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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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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Betsy Goldmuntz, MD is a pediatric cardiologist who studies the genetic basis of congenital heart disease.
Current projects in this research group include:
- Genome wide analyses of large patient populations to identify genetic risk factors for disease
- Mutation and SNP studies of candidate genes
- Translational studies on the impact of genotype on clinical outcome.
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We run a large patient-oriented research program with 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. Judd Hollander, MD 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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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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The Krymskaya Lab is investigating signaling mechanisms of vascular smooth muscle remodeling under chronic hypoxia as it relates to the pathobiology of PAH and COPD. M.D.'s with interest in pulmonary biomedical and translational research are welcome to participate in my research projects. Initial 2-3 month work in an interactive group in this lab will provide an introductory experience in signal transduction, cell biology, confocal microscopy and use of genetically engineered mice. Successful participation in specific research project during residency training may culminates in co-authorship in scientific publications.
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The Poncz Lab focuses on issues related to platelet biology and thrombus 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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Project One Description
In our Center for Hereditary Hemorrhagic Telangiectasia, the preferred approach to screening for the presence of pulmonary arteriovenous malformations is a contrast echocardiogram ('bubble study'). Those found to be positive for late passage (ie, contrast appearing in the left atrium 4-10 beats after appearance on the right side), undergo high-resolution CTA of the lungs. We are interested in quantifying the findings on the echocardiogram and correlating these data with the findings on CT and on subsequent pulmonary angiography if the patient is deemed to have lesions needing embolization. This project will be a collaboration among the echocardiography faculty, Dr. Scott Trerotola in Interventional Radiology and myself.
Project Two Description
We have demonstrated recently in patients with hereditary hemorrhagic telangiectasia (HHT) that transillumination of the fingers can detect arteriovenous and other vascular malformations that are not visible on examining the skin. Further, such defects correlate with increased blood flow as shown by Doppler. We now want to extend these studies to include a systematic survey of patients with, and suspected as having, HHT as they present to our Center (typically, we see 2-4 new patients each week). Furthermore, we have detected similar digital vascular anomalies in patients with aneurysm of the aorta, and plan to survey such subjects systematically as well. Typically we evaluate 4-6 such patients weekly.
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We currently welcome students for three projects:
The physiology of cardiac and ventilatory reserve capacity in health and inherited muscle disease
Translational research: Gene therapy for Duchenne Muscular Dystrophy
Physical Fitness in Recently Returning Combat Veterans
For more information about these projects email firstname.lastname@example.org or call 215-823-5880.
Structure and function of ADAMTS13 metalloprotease
Cofactor dependent regulation of ADAMTS13 function
Characterization of autoantibodies against ADAMTS13 in patients with thrombotic thrombocytopenic purpura (TTP)
Gene therapy correcting ADAMTS13 deficiency in mouse models.
In vivo (animal) thrombosis models.
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