Genetics and Genomics Commons^™

Newborn Screening For X-Linked Adrenoleukodystrophy: Experiences, Perspectives, And Future Directions For Genetic Counseling, Sophia Salvatore

Theses and Dissertations

There is a notable lack of research regarding genetic counseling practices for infants with screen-positive results for X-linked adrenoleukodystrophy (X-ALD) via newborn screening (NBS). The exploratory study aimed to understand the experiences of genetic counselors providing follow-up care for these infants, assess the complexities associated with NBS for X-ALD, identify potential gaps in genetic counseling practices, and describe the subsequent impact on patient care. A mixed-methods approach was utilized, incorporating an initial survey and optional semi-structured interviews with practicing genetic counselors who had seen a minimum of five cases of infants with screen-positive results for X-ALD in the last two …

Differential Gene Coexpression In 16p11.2 Autism Spectrum Disorder, Joseph Patacsil

Senior Theses

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has been associated with several genetic factors. One of these factors is a mutation of the 16p11.2 region on chromosome 16, in which both deletions and duplications have been strongly associated with ASD. KCTD13 is a gene in the 16p11.2 gene locus that has recently been shown to influence brain development and is also associated with ASD. This study analyzes the differential gene expression and gene pathways of these different phenotypes. KCTD13 deletion had a significant up-regulation effect on genes and shares similar pathways to the 16p11.2 duplication mutation. Mutations in …

The Cellular Trafficking And Targeting Of Angiotensin-Converting-Enzyme-2 (Ace2) And Neutral-Amino-Acid-Transporter (B0at1) Variants: Implications For The Pathogenesis Of Associated Diseases And Therapy, Nesreen Fayyad Alkhofash

Dissertations

Angiotensin-converting enzyme 2 (ACE2) and the neutral amino acid transporter B0AT1, encoded by SLC6A19, are membrane proteins with pivotal roles in human physiology. ACE2 is involved in regulating blood pressure and serves as the cellular entry receptor for SARS-CoV-2, while B0AT1 facilitates amino acid absorption in the intestine. The interplay between ACE2 and B0AT1, particularly their physical interaction and co-expression in the intestine, underscores their relevance in both normal physiology and disease. Dysregulation of these proteins has been implicated in conditions such as hypertension, and Hartnup disease and they have been usurped by SARS-CoV-2 to cause COVID-19. Despite their …

Crispr-Induced Mutagenesis Of Arabidopsis Thaliana Gene Apetala3, Hazel Frans, Tara Phelps-Durr

SACAD: Scholarly Activities

This project aims to create CRISPR-CAS9 mutations in the APETELA3 (AP3) gene of the model plant Arabidopsis thaliana. AP3 is a class B gene critical to the petal and stamen development of Arabidopsis flowers. AP3 is defined in a MADS domain, which binds directly to DNA and may be responsible for the expression of the CaRG-box genes. AP3 works in conjunction with PISTILLATA (PI), AGAMOUS (AG), APETALA1 (AP1), and SEPALLATA (SEP) genes to specify the development in the second and third whorls of the flower. While several alleles of AP3 already exist, these alleles are strong alleles that knockout gene …

Aspen Health On National Forests In The Northern Rocky Mountain Region (2008/2009 To 2024), James T. Blodgett, Kurt K. Allen, Megan Wilson, Bradley Lalande

Aspen Bibliography

Quaking aspen (Populus tremuloides) is a widely distributed species in the western United States, but in the northern Rocky Mountain Region it is a rare forest component. In national forests (NF) of the northern Rocky Mountain Region this species comprises only 1% of the Bighorn, 3% of the Black Hills, and 1% of the Shoshone cover types (DeBlander 2002, Menlove 2008, Witt 2008). Since aspen forests provide increased species richness, support wildlife, are an important component of watersheds, and have aesthetic value, there are concerns regarding the health of this relatively rare forest cover type.

Studies On Cell Cycle Regulation And Ecm Modification During Tubular Organ Formation In Drosophila Embryos, Jeffrey Matthew

LSU Doctoral Dissertations

The formation of tubular organs—such as the heart and kidneys—is a complex developmental process that requires the precise coordination of tissue remodeling with dynamic changes in cellular behavior. Key processes including cell proliferation, apoptosis, and extracellular matrix (ECM) formation must be tightly synchronized with mechanisms that generate and transmit physical forces, transforming a flat epithelial sheet into a three-dimensional organ. Disruptions in the homeostasis of these processes during organogenesis can lead to congenital defects, such as pulmonary atresia and renal hypoplasia.

To investigate the mechanisms underlying epithelial morphogenesis, the Chung laboratory employs the Drosophila embryonic salivary gland (SG) as a …

Genomics Yields Biological And Phenotypic Insights Into Bipolar Disorder, Kevin S. O’Connell, Maria Koromina, Tracey Van Der Veen, Toni Boltz, Ney Alliey Rodriguez

School of Medicine Publications

Bipolar disorder is a leading contributor to the global burden of disease¹. Despite high heritability (60–80%), the majority of the underlying genetic determinants remain unknown². We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings³, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes …

A Study To Identify The Causal Rare Genetic Variants In Primary Open And Closed Angle Glaucoma, Pseudoexfoliation Syndrome, And Associated Glaucoma, Suganya K

Theses and Dissertations

BACKGROUND: Glaucoma is the second most common cause of blindness globally typically diagnosed with a triad of clinical symptoms of increased intraocular pressure (IOP) with associated optic disc, optic nerve head (ONH) changes, and visual field defects. Genetic and environmental factors are some of the strong aetiology factors for glaucoma and identification of these factors has a potential implication in the management of the disease and its outcome. There is a paradigm shift towards understanding the genetics of glaucoma, wherein the variants in the nuclear, mitochondrial genome and other regulatory regions are being identified as contributing risk factors.

METHODOLOGY AND …

Contrasting Effects Of Climate Warming On Hosts And Parasitoids: Insights From Rocky Mountain Aspen Leaf Miners And Their Parasitoids, Alisha A. Shah, Emily Hamant, Juan G. Rubalcaba, Beau Larkin, Andrew A. Forbes, H. Arthur Woods

Aspen Bibliography

Because temperature has pervasive effects on biological rates, climate warming may alter the outcomes of interactions between insect hosts and their parasitoids, which, for many host species, constitute the single largest source of mortality. Despite growing interest in parasitoid-host responses due to climate change, there are few empirical tests of thermal tolerance differences between non-model lepidopteran hosts and their parasitoids and almost none from mountain ecosystems where warming is occurring more rapidly. We examined the thermal ecology of a host–parasitoid interaction in the Rocky Mountains using the wild populations of the aspen leaf miner (Phyllocnistis populiella) and a …

Draft Genome Data Including Functional Annotation Of An Emerging Fungal Pathogen (Neodothiora Populina) Causing A Canker Disease Of Trembling Aspen In Interior Alaska, Ursel M. E. Schütte, Mace Wages, Aaron Buechlein, Jorda P. Kovash, Danielle C. Wrenn, Tereza Smrhova, Andrea Zubrova, Doug B. Rusch, Loretta M. Winton, Gerard C. Adams, Roger W. Ruess, Mary Beth Leigh, Devin M. Drown

Aspen Bibliography

Neodothiora populina is a black yeast-like fungus in the family Dothioraceae. It causes an aggressive canker disease of trembling aspen that results in widespread mortality of aspen across the boreal forest of Interior Alaska. Here we report a high-quality draft genome including functional annotation of this emerging fungal pathogen based on Oxford Nanopore Technologies long-read sequences. Our initial genome assembly totaled 23,960,169 bp and contained 18 contigs, and we identified 7,343 genes. This resource announcement provides new genomic data that are useful long term for improving our understanding of forest health in Alaska.

Morphological, Molecular, And Morphometric Analysis Of Aphelenchoides Besseyi On Organic Rice (Oryza Sativa) Seeds In The Beringin District, Deli Serdang Regency, Indonesia, Suswati Suswati, Azwana Azwana, Ifan Aulia Candra, Fitrianingrum Kuniawati, Khofifah Muhaimini Siregar, Asmaul Hasanah, Aldy Elvanandar Nasution

Makara Journal of Science

Aphelenchoides besseyi, a nematode, can infect rice resulting in the white shoot disease, which decreases the germina-tion rate and even causes seedling death. A. besseyi has recently been reported to mainly attack the organic rice varie-ties especially Pandanwangi and Ciherang in the Pasar Kawat, Beringin District, Deli Serdang, Indonesia. This research investigated A. besseyi via morphological, molecular, and morphometric approaches. The nematodes were observed in an area of 2000 m2, divided into five sample plots each with an area of 400 m2 on which Pandan Wangi and Ciherang rice were cultivated. Nematode morphology was observed using a stereo microscope at …

The Design, Construction, And Testing Of Mrna Vaccine Against Equine Herpes Virus, Bhawana Devkota

LSU Master's Theses

Equine Herpesvirus-1 (EHV 1) is a worldwide significant pathogen that causes respiratory illness, abortion, and neurological disorders in equine. Current vaccines, including live attenuated, inactivated, and subunit platforms, do not prevent viral latency, mucosal shedding, or cross-strain immunity, requiring alternative approaches. To address these gaps, this project explores the design, synthesis, and in vitro testing of an mRNA vaccine targeting immunogenic EHV 1 glycoprotein (gB, gC, gD, gG, and gM). Epitopes were computationally predicted using the Immune Epitope Database (IEDB), codon-optimized for Bos taurus, and cloned into pUCIDT vectors using SP6/T7 promoters. In vitro transcription (IVT) used nucleotide modifications …

What Single-Cell Rna Sequencing Taught Us About Mgmt Expression In Glioblastoma, Iyad Alnahhas, Mehak Majid Khan, Wenyin Shi

Department of Neurology Faculty Papers

Background.

The promoter methylation status of O-6-methylguanine-DNA methyltransferase (MGMTp) is an important prognostic marker in GBM. Previous studies showed that the expression of MGMT based on immunohistochemistry did not correlate with survival. This is partly because nontumor cells express MGMT. Single-cell sequencing assesses gene expression in tumor cells specifically.

Methods.

We used publicly available data from 3 recent single-cell/nucleus sequencing GBM studies that included MGMTp methylation status data for patients to evaluate MGMT expression at the single-cell level.

Results.

In the CPTAC study, a median of 0.82% and 5.7% of tumor cells expressed MGMT in the …

Rare Damaging Ccr2 Variants Are Associated With Lower Lifetime Cardiovascular Risk, Marios K. Georgakis, Rainer Malik, Omar El Bounkari, Natalie R. Hasbani, Jiang Li, Jennifer E. Huffman, Gabrielle Shakt, Michael C. Mahaney, Joanne E. Curran, John Blangero

School of Medicine Publications

Background

Previous work has shown a role of CCL2, a key chemokine governing monocyte trafficking, in atherosclerosis. However, it remains unknown whether targeting CCR2, the cognate receptor of CCL2, provides protection against human atherosclerotic cardiovascular disease.

Methods

Computationally predicted damaging or loss-of-function (REVEL > 0.5) variants within CCR2 were detected in whole-exome-sequencing data from 454,775 UK Biobank participants and tested for association with cardiovascular endpoints in gene-burden tests. Given the key role of CCR2 in monocyte mobilization, variants associated with lower monocyte count were prioritized for experimental validation. The response to CCL2 of human cells transfected with these variants was tested …

Bryce Canyon Aspen: Recent Trends, Future Actions, Paul C. Rogers

Aspen Bibliography

In cooperation with Bryce Canyon National Park, we undertook a survey of quaking aspen (Populus tremuloides Michx.) conditions throughout the Park with the intention of better understanding conditions and prescribing corrective measures where needed. There are clear disparities within the Park between sustainable aspen conditions and failing stands. Based on condition of mature trees, but most importantly regeneration and recruitment of juvenile stems, most aspen forests within Bryce Canyon are in poor condition. Aspen recruitment—generally sapling-sized trees that have survived browsing ungulates—is the most important metric of future stand resilience and here we found 83% of all aspen sample …

Exploring Religious Leaders’ Perspectives On Genetic Counseling, Testing, And Related Technologies, Kristina M. Wittenburg

USF Tampa Graduate Theses and Dissertations

Religion significantly influences healthcare decisions, including those related to genetic testing, by shaping ethical and emotional considerations. While some religious groups provide formal stances on genetic testing, others lack clear guidelines, leaving both patients and healthcare providers without consistent resources for navigating faith-informed decisions. Understanding religious leaders’ perspectives is critical to bridging this gap and supporting diverse patient needs. This study aimed to examine religious leaders’ perspectives on genetic testing, genetic counseling, in vitro fertilization (IVF), gene therapy, stem cell research, and abortion. These topics were explored to understand the role of religious beliefs in healthcare decisions, and to develop …

Identifying Racial Disparities In Patient Activation Outcomes In Genetic Counseling Sessions, Moriah M. Melhado

USF Tampa Graduate Theses and Dissertations

Patient empowerment and activation are critical determinants of health outcomes, fostering patients’ confidence, knowledge, and engagement in their care. While the influence of race and ethnicity on patient activation has been extensively studied with other healthcare providers such as physicians and nurses, limited research has explored this dynamic within genetic counseling (GC). This study combines a systematic literature review, following PRISMA guidelines, a secondary data analysis , and an exploratory qualitative analysis of patient interviews post-session to examine relationships between race, ethnicity, and patient activation or empowerment in GC. Search terms identified 536 peer-reviewed articles, of which 44 met inclusion …

Genetic Counseling Student Anxiety, Self-Efficacy, And Study Strategy Use For The Genetic Counseling Board Certification Exam., Teagan E. Nunnery

USF Tampa Graduate Theses and Dissertations

With a 76% pass rate for the 2024 American Board of Genetic Counseling (ABGC) certification exam, it's crucial to evaluate the study strategies used by candidates and their alignment with evidence-based practices. This study surveyed 84 genetic counseling students and graduates from 35 U.S. and Canadian training programs, focusing on demographic data, study strategy usage, anxiety, and self-efficacy. Study strategies were categorized into one of three groups: 1) active strategies, which promote recall and understanding, 2) passive strategies, and 3) hybrid, for strategies that involve both active and passive engagement as well as three metacognitive strategies: regulating learning, monitoring learning, …

Evaluating And Improving The Serious Game Life With Hereditary Cancer, Jenna K. Peterson

USF Tampa Graduate Theses and Dissertations

Hereditary cancer syndromes increase cancer risks for individuals with pathogenic variants and their family members, yet many at-risk individuals do not pursue genetic testing due to barriers in family communication. Serious games—interactive tools designed to educate through gameplay—offer a promising approach to addressing these barriers by engaging users and creating supportive learning environments. LIFE with Hereditary Cancer is a serious game designed to improve genetic literacy, promote informed decision-making, and encourage family conversations about hereditary cancer risks and genetic testing. This evaluation used a mixed-methods approach to assess participant emotions, perceptions, and experiences with LIFE with Hereditary Cancer and identify …

Cloning And Expression Of Scamp3 In Escherichia Coli Bl21(De3) With In Silico Sequence-Based Cancer Epitopes Prediction, Selly Setiati Rajagukguk, Sabar Pambudi, Astari Dwiranti, Doddy Irawan Setyo Utomo, Anom Bowolaksono

Makara Journal of Science

Secretory carrier membrane protein 3 (SCAMP3) is a crucial membrane protein involved in intracellular vesicle traffick-ing and exocytosis. The SCAMP3 expression has been observed in diverse cancer types, such as melanoma, glioma, hepatocellular and breast cancer. Increased SCAMP3 expression has been reported in certain cancer cells relative to that in normal cells, suggesting the potential role of SCAMP3 in cancer development or progression. In this study, we successfully cloned and expressed SCAMP3 in Escherichia coli strain BL21(DE3). SCAMP3 was amplified and insert-ed directionally into the prokaryotic expression vector pET21d(+). The transformation of recombinant plasmid into E. coli BL21(DE3) cells were …

Screening For Penicillin G Acylase (Pga)-Producing Bacteria And Gene Cloning Using Degenerate Oligonucleotide Primed-Pcr, Masdalifah Masdalifah, Sri Rezeki Wulandari, Gabriela Christy Sabbathini, Maria Ulfah, Dini Achnafani, Ahmad Wibisana, Feronika Heppy Sriherfyna, Is Helianti, Niknik Nurhayati

Makara Journal of Science

The growing concern over antibiotic resistance has driven global efforts to explore innovative solutions, including the use of Penicillin G acylase (PGA) to produce semisynthetic β-lactam antibiotics. This study screened four potential in-tracellular PGA-producing bacteria: Alcaligenes faecalis InaCC B444 (AfPGA), Kluyvera cryocrescens InaCC B850 (KcPGA), Providencia rettgeri InaCC B25 (Pr25PGA), and P. rettgeri InaCC B466 (Pr466PGA). Penicillin G Acylase encoding genes (pgas) were isolated from them using a Degenerate Oligonucleotide Primed-PCR (DOP-PCR) approach and sequenced. Microbiological assays confirmed all tested crude extracts to exhibit inhibitory effects. Penicillin G was used for evaluating hydrolytic activity and 6-Amino Penicillanic Acid (6-APA) coupled …

5-Hydroxymethylcytosine Sequencing Of Plasma Cell-Free Dna Identifies Epigenomic Features In Prostate Cancer Patients Receiving Androgen Deprivation Therapies, Qianxia Li, Chiang-Ching Huang, Shane Huang, Yijun Tian, Jinyong Huang, Amirreza Bitaraf, Xiaowei Dong, Marja T. Nevalainen, Manishkumar Patel, Jodie Wong, Jingsong Zhang, Brandon J Manley, Jong Y. Park, Manish Kohli, Elizabeth M. Gore, Deepak Kilari, Liang Wang

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: We evaluated whether 5hmC signatures in cell-free DNA (cfDNA) are associated with treatment failure to androgen-deprivation therapies (ADT) among men with hormone-naive prostate cancer.

METHODS: We collected a total of 139 serial plasma samples from 55 prostate cancer patients receiving ADT at 3 time points including baseline (before initiating ADT, n = 55); 3 months (after initiating ADT, n = 55); and disease progression (n = 15) within 24 months or 24 months if no progression was detected (n = 14). We used selective chemical labeling sequencing to quantify 5hmC abundance across the genome and Kaplan-Meier analysis to assess …

Emerging Technologies For Forensic Genetic Identification, Lilly Llanos

Senior Honors Theses

There are many new innovations in forensic science that are being developed for the identification of biological evidence. These techniques include next-generation DNA sequencing, DNA phenotyping, and forensic genetic genealogy. This thesis will explore each, as well as newer applications of proteomics. The methodologies, reliability, practicality of cost and training, moral implications, and past research of each will be discussed. Finally, some ideas for future research and steps to drive growth and greater understanding will be suggested. This will encourage further innovations and the increased acceptance of forensic evidence in court. Each method was found to have both advantages and …

Epigenetic Landscapes Of Aging In Breast Cancer Survivors: Unraveling The Impact Of Therapeutic Interventions-A Scoping Review, Nikita Nikita, Zhengyang Sun, Swapnil Sharma, Amy L Shaver, Victoria Seewaldt, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Breast cancer therapies have dramatically improved survival rates, but their long-term effects, especially on aging survivors, need careful consideration. This review delves into how breast cancer treatments and aging intersect, focusing on the epigenetic changes triggered by chemotherapy, radiation, hormonal treatments, and targeted therapies. Treatments can speed up biological aging by altering DNA methylation, histone modifications, and chromatin remodeling, affecting gene expression without changing the DNA sequence itself. The review explains the double-edged sword effect of therapy-induced epigenetic modifications, which help fight cancer but also accelerate aging. Chemotherapy and targeted therapies, in particular, impact DNA methylation and histone modifications, promoting …

Cargo Hitchhiking Autophagy - A Hybrid Autophagy Pathway Utilized In Yeast, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Macroautophagy is a catabolic process that maintains cellular homeostasis by recycling intracellular material through the use of double-membrane vesicles called autophagosomes. In turn, autophagosomes fuse with vacuoles (in yeast and plants) or lysosomes (in metazoans), where resident hydrolases degrade the cargo. Given the conservation of autophagy,

Morphological Characterization, Pollen Viability, And Germinability Evaluation Of Two Plumeria Species In The University Of The Philippines Los Baños, Darel Kenth S. Antesco, Maria Charito E. Balladares, Alangelico O. San Pascual, Pablito M. Magdalita, Fernando C. Sanchez Jr

The Philippine Agricultural Scientist

The genus Plumeria, locally known as kalachuci, is a popular ornamental tree belonging to the Apocynaceae family. The University of the Philippines Los Baños (UPLB) maintains a collection of Plumeria trees scattered across its campus; however, the origin of these trees remains unclear due to a lack of proper documentation. This study conducted morphological characterization and pollen analysis to provide information for further research. Results revealed the presence of 2 Plumeria species in the campus. P. obtusa has a linear leaf shape with acute tips and revolute margins while P. rubra has a lanceolate leaf shape. Additionally, P. …

Sequencing In Over 50,000 Cases Identifies Coding And Structural Variation Underlying Atrial Fibrillation Risk, Seung Hoan Choi, Sean J. Jurgens, Ling Xiao, Matthew C. Hill, John Blangero, Joanne E. Curran, Ravi Duggirala, Harald Hh Goring, Michael Mahaney, Juan M. Peralta

School of Medicine Publications

Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component. Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls. In burden tests of rare coding variation, we identified novel associations between AF and the genes MYBPC3, LMNA, PKP2, FAM189A2 and KDM5B. We further identified associations between AF and rare structural variants owing to deletions in CTNNA3 and duplications of GATA4. We broadly replicated our findings in independent samples from MyCode, deCODE and UK Biobank. Finally, we found …

Lagging Brain Gene Expression Patterns Of Drosophila Melanogaster Young Adult Males Confound Comparisons Between Sexes, Flannery Mclamb, Zuying Feng, Jeanne P. Vu, Lindsey Griffin, Miguel F. Vasquez, Goran Bozinovic

Center for Life in Extreme Environments Publications

Many species, including fruit flies (Drosophila melanogaster), are sexually dimorphic. Phenotypic variation in morphology, physiology, and behavior can affect development, reproduction, health, and aging. Therefore, designating sex as a variable and sex-blocking should be considered when designing experiments. The brain regulates phenotypes throughout the lifespan by balancing survival and reproduction, and sex-specific development at each life stage is likely. Changes in morphology and physiology are governed by differential gene expression, a quantifiable molecular marker for age- and sex-specific variations. We assessed the fruit fly brain transcriptome at three adult ages for gene expression signatures of sex, age, and sex-by-age: 6698 …

Antibiotic Resistome, Mobile Genetic Elements, And Virulence Profile Of Multidrug-Resistant Enterobacteriaceae Isolated From Healthy Philippine Native Chicken As Revealed By Analysis Of Whole Genome Sequence, Alvin P. Jimenez, Grignard James R. Buday, Rina B. Opulencia

The Philippine Agricultural Scientist

Gram-negative bacteria, particularly Enterobacteriaceae, acquire antibiotic resistance via horizontal transmission of resistance genes in poultry farms that give rise to multidrug-resistant (MDR) strains. The presence of MDR strains that are potentially pathogenic and zoonotic poses a concern to animal and human health. The aims of this study were to isolate MDR, potentially pathogenic Enterobacteriaceae from Philippine native chicken (PNC) and to analyze the genome of a representative MDR isolate to gain insights into the mechanisms, acquisition, and transmissibility of antibiotic resistance genes (ARGs). Cloacal swabs from PNC were used to isolate putative Salmonella that were then tested for antimicrobial …

Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the INSR gene in human LX2 HSC cells (INSRe5- 8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The INSRe5- 8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble …