 |
 |
|
| |
 |
|
|
|
|
|
|
 |
||
Curriculum
Research and training in Cancer Pharmacology is at the interface of characterizing fundamental processes in cancer biology and understanding the mechanisms of actions of agents that modulate proliferation, survival, mutagenesis, and tumorgenesis. Diverse research approaches are being used and range from modern techniques in cell and molecular biology using in vitro model systems to in vivo models of carcinogenesis to cutting edge analytical approaches to identify and measure DNA adducts and mutations. Major areas of research include defining and characterizing disordered signaling pathways in cancerous cells, mass spectrometry analysis of DNA modifications and vital cellular structures by carcinogens, and actions of anticancer drugs at both the basic and clinical levels. Research and training in basic and clinically related cancer pharmacology are enhanced by the multi-disciplinary and integrated approach provided by the Center for Cancer Pharmacology which serves as a focal point for research and training in cancer pharmacology. Course work emphasizes broad training in the fundamentals of cell biology, pharmacology, mechanisms of carcinogenesis, eukaryotic molecular genetics, and signal transduction, along with courses specifically focused on cancer pharmacology and new pharmacology-based methods for treating cancer. For more information on research and training see: http://www.med.upenn.edu/ccp/. Research and training in Cardiovascular Pharmacology focuses on vascular biology and thrombosis. Research programs explore the cellular and molecular basis of atherogenesis and thrombosis using a variety of approaches including knockout and transgenic technologies, gene therapy techniques, and modern approaches in chemistry, biochemistry, molecular biology and cell biology. Through multi-disciplinary research projects, collaborative research grants, and seminar series the Cardiovascular Pharmacology program is closely integrated with research groups in the Department of Medicine, the Institute of Medicine and Engineering, and the Wistar Institute. Research in the pharmacology of thrombosis and vascular biology focuses on understanding the roles of proteins, lipids, and small molecule mediators of cardiovascular function and dysfunction. Particular efforts are directed at understanding the pharmacology and signaling of eicosanoids, thrombin, integrins and adenosine in vascular and cardiac cells as well as isoprostane biochemistry and the pharmacology of lipid mediators of cardiovascular function. Understanding mechanisms of pathophysiology and actions of drugs under normal and pathophysiological conditions is the focus of research investigating the response of vessel walls to apoplipoproteins and defining molecular actions of hypolipidemic, antihypertensive, antiinflammatory and antithrombotic drugs. Didactic and literature survey courses in Cardiovascular Pharmacology along with research rotations covering a broad range of techniques and approaches provide students with a strong foundation to pursue thesis research in the area of Cardiovascular Pharmacology.Environmental Health Sciences (EHS) This program focuses on the mechanistic links that exist between environmental exposures, the molecular and cellular affects that ensue, and diseases of environmental etiology. Many common diseases/disorders are "linked" to environmental exposures. Areas of interest include: lung and airway disease (asthma, lung cancer, mesothelioma and chronic obstructive pulmonary disease) that can result from exposure to allergens, ozone, inhaled carcinogens, asbestos and air pollutants; diseases linked to oxidative stress (neurodegenerative disease, cardiovascular disease and inflammation), and endocrine, reproductive and developmental disorders (oocyte quality, pre-term rupture of the fetal membranes, hypospadia and cryptochordism). Elucidating the mechanistic links will lead to improved prevention and intervention strategies of major disease. EHS encompasses the study of gene-environmental interactions that influence individual susceptibility to environmental exposures and disease, and exposure biology, which encompasses the development of validated biomarkers for risk assessment. Trainees will receive broad training in these areas for careers in EHS and will be encouraged to be board certified as "Diplomats of the American Board of Toxicology". Research work includes:
In terms of morbidity, mortality, and dollars spent, the cost of neurologic and psychiatric disorders to society is phenomenal. Stroke and traumatic brain injury represent the number one cause of disability and the third leading cause of death in the United States. Ten percent of the population experiences at least one major depressive episode during life. Over 4 million people have Alzheimer’s Disease today and this is projected to increase dramatically in the future. The overall focus of Neuropharmacology research and training is to provide students with an integrated understanding of the interactions of neurotransmitters with receptors and the biochemical and functional effects of these interactions. Over twenty laboratories use a variety of modern cellular, molecular, genetic, and behavioral strategies to study the molecular bases of brain function. Some laboratories use genetically engineered mouse models to study diverse issues, including the role of individual neurotransmitters/ signaling molecules in complex behaviors such as drug addiction, memory formation, Alzheimer’s Disease, and depression. Other laboratories use cellular systems to study issues ranging from receptor function and trafficking of RNAs and cellular proteins to cell death. The program includes a series of specialized courses that introduce students to the broad area of Neuropharmacology and is supported in part by a longstanding NIH funded training grant. Several different program projects/center grants support Faculty in the Program providing many opportunities for the development of collaborative research projects that enhance the quality of the training. Areas of expertise of these centers include: Traumatic Brain Injury, Serotonin Receptors in the Brain, Alzheimer’s Disease, and Mental Retardation and Developmental Disabilities Research. Pharmacogenetics focuses on the genetic basis of inter-individual variation in response to various classes of drugs and therapeutic protocols and makes use of this information to develop rationale therapeutic regimens and to identify genetic susceptibility factors for diseases. Pharmacogenetics encompasses the study of genetic factors and gene-environment interactions that influence drug delivery, bio-availability, metabolism, clearance, and toxicity. Research in Pharmacogenetics is at the interface of experimental pharmacology, genomics, epidemiology and bioinformatics and therefore draws on collaborative expertise in many areas of research at the University of Pennsylvania. Areas of research focus on the relationship between genotype and disease phenotype and the response to therapy as well as on population based polymorphisms in disease related genes and inheritance of predisposing genetic factors. Various models are being established using transgenic animals to investigate drug-genotype interactions as a function of environment or in the context of other disease causing genetic factors. Expression profiling is being used to track the natural progression of pathology in disease and to monitor responses to drug therapy while various approaches are being developed to determine the impact of genetic factors on planning, executing, and interpreting clinical trials. Students use the flexibility of the training program in the Graduate Group to supplement core courses with specialized courses and training in areas selected to complement the area of their eventual thesis research. Understanding the chemistry of molecular recognition between drugs and their targets (receptors, ion-channels, enzymes and nucleic acids) is a primary focus of research and training in Pharmacological Chemistry. Approaches being used include protein engineering, rational and irrational approaches to drug design, and identifying novel pathways of drug and xenobiotic metabolism and chemical transformations involved in these pathways. Research and training in structural aspects of Pharmacological Chemistry involve elucidating 3-dimensional structures of drugs bound to their targets, identifying pharmacophores (atomic arrangement of functional groups in a ligand) essential for drug activity, the structure and folding of drugs and their targets in lipid membranes, and computer-modeling to define ligand binding sites in drug targets. Other research and training focuses on the chemistry and enzymology of drug targets, activation of carcinogens, synthesis of specific receptor ligands and inhibitors, and engineering proteins with altered/mutated specificity and function. Techniques and resources available include: steady-state and stopped-flow absorbance/fluorescence spectrometers; a 32-node computational chemistry cluster; a computer graphics laboratory; x-ray crystallography; PET-imaging; internal reflection infrared spectroscopy; and state-of-the art analytical instrumentation including mass spectrometry and HPLC systems with EC, UV/Vis and diode-array detection capabilities. Three graduate level courses in Pharmacological Chemistry have been developed to supplement the core pharmacology curriculum. |
||
© The Trustees of the University of Pennsylvania  |
Most students spend two pre-thesis years in coursework,
laboratory rotations,
and related activities. Students
may begin graduate work in the summer preceding
the usual fall starting date by carrying out a
laboratory research rotation.
Program advisers can help students select courses and create programs that
are relevant to their particular interests and aptitudes. Many students choose
a broad curriculum with a variety of Pharmacology courses, as well as electives
outside Pharmacology. Students may also choose more specialized courses within
Pharmacology.
Presently there are five distinct training tracks: