Summer Research Fellowship Program
Integrative Medical Sciences
Yeong-Renn Chen, Ph.D.
Phenotypic switch of cardiac metabolism in the disease of heart failure
The objectives of this research are to assess the role of metabolic switch in the pathogenesis of heart failure and to explore new insights into the specific disease biomarker of mitochondria in order to more fully understand the mechanisms of cardiovascular disease. As metabolic switch associated FAO downregulation in the mitochondria is likely to have an impact on fuel homeostasis in myocardium, it is desirable to obtain further information on how metabolic switch affects the function of mitochondria, overall cardiac function, and regulation of the heart remodeling and related pathogenesis of heart failure development. To partially address this issue in 8 weeks and optimize the efficacy of summer fellowship training in biomedical research, the proposed studies have been designed to narrow the scope of investigation focusing on mapping the metabolic pathways of FAO and GO in the mitochondria from the disease model of chronic myocardial infarction using proteomic approach.
William Chilian, Ph.D.
Unraveling Mechanisms of Mitochondrial Disease: Therapeutic Implications
Our goal is to generate iPS cells from the patients (and normal parent or sibling for a control), and then differentiate the iPS cells into the somatic cells affected in the patient, e.g., cardiac myocytes for a cardiomyopathy. The long-range goal for this strategy is to catalyze “precision medicine” treatments unique for each patient. Rather than having to test drugs, or combinations, in patients, our goal is to use the cell models as a system to individualize the treatment for the specific patient and tune the treatment to correcting the problem in the iPS cell-based models.
Feng Dong, Ph.D.
A mechanism in the development of diabetic cardiomyopathy
What aspect of the overall research will be the focus of the student’s summer research experience? What is the specific research question being addressed by the summer research project? The goal of our proposed studies is to define the molecular mechanisms and physiology associated with the development of DCM. We further propose that our novel hypothesis may yield therapies that can prevent and treat DCM. The focus of the student’s summer research experience will be the scientific research procedures and principles on the cardiovascular complication of diabetes. The specific research question being addressed by the summer research project are:
- Determine the role of cardiac CXCR4 in DCM using our cardiac CXCR4 null mouse model.
- We will answer an important question: will cardiac CXCR4 deletion rescue or exacerbate cardiac dysfunction in mice with diabetes?
Jessica Ferrell, Ph.D.
The effects of high fat, high fructose diet on the development of liver fibrosis
The goal of this research project is to determine the pathogenesis of fatty liver disease and liver fibrosis. The goals for the summer research student(s) are to learn scientific technique and experimental design, data analysis and interpretation, and to demonstrate professional presentation of scientific results.
James Hardwick, Ph.D.
Isolation and characterization of CYP4F2b in human hepatic tumors that
The goal of this research is determining the absolute levels of human CYP4F2 genes in the prevention of inflammation and progression of fatty liver disease. The objective of this proposal is to characterize the expression of the human CYP4 genes in hepatic tumors and associated normal liver tissues. A second objective is to isolate the tumor specific CYP4F2b gene and characterize its role in tumor development Investigative methods to be used: Normal human liver and matched tumors will be used to isolated RNA and microsomes. RNA will be reversed transcribed into cDNA and the level of absolute expression of members of CYP4 families is determined by using gene specific primers and PCR. The CYP4F2b gene will be isolated by gene synthesis and its expression using adeno-associated virus will be characterized.
James Hardwick, Ph.D.
Characterization of CYP4F2b P450 metabolism in human hepatic tumors that reduces the immune response to tumorigenesis through inactivation of pro-inflammatory eicosanoids
The goal of this research is determining the absolute levels of human CYP4F2 genes in the prevention of inflammation and progression of fatty liver disease. The objective of this proposal is to characterize the level of omega hydroxylated eicosanoid and fatty acid in hepatic tumors and associated normal liver tissues. A second objective is to define the substrate specificity and sensitivity of the tumor specific CYP4F2b P450 and characterize its role in tumor development.
William Lynch, Ph.D.
Neural stem cell-based model of HTLV-1 neurodegeneration
In this project we propose to examine whether the expression of HTLV-1 ENV in murine NSCs alters their differentiation profile using culture and mouse chimera model systems. The goal is to determine whether the paralytic phenotype observed in murine RV-infected mice, is predictive for mechanistic changes that are causative in humans with HAM-TSP. The expectation is that these experiments will provide proof of principle for a NSC-based chimera model system for more easily probing the molecular and cellular causes of human motor neurodegenerative diseases.
Vahagn Ohanyan, Ph.D.
Chemotherapy related cardiac dysfunction
The goal of this summer research is to test the hypothesis that heart failure occurring after chemotherapy treatment is caused by microvascular dysfunction. We will test whether Chromonar treatment will prevent and reverse the consequences of chemotherapy treatment. We currently have all the resources necessary for this project, and believe the goal is attainable over the course of the summer.
Priya Raman, Ph.D.
Effect of Metformin on Cognitive Function in Diabetic Mice
Goal: We will investigate the effect of chronic metformin therapy on AD progression in diabetic obese mice.
- To examine cognitive performance in diabetic KKAy+/- mice treated with and without metformin.
- To assess the effect of metformin administration on AD-related pathology in diabetic KKAy+/- mice.
Charles Thodeti, Ph.D., FAHA, FCVS
Mechanical control of pericyte migration in tumor angiogenesis
The goal will be to determine the molecular mechanism by which TRPV4 channels regulate pericyte migration in response to tumor stiffness. To achieve this, we will culture human pericytes and measure their attachment, spreading and migration on ECM gels that mimic tumor stiffness. To determine the role of TRPV4, we will use pharmacological inhibitors/siRNAs to inhibit TRPV4 activity/downregulate TRPV4 expression.
The first objective will be to instruct he/she on pericyte culture techniques necessary to permit unassisted cell culture. The second will be to perform an immunofluorescence analysis of the pericytes using fluorescently labeled antibodies with on a fluorescence microscope. The third will be to teach Western blot methods to measure TRPV4 protein expression in the. The fourth will be to do real-time PCR to quantify gene expression. The fifth will be to measure pericyte migration on ECM gels of varying stiffness (that mimic stiffness of tumor) using scratch wound assays. The seventh will be to analyze data and images acquired and perform statistical analysis.
The feasibility of performing these experiments in my laboratory has been previously demonstrated.
Liya Yin, Ph.D.
The regulation of mouse coronary collateral growth
The goal of this summer research is to study the mechanism of coronary collateral growth and how to stimulate and amplify the effect of CCG.
Yanqiao Zhang, M.D.
Hepatocyte CYP27A1 in metabolic homeostasis
To study the role of hepatocyte CYP27A1 in regulating fatty liver disease and lipid homeostasis. The student will learn how to perform studies on fatty liver disease or lipid homeostasis. The student will also learn a number of techniques, such as lipid extraction, lipid assays, sectioning, staining, RNA or protein extraction, qRTPCR, etc.
*Requires Acrobat Adobe Reader