IWHR Scholar Graduates

January 1, 2006-December 31, 2006

Grace Liejun Guo, Ph.D.SCHOLAR: Grace Liejun Guo, Ph.D., Assistant Professor, Department of Pharmacology, Toxicology and Therapeutics, School of Medicine MENTORS: Yvonne Wan, Ph.D., Professor, Department of Pharmacology, Toxicology and Therapeutics, School or Medicine; Dr. Beth Levant, Associate Professor, Department of Pharmacology, Toxicology and Therapeutics PROJECT TITLE: The Role of Farnesoid X Receptor in Cholestasis and Atherosclerosis

ABSTRACT: My long-term career goal is to elucidate the pathophysiological roles of the FXR in human diseases, such as gallstone and atherosclerosis. FXR is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. It is highly expressed in liver, intestine and kidney. Bile acids are the endogenous ligands for FXR. FXR has been proven to be essential in maintaining bile-acid homeostasis and to be critical in regulating cholesterol and triglyceride metabolism. I will use genetically modified mouse models (whole-body FXR knockout, hepatocyte-specific FXR knockout, and enterocyte-specific FXR knockout mice) to investigate the role of FXR in bile-acid synthesis, metabolism and transport, with implication to gallstone formation and prevention in human. Furthermore, we will study the genetic polymorphism of FXR and its target genes that are involved in the bile-acid synthesis and transport pathway in human patients with gallstone disease. In addition, using FXR/ApoE or FXR/LDLr double-knockout mice, we will investigate the role of FXR in regulating lipid metabolism and foam-cell formation, with implication in atherosclerosis development. In summary, I believe that FXR regulates the homeostasis of bile acids, cholesterol, and triglycerides in a sex-specific manner. Dysfunction of FXR will affect the development of diseases in women. Elucidation of these areas will certainly be my research focus in the next few years and the results generated will provide a scientific basis to improve the current strategy of pharmacological therapy in treating gallstone diseases and atherosclerosis.

January 1, 2006-March 31, 2007

Andrea Charbonneau, M.D., M.Sc.SCHOLAR: Andrea Charbonneau Ely, M.D., M.Sc., Assistant Professor, Division of General and Geriatric Medicine, Department of Internal Medicine, School of Medicine MENTOR: Debra Sullivan, Ph.D., Chair, Department of Dietetics and Nutrition, School of Allied Health PROJECT TITLE: Weight Control Practices Among Women in Rural Kansas

ABSTRACT: Coronary heart disease (CHD) has been the leading overall cause of death in the US for several decades, and was responsible for 258.2 deaths per 100,000 population in 2000. CHD is the leading cause of death among women, resulting in nearly 500,000 deaths among women per year. Obesity is a strong independent predictor for CHD, conferring a degree of risk similar to that associated with hypertension, hyperlipidemia, tobacco use, and physical inactivity. Reducing obesity has demonstrated improved blood pressure, lipid, and glucose control. In fact, modest weight loss (5-10%) followed by weight maintenance/control is the recommended first-line treatment for the metabolic syndrome (i.e., hypertriglyceridemia, hypertension, low high density lipoprotein, and hyperglycemia), and for each of these disorders occurring independently. The goals of the proposed research program are to further the understanding of obesity among women in rural Kansas primary care settings, to develop a chronic care model approach for treating obesity among rural women primary care patients (phase 1), and to test a chronic care model program for obesity among rural women primary care patients (phase 2). During phase 1, we will conduct a series of three focus groups among obese primary care patients of each distinct primary care practice (i.e., 3 focus groups x 4 primary care practices=12 focus groups total). The goals of these 12 sessions will be to identify a) interest in losing weight, b) facilitators and barriers to losing weight, c) expected role of the primary care provider in diagnosing and managing weight, d) treatment preferences for weight loss and weight control, e) existing community resources for weight loss and weight control, and f) unique environmental features linked to weight loss and weight control.These proposed focus group themes are linked to the following chronic care model constructs: 1) patient self-management and activation, 2) clinical practice supports, and 3) community resources. Findings from the patient focus groups will be critical to the design of phase 2, during which we will pilot test a chronic care model program for obesity care among rural women primary care patients.

January 1, 2006-July 20, 2007

Karen E. Kuphal, Ph.D.SCHOLAR: Karen E. Kuphal, Ph.D., Assistant Professor, Department of Physical Therapy and Rehabilitation Science, School of Allied Health MENTORS: Peter G. Smith, Ph.D., Department of Molecular & Integrative Physiology, Director, Mental Retardation and Developmental Disabilities Research Center, School of Medicine, Lisa A. Stehno-Bittel, Ph.D., P.T., Associate Professor and Chair, Physical Therapy and Rehabilitation Science Department PROJECT TITLE: The Effect of Exercise on Hypersensitivity Between Males and Females in the Setting of Neuropathic Pain

ABSTRACT: Chronic pain in females has drawn increased attention due to an elevated number of reports of persistent pain, higher use of analgesic medications, lower pain thresholds with concurrent higher pain ratings, and less tolerance to noxious stimuli than males. Diabetic neuropathy, a form of neuropathic pain, has been implicated as a primary limiting factor for performing self-care behaviors responsible for minimizing disease-related complications in females. Reducing or eliminating neuropathic pain in females could improve adherence to self-care behaviors. Although several studies suggest that exercise can inhibit acute pain in the healthy individual, much less is known regarding the long lasting effects of exercise in individuals suffering from chronic (or neuropathic) pain-especially in the female population. To address this need, we are currently investigating the effects of exercise training on sensitivity in the setting of neuropathic pain. We incorporate models of diabetes and neuropathic pain in non-clinical and clinical settings to examine the effect of exercise in modulating this pain. Our goal is to evaluate exercise training as an effective treatment option to complement a multidisciplinary management plan for individuals with neuropathic pain.

July 1, 2006-June 30, 2008

Kristine WilliamsSCHOLAR: Kristine Williams, R.N., Ph.D., Assistant Professor, School of Nursing MENTOR: Carol E. Smith, R.N., Ph.D., School of Nursing PROJECT TITLE: Promoting Elder Women’s Functional and Cognitive Health in Assisted Living

ABSTRACT: Elder women are a vulnerable population expected to grow, reaching 71.5 billion by 2030. Because of rising life expectancies and chronic diseases, women represent over 75% of today’s 1.5 million nursing home residents, which will triple by 2050. Nursing home staff communication is critical to older residents, but research documents that it is infrequent, task-oriented, controlling, and patronizing. This poor communication has been shown to increase elder women’s physical dependency, depression, withdrawal, and cognitive decline. In contrast, staffs’ use of easily implemented communication interventions results in nursing home residents increased self-care, social engagement, satisfaction, and survival with reduced depression and cognitive decline.

Assisted living facilities are fast growing alternatives to nursing homes for elders. Assisted living facilities are logical sites to test communication interventions that promote independence, decision making, and physical and cognitive functioning. This proposed research will identify issues related to communication and functional abilities of women in assisted living. Nursing home communication interventions that have improved resident outcomes will be modified for women in assisted living and pilot tested. Effects of communication on reducing cognitive decline, depression, and dependency, the three key factors precipitating nursing home placement, will be evaluated as a basis for subsequent clinical trial research.

July 1, 2008 - August 31, 2008

Nikki Cheng, Ph.D.SCHOLAR: Nikki Cheng, Ph.D., Assistant Professor, Department of Pathology and Laboratory Medicine, Kansas Cancer Institute, School of Medicine MENTORS: Roy A. Jensen, M.D., Director, Kansas Masonic Cancer Research Institute and William R. Jewell Distinguished Kansas Masonic Professor, Department of Pathology & Laboratory Medicine, School of Medicine; Michael J. Soares, Ph.D., University Distinguished Professor and Vice Chair for Research, Department of Pathology and Laboratory Medicine, Director, Institute of Maternal-Fetal Biology Director, Division of Cancer & Developmental Biology, School of Medicine PROJECT TITLE: Potential Functions of the Inflammatory Chemokines, CCL2 and CXCL1 in Regulating the Breast Cancer Microenvironment

ABSTRACT: While studies in my postdoctoral laboratory show that CCL2 chemokine signaling interacts with TGF-beta signaling in fibroblasts, secretion of chemokines from fibroblasts has broader implications in breast cancer.  Studies performed in my postdoctoral laboratory have revealed that mouse and human fibroblast express a common set of chemokines, including CCL2 and CXCL1. These chemokines may play important roles in regulating epithelial cell invasion and metastatic spread carcinoma progression. In addition, CCL2 and CXCL1 may also play important roles in regulating the inflammatory process during carcinoma progression, in particular, recruitment of macrophages to the primary tumor site.  Tumor- associated macrophages have been shown to promote tumor growth by altering the tumor microenvironment, in part through secretion of angiogenic, survival and growth factors. Currently, the functional contribution of chemokine signaling in regulating fibroblast interactions with epithelial cells and immune cells during carcinoma progression remains largely unclear.

Based on published and unpublished findings, I am very interested in investigating the hypothesis that chemokine signaling regulates fibroblast interactions with carcinoma cells and macrophages to mediate breast carcinoma growth, invasion and metastatic spread. To address this hypothesis, I will focus on the following research areas:

  1. Examining the interactions between fibroblasts and epithelial cells during mammary carcinoma progression. This research area will encompass the use of transgenic and transplantable mouse models of breast cancer and human and mouse cell lines to understand the role of CCL2 chemokine signaling interactions between fibroblasts and epithelial cells in carcinoma growth, invasion and metastases.
  2. Examining the contribution of fibroblasts in regulating the inflammatory processes during carcinoma progression, in particular, recruitment of macrophages. This research area will encompass the use of transgenic mouse models of breast cancer, transplantable mouse models of cancer and human and mouse cell lines to understand the interactions between fibroblasts and immune cells in carcinoma growth, invasion and metastases.
  3. Analyzing the functional contributions of CCL2 and CXCL1 chemokine signaling in fibroblast: macrophage cell interactions and fibroblast: epithelial interactions at the cellular and molecular levels. This will encompass the use of cell culture systems, biochemistry and molecular biology techniques as well gene profiling technologies to identify and understand the signaling pathways involved in these regulating cell: cell interactions involved in these regulating cell: cell interactions in cell motility and invasion.
While diagnosis and treatment for breast cancer has steadily improved over decades, metastatic breast cancer is still a deadly disease with few treatment options. My long-term goals for this research are to understand the molecular and cellular functions of stromal cells in the tumor microenvironment during breast cancer progression, particularly during metastatic spread, which remains a leading cause of death among breast cancer patients. My hope is that this research will identify potentially novel signaling mechanisms for therapeutic intervention.

January 1, 2006 - December 31, 2008

Nicole L. Nollen, Ph.D.SCHOLAR: Nicole L. Nollen, Ph.D., Assistant Professor, Department of Preventive Medicine and Public Health, School of Medicine MENTORS: Susan E. Carlson, Ph.D., Professor, Department of Dietetics and Nutrition, School of Allied Health; Edward Ellerbeck, M.D., MPH, Associate Professor, Departments of Preventive Medicine and Internal Medicine and Interim Chair, Department of Preventive Medicine; Michael Rapoff, Ph.D., Professor, Department of Pediatrics. PROJECT TITLE: A Technology Delivered Intervention to Promote Healthy Habits and Prevent Weight Gain Among Rural Adolescents

ABSTRACT: The prevalence of overweight and obesity among children and adolescents in the United States has reached epidemic proportions. Children and adolescents residing in rural areas are at increased risk; however few obesity prevention interventions have been undertaken with this hard-to-reach population. The use of technology (e.g.,internet, hand-held computers, cell phones, pagers) as an intervention tool may offer a viable alternative. Specifically, these devices, which provide tremendous potential to develop and deliver highly tailored behaviorally-oriented obesity prevention interventions to individuals in virtually all settings, may be particularly advantageous in rural communities where access to behavioral treatment is limited. Given the paucity of data available on behaviorally-oriented obesity prevention approaches for rural adolescents, the primary aim of this pilot intervention is to develop and examine the feasibility and acceptability of a technology-delivered, obesity prevention intervention for 6th grade girls in rural Kansas. Two phases are proposed to accomplish this aim: Phase 1 will consist of a series of iterative focus groups with 6th grade girls and their parents to determine the preferred technology modality as well as the relevant content and themes. Phase II will consist of a small pilot study to examine the feasibility and acceptability of the technology-delivered behavioral intervention. Outcome variables will be measured at baseline, week 8 (end of treatment), and month 6 and will include nutrition and physical activity knowledge, changes in body mass index, dietary intake, screen time, sedentary behaviors, and physical activity. Process outcomes, including program satisfaction and use, personal relevance, and salience will also be measured.

January 1, 2007 - July 31, 2011

Sarah KiewegSCHOLAR: Sarah L. Kieweg, Ph.D., Assistant Professor, Mechanical Engineering, University of Kansas - Lawrence MENTOR: Kenneth L. Audus, Ph.D., Dean, School of Pharmacy, University of Kansas - Lawrence PROJECT TITLE: Optimizing Drug Delivery of Vaginal Anti-HIV Microbicides ABSTRACT: Microbicides - vaginally or rectally delivered anti-HIV products - hold great promise as new HIV prevention methods controlled by the woman. The goals of my 5-year research plan are to measure and model the biophysical processes governing vaginal drug delivery of microbicides, and to create tools for optimizing vaginal drug delivery. The central hypothesis is that the vaginal physical environment will determine how a gel is spread in the vagina, and will affect HIV transmission and epithelial permeability via cellular responses to mechanical stimuli. The proposed research is innovative because it capitalizes on new vaginal instruments designed to quantify unknown vaginal properties that will be used in new optimization tools. The outcomes of this research plan will be new information about (1) vaginal tissue properties, (2) mathematical models of non-Newtonian fluid flow, and (3) epithelial mechanotransduction, and its relationship to epithelial permeability and HIV transmission. The results of the proposed interdisciplinary research will benefit women’s health because the outcomes are a necessary step to making tools to efficiently design and optimize vaginal drug delivery. These screening tools will reduce the time and cost of clinical trials and help to bring urgently needed microbicides to women faster.

January 1, 2008 - July 31, 2011

Christie BefortSCHOLAR: Christie A. Befort, Ph.D., Assistant Professor, Preventive Medicine, School of Medicine MENTOR: Debra Sullivan, Ph.D. RD, Associate Professor and Chair, Dietetics and Nutrition, School of Allied Health and Edward Ellerbeck, MD MPH, Associate Professor and Chair, Preventive Medicine and Public Health, School of Medicine. PROJECT TITLE: Group Versus Individual Phone-Based Weight Management for Rural Women

ABSTRACT: Women of the most rural counties are 1.6 times more likely to be obese compared to suburban women, yet few studies have tested obesity interventions among rural women. Group phonebased weight loss treatment holds great promise because it has the most reach, is cost efficient, and capitalizes on the same mechanisms of face-to-face group treatment by allowing participants to develop support, accountability to one another, and problem-solving strategies that are believed to be important for successful outcomes. Although group treatment has resulted in greater weight loss than individual treatment when delivered face-to-face, it is unknown whether or not group treatment is more effective when delivered by phone. The purpose of this proposal is to develop and pilot test a behavioral weight loss treatment for obese rural women delivered in two formats: individual phone counseling and group phone counseling. It is hypothesized that compared to individual treatment, group treatment will result in greater weight loss and improvements in diet and physical activity behaviors at 16 and 24 weeks. We will also assess feasibility and acceptability, explore intervention treatment process variables that may influence effectiveness, and develop cost analysis procedures in preparation for a large-scale trial.

August 1, 2011- January 31, 2012

Cliff MasonSCHOLAR: Clifford Mason, PhD, Research Assistant Professor, Obstetrics and Gynecology, School of Medicine LEAD MENTOR: Carl Weiner, MD, MBA, Professor and Chair, Obstetrics and Gynecology, School of Medicne PROJECT TITLE: Impact of Pregnancy Related Disease on the Regulation of Placental Drug Transport

ABSTRACT: The core of my research focuses on the pathopharmacology of the maternal-placental-fetal unit. One third of preterm births are associated with inflammation frequently secondary to bacterial infection. Preliminary data indicate there is, in human placenta associated with chorioamnionitis, up-regulation of drug efflux pumps, multidrug resistance protein 1 (P-gp, MDR1) and breast cancer resistance protein (BCRP). Such changes could restrict the delivery of essential drugs to affected fetuses in contrast to unaffected fetuses. My proposed research addresses three core questions. First, how do pathophysiological responses to infection affect placental drug transporters? Second, do pathological changes in transporter expression levels correlate with placental transfer (and thus efficacy) of drugs targeted to the fetus? Finally, what are the regulatory pathways that drive transporter expression and can pharmacoresistance to drugs be overcome by targeted inhibition of proteins within these pathways? My research objective seeks to test the hypothesis that infection-induced chorioamnionitis alters the placental transfer of drugs through modulation of drug transport proteins, Mdr1a/b and Bcrp1 (mouse homologs), and that these changes are influenced by the activation of distinct signaling pathway(s). By the completion of these studies, I will have greatly expanded the existing knowledge of the regulation of transport mechanisms relevant to pregnancy.

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