Medicine and Health Sciences Commons^™

Tumor Immune Contexture Is A Determinant Of Anti-Cd19 Car T Cell Efficacy In Large B Cell Lymphoma, Nathalie Scholler, Armin Ghobadi, Et Al

2020-Current year OA Pubs

No abstract provided.

The Secreted Protein Cowpox Virus 14 Contributes To Viral Virulence And Immune Evasion By Engaging Fc-Gamma-Receptors, Ravi F. Iyer, David M. Edwards, Philipp Kolb, Hans-Peter Raué, Chris A. Nelson, Megan L. Epperson, Mark K. Slifka, Jeffrey C. Nolz, Hartmut Hengel, Daved H. Fremont, Klaus Früh

2020-Current year OA Pubs

The genome of cowpoxvirus (CPXV) could be considered prototypical for orthopoxviridae (OXPV) since it contains many open reading frames (ORFs) absent or lost in other OPXV, including vaccinia virus (VACV). These additional ORFs are non-essential for growth in vitro but are expected to contribute to the broad host range, virulence and immune evasion characteristics of CPXV. For instance, unlike VACV, CPXV encodes proteins that interfere with T cell stimulation, either directly or by preventing antigen presentation or co-stimulation. When studying the priming of naïve T cells, we discovered that CPXV, but not VACV, encodes a secreted factor that interferes with …

Gapdh Mediates Drug Resistance And Metabolism In Plasmodium Falciparum Malaria Parasites, Andrew J. Jezewski, Ann M. Guggisberg, Dana M. Hodge, Naomi Ghebremichael, Gavin Nicholas John, Lisa K. Mclellan, Audrey Ragan Odom John

2020-Current year OA Pubs

Efforts to control the global malaria health crisis are undermined by antimalarial resistance. Identifying mechanisms of resistance will uncover the underlying biology of the Plasmodium falciparum malaria parasites that allow evasion of our most promising therapeutics and may reveal new drug targets. We utilized fosmidomycin (FSM) as a chemical inhibitor of plastidial isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway. We have thus identified an unusual metabolic regulation scheme in the malaria parasite through the essential glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Two parallel genetic screens converged on independent but functionally analogous resistance alleles in GAPDH. Metabolic profiling of FSM-resistant …

Sleep-Promoting Neurons Remodel Their Response Properties To Calibrate Sleep Drive With Environmental Demands, Stephane Dissel, Markus K. Klose, Bruno Van Swinderen, Lijuan Cao, Melanie Ford, Erica M. Periandri, Joseph D. Jones, Zhaoyi Li, Paul J. Shaw

2020-Current year OA Pubs

Falling asleep at the wrong time can place an individual at risk of immediate physical harm. However, not sleeping degrades cognition and adaptive behavior. To understand how animals match sleep need with environmental demands, we used live-brain imaging to examine the physiological response properties of the dorsal fan-shaped body (dFB) following interventions that modify sleep (sleep deprivation, starvation, time-restricted feeding, memory consolidation) in Drosophila. We report that dFB neurons change their physiological response-properties to dopamine (DA) and allatostatin-A (AstA) in response to different types of waking. That is, dFB neurons are not simply passive components of a hard-wired circuit. Rather, …

First-In-Human Phase I/Ii Iconic Trial Of The Icos Agonist Vopratelimab Alone And With Nivolumab: Icos-High Cd4 T-Cell Populations And Predictors Of Response, Timothy A Yap, Russell K Pachynski, Haeseong Park, Et Al

2020-Current year OA Pubs

PURPOSE: The first-in-human phase I/II ICONIC trial evaluated an investigational inducible costimulator (ICOS) agonist, vopratelimab, alone and in combination with nivolumab in patients with advanced solid tumors.

PATIENTS AND METHODS: In phase I, patients were treated with escalating doses of intravenous vopratelimab alone or with nivolumab. Primary objectives were safety, tolerability, MTD, and recommended phase II dose (RP2D). Phase II enriched for ICOS-positive (ICOS+) tumors; patients were treated with vopratelimab at the monotherapy RP2D alone or with nivolumab. Pharmacokinetics, pharmacodynamics, and predictive biomarkers of response to vopratelimab were assessed.

RESULTS: ICONIC enrolled 201 patients. Vopratelimab alone and with nivolumab was …

Risk Factors And Medical Resource Utilization In Us Adults Hospitalized With Influenza Or Respiratory Syncytial Virus In The Hospitalized Acute Respiratory Tract Infection Study, Jessica Hartnett, Prina Donga, Gabriela Ispas, Yannick Vandendijck, David Anderson, Stacey House, Selim Suner

2020-Current year OA Pubs

BACKGROUND: Influenza and respiratory syncytial virus (RSV) are associated with substantial morbidity and mortality in the United States. We assessed risk factors for severe disease and medical resource utilization (MRU) among US adults hospitalized with influenza or RSV in the Hospitalized Acute Respiratory Tract Infection (HARTI) study.

METHODS: HARTI was a prospective global (40 centers, 12 countries) epidemiological study of adults hospitalized with acute respiratory tract infections conducted across the 2017-2019 epidemic seasons. Patients with confirmed influenza or RSV were followed up to 3 months post-discharge. Baseline characteristics, prevalence of core risk factors (CRFs) for severe disease (age ≥65 years, …

Does Social Intolerance Vary According To Cognitive Styles, Genetic Cognitive Capacity, Or Education?, Aino Saarinen, Liisa Keltikangas-Järvinen, Henrik Dobewall, C Robert Cloninger, Ari Ahola-Olli, Terho Lehtimäki, Nina Hutri-Kähönen, Olli Raitakari, Suvi Rovio, Niklas Ravaja

2020-Current year OA Pubs

BACKGROUND: Low education, low cognitive abilities, and certain cognitive styles are suggested to predispose to social intolerance and prejudices. Evidence is, however, restricted by comparatively small samples, neglect of confounding variables and genetic factors, and a narrow focus on a single sort of prejudice. We investigated the relationships of education, polygenic cognitive potential, cognitive performance, and cognitive styles with social intolerance in adulthood over a 15-year follow-up.

METHODS: We used data from the prospective population-based Young Finns Study (n = 960-1679). Social intolerance was evaluated with the Social Intolerance Scale in 1997, 2001, and 2011; cognitive performance with the Cambridge …

Exposure Contrasts Of Pregnant Women During The Household Air Pollution Intervention Network Randomized Controlled Trial, Michael Johnson, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure to

OBJECTIVES: This paper reports exposure reductions achieved by a liquified petroleum gas (LPG) stove and fuel intervention for pregnant mothers in the Household Air Pollution Intervention Network (HAPIN) randomized controlled trial.

METHODS: The HAPIN trial included 3,195 households primarily using biomass for cooking in Guatemala, India, Peru, and Rwanda. Twenty-four-hour exposures to

RESULTS: Median postrandomization exposures of particulate matter (PM) with aerodynamic diameter

DISCUSSION: Postintervention

Association Of Male Hypogonadism With Risk Of Hospitalization For Covid-19, Sandeep Dhindsa, Cosette Champion, Ekamjit Deol, Matthew Lui, Robert Campbell, Jennifer Newman, Aparna Yeggalam, Srikanth Nadella, Vaishaliben Ahir, Ekta Shrestha, Thomas Kannampallil, Abhinav Diwan

2020-Current year OA Pubs

Importance: Male sex is associated with severe COVID-19. It is not known whether the risk of hospitalization differs between men with hypogonadism, men with eugonadism, and those receiving testosterone therapy (TTh).

Objective: To compare COVID-19 hospitalization rates for men with hypogonadism who were not receiving TTh, men with eugonadism, and men receiving TTh.

Design, Setting, and Participants: This cohort study was conducted in 2 large academic health systems in St Louis, Missouri, among 723 men with a history of COVID-19 who had testosterone concentrations measured between January 1, 2017, and December 31, 2021.

Exposures: The primary exposure was gonadal status …

Consensus-Based Recommendations On Priority Activities To Address Acute Kidney Injury In Children: A Modified Delphi Consensus Statement, Stuart L Goldstein, Tara M Neumayr, Et Al.

2020-Current year OA Pubs

Importance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge.

Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy.

Evidence Review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and …

Coronavirus Disease 2019 (Covid-19) Vaccination Preparedness Policies In Us Hospitals, Susan E Beekmann, Hilary M Babcock, Mark S Rasnake, Thomas R Talbot, Philip M Polgreen

2020-Current year OA Pubs

We surveyed infectious disease specialists about early coronavirus disease 2019 (COVID-19) vaccination preparedness. Almost all responding institutions rated their facility's preparedness plan as either excellent or adequate. Vaccine hesitancy and concern about adverse reactions were the most commonly anticipated barriers to COVID-19 vaccination. Only 60% believed that COVID-19 vaccination should be mandatory.

Systemic Perturbations Of The Kynurenine Pathway Precede Progression To Dementia Independently Of Amyloid-Β, Marcela Cespedes, Kelly R. Jacobs, Paul Maruff, Alan Rembach, Christopher J. Fowler, Brett Trounson, Kelly K. Pertile, Rebecca L. Rumble, Stephanie R. Rainey-Smith, Christopher C. Rowe, Victor L. Villemagne, Pierrick Bourgeat, Chai K. Lim, Pratishtha Chatterjee, Ralph N. Martins, Arne Ittner, Colin L. Masters, James D. Doecke, Gilles J. Guillemin, David B. Lovejoy

Research outputs 2022 to 2026

Increasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild …

Abdominal Aortic Calcification On Lateral Spine Images Captured During Bone Density Testing And Late-Life Dementia Risk In Older Women: A Prospective Cohort Study, Tenielle Porter, Marc Sim, Richard L. Prince, John T. Schousboe, Catherine Bondonno, Wai H. Lim, Kun Zhu, Douglas P. Kiel, Jonathan M. Hodgson, Simon M. Laws, Joshua R. Lewis

Research outputs 2022 to 2026

Background: Dementia after the age of 80 years (late-life) is increasingly common due to vascular and non-vascular risk factors. Identifying individuals at higher risk of late-life dementia remains a global priority. Methods: In prospective study of 958 ambulant community-dwelling older women ( ≥ 70 years), lateral spine images (LSI) captured in 1998 (baseline) from a bone density machine were used to assess abdominal aortic calcification (AAC). AAC was classified into established categories (low, moderate and extensive). Cardiovascular risk factors and apolipoprotein E (APOE) genotyping were evaluated. Incident 14.5-year late-life dementia was identified from linked hospital and mortality records. Findings: At …

Moderate Increase Of Serum Uric Acid Within A Normal Range Is Associated With Improved Cognitive Function In A Non-Normotensive Population: A Nationally Representative Cohort Study, Jinqi Wang, Rui Jin, Zhiyuan Wu, Yueruijing Liu, Xiaohan Jin, Ze Han, Yue Liu, Zongkai Xu, Xiuhua Guo, Lixin Tao

Research outputs 2022 to 2026

Background: Associations between serum uric acid (SUA) and changes in cognitive function are understudied in non-normotensive populations, and many previous studies only considered the baseline SUA at a single time point. We aimed to examine the effects of baseline SUA and 4-year changes in SUA on cognitive changes in the non-normotensive population. Materials and methods : In the China Health and Retirement Longitudinal Study (CHARLS), cognitive function was measured based on executive function and episodic memory in four visits (years: 2011, 2013, 2015, and 2018). We identified two study cohorts from CHARLS. The first cohort included 3,905 non-normotensive participants. Group-based …

Pharmacophore Modeling For Biological Targets With High Flexibility: Lxrβ Case Study, Sophia Kchouk, Lamees Hegazy

2020-Current year OA Pubs

No abstract provided.

Safety Experience With Continued Exposure To Ofatumumab In Patients With Relapsing Forms Of Multiple Sclerosis For Up To 3.5 Years, Stephen L Hauser, Anne H Cross, Kevin Winthrop, Heinz Wiendl, Jacqueline Nicholas, Sven G Meuth, Paul S Giacomini, Francesco Saccà, Linda Mancione, Ronald Zielman, Morten Bagger, Ayan Das Gupta, Dieter A Häring, Valentine Jehl, Bernd C Kieseier, Ratnakar Pingili, Dee Stoneman, Wendy Su, Roman Willi, Ludwig Kappos

2020-Current year OA Pubs

BACKGROUND: Ofatumumab is approved for the treatment of relapsing multiple sclerosis (RMS). Ongoing safety reporting is crucial to understand its long-term benefit-risk profile.

OBJECTIVE: Report the safety and tolerability of ofatumumab in RMS after extended treatment up to 3.5 years.

METHODS: Patients completing ASCLEPIOS I/II (phase 3), APLIOS, or APOLITOS (phase 2) trials could enter ALITHIOS, a phase 3b, open-label, long-term safety study. We analyzed cumulative data of continuous ofatumumab treatment and of patients newly switched from teriflunomide.

RESULTS: The safety population had 1969 patients: 1292 continuously treated with ofatumumab (median time-at-risk 35.5 months, 3253 patient-years) and 677 newly switched …

Precision Requirements And Data Compression In Cryoem/Cryoet, Adam C Fluty, Steven J Ludtke

Faculty, Staff and Students Publications

With larger, higher speed detectors and improved automation, individual CryoEM instruments are capable of producing a prodigious amount of data each day, which must then be stored, processed and archived. While it has become routine to use lossless compression on raw counting-mode movies, the averages which result after correcting these movies no longer compress well. These averages could be considered sufficient for long term archival, yet they are conventionally stored with 32 bits of precision, despite high noise levels. Derived images are similarly stored with excess precision, providing an opportunity to decrease project sizes and improve processing speed. We present …

Updated Diagnostic Criteria And Nomenclature For Neurofibromatosis Type 2 And Schwannomatosis: An International Consensus Recommendation, Scott R Plotkin, David H Gutmann, Et Al.

2020-Current year OA Pubs

PURPOSE: Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are genetically distinct tumor predisposition syndromes with overlapping phenotypes. We sought to update the diagnostic criteria for NF2 and SWN by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging.

METHODS: We used a multistep process, beginning with a Delphi method involving global disease experts and subsequently involving non-neurofibromatosis clinical experts, patients, and foundations/patient advocacy groups.

RESULTS: We reached consensus on the minimal clinical and genetic criteria for diagnosing NF2 and SWN. These criteria incorporate mosaic forms of these conditions. In addition, we recommend updated nomenclature for these disorders to emphasize their …

Perspectives Of Participation In Daily Life From Cancer Survivors: A Qualitative Analysis, Allison J L'Hotta, Nirmala Shivakumar, Kathleen D Lyons, Audrey Trebelhorn, Annamayil Manohar, Allison A King

2020-Current year OA Pubs

OBJECTIVE: To characterize how survivors of cancer define participation.

DESIGN: Cross-sectional qualitative study.

SETTING: Participants were enrolled from a large academic medical center in the Midwestern United States. Interviews were conducted over Zoom or phone.

PARTICIPANTS: Survivors of cancer (N=40) with brain, breast, colorectal, or lung cancer (n=10 per group). Participants were purposively sampled to maximize variation in the study sample. Participant ages ranged from 26-83 years, with a mean age of 55 years. Seventy percent of participants were receiving active cancer treatment at the time of the interview.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Participant perspectives gathered from 1-on-1 …

Living With Cervical Spinal Cord Injury During The Covid-19 Pandemic: A Qualitative Study, Elspeth J R Hill, Allison J L'Hotta, Carie R Kennedy, Aimee S James, Ida K Fox

2020-Current year OA Pubs

OBJECTIVE: To understand how COVID-19 has affected the daily lives of people living with cervical spinal cord injury (SCI).

DESIGN: Cross sectional qualitative study.

SETTING: Academic medical center in the Midwestern United States.

PARTICIPANTS: Ten community-dwelling individuals (8 men, 2 women), average 11.6 years post-mid-cervical level SCI (N=10).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Semistructured interviews were completed by phone. The research team used thematic analysis and inductive strategies to analyze the data in this exploratory investigation.

RESULTS: People with cervical SCI living in the United States during the spring of 2020 experienced changes to their daily lives. Participants described …

Outcomes For Endoscopic Submucosal Dissection Of Pathologically Staged T1b Esophageal Cancer: A Multicenter Study, Abel Joseph, Peter V Draganov, Fauze Maluf-Filho, Hiroyuki Aihara, Norio Fukami, Neil R Sharma, Amitabh Chak, Dennis Yang, Salmaan Jawaid, John Dumot, Omar Alaber, Tiffany Chua, Rituraj Singh, Lady Katherine Mejia-Perez, Ruishen Lyu, Xuefeng Zhang, Suneel Kamath, Sunguk Jang, Sudish Murthy, John Vargo, Amit Bhatt

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) for T1b esophageal cancer (EC) and its recurrence rates remain unclear in the West. Using a multicenter cohort, we evaluated technical outcomes and recurrence rates of ESD in the treatment of pathologically staged T1b EC.

METHODS: We included patients who underwent ESD of T1b EC at 7 academic tertiary referral centers in the United States (n = 6) and Brazil (n = 1). We analyzed demographic, procedural, and histopathologic characteristics and follow-up data. Time-to-event analysis was performed to evaluate recurrence rates.

RESULTS: Sixty-six patients with pathologically staged T1b EC after …

Characterizing The Serum Resistance Function Of Plasmid-Encoded Virulence Factor Trat, Chaehee Lim

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Did Medicaid Expansion Close African American-White Health Care Disparities Nationwide? A Scoping Review, Lonnie R. Snowden, Genevieve Graaf, Latocia Keyes, Katherine Kitchens, Amanda Ryan, Neal Wallace

OHSU-PSU School of Public Health Faculty Publications and Presentations

Objectives: To investigate the impact of the Affordable Care Act’s (ACA) Medicaid expansion on African Americanwhite disparities in health coverage, access to healthcare, receipt of treatment, and health outcomes. Design: A search of research reports, following the PRISMA-ScR guidelines, identified twenty-six national studies investigating changes in health care disparities between African American and white non-disabled, non-elderly adults before and after ACA Medicaid expansion, comparing states that did and did not expand Medicaid. Analysis examined research design and findings. Results: Whether Medicaid eligibility expansion reduced African American-white health coverage disparities remains an open question: Absolute disparities in coverage appear to have …

Issues With Variability In Electronic Health Record Data About Race And Ethnicity: Descriptive Analysis Of The National Covid Cohort Collaborative Data Enclave, Lily A. Cook Ma, David A. Dorr, Nicole G. Weiskopf, Nisha Mathews, Kelly L. Gonzales, Adam Wilcox, Charisse Madlock-Brown, N3c Consortium

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background:The adverse impact of COVID-19 on marginalized and under-resourced communities of color has highlighted the need for accurate, comprehensive race and ethnicity data. However, a significant technical challenge related to integrating race and ethnicity data in large, consolidated databases is the lack of consistency in how data about race and ethnicity are collected and structured by health care organizations.

Objective:This study aims to evaluate and describe variations in how health care systems collect and report information about the race and ethnicity of their patients and to assess how well these data are integrated when aggregated into a large clinical database. …

Evaluating The Effect Of San Francisco’S Paid Parental Leave Ordinance On Birth Outcomesf, Deborah Karasek, Sarah Raifman, Rita Hamad, William H. Dow, Julia M. Goodman

OHSU-PSU School of Public Health Faculty Publications and Presentations

Since 2017, San Francisco’s Paid Parental Leave Ordinance (PPLO) has allowed parents who work for private-sector employers to take 6 weeks of fully paid postnatal parental leave. Previous studies have linked paid parental leave with health improvements for birthing people and babies, although evidence for birth outcomes is limited. We hypothesized that the PPLO may have improved birth outcomes via reduced stress during pregnancy due to anticipation of increased financial security and postnatal leave. We used linked California birth certificate and hospital discharge records from January 2013 to December 2018 (n = 1,420,781). We used quasi-experimental difference-in-difference (DD) models to …

Is Strongyloides Stercoralis Hyperinfection Induced By Gglucocorticoids A Result Of Both Suppressed Host Immunity And Altered Parasite Genetics?, De'broski R Herbert, Jonathan D C Stoltzfus, Heather L Rossi, David Abraham

Department of Microbiology and Immunology Faculty Papers

The gastrointestinal (GI) nematode Strongyloides stercoralis (S.s.) causes human strongyloidiasis, a potentially life-threatening disease that currently affects over 600 million people globally. The uniquely pernicious aspect of S.s. infection, as compared to all other GI nematodes, is its autoinfective larval stage (L3a) that maintains a low-grade chronic infection, allowing undetectable persistence for decades. Infected individuals who are administered glucocorticoid therapy can develop a rapid and often lethal hyperinfection syndrome within days. Hyperinfection patients often present with dramatic increases in first- and second-stage larvae and L3a in their GI tract, with L3a widely disseminating throughout host organs leading to sepsis. How …

The Scoop, Vol. 9 Issue 6, September 2022, Health Sciences Library

Volume 9

Latest news and updates from the Health Sciences Library in our monthly newsletter for September 2022.

Role Of The G Protein Beta Gamma Subunits In Serotonin Transporter Dynamics, Nora Awadallah

Dissertations, Theses, and Capstone Projects

Serotonin is a vital neurotransmitter and hormone with significant roles in almost every organ system. In the central nervous system, serotonin mediates physiological functions that in turn guide behavior and mood. Here, serotonin is released from serotonergic neurons and exerts its effects through serotonin receptors. Regulation of serotonin neurotransmission is important for the maintenance of its physiological functions; thus, extracellular serotonin must be sequestered to limit the intensity and duration of serotonin transmission. Disproportionate transmission is strongly linked with neurological and psychiatric ailments.

Extracellular serotonin levels are primarily mediated by the serotonin transporter (SERT), a critically important plasma membrane protein …

Substrate Stiffness Modulates Migration And Local Intercellular Membrane Motion In Pulmonary Endothelial Cell Monolayers, Sunita Subedi Paudel, Althea Deweever, Sarah Sayner, Troy Stevens, Dhananjay T. Tambe

University Faculty and Staff Publications

The pulmonary artery endothelium forms a semipermeable barrier that limits macromolecular flux through intercellular junctions. This barrier is maintained by an intrinsic forward protrusion of the interacting membranes between adjacent cells. However, the dynamic interactions of these membranes have been incompletely quantified. Here, we present a novel technique to quantify the motion of the peripheral membrane of the cells, called paracellular morphological fluctuations (PMFs), and to assess the impact of substrate stiffness on PMFs. Substrate stiffness impacted large-length scale morphological changes such as cell size and motion. Cell size was larger on stiffer substrates, whereas the speed of cell movement …

Cell-Intrinsic Melanin Fails To Protect Melanocytes From Ultraviolet-Mutagenesis In The Absence Of Epidermal Melanin, Tirzah J. Weiss, Emma R. Crawford, Valentina Posada, Hafeez Rahman, Tong Liu, Brandon M. Murphy, Tiffany E. Arnold, Shannon Gray, Zhexuan Hu, Rebecca C. Hennessey, Lianbo Yu, John August D'Orazio, Craig J. Burd, Jonathan H. Zippin, Douglas Grossman, Christin E. Burd

Markey Cancer Center Faculty Publications

Melanin is a free-radical scavenger, antioxidant, and broadband absorber of ultraviolet (UV) radiation which protects the skin from environmental carcinogenesis. However, melanin synthesis and UV-induced reactive melanin species are also implicated in melanocyte genotoxicity. Here, we attempted to reconcile these disparate functions of melanin using a UVB- sensitive, NRAS-mutant mouse model, TpN. We crossed TpN mice heterozygous for an inactivating mutation in Tyrosinase to produce albino and black littermates on a C57BL/6J background. These animals were then exposed to a single UVB dose on postnatal day three when keratinocytes in the skin have yet to be melanized. Approximately one-third (35%) …