachael M Martin-Paulpeter, Peter A Balter, Luis A Perles, Ethan B Ludmir, Joshua S Niedzielski

Faculty, Staff and Student Publications

Introduction: Lattice radiation therapy (LRT), a form of spatially fractionated radiation therapy (SFRT), has shown promise in treating bulky tumors. It consists of hot and cold spots within the tumor, and the ratio between these doses is thought to be important in clinical outcomes. Respiratory motion is expected to degrade these peak-to-valley dose ratios (PVDRs) but has largely been ignored in LRT literature and clinical practice. This work aims to quantify the response of LRT dose distributions to motion to better inform motion management decisions and improve clinical outcomes.

Methods: Respiratory motion of peak-to-peak amplitudes from 0.3 to 2 cm …

Freeze-Dried, Not Frozen: Lyophilized Mesenchymal Stromal Cell-Derived Extracellular Vesicles And Therapeutic Function In Neuroinflammatory Models, Janet R Ashley, Aidan M Collier, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Background: Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) offer a promising acellular therapy for immune modulation, but clinical translation is hindered by variability and storage constraints. Lyophilization (freeze-drying) could enable shelf-stable EV therapeutics, although its effects on biological activity remain incompletely defined.

Study design: We compared the immunomodulatory effects of frozen and lyophilized EVs from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) MSCs using lipopolysaccharide-stimulated rodent splenocytes and microglial models and human peripheral blood mononuclear cells (PBMCs). Variables included batch scale (small vs large), cytokine priming, and MSC source. Tumor necrosis factor alpha (TNF-α) secretion was measured …

Single-Cell Lineage Trajectory Defines Cyclin-Dependent Kinase Inhibitor-Sensitive Cells-Of-Origin In Esophageal Squamous Cell Carcinoma, Kyung-Pil Ko, Jie Zhang, Sohee Jun, Jae-Il Park

Faculty, Staff and Student Publications

Background and aims: Understanding the cells of origin is essential for overcoming therapy resistance and improving early intervention strategies in esophageal squamous cell carcinoma (ESCC). Despite recent advances in genomic profiling, the precise cellular hierarchies and molecular programs driving ESCC initiation remain poorly defined.

Methods: We utilized machine learning-based single-cell trajectory analysis on 4-nitroquinoline 1-oxide-induced murine models and genetically engineered organoids to identify cellular lineages during tumorigenesis. Combined with gene regulatory network analysis, we identified transcriptional drivers of tumor initiation and employed transcriptome-based drug repurposing to predict compounds targeting these initiating populations.

Results: Our analyses revealed multiple distinct epithelial clusters …

Key Regulatory Roles Of Prdm1 In Human Nk-Cell Differentiation And Activation, Xuxiang Liu, Yunfei Shi, Jibin Zhang, Kunal Shetty, Krystie Chew, Can Küçük, Qiang Gong, Esra Esmeray, Haiqing Li, Ru Chen, Sheng Pan, Katarzyna Dąbrowska, Roger E Moore, Krystine Garcia-Mansfield, Patrick Pirrotte, Jinhui Wang, Yuping Li, Gehong Dong, Logan Lee, Timothy W Mckeithan, Javeed Iqbal, Wing C Chan

Faculty, Staff and Student Publications

PRDM1, encoding a transcription factor (TF), regulates plasma cell and CD8+ T-cell terminal differentiation and Th2 lineage specification, while its role in human NK-cell differentiation and homeostasis is largely unknown. Here, we employed a multi-omics approach to dissect the transcriptional control of PRDM1 on human NK-cells. PRDM1 is important in NK-cell terminal differentiation based on gene expression profiling and its targeting of key regulators in the process. PRDM1-deleted NK-cells displayed a less mature phenotype simulating the CD56bright NK-cell population accompanied by upregulation of stem-like gene signatures. PRDM1-bound genes were enriched in T/NK-cell receptor signaling, activation, and NK-cell effector …