Pharmacological sciences represent an extremely large field of modern science, intertwined with many other biomedical disciplines: cancer and cardiovascular pharmacology, cell signaling, neuropharmacology, pharmacogenetics, pharmacological chemistry, environmental health sciences, and targeted therapeutics. Core courses include Cell Biology, Fundamentals in Pharmacology, Human Physiology, and Medical Pharmacology. Electives are chosen by the student to suit their interests. Pharmacology students may rotate in labs doing very different types of research, to enrich their background and allow unrushed, instructed selection of direction of their future thesis research.
Studies in the Pharmacology Graduate Group (PGG)
Most students spend two pre-thesis years in coursework, laboratory rotations, seminars, journal clubs and related activities. Academic Review Committee Chair and Program advisers help students select courses and create academic plans 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 using courses offered by Biomedical Graduate Studies (BGS) Program. Students may also choose more specialized courses within thematic programs.
Students may begin graduate work in the summer preceding the usual fall starting date by carrying out a laboratory research rotation. Usually students take three semesters to rotate in three different labs, often working in very different areas. This endows them with a spectrum of knowledge of modern experimental approaches, familiarizes them with the faculty and students across the group and supports optimal selection of the thesis direction and lab. After each rotation students give short post-rotational presentation to their peers and faculty.
In the spring semester of the second year, students prepare to a qualifying Candidacy Exam. This process starts with selection of a research topic in a future thesis lab and submission of an abstract of the proposed research project. After approval of an abstract by the Chair of the Candidacy Exam Committee and appointing three members of the Committee, a student prepares written exam in a form of NIH-type (20-pages) grant and submits it to the Committee for primary evaluation and admission to an oral exam that consists of a 25 minute seminar presentation on the literature background the hypothesis and experimental strategy for the proposal in front of peers and faculty, followed by oral defense of the written proposal in form of answering questions and discussion with the Committee members. After passing the exam, students embark on the full-time thesis research in selected labs. More details on academic pursuits of the students in the PGG are given in the Student Handbook.
Above you will find the list of courses currently offered by the Pharmacology Graduate Program, and their brief description, linked to detailed syllabi of each course.
Teaching and research in Pharmacology at the University of Pennsylvania dates back more than a century. Our academic tradition is embodied in the figures of A.N.Richards, Carl Schmidt, George Koelle, Solomon Erulkar and other researchers. Annual lectures named after some of these eminent scientists (e.g., Lambertsen and Schmidt Lectures) are presented yearly by renowned scientists. Students not only attend the lectures but also meet (actually, have a lunch) with the speakers, to discuss with them not only the scientific subject matter of their lectures, but also diverse aspects of career and life in science. All students in the program are eligible to apply for a Solomon Erulkar Traveling Fellowship to visit any laboratory in the world to learn new techniques and approaches to their research problem.
Pharmacological sciences represent an extremely large field of modern science, intertwined with many other biomedical disciplines. Reflecting the research focus of the Penn Department of Pharmacology in the 1980’s, the Pharmacology Graduate Group enjoyed an outstanding reputation in cell signal transduction and neuropharmacology. During the last decade, while retaining strength and leadership in these areas, the Graduate Group significantly broadened and diversified the scope of research carried out by the faculty within the Department of Pharmacology and about twenty other Departments participating in our Graduate Group. In particular, the curriculum and research training opportunities in our Graduate Group were expanded in the areas of cancer and cardiovascular pharmacology, pharmacogenetics, pharmacological chemistry, and environmental health sciences.
A brief outline of research in these thematic programs is shown below in this section and description of related courses is shown i. Of course, this section shows only a tip of an iceberg! To learn more about our research in areas of your interest, visit individual sites of our faculty and take a look of their key publications, or simply e-mail them with your enquiries. As icebergs float freely in oceans, there are no boundaries between our programs: you can take a course in cancer pharmacology, have one of rotations in a neuropharmacology lab, and embark on a thesis in a cell signaling lab – and other way around, too! In fact, we encourage students to rotate in labs doing very different types of research, to enrich their background and allow unrushed, instructed selection of direction of their future thesis research. And, of course, as icebergs constantly change their shape, our programs are dynamic and evolving creatures. Elements and nebulas of new programs constantly emerge – translational pharmacology, biotherapeutics, and targeted therapeutics, just to mention a few:
- Cancer Pharmacology
- Cardiovascular Pharmacology
- Cell Signaling
- Environmental Health Sciences
- Pharmacological Chemistry
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.
The mechanisms by which signals converging on cells are perceived and translated into appropriate cellular responses represent a fundamental aspect of pharmacological inquiry. Signals of special interest include hormones, neurotransmitters, sensory stimuli, and cell-cell or cell-substratum contacts. Understanding the range and nature of cellular signals is an important pursuit, as over 80% of all therapeutic agents currently in use operate through mimicry or antagonism of such signals, a value not likely to decrease as receptors for these signals continue to emerge at a high pace through genomic screens. Understanding derangements in signaling is an equally important pursuit, as a vast number of human disorders, ranging from cancer to neuropsychiatric deficits, are related to abnormal signaling.
Some components of the curriculum cover signaling alone, permitting an exacting and quantitative treatment of the subject. Others place signaling in the context of additional pharmacological and pathophysiological disciplines. The integrative aspects of research in signaling are reinforced by journal clubs, seminars, and actively shared interests among laboratories.
Approximately 40 laboratories within the Pharmacology Graduate Group carry out basic research in cell signaling. Research topics include structural and functional characteristics of cellular receptors, G-proteins and adaptor molecules, and signal transduction pathways including post-translational protein modification and ion homeostasis in diverse models of pathological and physiological processes and specific disease conditions. The methodological approaches employed rely on the most sophisticated cell and molecular biological technologies available.
Examples of specific research work include:
- G protein-coupled receptors, receptor tyrosine kinases, ligand-activated ion channels, and nuclear receptors.
- Mechanisms of signal transduction, with an emphasis on monomeric and heterotrimeric G proteins, adapters and scaffolds, protein kinases, ion channels and sites of crosstalk between signaling pathways.
- Impact of signaling on gene expression, cell morphology, cell proliferation, apoptosis, and, upon integration, cell function at an organism
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:
- Protein modification in neurodegenerative disease
- Oxidant stress and cardiovascular disease
- Lung cancer and exposure to polycyclic aromatic hydrocarbons
- Endocrine and reproduction disruption and use of transgenics
- Mutagenesis of tumor suppressor genes by reactive oxygen
- Abberant signal transduction and epigenetic effects
- Phase I and II enzymes and toxicant exposure: function and gene regulation
- Molecular epidemiology of environmental disease
- Mass spectral methods to validate biomarkers
- Toxicogenomics (genomic profiling following toxicant insult)
- Toxicoproteomics (proteome changes following toxicant insult)
- Use of toxicants to probe disease mechanism
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.
Targeting therapeutic and imaging agents to desired tissues, cells and sub-cellular compartments is one of the biomedical Holy Grails. Such a targeting of chemical drugs and more novel biotherapeutics, pro-drugs and multimodal agents holds a promise to improve diagnosis, prophylaxis and treatment of a plethora of diseases – inflammation, infections, cancer, cardiovascular, pulmonary, metabolic, neurological, genetic and other maladies. Targeted therapeutics provide spatiotemporal and mechanistic precision of imaging and therapeutic interventions, with control over timing, duration, localization and amplitude of the desirable effects, along with alleviation of side effects, doses and inconvenient treatment regimens. Further, targeted therapeutics provide unique means to test the role of specific molecules, pathways and cells in animal models of pathology. This highly translational area of research offers a slew of both hypothesis-driven and technology-driving paradigms, projects and approaches.
Goals and approaches of targeted therapeutics include identification of site-specific therapeutic targets and molecular markers of pathologies, molecular and supramolecular design of affinity moieties and nanocarriers for targeted delivery of therapeutic and imaging agents, studies of sub-cellular trafficking and effects of targeted therapeutics and ultimate translation of these novel compounds into industrial development and clinical domain, via characterization of their pharmacokinetics, effects and toxicity. Studies in this exciting and truly interdisciplinary area of research transcend disciplines of pharmacology and pharmaceutical sciences, bioengineering and biotechnology, cell biology and immunology, radiology and many basic and clinical disciplines.
Targeted Therapeutics houses more than ten PGG faculty members from the Schools of Medicine, Engineering and CHOP and offers a rich and diverse training and research environment. It is closely associated with its counterparts at ITMAT and CTSA and features activities including the weekly Journal Club, The Provost’s Interdisciplinary Seminar Series in Targeted Therapeutics and Drug Delivery and monthly Work-in-Progress presentations of the participating Principal Investigators.