Ohio University
Heritage College of Osteopathic Medicine
Office of Research & Grants
Research & Scholarly Advancement Fellowship
Summer, 2014
APPLICATION DEADLINE: February 10, 2014
ACCEPTANCE NOTIFICATION: March 7, 2014
PROGRAM DATES: June 2 - August 8, 2014
Since 1978, OU-HCOM has sponsored a program to provide summer research experiences to medical
students. We invite you to help us celebrate the past 36 years and continue the tradition in the future.
Summary of Program
The core of the program is a research project that you will pursue under faculty direction. Projects can
include contributing to ongoing faculty research in the laboratory or clinic or initiation of your own
project under faculty direction. In addition to your research project, you will be required to attend the
program orientation, seminars on various research topics, and the program closing session; submit project
progress reports; and prepare and present a poster on the project at the OU-HCOM Research Day during
the fall semester following the fellowship program.
The fellowship pays $3,000 to assist fellows with living expenses over the ten-week program. Fellowship
payments will be paid intermittently throughout the program and will be paid through the Disbursement
Office, located in Chubb Hall.
Upon successful completion of the fellowship program, fellows will receive one hour of academic credit.
There will be no tuition cost to the fellows for participation in the program and the program will be
graded on a pass/fail basis. Upon acceptance into the program, fellows will be required to register for the
fellowship with the permission of the Office of Research & Grants.
Funding for up to four RSAF fellowship awards will be provided by the Osteopathic Heritage Foundations.
Funding for up to eleven RSAF fellowship awards will be provided by OU-HCOM. Additional RSAF
fellowship awards may be made based on the availability of funds.
Eligibility
All students who will successfully complete the Year 1 medical school curriculum by the end of spring
semester 2014 are invited to apply for the Research & Scholarly Advancement Fellowship (RSAF) program.
Students must also be in good professional and judicial standing at the time of application through the
completion of the program (OU-HCOM Research Day). This ten-week summer program is designed to
introduce osteopathic students to basic science and clinical research and scholarly activities under the
guidance of an OU-HCOM faculty mentor.
Student Selection



Faculty mentors will be provided with the applications for students who have applied to work with
the mentor and on his/her research project. After review of applications and consultation with
applicants, mentors are required to rank applicants in order of preference.
After all mentor rankings have been received, the Office of Research & Grants will then review
rankings and place students. We will make our best effort to place students according to the
faculty mentor’s preference, but there is no guarantee. Final placement of students will be made
at the discretion of the Office of Research & Grants.
Exceptions to the student selection process will be made for students participating in the DO/PhD
program through the OU-HCOM Office of Advanced Studies. These students are not exempt
from the application process, but will be guaranteed placement within the RSAF program due
to their required participation as part of the DO/PhD program.
Conditions of Appointment
Appointment of a fellow is contingent upon successful completion of the Year 1 medical school
curriculum by the end of spring semester 2014 and that the student is in good professional and judicial
standing at the time of application through the completion of the program (OU-HCOM Research Day).
Fellows are expected to conduct research according to the highest scientific and ethical standards and in
compliance with all applicable laws, regulations, and policies regarding protection of human research
subjects, humane care and use of laboratory animals, and laboratory safety.
Application Process
1.
2.
3.
Read the faculty mentor/research project profiles provided. You must select only from faculty
mentors/research projects included in this application package.
Contact the faculty mentor(s) with whom you may be interested in working and talk with them about
your interests. Students must consult with potential faculty mentors, in person, prior to submission of
the student application package. Complete the Project Discussion Form (signed by both you and
your proposed faculty mentor) and return it as part of your application package. One form must be
completed for each faculty mentor/research project for which you are applying.
Complete and return the RSAF application package (provided), no later than Monday, February 10,
2014. Application package includes:
 Document Checklist Form – Applicant must sign this form and insure that all documents are
included
 Program Application Form – Applicant must sign this form
 Driver’s License and Ohio University Identification Card – Copy of driver’s license and OU ID
card
 Résumé/Curriculum Vitae – Must include: academic history, employment history, research
experience, list of honors/awards received, and publications
 Project Discussion Form(s) – Applicant and Faculty Mentor(s) must sign this form. One form is
required for each project for which the student applies.
Submission Procedures
Application Deadline: February 10, 2014
All forms must be submitted in one large envelope by the application deadline. Electronic applications
will not be accepted. Please deliver application envelopes to:
Jessica Wingett
Office of Research & Grants
234 Grosvenor Hall
IMPORTANT DATES
Application Deadline
Acceptance Notification
Program Begins/Orientation Session
Research Seminars
Program Ends/Closing Session
February 10, 2014
March 7, 2014 (approximate)
June 2, 2014
June 2-6, 2014
August 8, 2014
For more information, contact:
Jessica Wingett, Program Director, at 740-593-2336 or [email protected]
Ohio University
Heritage College of Osteopathic Medicine
Office of Research & Grants
Research & Scholarly Advancement Fellowship
Summer, 2014
CHECKLIST
To the Applicant:
Please complete and sign below. Make sure to have ALL requirements in one sealed envelope.
Incomplete application packages will NOT be reviewed.
 Document Checklist Form – Sign below and include this form in application envelope
 Program Application Form
 Driver’s License and Ohio University Identification Card – Copy of driver’s license and OU ID
card
 Résumé/Curriculum Vitae – Must include: academic history, employment history, research
experience, list of honors/awards received, and publications
 Project Discussion Form – Applicant and Faculty Mentor(s) must sign this form. One form is
required for each project for which the student applies.
I verify that I have included all of the above documents in my application package. I understand that if all
of the above documents are not included, my application will not be reviewed.
Name of Applicant: __________________________________________________________________________________________
______________________________________________
Signature of Applicant
___________________________________________
Date
Ohio University
Heritage College of Osteopathic Medicine
Office of Research & Grants
Research & Scholarly Advancement Fellowship
Summer, 2014
PROGRAM APPLICATION
General Information
Applicant’s Name (Last, First, Middle Initial)
Daytime Phone
Date of Birth (mm/dd/yy)
Evening/Alternate Phone
OU PID #
Email (OHIO)
Current Mailing Address (Street and Apt. or PO Box Number, City, State, Zip Code)
Permanent Mailing Address (if different than above)
Program Preferences
Choose faculty mentor/research project in preference order (maximum 2 options)
1.
2.
Colleges or Universities Attended: (start with most recent)
Name of School, City, State
Degree
Date of
Degree
Major
Minor
1. Describe honors, hobbies, special interests or previous work experience that you would
like considered. (use additional pages as needed)
2. Have you done research or independent study previously?
If yes, please describe:
3. Publications? (List)
YES
NO
4. Why did you decide to apply for this program? How will it help you?
Use additional pages as needed
Certification & Eligibility Verification
I certify that the above information is accurate and true to the best of my knowledge. I give permission to
the Ohio University Heritage College of Osteopathic Medicine Office of Research & Grants to share this
information for the purpose of recruitment, placement, monitoring, and evaluation. I certify that I meet all
the eligibility criteria stated in the Research & Scholarly Advancement Fellowship Program Summary.
Name of Applicant: ___________________________________________________________________________________________
_______________________________________________
Signature of Applicant
___________________________________________
Date
Ohio University
Heritage College of Osteopathic Medicine
Office of Research & Grants
Research & Scholarly Advancement Fellowship
Summer, 2014
PROJECT DISCUSSION FORM
This form is designed to insure that students and faculty members meet (in person) to discuss projects
that interest students prior to application. This meeting will provide students and faculty members with
an opportunity to meet outside of the classroom, discuss the project and the fellow’s role in the project,
and allow for questions. This form must be completed by the student, signed by both the student and
faculty mentor and included in the application package. One form must be completed and included
for each project for which the student applies.
Applicant Name
Faculty Mentor
Project Title
Meeting Date
1. Overall Objective/Goal of the Project
2. Role of Fellow in Project
3. Role of Fellow in Lab/Clinic
4. Other (if applicable)
_______________________________________________
Signature of Applicant
_______________________________________________
Date
_______________________________________________
Signature of Faculty Mentor
_______________________________________________
Date
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
Jane Broecker, MD
Department of Obstetrics & Gynecology
River Rose Ob/Gyn
75 Hospital Drive, Suite 260, Athens
(740) 818-6267 (Cell)
Email: [email protected]
Project Classification:
Clinical Research & Social/Behavioral Research
Techniques and/or skills that the student will learn:
1. Data Analysis
2. Writing a research paper
3. Working with computer specialists
4. Informed Consent
5. Potentially, study design and the IRB process
Project Title: Internet Impressions of Long Acting Contraceptive Methods: College students' impressions
of internet based health information concerning contraceptive devices.
Project Description:
My ongoing research is about long acting contraceptives and our ongoing project will involve data
analysis of surveys administered by our student from last summer, Robin Fuchs. We will be working with
Joan Jurich to code the responses and analyze the data collected. We will write a paper about our
findings and how knowledge and attitudes toward contraceptives may affect decision making about birth
control, and how parental influences affect patient attitudes.
My new study will be a study about how female (and possibly male) college students interact with the
internet to find information on short acting and long acting methods of contraception. This will involve
working with computer specialists, learning how to contact and consent patients for the study, and
analysis of the data collected. It has not yet been submitted for IRB approval, but I anticipate approval in
the Spring.
I would also welcome a student to create his or her own study and go through the design, creation and
IRB approval of a simple study, if he or she desires.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
Brian Clark, PhD
Department of Biomedical Sciences
251 Irvine Hall
(740) 593-2354
Email: [email protected]
Project Classification:
Basic Science & Clinical Research
Techniques and/or skills that the student will learn:
1. Clinical trial management
2. EMG
3. Brain stimulation
Project Description:
Dr. Clark, and other scientists affiliated with the Ohio Musculoskeletal and Neurological Institute (OMNI),
embrace a team-based approach to science. Accordingly, students rotating through OMNI will be asked
to assist will all ongoing research projects as needed. Some of these will be massive ongoing projects and
others will be projects that are just starting up and/or in development. At this time, it is not possible to
state exactly which projects the student will be most heavily engaged as it will depend on the status of
projects, grants, etc. The Ohio Musculoskeletal and Neurological Institute’s mission is to improve the
diagnosis, treatment, and prevention of musculoskeletal and neurological disorders. Accordingly, OMNI
scientists conduct basic and clinical research pertaining to the advancement of musculoskeletal and
neurological health. OMNI has strong programmatic efforts in two research divisions: 1) musculoskeletal
and neurological pain disorders, and 2) healthy aging. The research across these two divisions has an
overarching aim of developing interventions that remove barriers to independent physical mobility and
ultimately reduce disability. Potential studies for involvement range from: 1) clinical trials on the
effectiveness and physiological effects of manual therapies to treat low back pain; 2) the safety and
effectiveness of a new compound (myostatin-inhibitor) to treat muscle wasting disorders; 3) the
mechanisms of perceived fatigue in aging; 4) utilization of advanced medical imaging techniques to
quantify lumbar spine segmental motion; and 5) use of transcranial direct current stimulation to enhance
muscle endurance capacity.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
Leslie Consitt, PhD
Department of Biomedical Sciences
228 Irvine Hall
(740) 593-2404
Email: [email protected]
Project Classification:
Basic Science & Clinical Research
Techniques and/or skills that the student will learn:
1. Clinical skills with humans – Subject screening for diabetes study, insulin sensitivity testing, blood
pressure
2. Assist with skeletal muscle biopsies – Sample processing
3. Metabolic studies in human skeletal muscle (i.e. oxygen consumption in human skeletal muscle)
(Diabetics vs Healthy Controls)
4. Western blot techniques for the examination of protein activity/content in human skeletal muscle
tissue (Diabetics vs Healthy Controls)
Project Title: The Role of Skeletal Muscle SMAD2/3 in Insulin Resistance
Project Description:
Insulin resistance is considered a significant public health concern and is believed to contribute to a
number of co-morbidities including diabetes, cardiovascular disease, and hypertension. In the United
States, insulin resistance has reached epidemic proportions causing considerable anxiety regarding the
strain that will be placed on the health care system in the near future. Despite this concern, little is known
regarding the cellular mechanisms that contribute to insulin resistance, particularly in the primary target
tissue of insulin, skeletal muscle.
The research conducted in my laboratory identifies and examines the mechanism(s) contributing to
skeletal muscle insulin resistance. Research in animal models suggests that myostatin, a member of the
transforming growth factor-β (TGF-β) superfamily, may promote insulin resistance through the
phosphorylation of the conical myostatin signaling pathway mothers against decapentaplegic homolog
(SMAD2/3). Unfortunately, no known research has been conducted in Type 2 diabetics to determine if
myostatin intracellular signaling, specifically the SMAD2/3 pathway, is up-regulated and contributes to
skeletal muscle insulin resistance.
This fellowship will provide the individual with the opportunity to perform a number of research
techniques. The primary objective of the fellowship will be to perform metabolic testing in the skeletal
muscle of 1) lean healthy individuals; 2) obese individuals and 2) obese type 2 diabetics to determine a
cellular mechanism contributing to insulin resistance. The primary focus of the fellowship will be to
perform western blot analysis on the skeletal muscle of these individuals to determine an association
between SMAD2/3 activity/protein and insulin resistance. Other metabolic techniques will include the
measurement of mitochondrial oxygen consumption in skeletal muscle to determine a possible
mechanism through which SMAD2/3 inhibits insulin sensitivity. The fellow will also have the opportunity
to perform clinical skills when assisting with subject screening (i.e., interviewing, blood pressure, etc.).
This fellowship will expose the individual to both clinical and basic science.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
David Drozek, DO
Department of Specialty Medicine
Parks Hall
(678) 447-2509 (Cell)
Email: [email protected]
Project Classification:
Clinical Research
Techniques and/or skills that the student will learn:
1. Chart review and data collection
2. Statistical analysis
3. Literature review
4. Scientific paper writing
Project Title: Evaluation of effectiveness of a new hospital based lifestyle medicine clinic.
Project Description:
The RSAF fellow will review the results of three iterations of a new lifestyle medicine clinic funded as a
community benefit program by Doctors Hospital Nelsonville / Ohio Health. The final iteration will be
running during the winter/spring semester 2014, and the selected fellow will be encouraged to visit at
least one session of the clinic to better understand the format.
The study will compare biometrics (BMI, blood pressure, fasting glucose and lipids) as well as activity and
depression scale surveys done before and near the end of participation in the clinic.
The first two clinic populations were small. There have been several modifications to the program. The
third iteration, which will begin in February 2014, will likely be larger and more mature in its programming,
and will be the primary focus of the statistical evaluation.
The clinic is a series of 12 weekly sessions consisting of video content, live lecture, discussion, food
sampling, and exercise. The emphasis of the teaching is a healthy diet, exercise, stress reduction and
elimination of unhealthy habits. The focus of the class is to introduce sustainable lifestyle changes that
will prevent and/or reverse chronic Western diseases, such as overweight/obesity, hypertension, diabetes,
coronary artery disease, elevated cholesterol, many cancers, and others. Each week consists of a specific
theme to inform the participants of the scientific evidence, and to encourage them to make healthy
changes. Each session ends with setting goals for the next week, and begins with reviewing the goals
from the prior week. Five to ten minutes of exercise are included based on video segments available free
on the Internet, to give participants knowledge of a spectrum of exercise aids available to them. A healthy
food item is prepared in advance for the participants. They are given the recipe, and in many cases watch
a video of the food preparation. Shopping skills, label reading, and practical information on many chronic
disease entities are taught.
The materials utilized in the class include many free resources from Physicians Committee for Responsible
Medicine, Activity Bursts Everywhere, NutritionFacts.org, Full Plate Living, and other Internet sources, as
well as purchased videos from Jeff Novick and The Lifestyle Medicine Institute. Each participant receives a
notebook of resources and pages to record their progress.
The research fellow will collect the data from the clinic participants’ charts, run statistical analysis with Dr.
Masato Nakazawa, the co-investigator, do a literature review focused on lifestyle medicine programs, and
participate in writing a paper for publication.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
Jody M. Gerome, DO
Department of Obstetrics & Gynecology
Department of Medical Education
OhioHealth O’Bleness Hospital
55 Hospital Dr., Athens
(740) 594-9204
Email: [email protected]
Project Classification:
Clinical Research
Techniques and/or skills that the student will learn:
1. Participation in data collection and analysis
2. Participation in the informed consent and randomization process
3. If completed with data collection, participation in the generation of scholarly work for publication
4. Clinical exposure and observation
Project Title: Screening and Diagnosis of Gestational Diabetes
Project Description:
A diagnosis of gestational diabetes mellitus (GDM) is well known to increase the incidence of adverse
pregnancy outcomes for both moms and babies. Maternal complications can include hypertensive
disorders, increased risk for cesarean section and birth trauma. Infants have an increased likelihood of
being large for gestational age, to suffer from jaundice and hypoglycemia and are more prone to
operative delivery, shoulder dystocia and birth trauma. At this time, there is not a consensus with regards
to the optimal testing used to determine the diagnosis of GDM. While complications are well known, and
many feel that diagnosis strategies at this point are inadequate, current opinion suggests that further
research should be done before embracing any newly endorsed diagnostic paradigms.
Work is ongoing on a prospective, blinded protocol to evaluate two different screening tests for
gestational diabetes. Participation in this project will allow for involvement in this innovative trial.
Responsibilities would include obtaining informed consent from participants and data extraction from
electronic health records. Additionally, a new retrospective protocol which will address outcomes of
pregnancies that were diagnosed with GDM by screening in early pregnancy is under development.
Participation in this portion would include primarily data collection and synthesis. This project could be
accomplished by one or two students, based on availability and interest. Individuals who participate in
these projects will have the opportunity to work in a clinical setting, with practicing OB/GYN faculty. This
project demonstrates how clinical research can be completed in a community based clinical practice. The
chance to shadow in the clinical practice could be available, as well as interacting with patients in the
research setting.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
S. Lee Hong, PhD
Department of Biomedical Sciences
246 Irvine Hall
(740) 593-1041
Email: [email protected]
Project Classification:
Basic Science, Clinical Research, & Social/Behavioral Research
Techniques and/or skills that the student will learn:
1. Psychological/Cognitive Testing
2. EMG
3. EEG
4. Physiological Stress Measurements (Salivary Cortisol)
Project Description:
The OMNI PIs utilize a team-based model for conducting research. As a result, RSAF students affiliated
with Dr. Hong will have to opportunity to work on multiple projects during the summer. Because these
studies are fairly large, RSAF students will be able to take the lead on any aspect of any study or project.
There are two major efforts that are currently in progress. The first project is a study to measure cognitive
task difficulty in young and old. With all standardized tests, two people could receive the same score; one
struggled through the test, while the other sailed through. How can the level of difficulty faced by an
individual be measured? We plan to examine this problem using measures of motor output, respiration,
cardiovascular, and biological measures of stress (salivary cortisol). This project is run in collaboration
with the Psychology Department with OMNI Junior Scholar Dr. Peggy Zoccola. The second project seeks
to understand the role of the brain in complaints of fatigue in the elderly. We plan to measure EEG
activity during physical and mental tasks. Our goal is to test the hypothesis that aberrant patterns of
brain activity are the underlying cause of complaints of tiredness in seniors.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
John Kopchick, PhD
Department of Biomedical Sciences
EBI, Konneker Research Laboratory
The Ridges, Athens
(740) 593-4534
Email: [email protected]
Project Classification:
Basic Science
Techniques and/or skills that the student will learn:
1. Cloning of Growth Hormone Receptor Genes and mini genes
2. Generation of a targeting vector for disruption of the GHR gene
3. Continuation studies on the heart specific GHR Gene Disrupted mouse
4. Continuation studies on the bone marrow transplantations studies in mice
Project Title: The role of the growth hormone receptor (GHR) in heart physiology.
Project Description:
This project involves generation and subsequent analysis of mice in which the GHR gene is conditionally
disrupted, that is, specifically in the heart. Adam Jara, a D.O./Ph.D. student started this project and has
generated the mice along with appropriate ‘normal’ controls. Adam will be graduating this coming
summer and several experiments will need to be continued after he is gone. In particular, we will continue
to monitor the effect of the heart GHR gene disruption of insulin sensitivity and life expectancy. The
summer medical student will become intimately involved in the project in that he/she will weigh the mice
weekly, determine body composition monthly, perform glucose and insulin tolerance tests bi-weekly, and
determine the levels of several hormones and blood constituents monthly (insulin, GH, glucagon,
adiponectin, and glucose, IGF-BPs). I anticipate that the student’s name will appear on publications
dealing with these mice.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
John Kopchick, PhD
Department of Biomedical Sciences
EBI, Konneker Research Laboratory
The Ridges, Athens
(740) 593-4534
Email: [email protected]
Project Classification:
Basic Science
Techniques and/or skills that the student will learn:
1. Cloning of Growth Hormone Receptor Genes and mini genes
2. Generation of a targeting vector for disruption of the GHR gene
3. Continuation studies on the heart specific GHR Gene Disrupted mouse
4. Continuation studies on the bone marrow transplantations studies in mice
Project Title: The effect of bone marrow transplant on mouse physiology and aging.
Project Description:
This project involves the transplant of bone marrow from normal mice to GH transgenic or GHR gene
disrupted mice. Dr. Shigeru Okada has already generated the mice and controls for this study. We
hypothesize that transfer of ‘normal’ bone marrow to GH transgenic mice (mice with short life spans) will
result in mice with normal lifespans. Likewise, we plan to transplant normal bone marrow to GHR gene
deleted mice (mice with extended life spans) and expect that this will result in mice with normal life spans.
As per the Project #1, the following physiological characterization of the mice will be determined. The
summer medical student will become intimately involved in the project in that he/she will perform the
bone marrow transfers, weigh the mice weekly, determine body composition monthly, perform glucose
tolerance tests weekly, and determine the levels of several hormones and blood constituents monthly
(insulin, GH, glucagon, adiponectin, and glucose, IGF-BPs). Also, complete blood counts and differentials
will be determined. I anticipate that the student(s) names will appear on subsequent publications dealing
with these mice.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
Ramiro Malgor, MD
Department of Biomedical Sciences
Academic & Research Center 202B
(740) 593-2324
Email: [email protected]
Project Classification:
Basic Science
Techniques and/or skills that the student will learn:
1. Cell Culture
2. Immuno Staining
3. Western Blot
4. RT PCR
Project Title: Regulation of Wnt5a expression and its role in the pathogenesis of atherosclerosis
Project Description:
Atherosclerosis (ATH) is a chronic systemic inflammatory disease highly prevalent in the United States
which is the major risk factor for cardiovascular disease. Despite concerted efforts in changing lifestyles
and the use of new pharmacologic approaches, cardiovascular disease continues to be the principal cause
of death in the United States and the rest of the world. The Wnts are a family of secreted glycoproteins
that upon binding to their receptors can lead to the activation of various signaling pathways that regulate
diverse biological processes including cell proliferation, polarity, differentiation and apoptosis. Wnt5a is a
non-canonical non-transforming member of this family that has been implicated in pathogenesis of
chronic inflammatory diseases as a macrophage-derived effector molecule, and recently as an inducer of
anti-inflammatory (M2) macrophage accumulation and as a blocker of pro-inflammatory (M1)
macrophages. We previously reported an association between Wnt5a expression and histopathological
severity of human atherosclerotic lesions as well as co-expression of Wnt5a and TLR4 in foam
cells/macrophages of murine and human atherosclerotic lesions. Based on these observations, we
hypothesize that ox-LDL induces Wnt5a expression through TLR signaling and that this occurs
predominantly in M2 macrophages. We also hypothesize that Wnt5a induces smooth muscle cell
(SMC) proliferation, migration and production of ECM components.
We propose to test our hypotheses through three specific aims:
1: To determine if the transcriptional up-regulation of Wnt5a in macrophages is modulated by TLR
signaling.
2: To determine which subset of polarized macrophages are involved in Wnt5a
transcription/secretion in atherosclerosis.
To approach the problems, a series of in vitro experiments utilizing established cell lines or human
monocytes isolated from peripheral blood are outlined. The objectives of this project are to investigate
the regulatory pathway and specific type of macrophage involved in Wnt5a expression and secretion as
well as its role in the pathogenesis of ATH. The results from this project will provide important information
about the cellular and molecular mechanisms involved in the pathogenesis of atherosclerosis, which in
turn will help in the development of new therapeutic strategies.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
Ramiro Malgor, MD
Department of Biomedical Sciences
Academic & Research Center 202B
(740) 593-2324
Email: [email protected]
Project Classification:
Basic Science
Techniques and/or skills that the student will learn:
1. Immuno Staining
2. LCM
3. RT PCR
Project Title: Wnt5a expression in urothelial carcinoma of the bladder: a novel prognostic marker
Project Description:
Urinary bladder cancer is the fourth most frequent cancer overall in men in developed countries [1] and
the most common malignancy of the urinary tract. In the United States, it is estimated that there will be
54,610 new cases of bladder cancer and 10,820 deaths in 2013.
We recently reported a positive correlation between Wnt5a protein expression by tumor cell and
histopathological features of urothelial carcinoma (UC) of the bladder (Malgor et al. Diagnostic Pathology
2013, 8:139). This study suggested a potential application of Wnt5a as a biomarker in the diagnosis and
prognosis of UC.
Our long term goal is to study the role of the Wnt5a signaling pathway in the pathogenesis of UC. Our
working hypothesis is that increased Wnt5a expression is associated with epithelial-mesenchymal
transition (EMT) in UC, leading to invasion and metastatic disease. This proposal has the specific objective
of evaluating the correlation between Wnt5a expression, histopathological characteristics of
aggressiveness and loss of epithelial biomarkers in human UC tissue samples, as well as investigating the
Wnt signaling pathways that may be involved.
Specific Aim 1: Analyze the correlation between expression of Wnt5a, localization of β-catenin and
E-cadherin, and histopathological features in human urothelial carcinoma of the bladder by
immunohistochemistry (IHC).
Specific Aim 2: Investigate the expression of a panel of Wnt signaling genes in tissue samples of
human urothelial carcinoma of the bladder using laser capture microdissection (LCM) followed by
RNA extraction and profiler PCR array analysis.
This project will provide knowledge regarding the role of Wnt signaling in the pathogenesis of UC. In the
first aim we expect to find a positive correlation between increased expression of Wnt5a, loss of
expression of E-cadherin and β-catenin from the cell membrane, and histopathological characteristics of
aggressiveness, e.g. increase in tumor histological grade or pathological stage. Our second aim will
provide information regarding the expression of specific genes related to Wnt mediated signal
transduction in UC.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
Felicia V. Nowak, MD/PhD
Department of Biomedical Sciences
228 Irvine Hall
(740) 593-2223
Email: [email protected]
Project Classification:
Basic Science
Techniques and/or skills that the student will learn:
1. Cell Culture
2. Transfection with siRNA, selection and development of stable knock-down cell lines
3. Processing cells for protein extraction and RNA isolation
4. Western Blots
5. PCR
Project Title: Role of Insulin and IGF-1 Receptors in Regulation of the Pro-apoptotic Factor, Porf-2
Project Description:
Preoptic regulatory factor-2 (Porf-2) is a RhoGAP domain-containing protein that has been shown to
inhibit proliferation and enhance apoptosis in neural stem cells. It is expressed in renal cortex and
medulla, and expression is up-regulated in the diabetic kidney, but the role of Porf-2 in diabetic
nephropathy (DN) has not been established. In vitro, we have demonstrated that both insulin and insulin
like growth factor-1 (IGF-1) suppress expression of PORF-2. We have also shown that specific inhibitors of
IGF-1 and insulin intracellular signaling pathways reverse the suppression of Porf-2. However, studies on
the receptors for insulin (IR) and insulin growth factor-1(IGF-1R) have not been conducted. The purpose
of this study is to knock down the insulin and IGF-1 receptor mRNAs to confirm their role in modulation
of Porf-2 expression. Identification of these mechanisms will open new avenues for development of novel
diagnostic, therapeutic and preventative strategies for regulation of apoptotic factors in diabetic kidney.
The significance of the proposed work is that we have identified a pro-apoptotic factor with a potential
role in DN. The specific aim of this project is to investigate the role of the insulin and IGF-1 receptors on
expression of the Porf-2 gene. In a normal kidney, Porf-2 expression is suppressed by insulin. Currently,
the role of pro-apoptotic Porf-2 expression in diabetic nephropathy is not clear. In a diabetic kidney, Porf2 expression may increase because insulin signaling is impaired. This increase in Porf-2 may promote the
worsening of DN. The overall hypothesis is that a change in Porf-2 expression contributes to the
pathogenesis of diabetic nephropathy. Our previous work has shown that Porf-2 expression in diabetic
kidney is decreased in animals with better preservation of renal function due to ingestion of an
antioxidant fortified diet. During initial studies of Porf-2 expression in FRTL-5 cells, we also observed that
in media containing physiological levels of insulin or IGF-1, the expression of Porf-2 was decreased.
Insulin, as does IGF-1, binds to both IR and IGF-1R to exert its biological effects on metabolism and
growth via two major pathways- PI3K/AKT and MAPKK pathways. We have shown that inhibition of
specific intracellular mediators in these pathways blocks the down-regulation of Porf-2 by IGF-1. We will
test the specific hypothesis that insulin/IGF-1 effects on Porf-2 are mediated through IR and IGF-1R
receptors and knock down of these receptors will abrogate the effect of insulin and IGF-1 on proapoptotic Porf-2.
Cell lines in which IGF-1R has been knocked down have already been analyzed for levels of IGF-1R by
polymerase chain reaction (PCR) and the effects on Porf-2 expression. Knockdown of IGF-1R resulted in an
increase in Porf-2 expression. Initially we will generate at least one and preferably two stable cell lines in
which IR is knocked down to  60% of wild type. Western blots will be performed to quantify the level of
IR being expressed. We will also complete the studies on IGF-1R depleted cells by Western blot analysis
of IGF-1R. PCR will be conducted to quantify the levels of IR mRNA. We will then determine the effects of
depletion of IRs on the expression of the Porf-2 gene, by PCR. Samples with intact IR will be compared to
samples from cells where IR expression has been decreased by at least 60%.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
Jay Shubrook, DO
Department of Family Medicine/Diabetes Institute
320 Grosvenor Hall
(740) 593-2137
Email: [email protected]
Project Classification:
Clinical Research
Techniques and/or skills that the student will learn:
1. Provision of diabetes education
2. Clinical management of diabetes
3. Clinical research design, data collection, data analysis and dissemination
Project Title: Advancing Diabetes Care through Awareness, Compliance and Education (ADVANCE)
Project Description:
The worldwide burden of diabetes mellitus is increasing at an alarming rate. Even with numerous public
awareness campaigns directed at patients and health care providers, the major targets of diabetes
management, namely hemoglobin A1c, blood pressure, and cholesterol, are inadequately controlled.
There are many factors that contribute to the complexity of diabetes management, such as
communication between health care providers and patients, patient knowledge and awareness of
diabetes and the potential long-term complications, health literacy, and non-adherence with diabetes
interventions. Interventions to address these barriers have had limited success, particularly when it comes
to successful and practical utilization outside of the study setting.
Diabetes is largely self-managed. However, very few people have the knowledge and skill set to properly
self-manage diabetes. This requires intensive initial education and ongoing refresher courses to maximize
self-care. Physicians typically have little time for discussions of risk reduction and diabetic complications
due to many issues, such as competing illnesses, medication management, test orders, required
documentation, and health maintenance. In addition, physicians do not feel that they have the time or
expertise to provide proper lifestyle counseling.
Even though many patients are referred for diabetes education, most do not go. There is a myriad of
reasons for this. Cost of the program is typically not covered in Ohio, time needed for classes may be too
long, the person may not fell that they need education. All in all about 25% of people diagnosed with
diabetes ever receive diabetes education.
Currently, diabetes education is most often offered by diabetes educators in a set class of 8-12 hours. As
a result the volume of info for most diabetes education sessions is more than a person can absorb.
We propose a diabetes education intervention in a convenient, patient-friendly and readily available
manner. We plan to provide patients with focused diabetes education, i.e. education on one aspect of
management or one complication of diabetes per office visit, allowing time for review of the materials
provided and review of any questions at the next office visit. We also plan to incorporate a cell phonebased system for patients to deliver information on their blood sugars and body weights to their
providers on a weekly basis. This system will deliver weekly reminder messages to those patients who fail
to respond. Also, a weekly statement or “bullet point” from the educational material covered will be
delivered. Finally, we will encourage the participation of family members in these interventions, not only
to improve the patient’s self-management, but also as a means to deliver the same educational message
to other people who are likely at risk for or have diabetes.
The student involved in this project will be involved in the implementation of the programs at the
diabetes center and local primary care offices, the collection and analysis of the data. They will be involved
in diabetes clinical care and diabetes education-through classes and the proposed intervention. They will
gain valuable insight into optimal ways to share information with patients and improve self-care and
adherence.
Research & Scholarly Advancement Fellowship
Summer, 2014
Faculty Mentor and Research Project Profile
Jay Shubrook, DO
Department of Family Medicine/Diabetes Institute
320 Grosvenor Hall
(740) 593-2137
Email: [email protected]
Project Classification:
Clinical Research
Techniques and/or skills that the student will learn:
1. Clinical diabetes management
2. Clinical research design, data collection, data analysis and dissemination
3. Harvesting of existing data
Project Title: The Effectiveness of the CHIP program in those with type 2 Diabetes
Project Description:
Therapeutic lifestyle changes focusing on diet, exercise and tobacco could prevent about 40% of all
cancer deaths and 82% of cardiac deaths in the US. It is estimated that 71% of colon cancers, 70% of
strokes, and 91% of diabetic cases could be avoided by living a healthy lifestyle. Chronic diseases that
affect Western populations add a tremendous burden to our healthcare budget, and to the loss of
productivity of our society. In 2007, an estimated $2.3 trillion was spent on healthcare in the US, or
approximately $7,600 for each individual. Projections are that without dramatic change, this cost will
continue to increase to unsustainable levels.
The Complete Health Improvement Program (CHIP) is a lifestyle medicine program with proven
effectiveness in addressing the problem of chronic disease experienced in those who live the Western
lifestyle. Poverty complicates this further. Athens County is struggling with the highest poverty rate in
Ohio at 32.8% with nearly 18% of the population uninsured. Many people in poverty, have significant
health issues, and struggle with other disadvantages and insufficiencies, which may include lack of
transportation, lack of sufficient housing, limited education, mental illness and limited access to health
care. These socioeconomic factors also increase their risk for diabetes.
Type 2 diabetes is an American epidemic that currently affects 1 in 8 adults. It is projected that this will
increase to 1 in 3 adults by 2030. Type 2 diabetes is a chronic disease that is largely preventable and
wholly treatable. Most effective early interventions have been lifestyle based.
In the proposed study we will evaluate both the Athens area CHIP program data as well as the national
CHIP data for the effect of this therapeutic lifestyle program on people with type 2 diabetes. The student
researcher will be trained on the CHIP program, will learn to explore existing data sets, and do a subanalysis for those participants who have diabetes. They will gain valuable information about chronic
disease management and will be able to apply clinical research to the community setting-bedside to
community and ultimately population health.
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