Mildred Elizabeth Edmundson Research Grant
Mildred Elizabeth Edmundson Research Grant Program supports proposals of outstanding scientific merit addressing translational research of women's health issues. Proposals focusing on prevention and early detectionand are highly encouraged. All funded project teams are expected to gather preliminary data to submit competitive applications to external funding agencies, or to seek support from an outside organization (e.g. companies, foundations, etc.) for continuation of the research. Matching funds are encouraged. The program is in partnership with the Indiana Clinical and Translational Sciences Institute (CTSI).
Awarded Proposals
2023
Multi-PI:
Jennifer Brown, Ph.D.
Associate Professor of Psychological Sciences
Department of Psychological Sciences
Lochner Marais, Ph.D.
Professor
Center for Development Support
University of the Free State, South Africa
Project title: “Development of a culturally-tailored, adolescent-driven dual protection intervention approach for South African adolescents.”
Black South African adolescent girls experience health disparities related to both unintended pregnancies and sexually transmitted infections (STI) including human immunodeficiency virus (HIV). Our team, with funding from the Bill & Melinda Gates Foundation, has previously employed Cultural Consensus Modeling with South African adolescent girls to examine cultural factors associated with dual protection methods (i.e., methods that prevent both unintended pregnancy and HIV/STI). To shift the current dominant school-based sexual health messaging to one that incorporates culturally-appropriate, highly effective dual protection strategies, the proposed study will adapt a nationally implemented school-delivered sexual health curriculum (love4life), using a youth-led Community Based Participatory Research (CBPR) approach. We will also evaluate potential barriers to the widespread implementation of the modified curriculum. This pilot study will produce the first culturally-adapted sexual health curriculum to focus on dual protection to reduce both unintended pregnancies and STIs/HIV among South African adolescent girls. The successful execution of our proposal will provide foundational pilot research for subsequent external funding applications to conduct a randomized clinical trial of the adapted school-delivered sexual health education intervention. If efficacious, the intervention has the potential to reduce both unintended pregnancies and STIs/HIV among South African adolescent girls.
Effect of Ovariectomy on the Progression of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) in Rats
Kathleen Hill Gallant, Assistant Professor of Nutrition Science, Director of Didactic Program in Dietetics
Chronic kidney disease (CKD) afflicts ~1/2 of Americans over 65y, and affects both men and women. CKD-mineral bone disorder (CKD-MBD) is a related condition affecting virtually all patients by advanced CKD. Clinical consequences of CKD-MBD include bone fractures, cardiovascular events, and increased mortality. Studying the earlier stages of kidney decline may give better insight to the prevention of CKD-MBD progression. However, animal models of CKD are sometime limited to males only in this regard. As most women with CKD are postmenopausal or amenorrheic, a model of postmenopausal CKD-MBD is highly relevant to a majority of women with CKD. This project aims to develop such model that will allow for studies on sex differences, the protective influence of estrogen on kidneys, and studies on preventing renal failure and CKD-MBD in both sexes.
Development of Nanoparticle Depot for Intraperitoneal Chemotherapy of Ovarian Cancer
Yoon Yeo, Associate Department Head and Associate Professor of Industrial and Physical Pharmacy
Intraperitoneal chemotherapy is an appealing therapeutic option for ovarian cancer therapy, with pharmacokinetic advantages and survival benefits. However, intraperitoneal chemotherapy is not widely used in practice due to toxicities and complications. For intraperitoneal chemotherapy to serve ovarian cancer patients to the full potential, it is critical to employ an adequate drug delivery system and reduce these problems. This project is to develop an intraperitoneal drug delivery system that will facilitate drug delivery into tumors in the peritoneal cavity. This delivery system will concentrate a drug effect persistently on tumors, ensuring effective eradication of tumors at reduced IP doses, and provide greater locoregional effect.
The Estrogen Receptor-beta in Mechanosensitive and Estrogenic Pathways in Osteocytes
Russell Main, Assistant Professor of Biomedical Engineering and Basic Medical Sciences
There is a fundamental gap in understanding how mechanotransductive pathways in the skeleton become “desensitized” with age and how they can be harnessed as potent anabolic mechanisms, through pharmacologic and physical combination therapies, to prevent age-related bone loss. Continued existence of this knowledge gap represents a significant medical problem because, until it is addressed, failure to maintain these homeostatic mechanisms of bone’s resistance to fracture will continue to result in mortality and morbidity among the elderly. The objective of this project is to characterize the role of estrogen receptor β (ERβ) in regulating estrogenic and mechanosensitive pathways in the skeleton. it will identify osteocyte ERβ as a potent inhibitor of mechanosensitive anabolic pathways and skeletal maintenance following sex hormone withdrawal, providing an explanation for the reduced efficacy of physical therapies to maintain bone mass in the elderly.
Epigenetic Mechanisms Linking Exposure to Dietary Polyphenols with Breast Cancer Prevention
Barbara Stefanska, Assistant Professor of Nutrition Science
Epigenetic modifications, particularly DNA methylation, have attracted a significant amount of attention for the prevention and treatment of different illnesses with cancer at the forefront, mainly due to the inherent reversibility of epigenetic states. A number of studies provide evidence that dietary bioactive compounds can modulate disease state by targeting gene expression although the underlying mechanisms are unclear. This project is intended to elucidate epigenetic mechanisms of two polyphenols, resveratrol and pterostilbene, in gene regulation and chemoprevention in breast cancer. The findings of this project will increase our understanding of complex regulation of the epigenome by dietary polyphenols and consequences of this regulation to cancer prevention. New evidence will be discovered for novel applications of the compounds in cancer prevention and therapy and increase awareness of the general community about beneficial effects of plant-derived bioactives.
Effects of Dietary Protein Source on the Physiological and Mechanical Properties of Bone Following a High-Protein Weight-Loss Diet in a Rat Model for Postmenopausal Obesity
Wayne Campbell, Professor of Nutrition Science
Obesity is common amongst post-menopausal women and further increases their risk for several metabolic disorders. Weight loss is an effective and widely used strategy for decreasing adiposity and improving overall metabolic health, but is shown to decrease bone density, reduce bone quality, and increase the risk of skeletal fracture. High-protein diets are commonly used for weight loss as they are shown to decrease fat mass and improve metabolic health. However, their impact on bone during energy restriction is still unclear and somewhat controversial. The project is to investigate the effects of protein source on bone physiology and strength to identify an optimal dietary strategy for the treatment of obesity in post-menopausal women without comprising bone.
Vitamin D Regulation of Metastasis - Developing New Models and Mechanistic Preliminary Results
Dorothy Teegarden, Professor and Associate Dean for Research and Graduate Programs
Breast cancer continues to be a major killer of women worldwide, and most of the deaths are due to metastasis. Because the onset of metastasis may occur early in the development of a tumor, it is critical to identify health strategies that are preventative for metastasis of breast cells. Higher lipid levels within breast cancer cells are associated with greater breast cell metastatic events. Evidences suggest vitamin D reduces metastasis of several cancers, including breast. The goal of this project is to develop evidence‐based recommendations for vitamin D intake for the purpose of reducing metastasis of cells in early tumor development, as well as in survivors.
Novel Statistical Approaches to Uncover the Genetic Architecture of Alzheimer's Disease
Min Zhang, Professor of Statistics
As the most common neurodegenerative diseases, Alzheimer's disease touches everyone's lives in the U.S. and around the world. In 2015, an estimated 5.3 million Americans of all ages have Alzheimer's disease, and almost two thirds of them are women. With the aging U.S. population, the number of individuals with Alzheimer's disease is expected to reach 13.8 million by 2050. Despite the fact that Alzheimer's disease was discovered over 100 years ago, the exact cause remains unknown and there is no effective prevention or treatment. This project is to investigate the genetic architecture of Alzheimer's disease using a newly developed statistical methods for biomedical big data. Furthermore, we will evaluate the gene by gender interactions to explore why women has a high incidence and worse progression.
A Contextualized Community Based Approach for the Early Identification and Treatment of Breast and Cervical Cancer in Rural Western Kenya
Sonak Pastakia, Associate Professor of Pharmacy Practice, Pharmacist, Indiana University Kenya Partnership
This project focuses on the lack of access to preventative screening and early treatment for cancer amongst rural women living in low- and middle- income countries (LMICs). Countries like Kenya, continue to face an unacceptably high mortality to cervical and breast cancer owing in large part to late presentation of patients for care and limited access to treatment. We intend to address this deficiency by bringing together an internationally renowned interdisciplinary team of experts to assess the difference in care accession for cervical and breast cancer when utilizing the novel Bridging Income Generation through grouP Integrated Care Model (BIGPIC) compared to the standard facility based model typically used by the Ministry of Health.
Vitamin E tocotrienols as effective agents for preventing colon cancer
Qing Jiang, Professor of Nutrition Science
Colorectal cancer (CRC) is the 3rd leading cause of cancer death among woman. Due to the lack of effective treatment of late-stage cancer, chemoprevention is an important strategy for reducing CRC mortality. One of the most recognized chemoprevention strategies against CRC is to block cyclooxygenase (COX-1/-2) catalyzed eicosanoids. However, long-term use of COX inhibitors is limited due to side effects and moderate anticancer efficacy shown in some trials. It is therefore necessary to search for better chemopreventive agents to improve cancer prevention efficacy and safety. We and others show that less known forms of vitamin E can block multiple cancer-promoting pathways and suppressing the growth of cancer cells. This project is to examine chemopreventive efficacy of the vitamine E forms in preventing sporadic CRC. Ultimately, the success of the study will develop new and effective chemoprevention agents protecting individuals with high-risk CRC, and generate critically-needed preclinical data for future clinical studies.
Treatment to reduce the burden of swallowing difficulties in ageing and neurodegenerative disorders
Cordelia Running, Assistant Professor of Nutrition Science
Neurodegenerative disorders disproportionately affect women. Compared to men, women more frequently develop the diseases and also more frequently provide care to those who suffer from the diseases. A prevalent symptom associated with neurodegenerative disorders is dysphagia, i.e. swallowing difficulties, particularly when attempting to swallow thin liquids. These thin liquids can be aspirated into the airway, increasing risk for pneumonia. To prevent this, the most common practice is to thicken the beverages. However, thickened beverages are harder to clear from the airway if aspirated, the thickness is not always able to be adjusted by caregiver, and they taste bad. Patients will often refuse the beverages, increasing their risk for dehydration. This project tests some promising alternatives to thickened beverages with higher acceptability, efficacy, and safety, which will lead to larger scale clinical trials on the efficacy of treatment options for individuals with swallowing difficulties related to neurodegenerative diseases.
Targeting metabolic plasticity in metastatic breast cancer
Michael K. Wendt, Associate Professor of Medicinal Chemistry and Molecular Pharmacology
Ninety percent of breast cancer-related deaths are a consequence of metastasis, and currently available therapeutics do not effectively target these lethal, disseminated tumors. Thus, there is a critical need to better understand the molecular and metabolic mechanisms by which metastatic breast cancers adapt to the environment of alternate organ systems and eventually grow to impede their function. During breast tumorigenesis, primary mammary tumors become increasingly rigid, hypoxic and acidic. To adapt to these conditions tumor cells undergo metabolic reprogramming, start consuming large amounts of glucose and utilizing mitochondrial-independent glycolysis as a primary means of energy production. Despite these recent advances there remain fundamental gaps in our understanding of the metabolic plasticity of tumor cells as they disseminate and grow throughout the body. This project aims to elucidate the mechanisms of metabolic plasticity in metastatic breast cancer, particularly the role of FGFR. The success will initiate a therapeutic protocol that has high potential to extend the survival of metastatic breast cancer patients.
Automated Supine Pressor Test Device for Prediction of Preeclampsia
Craig Goergen, Leslie A. Geddes Associate Professor of Biomedical Engineering
Preeclampsia is an advanced form of pregnancy-induced hypertension that can lead to multi-organ dysfunction and preterm birth and can be fatal for both the expecting mother and the fetus. In the 1970s, the supine pressor test (SPT) was developed to predict the risk for preeclampsia in pregnant women based on elevation in their diastolic blood pressures between different body positions. This test fell out of favor due to its low sensitivity, manual application and lack of specific instructions. This project aims to automate the SPT (Auto-SPT) to ensure both repeatability and accuracy of test results through an innovative mobile phone application that will provide feedback to users as they conduct the test. Ultimately the Auto-SPT device will allow pregnant women to track blood pressures at home related to position changes in order to monitor their risk for preeclampsia development and to improve the wellness outcomes of expecting mothers and their children.