Grant and Contract Awards

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NEW & TRANSFER AWARDS

(New grants, funding transferred from a PI’s previous institution, and NIH competitive renewal funding)

Naomi Chaytor – Elson S. Floyd College of Medicine
Arizona State University/National Science Foundation
“CPS: Small: Human-in-the-Loop Learning of Complex Events in Uncontrolled Environments”
This is a subaward of a project that aims to advance knowledge of machine learning for human-in-the-loop cyber-physical systems. Mobile and wearable devices are a promising technology for health monitoring and behavioral interventions. Designing these types of systems involves collecting and labeling sensor data in free-living environments through an active learning process. In active learning, the system repeatedly queries a human expert (such as a patient or a clinician) for correct labels. Designing active learning strategies in uncontrolled settings is challenging because active learning places a considerable burden on the user and compromises adoption of the technology; and labels expressed by humans exhibit a significant amount of inter-user and intra-user noise leading to poor performance of the machine learning algorithms. This research will address these technical challenges in designing high performance systems and enable accurate monitoring and interventions in many applications beyond behavioral medicine.

Thomas Gooding (PI); Hans Haverkamp – Elson S. Floyd College of Medicine
American College of Sports Medicine
“Identification of early (non)functional overreach warning signs following a 3-week lab-controlled cycling protocol”
Rigorous training programs designed to improve athletes’ performance consist of high-volume training periods followed by taper periods. These programs are used to induce functional overreach, a brief state in which an individual initially has lowered performance and increased fatigue, followed by significantly improved performance. However, if the imbalance between training and recovery is prolonged, athletes may become non-functionally overreached, which is characterized by more severe performance decreases, excessive fatigue, and altered psychological health, with recovery lasting weeks to months. Non-functional overreach may over time progress to overtraining syndrome, the most severe form of overtraining lasting months to years. This study involves a 3-week, intensive, lab-controlled training protocol designed to identify early signs of overtraining in recreationally active males and females. The goal is to better understand the biological mechanisms that lead to overtraining and address the lack of diagnostic criteria to detect overtraining or predict its occurrence, with the ultimate goal of developing methods to proactively detect and prevent overtraining.

Devon Hansen (PI); Hans Van Dongen – Elson S. Floyd College of Medicine/Sleep and Performance Research Center
trackthatsleep, LLC
“Postpartum Maternal Sleep Project”
This contract provides funding for WSU to conduct a field study to characterize postpartum sleep in families with first-time parents in a naturalistic setting. The researchers will use wearable devices to track sleep quantity and quality in mothers, their caregiving partners, and infants. Data from the study will be used to show day-to-day variability in maternal sleep across the first postpartum year, quantify the severity of postpartum sleep restriction, quantify the amount of change in postpartum maternal sleep timing compared to prior to the pregnancy, and predict when moms and their caregiving partners can expect to have longer uninterrupted stretches of sleep.

Luciana Hebert (PI) – Elson S. Floyd College of Medicine/Community Health
University of Colorado Denver/ National Institutes of Health, National Institute of Mental Health
“Exploring Food Insecurity as a Social Determinant of Health Among American Indian and Alaska Native Adolescents at Risk for Gestational Diabetes”
Living in a food insecure household during pregnancy and prior to conception may increase the risk of greater weight gain and perinatal complications. This includes a risk of gestational diabetes (GDM) and subsequent diagnosis of type 2 diabetes, which is twice as likely to occur in American Indian/Alaska Native (AI/AN) women as in non-Hispanic white women. This subaward provides funding to describe food insecurity and examine the relationship between food insecurity and healthy eating self-efficacy and behaviors among American Indian and Alaska Native adolescent girls. The researchers will achieve this through a secondary analysis of data from Stopping GDM, an online program to reduce the risk of gestational diabetes and provide preconception counseling to AI/AN adolescent girls. In combination with data from qualitative interviews, findings from this study will inform the adaptation of Stopping GDM to address food insecurity to help decrease health disparities related to gestational diabetes and break the intergenerational cycle of diabetes in AI/AN communities.

Patrik Johansson (PI) – Elson S. Floyd College of Medicine/Community Health
Patient-Centered Outcomes Research Institute
“Building Capacity for Patient-Centered Outcomes Research in Rural Washington”
This grant provides funding for the Northwest Health Education Research Outcomes Network (NW HERON) to convene a community advisory board whose members will participate in the SEED method, a stakeholder engagement methodology that combines review of existing evidence and primary data collection from patients and other stakeholders. The aim is to identify priority health issues for future comparative effectiveness patient-centered outcomes research projects. The ultimate goal of NW HERON is to enhance the health and health care of Washington residents, with a specific focus on reducing health disparities and improving health outcomes for those living in rural, tribal, and urban medically underserved areas.

Andrea Lazarus (PI) – College of Pharmacy & Pharmaceutical Sciences
University of Washington/National Institutes of Health, National Center for Advancing Translational Sciences
“Institute of Translational Health Sciences”
This grant provides funding for WSU to work with the University of Washington to develop an educational program that can be rolled out at institutions that participate in the WWAMI medical education program. The program will provide a track in translational health sciences to incorporate into existing programs, such as the PharmD Honors program at WSU.

Weimin Li (PI) – Elson S. Floyd College of Medicine/College of Nursing
United Health Group/Everett Clinic PLLC
“Extracellular Matrix Protein Profiling for Improved Risk Stratification of Ductal Carcinoma in Situ”
This study will assess whether differences in protein expression in the extracellular matrix of a tumor can be used to stratify ductal carcinoma in situ (DCIS) into high-risk and low-risk groups. DCIS is the earliest stage of ductal carcinoma, representing about 25 percent of breast cancer cases diagnosed in the United States. Because DCIS is non-invasive, the prognosis is usually excellent, with a breast cancer-specific mortality rate of only 3.3% 20 years after diagnosis. Even without treatment, only an estimated 20 to 50 percent of DCIS will progress to invasive ductal carcinoma. However, because the clinical behavior of DCIS can vary quite a bit and is difficult to predict, most patients with DCIS are treated similar to patients with more aggressive invasive ductal carcinoma: with mastectomy alone or lumpectomy followed by radiation and an oral anti-estrogen. Successful stratification of DCIS into low-risk and high-risk disease would ensure that patients with low-risk disease can receive less rigorous treatment, or perhaps no treatment at all.

Michael McDonell (PI) – Elson S. Floyd College of Medicine
Mayo Clinic/National Institutes of Health, National Institute on Drug Abuse
“Alaska Native Family-Based, Financial Incentives Intervention for Smoking Cessation: an RCT”
As part of this study, McDonell will help the Alaska Native Tribal Health Consortium team to adapt an effective smoking cessation intervention that uses financial incentives so that it is relevant to Alaska Native families and culture. The study will be conducted in Anchorage/Matanuska-Susitna and Maniilaq regions and will involve conducting focus groups with AN smokers and family members to adapt the intervention; a pilot phase to test the financial incentives; and a trial phase to assess the impact of financial incentives on smoking cessation confirmed through urine testing.

Michael McDonell and Marian Wilson; (co-PIs); Sterling McPherson; Crystal Smith; Katherine Hirchak; Naomi Bender – Elson S. Floyd College of Medicine/College of Nursing/WSU Spokane
Northwest Indian College/National Institutes of Health, Native American Research Centers for Health
“Association between cannabis and pain outcomes in a Tribally operated clinic”
This new grant funds a four-year study of the relationship between cannabis use and pain at a Native health clinic. Previous research suggests that THC in cannabis may have a positive effect on anxiety, depression, and sleep. This raises the possibility that THC not only provides direct pain relief but may also ease symptoms associated with pain, such as poor sleep and mood. The WSU research team will conduct a comprehensive analysis of patient demographics and data on cannabis use, pain, mood, and sleep to determine how cannabis impacts pain intensity and interference in 350 adults seeking pain care at a Native-owned and operated natural healing clinic in Washington State. The grant will also provide opportunities for research training for Native students through Northwest Indian College—a partner on this grant—and WSU’s Native American Health Sciences Program.

Bhagwat Prasad (PI) – College of Pharmacy & Pharmaceutical Sciences
Takeda Millennium
“Proteomics-informed in vitro to in vivo extrapolation of non-cytochrome P450 drug metabolism”
This funding supports a project that is part of the Proteomics-based Research Initiative for Non-CYP Enzymes (PRINCE), a research collaboration between Washington State University and pharmaceutical companies Genentech, Gilead, and Takeda Millennium. The project is aimed at improving the predictability of drug metabolism and drug interaction of new candidate drugs. Non-cytochrome P450 (non-CYP) enzymes play an important role in the metabolism of many drugs. When drug metabolism findings in non-CYP enzymes cannot be reliably extrapolated from an in vitro environment (i.e., test tube or petri dish) to in vivo (a living organism), this results in unpredictable pharmacokinetics and safety of drugs. To address these challenges, Prasad and his team will test a novel in vitro to in vivo extrapolation approach in both an in vitro system and human tissues.

Victoria Sattler (PI); Kristin Courtney; Kelly Kleiderer – College of Nursing/Elson S. Floyd College of Medicine
Washington State Department of Health
“Youth Sexual Health Mentorship in Rural Communities”
To address recent increases in the rates of sexually transmitted infections, unwanted sexual contact, and dating violence among youth in Washington State, this project will involve implementing a sexual health curriculum for 7^th and 8^th graders as part of the existing Stevens County mentorship program, which was developed in 2019 as a way to bring the idea of health care careers and healthy living to the minds of young people. The mentorship program is offered in four rural school districts in communities that have teen pregnancy rates higher than the state average and disproportionally higher rates of sexually transmitted infections in minority populations. By implementing this youth sexual health curriculum into the existing mentorship program youth will learn about their own sexual health and how they can positively impact the health of others within the role of a healthcare professional.

Ka’imi Sinclair (PI); Amanda Boyd – College of Nursing/Murrow College of Communication/Community Health
American Heart Association
“Community Engaged, mHealth and Data Science to Enhance Clinical Trial Diversity and Cardiometabolic Health”
The goal of this project is to increase the participation of American Indians in clinical trials. American Indians experience considerable health disparities compared to the general US population yet remain underrepresented in research. Without participants from a broad range of backgrounds, researchers cannot fully understand how study findings will translate into real-world application. This new project will involve a study to identify key factors that facilitate or hinder American Indian participation in clinical trials. This will be followed by the development and evaluation of a novel intervention—“Research Is Ceremony”—to promote participation and retention of American Indians in an existing clinical trial on the effects on cognition of positive airway pressure treatment for obstructive sleep apnea. Findings from this research may be broadly applicable to other populations and help advance the science of diversity in clinical trials.

Astrid Suchy-Dicey (PI) – Elson S. Floyd College of Medicine/Community Health
University of Oklahoma Health Sciences Center/National Institutes of Health, National Heart, Lung and Blood Institute
“Strong Heart Study (SHS)- Field Center(s) 20001424 Task A”
This subaward provides funding for the principal investigator to contribute research expertise and assistance to the Strong Heart Study, a long-running study of two cohorts that together form the largest, multicenter, prospective epidemiological study of cardiovascular disease in Native Americans. The study involves a partnership with 12 Tribal Nations who live in Arizona, Oklahoma, and the Dakotas.

AWARDS FOR ONGOING WORK

(Renewal, continued, and supplemental funding for projects awarded previously)

Zhaokang Cheng (PI); Boyang Wu – College of Pharmacy & Pharmaceutical Sciences
National Institutes of Health; National Heart, Lung, and Blood Institute
“Cell cycle proteins as key regulators of cardiac chemosensitivity”
Anthracycline-based chemotherapy, an effective treatment for many types of cancer, has long been associated with substantial toxicity to the heart. The anthracycline drug doxorubicin induces DNA damage and subsequent heart cell death, which eventually results in cardiomyopathy and heart failure. Previous research led by the principal investigator of this award has identified cyclin-dependent kinase 2 (CDK2) as a key player in heart toxicity resulting from treatment with anthracycline drugs and suggested that cardiac CDK2 activity determines how sensitive the heart is to chemotherapy. This award provides a funding increase for a study to determine the role of two cell cycle proteins known to control CDK2 activity—CDK7 and RBL2—in heart cell death and cardiac chemosensitivity. This research could help lay the foundation for developing new strategies to protect the heart during cancer treatment.

Christopher Davis (PI); William Vanderheyden – Elson S. Floyd College of Medicine/Sleep and Performance Research Center
HEEL (Biologische Heilmittel Heel GmbH)
“Neurexan mitigates trauma-induced sleep disturbances and improves fear-associated memory impairments in a rodent model of PTSD”
Sleep disorders are hallmark trait of post-traumatic stress disorder and impair physical health, interfere with cognitive functioning, and exacerbate other mental or physical health impairments. Trauma-induced sleep disorders may contribute to the development of a vicious cycle where PTSD symptoms and disturbed sleep promote each other. Commonly used pharmaceutical treatments for PTSD, such as SSRIs and SNRIs, do not address trauma-induced sleep disorders and in many cases further interfere with sleep, which may compromise their effectiveness as treatments for PTSD symptoms. Previous studies by the investigators on this study has shown—in a rodent model—that increasing sleep duration after trauma exposure can ease the negative consequences of the trauma and help to break the vicious cycle of PTSD symptoms being aggravated by poor sleep and vice versa. This contract provides supplemental funding for a project that will test the drug Neurexan in a rodent model to determine its effectiveness as a treatment to alleviate trauma-induced sleep disruptions and/or prevent the development of PTSD.

Dawn DeWitt (PI); Jennifer Miller; Skye McKennon; Marian Wilson; Tracy Klein; Connie Remsberg; Elizabeth Wood – Elson S. Floyd College of Medicine/College of Nursing/College of Pharmacy & Pharmaceutical Sciences
US Department of Health Resources & Services Administration, Bureau of Health Workforce
“Cornerstone: Rethinking Education on Substance use through inter-Professional Education and Rural Community Training (RESPECT)”
This award continues funding for a five-year project to train faculty, students, and rural primary care providers in Washington State on interprofessional education approaches to caring for patients at risk for opioid use disorder. The program will build on an interprofessional curriculum that was previously created and piloted by the core WSU project team. The curriculum is a team-based facilitated interprofessional education simulation that uses standardized patients to enhance student learning about providing care to patients taking opioids. It will be used to train faculty and students in a variety of health professions disciplines—including medicine, nursing, physician assistant, pharmacy, social work, and chemical dependency—as well primary practice teams at rural clinic sites across Washington State. The curriculum will be tailored, implemented, and continuously evaluated across five years’ time with an active examination of changing policies and best practices on opioid use for pain and opioid use disorder.

Marcos Frank (PI) – Elson S. Floyd College of Medicine
National Institutes of Health/National Institute on Neurological Disorders and Stroke
“Astroglial mechanisms in sleep homeostasis”
Common sleep problems such as excessive daytime sleepiness and insomnia may be caused in part by changes in sleep homeostasis, the process that increases sleep drive, sleep amounts, and sleep intensity based on prior time awake. This grant-funded project builds on a previous discovery by the researchers that this process involves a type of brain cells known as glial astrocytes, even though the cellular mechanisms sleep homeostasis had been thought to be neuronal before then. The goal of this continuing study is to test the researchers’ hypothesis that sleep homeostasis arises from interactions between astrocytes and neurons and that sleep loss drives intracellular and molecular changes in astrocytes. The researchers will also study the role of astroglial mechanisms in sleep in mouse models of neurodegenerative disease, such as Alzheimer’s disease. The work will provide new insight into the processes that drive abnormal sleep and could eventually lead to the development of new therapeutics that target glia to combat not only excessive daytime sleepiness and insomnia but also Alzheimer’s disease.

Amber Fyfe-Johnson (PI) – Elson S. Floyd College of Medicine/Community Health
Storer Fund at The Miami Foundation
“Health Outcomes in Preschool: INnovations for Obesity Prevention (HOP-IN)”
This award provides supplemental funding to pay for a research assistant assigned to an NIH-funded project to evaluate the impact of an outdoor preschool model on health outcomes and academic achievement in early childhood. The Health Outcomes in Preschool: INnovations for Obesity Prevention (HOP-IN) will partner with Tiny Trees, a preschool in Seattle, Washington, with an entirely outdoor, play-based curriculum. The study will collect data on the physical activity, sleep, body mass index, gut microbiome, and academic performance of 200 children ages 3 to 5 for a period of five years. This includes 100 children attending Tiny Trees and a control group of 100 waitlisted children who are currently attending a traditional indoor preschool. The researchers will compare various outcomes between the two groups and will also perform a cost-benefit analysis to evaluate the longer-term sustainability of the Tiny Trees outdoor preschool model.

Michael Gibson (PI); Jean-Baptiste Roullet – College of Pharmacy & Pharmaceutical Sciences
National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health & Human Development
“Natural History of Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD), a Heritable Disorder of GABA Metabolism”
This award continues funding for a natural history study of patients with succinic semialdehyde dehydrogenase (SSADH) deficiency, a rare inherited disorder that inhibits the breakdown of a neurotransmitter known as gamma-aminobutyric acid (GABA) and is associated with developmental delays and neurological problems. The study will follow 55 patients at Boston Children’s hospital and other sites around the world over a period of five years. Through yearly assessments of the patients, the researchers will determine the natural course of the clinical presentation of SSADH deficiency, using a novel clinical severity score to quantify the most prominent clinical features of the disease. They will also determine the natural evolution of known neurophysiological and biochemical abnormalities in SSADH—such as those related to brain volume, brain GABA concentration, brain myelination, cortical GABAergic function, and blood and urine levels of GABA and related metabolites. Finally, they will try to identify neurophysiological and biochemical predictors of clinical severity. The study will provide the information needed to better predict the natural course of SSADH deficiency and monitor the success of future therapeutics, as well as lay the foundation for the addition of SSADH deficiency screening to existing newborn screening panels.

Janessa Graves (PI) – College of Nursing
University of Washington/Centers for Disease Control and Prevention
“Injury Health-related Equity across the Lifespan (iHeal)”
This award provides continued funding for WSU faculty to offer expertise and support to an Injury Control Research Center at the University of Washington-affiliated Harborview Injury Prevention and Research Center. The center is focused on injury prevention related to prescription opioids, suicide, falls among older adults, and pediatric concussions. The WSU team will support the new center’s research core, and the PI will also serve as co-investigator on a project evaluating state policies and suicide training.

Stephen Hall (PI) – Elson S. Floyd College of Medicine
University of Washington
“Washington State University Family Medicine Residency Network – Pullman, WA”
This grant provides renewal funding for WSU’s family medicine residency program at Pullman Regional Hospital, a critical access hospital that covers rural southeastern Washington as well as parts of Idaho and Oregon. This residency program helps enhance access to care, improve quality of patient care, and address the regional physician shortage while at the same time providing excellent clinical education and a superb clinical learning environment for residents, medical students, and other clinical learners.

Kimberly McKeirnan (PI); Megan Undeberg – College of Pharmacy & Pharmaceutical Sciences
Empire Health Foundation
“Building the Prototype of a Regional System that Will Increase Access to Quality Patient Care through Medication Optimization”
This is renewal funding for a project in which WSU is partnering with Better Health Together and the Alliance for Integrated Medication Management to develop, implement, and evaluate a prototype medication delivery system to serve patients with chronic disease in seven counties in eastern Washington. The partner organizations have worked with primary care providers, pharmacies, and community partners in the counties to develop the system, which offers integrated medication management and medication optimization and has the potential to improve patient outcomes, increase access to care, and decrease costs. This round of funding supports the WSU team’s goals of demonstrating the value of the project work, supporting the project team as they provide ongoing patient care, developing a certificate training program for the advanced medication care coordinators, and supporting attainment of sustainable financing.

Sterling McPherson (PI) – Elson S. Floyd College of Medicine
US Department of Veterans Affairs/Portland Veterans Affairs Medical Center
“Chronic pain management and patient-centered outcomes following discontinuation of long-term opioid therapy”
This subaward renews funding for Sterling McPherson to contribute statistical expertise and data analysis to a study being conducted at the Portland VA Medical Center. The study will follow a cohort of 1,144 VA patients who are being prescribed long-term opioid therapy for a period of two years. The goal of the study is to learn about patients’ experiences with the opioid discontinuation process; alternate pain management strategies patients use after discontinuation—either through VA or non-VA resources; and patient-centered outcomes such as quality of life, pain, substance use, and mental health symptom severity following discontinuation. Patients will be surveyed periodically to assess quality of life, pain, substance use, and mental health symptoms; those who discontinue opioid therapy will complete an additional assessment and may be invited to participate in a qualitative interview. The study will help inform best practices for discontinuing opioid therapy, when clinically indicated, while simultaneously mitigating negative consequences of discontinuation and engaging and empowering patients to manage chronic pain with evidence-based non-opioid treatment options.

Becki Meehan (PI); Jenna McCoy – WSU Spokane; Office of Student Affairs
U.S. Dept. of Education; Office of Postsecondary Education
“TRIO: Washington State University Spokane Stevens County Upward Bound”
This grant provides renewal funding from the federal TRIO programs for the Upward Bound program. Upward Bound is designed to generate the skills and motivation necessary for success in education beyond high school among young people from low‐income families and families where neither parent has acquired a bachelor’s degree. Upward Bound provides program participants with fundamental support in their preparation for college entrance. This Upward Bound project housed at WSU Spokane focuses on four small high schools in Ferry and Stevens Counties.

Kathryn Meier (PI) – College of Pharmacy & Pharmaceutical Sciences
American Society for Pharmacology and Experimental Therapeutics (ASPET)
“ASPET Summer Undergraduate Research Fellowship Program at Washington State University”
This grant provides funding for the 2022 ASPET Summer Undergraduate Research Fellowship (SURF) program offered by the WSU College of Pharmacy. The program provides undergraduate students with hands‐on experience in pharmaceutical or biomedical research to promote graduate education and research careers in the field.

Clemma Muller (PI) – Elson S. Floyd College of Medicine/Community Health
National Institutes of Health; National Institute of Nursing Research
“Increasing Colorectal Cancer Screening in Alaska Native Men”
Colorectal cancer occurs more frequently in Alaska Native men than in any other US racial or ethnic group. Though screening can prevent colorectal cancer and improve treatment outcomes through early detection, low screening rates are seen Alaska Native men. As part of this continuing project, the researchers will culturally tailor an existing intervention that used text messaging to promote colorectal screening among Alaska Native people, which successfully increased screening in Alaska Native women but not men. The study will use patient surveys and focus groups and key informant interviews with healthcare providers to determine barriers and facilitators to optimizing colorectal cancer screening in Alaska Native men. Based on the findings, the team will revise the content and/or frequency of the text messages and test the effectiveness of the tailored intervention with 600 Alaska Native men ages 40-75 who are active patients at the Southcentral Foundation, an Alaska-based non-profit healthcare system.

Lonnie Nelson (PI); Hans Van Dongen; Astrid Suchy-Dicey; Kimberly Honn; Celestina Barbosa-Leiker – College of Nursing/Community Health; Elson S. Floyd College of Medicine/Sleep and Performance Research Center
National Institutes of Health; National Institute of Minority Health Disparities
“American Indian CHronic disEase RIsk and Sleep Health (AI-CHERISH)”
Studies have suggested that sleep disorders are at least as prevalent among American Indians and Alaska Natives as they are in the U.S. population overall. However, there have not been any studies that have extensively examined the epidemiology of sleep problems in a representative sample of American Indians. This award provides funding to continue an innovative mixed-methods study that will allow the research team to estimate the prevalence of sleep problems in Native populations and their associations with specific cardiovascular and metabolic risk factors. In addition, they will characterize cultural factors related to sleep health. The study will recruit 750 American Indian participants who were previously enrolled in the Strong Heart Family Study and will be the largest epidemiological examination of sleep health and cardiovascular and metabolic risk to date.

Cassandra Nguyen (PI); Brian French; Ka’imi Sinclair – Elson S. Floyd College of Medicine/Community Health/College of Education
Tufts University/US Department of Agriculture, Economic Research Service
“Validity Evidence for the use of the USDA Adult Food Security Survey Module with American Indian and Alaska Native Adults”
Research suggests that households led by American Indians or Alaska Natives (AI/AN) are at elevated risk of food insecurity. However, efforts to understand and address food insecurity among AI/ANs in the U.S. are weakened by the absence of research to validate the Food Security Survey Module (FSSM), which the U.S. Department of Agriculture uses to assess household food security, in this specific subpopulation. This award provides continued funding for a study that will test the validity of the FSSM in 556 AI/AN adults in the 2019 National Health Interview Survey. Findings from the project will determine whether the FSSM survey functions well for AI/ANs or whether adaption is needed to account for the AI/ANs’ unique historical, cultural, and sociopolitical influences. This will help to establish accurate measures of food insecurity among AI/ANs, which is essential to creating health equity.

Anil Singh (PI) – College of Pharmacy & Pharmaceutical Sciences
Arthritis National Research Foundation
“Molecular reprogramming of Rheumatoid arthritis synovial fibroblasts by interleukin 6”
Interleukin-6 (IL-6) is a multifunctional cytokine protein that drives chronic inflammation and joint destruction seen in rheumatoid arthritis. This grant provides renewal funding for a study that will look at the mechanisms by which IL-6 induces the transformation of rheumatoid arthritis synovial fibroblasts into cells that act like osteoclasts, a type of bone cells that break down bone tissue. Unraveling these mechanisms may help scientists open up new avenues for the development of novel targeted treatments for rheumatoid arthritis.

Éva Szentirmai (PI); Levente Kapas – Elson S. Floyd College of Medicine
National Institutes of Health, National Heart, Lung and Blood Institute
“Novel mechanism in microbiota-brain communication: the role of the hepatoportal region”
This continuing study seeks to unravel novel mechanisms by which the brain aligns sleep-wake activity with metabolic, nutritional, and immune activity. The long-term objective is to identify mechanisms by which micro-organisms in the intestines communicate with the brain and their relevance to sleep regulation. Changes in the composition of these micro-organisms, as well as increased translocation of microbial products to the systemic circulation, are related to diseases such as central nervous system disorders. Identifying the role of bacterial products in sleep regulation is important because the gut flora is susceptible to changes in diet, environment, food additives and antibiotic treatment, which could lead to altered sleep. At the same time, the intestinal micro-organisms could also provide an easily accessible target for translational research to improve sleep.

Zhenjia Wang (PI); Santanu Bose – College of Pharmacy & Pharmaceutical Sciences/College of Veterinary Medicine
National Institutes of Health, National Institute of Biomedical Imaging and Bioengineering
“Active Drug Loading to Nanovesicles for Targeted Drug Delivery”
As part of this continuing study, the researchers will test a new drug delivery platform based on neutrophils—a type of white blood cells that play a key role in the body’s natural immune response. Neutrophil-based nanovesicles—hollow cell membranes loaded up with drug molecules—have the same characteristics as neutrophils, which are driven by our immune system to travel to inflammatory sites to help fight infection. This award provides continued funding to validate and refine the new technology in an animal model of acute lung injury, a type of respiratory failure that involves inflammation in the lungs.

Jonathan Wisor (PI) – Elson S. Floyd College of Medicine
National Institutes of Health, National Institute for Neurological Disorders and Stroke
“Sleep Deprivation Elevates, and Sleep Alleviates, Oxidative Stress in the Brain”
Sleep is essential for the reversal of deficits in cognition and performance that build up during wakefulness. Scientists have known that brain metabolism slows down during sleep, which is shown by a decline in brain temperature and the brain’s decreased use of glucose and oxygen. It is believed that this metabolic down state is essential for the restorative function of sleep, but scientists are not sure what biochemical processes underlie this relationship. This continuing project will seek to establish a causal relationship between sleep/wake cycles and brain redox status—the balance of oxidation and reduction reactions in the brain—and will identify brain oxidation/reduction reactions that could be targeted for the diagnosis and treatment of sleep disorders.

Boyang Wu (PI); Kathryn Meier – College of Pharmacy & Pharmaceutical Sciences
National Institutes of Health/National Cancer Institute
“Deciphering Mechanisms of Tumor-Stromal Interactions in Prostate Cancer”
The grant provides year-two funding for a five-year study aimed at unraveling the molecular mechanisms by which non-cancerous stromal cells support the growth and progression of prostate cancer. The ultimate goal is to identify pathways that could be targeted with drugs to disrupt tumor-stromal interactions and potentially halt the spread of prostate cancer. Prostate cancer affects one in nine men and causes nearly 30,000 deaths in the United States each year.

Boyang Wu (PI); Lucia Peixoto; Philip Lazarus – College of Pharmacy & Pharmaceutical Sciences/Elson S. Floyd College of Medicine
National Institutes of Health/National Cancer Institute
“MAOA and AR Reciprocal Crosstalk in Prostate Cancer”
Prostate cancer is the second leading cause of cancer death in American men. The primary driver of prostate cancer growth is androgen receptor, which regulates male hormones such as testosterone. The main treatment for prostate cancer currently consists of androgen deprivation therapy, which reduces testosterone to very low levels. In more than 90 percent of cases, prostate cancer initially responds to this therapy but will eventually relapse and progress into fatal castrate-resistant prostate cancer, which grows despite low testosterone levels. This award continues funding for a study that will look at a new molecular target for treating advanced prostate cancer: monoamine oxidase A (MAOA). The researchers have identified a reciprocal relationship between MAOA and androgen receptor in prostate cancer cells. Based on their findings, they will determine the molecular mechanism by which MAOA and androgen receptor interact in prostate cancer cells; characterize the role of MAOA in the development and progression of castrate-resistant prostate cancer; and determine the efficacy of MAOA inhibitor drugs for treating castrate-resistant prostate cancer and reversing cancer cell resistance to the latest generation of antiandrogen drugs. The study may provide a basis for developing new combination therapeutic strategies for advanced prostate cancer.