Penn CVI Resident Research Projects
The Department of Medicine allows residents to schedule
a research elective for two to three consecutive months during the second or third year of training.
Residents in the Department of Medicine and other departments who wish to participate in CVI research projects
during the course of their residency training should refer to this project list and contact the appropriate faculty member.
Available Projects 2007 - 2008
Contact: Dr. James N. Kirkpatrick /
CVI Member Page / 215-662-7726
Projects:
1) Advance Directives for Implantable Cardiac Rhythm Management Devices (ICD's)
Study of patients admitted with heart failure decompensation to see if
completing a device advance directive increases rate of post-mortem or changeout return
of devices for analysis, or donation to patients in developing world nations.
2) Mortician attitudes regarding post-mortem retrieval of implantable cardiac rhythm management devices (pacemakers, ICD's).
3) Echocardiographic measures of hemodynamics in the ICU setting.
4) Echocardiographic predictors of cardiac dysfunction post liver transplantation.
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Contact: Dr. Muredach Reilly /
CVI Member Page / 215-573-1214
Description:
The following list of (8) Clinical and Translational Research Studies is sorted into two categories:
(A) Observational / Cohort Studies, and (B) Experimental Studies.
Dr. Muredach Reilly acts as the single contact for each study.
A. OBSERVATIONAL / COHORT STUDIES
1. Genetics of Atherosclerosis in Chronic Kidney Disease (Gen-CRIC)
Gen-CRIC (Chronic Renal Insufficiency Cohort) is a candidate gene/pathway human genetic study of inflammatory, metabolic, and cardiovascular (CVD) outcomes in the NIH-sponsored multi-center CRIC study (cohort study of CVD and renal outcomes) in patients with mild-moderate chronic kidney disease (CKD). Cohort recruitment will be complete fall 2006 and genotyping will proceed in 2007 with analyses of cross-sectional outcomes [biomarkers and coronary artery calcification (CAC)] in 2007 to 2008 and longitudinal outcomes (individual and composite of hard clinical CVD events) from 2009 to 2011.
2. Penn Diabetes Heart Study (PDHS)
The Penn Diabetes Heart Study is a study of genetic and biochemical factors related to the development of atherosclerosis in persons with type II diabetes. Approximately 1000 subjects have been enrolled to date with a goal of enrolling 2000 by the end of 2008. Subjects undergo a number of tests including ABI, heart rate variability, EKG and coronary artery calcification (CAC) by EBT. In fall 2006, we start examining a number of candidate biochemical and genetic risk factors for atherosclerosis in the first 1000 participants.
3. PENN-CATH
Persons undergoing cardiac catheterization at either HUP or Presby are consented for the Cath study to identify genetic and biochemical factors related coronary disease. More than 3800 subjects have been enrolled to date (began in 1998) from this have a subset of closely matched cases and controls as well as subjects with acute coronary syndrome (approximately 800).
4. Study of Inherited Risk of Atherosclerosis (SIRCA)
The Study of the Inherited Risk for Coronary Atherosclerosis (SIRCA) is a cohort study of approximately 900 singletons as well as 440 people that are part of 150 sibships. Subjects were recruited based on having a family history of CAD but few other traditional risk factors for heart disease. At the study visit they had several physical measurements, coronary artery calcification measurement by EBT and fasting lipids (blood and DNA saved for measurement of genetic and biomarkers). Currently recruiting additional subjects (approximately 500) and working analysis of initial cohort. Have identified several biomarkers and SNPs related to CAC and are analyzing results from a genome wide scan.
B. EXPERIMENTAL STUDIES
1. Inflammation and the Metabolic Syndrome (LPS-RO1)
This NIH-RO1 sponsored study examines the inflammatory response after LPS injection in normal subjects compared to subjects with the metabolic syndrome. We have enrolled 40 normal volunteers in the first phase of this project. We are currently focused on recruiting subjects with the metabolic syndrome.
2. A Pilot Study of Metabolic Effects of Low-Dose Endotoxemia
This study examines very low dose human endotoxemia as a model for low-grade inflammation induced insulin resistance and atherogenic dyslipidemia in humans. This pilot is currently enrolling and will be complete by December 2006.
3. Genetics of Atherogenic Responses to Low Dose Endotoxemia
This NIH-SCCOR sponsored translational study will recruit 300 subjects to examine the genetic predictors of gene expression, proteomic and metabolic atherogenic responses to very low dose endotoxemia in humans. This GCRC protocol forms part of a large integrated SCCOR project with Dr Rader – where the same subjects will be studies for the genetic predictors of the lipoprotein and metabolic responses to niacin therapy. This study will commence in January 2007.
4. Carotid Atherosclerosis Regression and Magnetic Resonance Assessment (CARMA)
The purpose of this is study is to assess the effects of low dose (20mg) simvastatin, low dose simvastatin + niaspan vs. high dose simvastatin (80 mg) on carotid plaque morphology over 1 year as assessed by MRI in patients with known carotid disease and LDL > 100. Enrollment is We wish to enroll 69 subjects and have thus far enrolled 54.
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Contact: Dr. Morris J. Birnbaum /
CVI Member Page / 215-898-5001
Description:
In spite of substantial research concerning the abnormalities in carbohydrate metabolism that define diabetes mellitus, relatively little attention has gone to the lipid abnormalities.
This is somewhat surprising given the intimate relationship of dyslipidemias with cardiovascular disease, the major source of morbidity and mortality in diabetes.
My lab studies the normal metabolic and regulatory pathways that govern lipid synthesis, transport and utilization in mice and in the fruit fly, Drosophila melanogaster.
In both species, there appear to be at least three pathways which regulate, for example, lipogenesis: insulin, whose secretion is governed by circulating nutrients; ChREBP,
a transcription factor positively regulated by glucose; and AMPK, a protein kinase activated by nutrient stress.
Projects are underway studying each of these pathways, ultimately to determine if any account for lipid abnormalities in Type 2 diabetes mellitus.
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Contact: Dr. Mortimer Poncz /
CVI Member Page / 215-590-3574
Description:
The Poncz lab focuses on issues related to platelet biology andthrombus development.
Projects range from looking at the regulated expression of megakaryocyte-specific genes, the biology of several platelet-specific
chemokines mostly in animal models, the molecular basis of heparin-induced thrombocytopenia and the biology of platelet integrin receptors.
We also have several interesting models for the ectopic delivery of proteins to sites of thrombosis/inflammation via platelets.
A variety of basic cell and molecular laboratory techniques, mouse models, and clinical research approaches are used in addressing these questions.
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Contact: Dr. Peter Lloyd Jones /
CVI Member Page / 215-898-0048
Description:
The aim of our laboratory research is to understand lung vascular development and disease.
A number of bedside-to-bench projects are underway, and many more are available.
All combine the use of clinical information, patient-based cell and tissue material, and state-of-the-art methodologies in cellular and molecular biology.
Overall, we aim to identify new molecules and signaling pathways that may be used for better diagnosis and treatment of all forms of vascular disease.
Residents and interns will be able to design projects that focus primarily at the basic science bench,
the clinical research setting, or a true combination of the two according to interest.
Other Jones Group basic science projects at the Institute for Medicine and Engineering (IME):
(1) The role of homeobox genes in vascular development
(2) Regulation & functions of tenascin-C in cardiovascular disease
(3) Cellular & molecular basis of lung branching morphogenesis
(4) Mechanisms of breast cancer cell homing to the lung vasculature
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Contact: Dr. Judd Hollander / CVI Member Page / 215-662-2767
Description:
We run a large patient oriented research program that has ongoing projects
involving risk stratification of patients with potential acute coronary syndromes including:
• Development of novel markers of acute coronary syndromes
• Evaluation of different diagnostic tests for 30-day risk stratification of these patients,
including CT coronary angiography and serum markers
• Cost effectiveness evaluation of different risk stratification strategies in the ED and observation unit
• Quality assurance projects evaluating different aspects of traditional care of these patients
We have a data base with over 7000 patient already enrolled in a variety of studies at HUP
and access to multicenter databases with over 20,000 additional patients in ACS and HF studies.
You will design your own specific research question, complete a more thorough and directed literature review.
Using the knowledge gained from this review along with your experience in the above studies,
you should prepare a well thought out research proposal including a Background, Specific Aims, Summary of Preliminary Studies and Research Methodology.
We will provide assistance with Statistical Design.
If your study proposal required additional data be collected prospectively,
we will adapt our data collection instruments and obtain the required data.
You will need to complete a manuscript during the 3 month period that will be submitted for publication.
You will be the first author. I will meet with you, as needed, on a daily basis to discuss your progress and participation.
This is opportunity for the resident to develop their own study question
and submit a first author manuscript within a 3 month time period.
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Contact: Dr. William M. Armstead /
CVI Member Page / 215-573-3674
Description:
The laboratory is interested in characterizing mechanisms important in the control of cerebral hemodynamics
under physiologic and pathologic conditions such as traumatic brain injury and cerebral hypoxia/ischemia,
particularly in the perinatal period, using a basic science piglet model.
Current research interests focus on tPA, its role in the physiologic and pathologic control of cerebral hemodynamics,
and its potential clinical utility in the treatment of central nervous system disorders.
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Contact: Dr. Sylvia Rosas / CVI Member Page / 215-615-3446
Description:
Dr. Rosas's primary research focus is on cardiovascular disease in patients with chronic kidney disease
including the role of novel risk factors in the development of coronary artery disease.
Non-invasive cardiovascular procedures such as electron beam computed tomography and
carotid intima-media thickness are used as measurements of subclinical cardiovascular disease in this high-risk population.
There are several studies underway to evaluate the prevalence and severity of coronary artery calcification (CAC)
in incident dialysis patients as well as renal transplant recipients.
For example, there is a database available of 118 renal transplant recipients who are currently undergoing a second EBCT
that could be used for a resident research project: examining the role of novel risk factors or the role of metabolic syndrome in the development or progression of CAC.
Contact: Dr. Stephen Kimmel / CVI Member Page / 215-898-1740
Description:
Our group is focused on improving patients' medication response through a
better understanding of, and interventions to improve, adherence and
through quantifying the effects of genetic variants on medication response.
Extensive database on warfarin treated patients, including clinical, adherence, and genetic data.
Clinical trial database on hypertensive patients, which can be used to understand predictors of response to drugs,
response to interventions to improve adherence.
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Contact: Dr. Vera Krymskaya / CVI Member Page / 215-573-9861
Description:
My laboratory is investigating signaling mechanisms of smooth muscle cell proliferation and migration as it relates to:
1) the pathobiology of lymphangioleiomyomatosis (LAM); 2) pulmonary arterial hypertension (PAH); and 3) asthma.
Recently, we had made a significant contribution to the understanding of the
molecular mechanisms regulating abnormal smooth muscle-like LAM cell proliferation.
We identified the role of tumor suppressor TSC2 as a negative regulator of S6K1, and S6K1 as a molecular target to treat LAM disease.
Our studies also identified rapamycin as a promising therapeutic strategy for LAM patients.
Based on our discovery a Phase 1-2 clinical trails of rapamycin are currently being conducted in US, England, and Germany.
Currently, we have (5) projects which are oriented to fellow participation:
1) Bench (basic, signal transduction) project: To determine a role of PI3K-TSC1/TSC2-mTOR-S6K1 signaling pathway in
regulating pulmonary arterial vascular smooth muscle cell growth, proliferation, and migration.
2) Bench (basic, signal transduction) project: Define a role of TSC1/TSC2-mTOR-S6K1
signaling pathway in regulating LAM cell growth and proliferation.
3) Bench to bedside (translational project): Determine the in vivo role of the constitutive activation of
S6K1 associated with TSC1 or TSC2 loss on tumorigenesis, and establish translational possibilities for the treatment of these tumors with rapamycin and IFNs.
4) Bench to bedside (basic, signal transduction/translational project): To define the molecular mechanisms of abnormal cell migration and invasiveness in LAM.
5) Bench (basic, signal transduction) project: To define the molecular signaling processes which modulate basal and growth factor-induced protein synthesis
and hypertrophy of human airway smooth muscle cells using cell-based and animal models.
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