Office of Research and Graduate Education


Appalachian Center for Cellular transport in Obesity Related Disorders (ACCORD)


Vision

Our vision is that the Marshall University Joan C. Edwards School of Medicine (MU JCESOM) Center of Biomedical Research Excellence (COBRE) named Appalachian Center for Cellular transport in Obesity Related Disorders (ACCORD) will be a national center of excellence focused on molecular mechanisms of cellular transport abnormalities in obesity-associated health disparities in West Virginia and Central Appalachia (WV/CA).

Project Summary

West Virginia is the only state that is entirely within historically and geographically defined Appalachia. Many of the innumerable health disparities of West Virginia and Central Appalachia have their roots in widespread obesity prevalent in the region. At the epicenter of these disparities, Marshall School of Medicine is well positioned to address these conditions.

There is strong junior investigators interest and senior investigators expertise in obesity-related cellular transport physiology at Marshall School of Medicine. Thus, the overall goal of this new Center of Biomedical Research Excellence (COBRE) application is to promote research training in obesity and related diseases emphasizing cellular transport in the next generation of biomedical investigators and to enhance the necessary infrastructure to accomplish this at Marshall School of Medicine.

The Appalachian Center for Cellular transport in Obesity Related Disorders (ACCORD) will serve as the academic home for this COBRE. ACCORD will leverage existing resources such as the WV IDeA Network of Biomedical Research Excellence (WV-INBRE) , excellent core facilities and new institutional resources to train the junior investigators. All COBRE projects are hypothesis-driven; with each addressing cellular transport in a distinct obesity-driven health complication, and each utilizing innovative experimental approaches (e.g., new polygenic models of obesity and effect of diet). An evaluation driven comprehensive and interactive mentoring plan with outstanding senior investigators that train the junior investigators to become independent scientists.

In order to sustain these many training opportunities while addressing one of the most prevalent diseases, obesity, that is at the heart of many health disparities in WV/CA and all other rural areas of this country, new resources (space, funding and faculty positions) have been committed to ACCORD by the institution. In turn, ACCORD, to enhance institutional obesity related biomedical research capacity, will develop new resources as future cores (e.g., Biostatistics and Study Design Resource), provide pilot funding and promote training of not just junior investigators, but the future generation of investigators (e.g., graduate students, post-doctoral fellows) as well. In summary, this ACCORD COBRE proposal is both innovative and significant. It focuses on a highly significant and extremely timely research problem, obesity and related disease. The novel projects of this COBRE will likely identify new targets that can potentially be modeled as new therapeutics to ameliorate and/or prevent obesity and related complications not only in WV/CA, but across the country.

Administrative Core


Sundaram
Uma Sundaram, MD
Chairman

Phone: (304) 691-1841
sundaramu@marshall.edu

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My training and career to date has ideally positioned me to serve as the Principal Investigator and Program Director of the Center of Biomedical Research Excellence (COBRE) ACCORD. I have demonstrated a commitment to basic, clinical and translational research since my undergraduate training in Bioengineering at Johns Hopkins University during which my research at the National Institutes on Aging led to multiple co-authored publications in blood brain barrier drug entry and distribution modeling. Since graduating from the Medical College of Ohio, completing my residency in internal medicine at the University of Michigan and gastroenterology subspecialty training at Yale University, I have been actively involved in patient care, teaching and research funded by NIH, AGA, AHA, and CCFA. Over the years investigator initiated and multi center prospective clinical studies have been in Hepatitis C, inflammatory bowel disease, peptic ulcer disease and Barrett’s esophagus. The basic and translational research has been funded by NIH RO1s and currently an NIH RO1 (DK 67420) to study regulation of glucose and Na homeostasis as it pertain to diseases such as obesity and hypertension. Most recently, I was the Principal Investigator of the newly funded NIGMS IDeA Clinical Translational Research (CTR) U54 grant (1 U54 RR033567-01) at the West Virginia Clinical and Translational Science Institute (WVCTSI).


Davies
Todd Davies, PhD
Assistant Professor
daviest@marshall.edu

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Dr. Davies has a diverse background. He received his Ph.D. in Medical Science from the University of Toledo Medical Center, his B.S. in Biology from Wesley College and his A.A.S. in Aerospace Ground Equipment from the Community College of the Air Force. Dr. Davies also served as the Commissioner of Economic Development for the City of Toledo and led the Bioscience activity of Rocket Ventures Pre-Seed Fund where he assisted in the creation and development of 22 medical technology start-up companies before joining another start-up, ADS Biotechnology, as its CEO.

Dr. Davies specializes in program planning and trial development.

Internal Advisory Committee (IAC)


An Internal Advisory Committee (IAC) has been established with senior leaders from MU JCESOM having the necessary expertise and experience in the success of the ACCORD and the COBRE. In addition to support and oversight of the progress of the COBRE, the IAC will hold quarterly progress meetings, review pilot grant proposals, and provide programmatic recommendations to the COBRE PD/PI. The IAC is also integral to the Evaluation Plan proposed for this COBRE. Emphasizing the importance of this COBRE for the institution, the Dean, Dr. Shapiro will chair the IAC, which will consist of the following individuals:

Davies
Joseph l. Shapiro, MD
Dean of School of Medicine
shapiroj@marshall.edu

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I have been the Dean of the Joan C Edwards School of Medicine (JCESOM) since July of 2012. Prior to this position, I served as Chairman of Medicine at the University of Toledo for nearly 14 years. Despite these administrative positions, I have been an active researcher for my entire career. My research has focused on the intersection between kidney and cardiovascular disease, and I have been active in both bench and clinical research. In particular, I have participated as the enrollment chairman for the CORAL trial which has recently been concluded, and I remain extremely interested Na/K-ATPase signaling and its relevance to disease.


Davies
John Maher, PhD
Vice President for Research
maherj@marshall.edu

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The COBRE proposal requires scientific and managerial leadership at the institutional, state and inter-institutional level to develop the collaborative and participative atmosphere necessary for effective performance. I have a broad background in scientific leadership and management of cross-functional programs that will facilitate Marshall’s successful growth through the project and the successful achievement of multi-institutional project objectives. My expertise in strategic planning and management of large, complex projects will be applied at the steering team level to assure that the organizational foundation of the project components is properly designed and executed.


Sundaram
Monica Valentovic, PhD
Professor & Research Cluster Coordinator

Phone: (304) 696-7332
valentov@marshall.edu

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Obesity is a serious health condition within the United States that contributes to increasing the risk of other disease. The current statistics have reported that 33% of Americans are obese. In West Virginia the incidence of obesity is over 35%. Postmenopausal women who are obese have a higher risk of developing breast cancer. It is anticipated that almost 232,000 women will be diagnosed with breast cancer in 2015 and many of these individuals will be obese. The mechanism for the increased risk of cancer in obesity is not known and probably is mediated through a complex interaction of various factors. New treatment modalities are needed to address reducing the development of breast cancer.


Davies
Nader G. Abraham, PhD, Dr. H.C., FAHA
Professor of Medicine and Pharmacology
New York Medical College
nader_abraham@nymc.edu

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My long-lasting research program centers on the biochemistry, biology and functional/clinical relevance of the heme-heme oxygenase (HO) system. As a postdoctoral fellow in the laboratory of Dr. Kappas at the Rockefeller University, I purified HO from rat and human liver and characterized its catalytic properties. I continued exploring the biology of HO throughout my scientific career in a prolific research program that made seminal contributions to this field of research.


Sundaram
Uma Sundaram, MD
Chairman

Phone: (304) 691-1841
sundaramu@marshall.edu

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My training and career to date has ideally positioned me to serve as the Principal Investigator and Program Director of the Center of Biomedical Research Excellence (COBRE) ACCORD. I have demonstrated a commitment to basic, clinical and translational research since my undergraduate training in Bioengineering at Johns Hopkins University during which my research at the National Institutes on Aging led to multiple co-authored publications in blood brain barrier drug entry and distribution modeling. Since graduating from the Medical College of Ohio, completing my residency in internal medicine at the University of Michigan and gastroenterology subspecialty training at Yale University, I have been actively involved in patient care, teaching and research funded by NIH, AGA, AHA, and CCFA. Over the years investigator initiated and multi center prospective clinical studies have been in Hepatitis C, inflammatory bowel disease, peptic ulcer disease and Barrett’s esophagus. The basic and translational research has been funded by NIH RO1s and currently an NIH RO1 (DK 67420) to study regulation of glucose and Na homeostasis as it pertain to diseases such as obesity and hypertension. Most recently, I was the Principal Investigator of the newly funded NIGMS IDeA Clinical Translational Research (CTR) U54 grant (1 U54 RR033567-01) at the West Virginia Clinical and Translational Science Institute (WVCTSI).

Mentoring Committee

Receipt of this COBRE grant will allow the individual junior investigators the unique opportunity for not only substantial financial support but also focused mentoring opportunities to aid them with the move to independence. Many IDeA institutions lack the senior funded faculty “bench strength.” While we have been actively growing this critical mass over the last few years at MU JCESOM, it behooves us to realize, mentoring requires a “village” having a deliberate infrastructure, not just individual mentors. Therefore, we had established a Mentoring Committee (MC) more than a year ago which includes not only individual project mentors, but also senior investigators from across the MU JCESOM with an equally impressive track record of investigation and mentorship. The junior investigators and mentors have been meeting regularly for more than a year to not only conduct review of research projects and grant proposals, but also to discuss career trajectories and pathways, promotion and tenure, time, fiscal and lab management, and networking. The MC is chaired by Dr. Elaine Hardman. In this capacity she will coordinate mentoring for this COBRE proposal. She has had an active and well-funded research laboratory for more than 20 years. As a Senior Faculty member in Biomedical Sciences, she has mentored newer faculty members including Drs. Piyali Dasgupta, Maria Serrat and Travis Salisbury. Drs. Dasgupta and Serrat have obtained NIH R15 funding and all are making good progress toward independence. Participation in ACCORD COBRE will greatly enhance this progress. Along with the MC, Dr. Hardman will coordinate mentoring activities to insure that mentors and junior investigators are meeting regularly and that junior investigators are receiving the expected guidance. She will review mentors’ quarterly reports prior to the IAC and EAC meetings and prepare a summary for these committees. She will review attendance at seminars, meetings with visiting professors and meeting presentations to ensure that junior investigators are meeting these obligations as outlined in their quarterly plans. The Mentoring Committee members are (in addition to individual project mentors in table below):

Gress
W. Elaine Hardman, PhD
Professor, Department of Biochemistry & Microbiology
hardmanw@marshall.edu

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I have almost 25 years of experience in studies on dietary interventions against cancer. About 20 years ago, my research evolved into studies of the effects of dietary fat, especially omega 3 fats on cancer growth and response to chemotherapy using xenograft models. My research remains focused on omega 3 fats and cancer using various models (including xenograft, carcinogen treated and transgenic models) and experimental designs to answer different experimental questions. I have completed a small clinical trial to assess the effects of omega 3 fatty acids on NFkB activation in the lymphocytes of patients with chronic lymphocytic leukemia. This study clearly demonstrated the ability of omega 3 supplementation to significantly reduce NFkB activation and to induce histone modification in the cancerous cells. I have 2 other pilot clinical trials in progress.


Sundaram
Richard Egleton, PhD
Associate Professor, Research Cluster Coordinator, & Co-Director of Biomedical Sciences Graduate Program

Phone: (304) 696-3523
egleton@marshall.edu

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I have two main roles in the CoBRE application. My primary role as co-director of the Biomedical Sciences program is to help mentor the COBRE mentees in graduate education. This includes guiding the CoBRE mentees through the various rules and regulations that govern graduate education, as well as being a resource for helping them develop mentoring plans and mentoring contracts with both undergraduate and graduate students that work in their laboratories. My secondary role in the grant is as another researcher with transport experience. My research over the last 20 years has focused on several aspects of transport and drug delivery during disease. This includes investigating the regulation of both transcellular transport and paracellular transport routes. Though these studies have largely been looking at the blood brain barrier, many of the core concepts (regulated ion transport, tight junctions) are common to other barrier tissues like the gut and kidney.


Sundaram
Todd L. Green, PhD
Associate Professor & Co-Director of Graduate Studies

Phone: (304) 696-3531
green@marshall.edu

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I am well suited for this project because of my role as Director of Graduate Studies of the Biomedical Sciences (BMS) Program. My responsibilities include managing admissions for M.S., Ph.D., and M.D./Ph.D. students, advising the M.S. and first year Ph.D. students, directing the M.D./Ph.D. program, and counseling students on education and career options. In this project I would be performing these duties with prospective and current students.

I am director for all of the introductory biochemistry and cell biology courses currently being taught to graduate students in the program, and I teach in many other courses. I also would be involved in developing new courses. This experience in teaching and leading the courses the students in our program take will be beneficial to this project.


Gress
Todd Gress, MD, MPH
MCRC Medical Director
gress@marshall.edu

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I have the expertise, leadership, training, and motivation necessary to successfully support the Biostatistics and Study Design Resource proposed in this COBRE titled Appalachian Center for Cellular transport in Obesity Related Disorders (ACCORD). I have a strong background in Biostatistics and Epidemiology. I have been teaching Biostatistics and Epidemiology for over 15 years. During this time, I have assisted numerous students, residents, and faculty with their research projects. This effort has led to numerous abstracts, regional and national presentations, and publications. We have formalized this process of assisting trainees and faculty in research through development of the Biostatistics and Study Design Clinic in the Department of Clinical and Translational Sciences (DCTS). I also serve as the medical director for clinical trials, overseeing all clinical trials activity for the school of medicine, including investigator-initiated clinical trials. I am actively involved in all of the pilot award efforts in the school of medicine, having served in the roles of leader, reviewer, and pilot award selection committee member.


Davies
Jung Han Kim, PhD
Professor, Department of Pharmacology
kimj@marshall.edu

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My experience and qualifications make me well suited for serving as a mentor in the project. Over the several years, I supervised more than one hundred undergraduate and twenty graduate students. I served as a Member in twenty graduate student thesis committees and served as Advisor/Chair for six M.S. and Ph.D. students. I have mentored three postdoctoral fellows who became a successful independent scientist. With my mentees I have produced multiple peer-reviewed publications. In addition, I have a solid background in genetics, nutritional sciences and physiology, with specific training and expertise in gene mapping, positional cloning, and physiological analysis. My research includes identifying genetic factors underlying obesity and type 2 diabetes and the related pathophysiological pathways. With my research endeavors I have developed useful animal models for obesity and type 2 diabetes including TALLYHO mice that are well served in the project. As PI on several Foundation- and NIH-funded grants, I have built a strong research program and have a track record of accomplished and productive research projects.


Davies
Hartmut H. Malluche, MD, F.A.C.P.
Chief, Division of Nephrology, Bone and Mineral Metabolism

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I have trained over 90 students, residents, fellows and young faculty members for over 30 years. My particular focus is now on raising young faculty to become academically-oriented investigators rather than merely acquiring clinical knowledge that is applied to patients in a private practice setting. For decades, I have been conducting NIH-funded research in renal osteodystrophy. The following references highlight my experience and qualification for this project.


Sundaram
Gary O. Rankin, PhD
Professor & Chair

Phone: (304) 696-7319
rankin@marshall.edu

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I am well qualified to serve as a mentor for junior scientists. I was Chair of the Department of Pharmacology from 1986-2005, and when my department was merged with the Department of Physiology, I was made Chair of the combined department, a position I still hold. Over the years, I have mentored numerous undergraduate (26), graduate (40) and medical students (18), postdoctoral fellows (7) and faculty members, both within and outside my department and institution. In addition, I am the principal investigator of the NIH-funded West Virginia IDeA Network of Biomedical Research Excellence (WV-INBRE). In this capacity, I oversee a state-wide network composed primarily of new investigators at primarily undergraduate institutions across West Virginia, and serve as mentor for several of them.


Santanam
Nalini Santanam, PhD, MPH, FAHA
Professor & Research Cluster Coordinator

Phone: (304) 696-7321
santanam@marshall.edu

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My laboratory, located at Marshall University School of Medicine, studies cardiometabolic disorders (atherosclerosis and obesity) and endometriosis. I have studied atherosclerosis for over 15 years and was funded a NIH R01 grant to study the effects of oxidized lipids in cardiovascular disease. I have been interested in studying the relationship between obesity and chronic inflammatory diseases such as coronary artery disease and diabetes. My current projects include (i) the effect of diet and exercise on microbiome changes and appetite regulation in a new “stress-less” mouse model of obesity; (ii) I have established collaborations with physicians from the Department of Cardiology and Thoracic Surgery and initiated the WV-Appalachian Heart Study, to study sex specific biomarkers in epicardial fat and its relation to coronary artery disease, hypertension and diabetes. I obtained a two-year NIH funding for this translational pilot project; (iii) In collaboration with the Department of Endocrinology, studying the effect of cell- phone technology on diabetic management in patients from rural West Virginia. My role in this study is to identify biomarkers of diabetes that are modified due to the study intervention. (iv) I was recently funded by National Institutes of Aging (R15) to study the role of microRNA editing in the adipose dysfunction seen with aging. My laboratory is well equipped to perform obesity related diseases. As the coordinator of the Cardiovascular, Obesity and Diabetes Research Cluster at Marshall University, it gives me a unique opportunity to collaborate with other scientists within Marshall SOM with similar research interests. I have more than 20 years of experience in mentoring undergraduate and graduate students as well as residents and clinical fellows.


Sundaram
Uma Sundaram, MD
Chairman

Phone: (304) 691-1841
sundaramu@marshall.edu

Click Here to View BioSketch

My training and career to date has ideally positioned me to serve as the Principal Investigator and Program Director of the Center of Biomedical Research Excellence (COBRE) ACCORD. I have demonstrated a commitment to basic, clinical and translational research since my undergraduate training in Bioengineering at Johns Hopkins University during which my research at the National Institutes on Aging led to multiple co-authored publications in blood brain barrier drug entry and distribution modeling. Since graduating from the Medical College of Ohio, completing my residency in internal medicine at the University of Michigan and gastroenterology subspecialty training at Yale University, I have been actively involved in patient care, teaching and research funded by NIH, AGA, AHA, and CCFA. Over the years investigator initiated and multi center prospective clinical studies have been in Hepatitis C, inflammatory bowel disease, peptic ulcer disease and Barrett’s esophagus. The basic and translational research has been funded by NIH RO1s and currently an NIH RO1 (DK 67420) to study regulation of glucose and Na homeostasis as it pertain to diseases such as obesity and hypertension. Most recently, I was the Principal Investigator of the newly funded NIGMS IDeA Clinical Translational Research (CTR) U54 grant (1 U54 RR033567-01) at the West Virginia Clinical and Translational Science Institute (WVCTSI).


Sundaram
Monica Valentovic, PhD
Professor & Research Cluster Coordinator

Phone: (304) 696-7332
valentov@marshall.edu

Click Here to View BioSketch

Obesity is a serious health condition within the United States that contributes to increasing the risk of other disease. The current statistics have reported that 33% of Americans are obese. In West Virginia the incidence of obesity is over 35%. Postmenopausal women who are obese have a higher risk of developing breast cancer. It is anticipated that almost 232,000 women will be diagnosed with breast cancer in 2015 and many of these individuals will be obese. The mechanism for the increased risk of cancer in obesity is not known and probably is mediated through a complex interaction of various factors. New treatment modalities are needed to address reducing the development of breast cancer.


Sundaram
Zijian Xie, PhD
Director, Marshall Institute of Interdisciplinary Research (MIIR)

Phone: (304) 696-3852
xiez@marshall.edu

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For the past 25 years, I have been interested in the cell biology of Na/K-ATPase in epithelial and cardiac cells. Specifically, I have been focused on revealing the non-pumping functions of this plasma membrane protein. Much of this investigation has been funded by grants from NIH. My lab has demonstrated that the Na/K-ATPase has an ion-pumping independent signaling function. Moreover, we have shown the relevance of the signaling function of Na/K-ATPase to the pathophysiology of renal and cardiovascular diseases. Recently, we have developed a novel peptide (pNaKtide) antagonist of receptor Na/K-ATPase and shown that pNaKtide blocks ouabain-induced signal transduction in cultured cardiac myocytes. We have further demonstrated the effectiveness of pNaKtide in intact animals. In the current project, Dr. Jiang Tian proposes to study the role of Na/K-ATPase and its signaling function in regulating cardiac fibrosis through miR-29b related mechanism using an animal model with chronic kidney disease. Dr. Tian’s lab has found that pNaKtide can attenuate ouabaininduced decrease in miR-29b expression, which is a novel finding and will potentially advance the understanding the role of Na/K-ATPase on regulation of cardiac fibrosis in CKD models. I will collaborate with Dr. Tian and provide him with my expertise and established tools for the proposed studies.

Project Investigators

Project 1 - Regulation of sodium dependent bile acid absorption in obesity

Mentor: Dr. Jung Han Kim

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Arthur
Subha Arthur, PhD
Assistant Professor

arthursu@marshall.edu

Dysregulation of lipid homeostasis is a key characteristic of obesity, resulting in sequelae such as diabetes, cardiovascular diseases, fatty liver diseases, etc. Assimilation of lipids is entirely dependent on bile acid availability in the intestine. Bile acids are absorbed in the terminal ileal villus cell brush border membrane (BBM) via Na-bile acid-co-transporter (ASBT) requiring a favorable transcellular Na gradient provided by basolateral membrane (BLM) Na/K-ATPase. Novel preliminary findings suggest that in multiple species (including human), ASBT is upregulated secondary to Na/K-ATPase downregulation. Thus, the hypothesis of this project is that ASBT is uniquely regulated at the level of the cotransporter in the BBM, along with Na/K-ATPase in the BLM in intestinal cells during obesity. The observations of this study will result in novel data which will enhance our understanding of bile acid absorption, thereby, lipid assimilation dysregulation during obesity, and potentially lead to more efficacious treatment modalities.


Project 2 - Oxidative Stress and Impaired Renal Sodium Excretion in Obesity: role of Na/K-ATPase signaling

Mentor: Dr. Gary Rankin

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Yanling
Yanling Yan, PhD
Assistant Professor

yan@marshall.edu

Obese individuals commonly have hypertension (HTN) and both obese animals and humans are at a higher risk of developing HTN. Obesity appears to be an important cause of treatment-resistant hypertension. However, the underlying mechanism of obesity-induced HTN is not fully understood. Chronic oxidant stress mediated by reactive oxygen species is well known in obesity. Studies have shown that protein carbonylation, a widely accepted marker for oxidative stress, is pervasive in renal proximal tubular (PT) Na/K-ATPase in hypertensive and obese mice. Thus, the central hypothesis of this proposal is that chronic oxidant stress leads to pervasive carbonylation of the renal PT Na/K-ATPase, which in turn leads to resistance to cardiotonic steroid mediated signal transduction and natriuresis. Because of this, animals with chronic oxidant stress induced by obesity have impaired natriuresis in response to increases in dietary Na and become hypertensive. The results of this study will provide compelling and novel data that Na/K-ATPase/Src/ROS signaling mediated renal PT Na handling is responsible for blood pressure regulation and that obesity impairs this handling because of excessive oxidant stress. These findings will potentially lead to new targets for interventions in obesity related hypertension.


Project 3 - Inhibition of Leucine-Stimulated Induction of mTOR1 to Suppress Breast Cancer in Obesity

Mentor: Dr. Uma Sundaram

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Salisbury
Travis Salisbury, PhD
salisburyt@marshall.edu

Obesity is a risk factor for breast cancer, a disease that was diagnosed in nearly 3 million women in this country in 2015. Based on preliminary data, it is hypothesized that altered levels of adiponectin, leptin, and estrogen hormones found in obesity interact to activate the L-Type Amino Acid Transporter 1 (LAT1) gene. The LAT1 gene encodes an amino acid transporter that specifically promotes the uptake of neutral amino acids, including leucine. High intracellular levels of leucine are required for the activation of Mechanistic Target of Rapamycin (mTOR), a kinase that is critical to tumor growth. It is proposed that leucine-mediated increases in mTOR activity in breast cancer cells in obese women, compared with lean women lead to larger, more aggressive breast tumors that are more resistant to cancer therapy. It is anticipated that findings of this proposal will significantly enhance our understanding of obesity associated breast cancer and will potentially lead to new and more efficacious therapeutic options.


Project 4 - Dysregulated Growth Factor Transport and Accelerated Bone Elongation in Childhood Obesity

Mentor: Dr. Hartmut Malluche

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Serrat
Maria Serrat, PhD

Serrat@marshall.edu

Appalachia (WV) leads the nation in childhood obesity with about 1 in 3 children already overweight or obese. Obese children have higher rates of linear growth, accelerated skeletal maturation, and diminished bone quality. These factors can contribute to painful and debilitating conditions such as limb bowing, joint instability, fractures, and slipped capital femoral epiphyses. Insulin-like growth factor (IGF)-I, is one of two essential hormones (Growth Hormone is the other) needed for proper bone growth and is altered in obesity. Novel preliminary data demonstrate that IGF binding proteins (IGFBPs) may regulate bone elongation by entrapping IGF-I and limiting its transport into the growth plate; however, IGFBPs levels are diminished in obesity. Thus, the overall hypothesis is that a decrease in local IGF binding proteins promotes bone lengthening by allowing more IGF-I transport into growth plates. Better understanding of how the perichondrium IGF binding proteins regulate IGF-I transport into growth plates will potentially result in IGFBP based therapies to modulate the rate of bone elongation in obesity, and thus minimize the associated obesity related morbidities of childhood.


Project 5 - Regulation of Tight Junction Molecular Composition by Na/K-ATPase

Mentor: Dr. Zijian Xie

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Larre
Isabel Larre', PhD
Assistant Professor

perezm@marshall.edu

Obesity is not only a risk factor for hypertension, but also causes hypertension to be more resistant to conventional treatment. Renal tubular cell transport of Na, mediated by Na/K-ATPase, as well as paracelluar movement of Na across tight junctions, is central to the pathogenesis of hypertension. Na handling, Na/K-ATPase and tight junctions are all altered in obesity associated hypertension. However, it is unknown whether the Na/K-ATPase signaling via cardiotonic steroids and Src (also known to be altered in obese hypertensive animals) may mediate the alterations in tight junction permeability. Novel preliminary studies demonstrated that ouabain activated Src and decreased paracellular permeability by changing the composition of tight junctions. Thus, the overall hypothesis of this proposal is that Na/K-ATPase regulates tight junctions by altering their molecular composition through Src-related pathways to affect renal handling of Na in hypertension associated with obesity. The findings of this study will reveal a novel regulatory function of Na/K-ATPase in the formation of tight junctions in obesity related hypertension and potentially result in new and more efficacious treatment options.

Evaluation Team

Sundaram
Uma Sundaram, MD
Chairman

Phone: (304) 691-1841
sundaramu@marshall.edu

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My training and career to date has ideally positioned me to serve as the Principal Investigator and Program Director of the Center of Biomedical Research Excellence (COBRE) ACCORD. I have demonstrated a commitment to basic, clinical and translational research since my undergraduate training in Bioengineering at Johns Hopkins University during which my research at the National Institutes on Aging led to multiple co-authored publications in blood brain barrier drug entry and distribution modeling. Since graduating from the Medical College of Ohio, completing my residency in internal medicine at the University of Michigan and gastroenterology subspecialty training at Yale University, I have been actively involved in patient care, teaching and research funded by NIH, AGA, AHA, and CCFA. Over the years investigator initiated and multi center prospective clinical studies have been in Hepatitis C, inflammatory bowel disease, peptic ulcer disease and Barrett’s esophagus. The basic and translational research has been funded by NIH RO1s and currently an NIH RO1 (DK 67420) to study regulation of glucose and Na homeostasis as it pertain to diseases such as obesity and hypertension. Most recently, I was the Principal Investigator of the newly funded NIGMS IDeA Clinical Translational Research (CTR) U54 grant (1 U54 RR033567-01) at the West Virginia Clinical and Translational Science Institute (WVCTSI).


Gress
W. Elaine Hardman, PhD
Professor, Department of Biochemistry & Microbiology
hardmanw@marshall.edu

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I have almost 25 years of experience in studies on dietary interventions against cancer. About 20 years ago, my research evolved into studies of the effects of dietary fat, especially omega 3 fats on cancer growth and response to chemotherapy using xenograft models. My research remains focused on omega 3 fats and cancer using various models (including xenograft, carcinogen treated and transgenic models) and experimental designs to answer different experimental questions. I have completed a small clinical trial to assess the effects of omega 3 fatty acids on NFkB activation in the lymphocytes of patients with chronic lymphocytic leukemia. This study clearly demonstrated the ability of omega 3 supplementation to significantly reduce NFkB activation and to induce histone modification in the cancerous cells. I have 2 other pilot clinical trials in progress.


Davies
John Maher, PhD
Vice President for Research
maherj@marshall.edu

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The COBRE proposal requires scientific and managerial leadership at the institutional, state and inter-institutional level to develop the collaborative and participative atmosphere necessary for effective performance. I have a broad background in scientific leadership and management of cross-functional programs that will facilitate Marshall’s successful growth through the project and the successful achievement of multi-institutional project objectives. My expertise in strategic planning and management of large, complex projects will be applied at the steering team level to assure that the organizational foundation of the project components is properly designed and executed.


Davies
Donald A. Primerano, PhD
Professor; Microbiology Section Head; and Co-Director, Genomics and Bioinformatics Core Facility
primeran@marshall.edu

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My primary research interests are in the discovery of chronic disease susceptibility genes using next generation sequencing, expression profiling and bioinformatic approaches. I currently serve as the Co-Director of the Genomics and Bioinformatics Core Facility (GABC) and as a member of the WV-IDeA Network of Biomedical Research Excellence (WV-INBRE) Administrative Core and WV Cancer Genomics Steering Committee. I have served as the Genomics Core Director from 1999-2011. As Co-Director, I have experience in (1) developing sequencing strategies and service relationships between the GABC and research networks needing genomic analyses, (2) providing overall direction to a core with evolving technologies and institutional responsibilities, (3) assisting individual investigators in designing genomic experiments and (4) providing training in genomic technologies.