HARVARD ‐ FMUSP LABORATORY RESEARCH OPPORTUNITIES AT HSPH AND HMS IN 2012
FMUSP STUDENTS AT HARVARD SCHOOL OF PUBLIC HEALTH (HSPH) AND HARVARD MEDICAL SCHOOL (HMS)
APPLICATION DEADLINE: AUGUST 15, 2011 To apply, visit: www.surveymonkey.com/s/Harvard‐FMUSP‐collaborative
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TABLE OF CONTENTS Please click on the links below to navigate to the desired section of this document.
INTRODUCTION:
Overview ‐ Collaborative Program Background ‐ Program Eligibility ‐ Application Process ‐ Funding ‐ Visas PARTICIPATING FACULTY:
Bernardo Lemos Assistant Professor of Environmental Epigenetics in the Dep. of Environmental Health (HSPH) ⇒ Opportunities in the Lab
Felipe Fregni Director of the Neuromodulation Laboratory at Spaulding Rehabilitation Hospital; Assistant Professor of Neurology (HMS); Instructor in Population and International Health (HSPH) ⇒ Opportunities in the Lab
Hiep Nguyen Associate Professor of Surgery in the Dep. of Urology (HMS); Director of Robotic Surgery Research and Training at Children’s Hospital in Boston ⇒ Opportunities in the Lab
John Godleski Associate Professor in the Dep. of Environmental Health (HSPH); Senior Pulmonary Pathologist at Brigham and Women’s Hospital ⇒ Opportunities in the Lab
Joseph Brain Professor of Environmental Physiology in the Dep. of Environmental Health (HSPH) ⇒ Opportunities in the Lab
Lester Kobzik Professor in the Dep. of Environmental Health (HSPH); Professor of Pathology (HMS) ⇒ Opportunities in the Lab
Richard Verrier Associate Professor, Dep. of Environmental Health (HSPH); Associate Professor of Medicine (HMS) ⇒ Opportunities in the Lab
Stephanie Shore Senior Lecturer in the Department of Environmental Health (HSPH) ⇒ Opportunities in the Lab
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OVERVIEW
ABOUT THE PROGRAM
Thanks to an ongoing research collaboration between professors at the Harvard School of Public Health, Harvard Medical School and Universidade de São Paulo Medical School (FMUSP), over 50 FMUSP students have had the opportunity to engage in a range of laboratory research experiences in areas such as the cardiopulmonary effects of air pollution and the newest methods of non‐invasive brain stimulation at Harvard. This document details the opportunities available to successful FMUSP applicants in 2012. This program builds on the multi‐year collaboration between Professors John Godleski (HSPH) and Paulo Saldiva (FMUSP) and others.
PROGRAM ELIGIBILITY
Any current FMUSP student is welcome to apply, bearing in mind that there are differences in program duration and administrative support.
APPLICATION PROCESS
The application process consists of two phases. The first phase requires applicants to complete a brief online application, including a personal statement, references, and CV. Applications are due by August 15, 2011. The second round consists of interview(s) by the selection committee. Successful applicants will be notified of their acceptance in September, at which point they will begin the visa application process. Application decisions are made by FMUSP in collaboration with host faculty (DRCLAS does not select students).
FUNDING
While participants in the initiative have successfully secured support in the past, financial aid is not guaranteed.
VISAS
Successful applicants will be responsible for preparing the appropriate documentation and applying for the appropriate student visa.
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Bernardo Lemos
Bernardo Lemos is an Assistant Professor in the Department of Environmental Health at the Harvard School of Public Health (HSPH). His main research interests are in the area of environmental epigenetics. He studies individual responses to direct exposures and the consequences of maternal and paternal exposures on daughters and sons. This includes the population epigenetics of heterochromatin and genotype‐by‐environment interaction, which may help explain the regulatory basis of human diseases and individual responses to environmental challenges. These themes are addressed mechanistically using model organisms, careful genetic manipulations, and genomic technologies. His approaches are integrative and combine laboratory experiments with computational analysis of genomic data.
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Opportunities in the Lab Students who spend a year in Dr. Lemosʹ research laboratory at the Harvard School of Public Health participate in a research program aimed at understanding the genetic and environmental determinants of gene regulation. Gene regulation is key to cellular differentiation, tissue morphogenesis, and physiology, whereas disruptions in the expression of genes lie at the source of most human diseases and cancer. Research projects in Dr. Lemosʹ laboratory focus on understanding the molecular mechanisms by which environmental exposures epigenetically modify the genome and lead to anomalous gene expression patterns. Basic research in the laboratory uses model organisms and can be pursued either through genome‐wide approaches or motivated through a keen interest in the regulation of specific disease associated genes. Opportunities include genome‐wide epigenetic responses of exposures to chemicals (e.g., BPA), nano‐materials, airborne pollution, and others. Also, a key component of the lab is the study of genotype‐by‐environment interaction, or how individual genotypes uniquely respond to specific exposures. Students will work closely with Dr. Lemos and other members of the laboratory to develop the experimental and analytical skills for whole genome analyses and for addressing key questions in environmental epigenetics. Students with a background in computer programming and/or keen interests in statistics will also find plenty of research opportunities in our laboratory. The team’s educational goal is for students to wholeheartedly engage in the research process: participate in laboratory discussions, carry out hands on genomic experimentation and data analysis, pursue specific hypothesis, develop new ideas, contribute to research progress of ongoing projects on a team atmosphere, and develop and lead their own specific project. The main research goal is for students to achieve significant research results to merit their writing of manuscripts for publication in scientific journals.
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Felipe Fregni
Felipe Fregni (MPH ʹ07 and Lemann Fellow 2007‐2008) is an Assistant Professor of Neurology at Harvard Medical School and the director of the Neuromodulation Laboratory at Spaulding Rehabilitation Hospital, Harvard Medical School (a state‐of‐the‐art laboratory focused on the investigation of novel methods of neuromodulation for neuropsychiatric disorders). Dr. Fregni has received numerous promising young researchers from Brazil in his lab. He has conducted several clinical trials and also mechanistic studies investigating the effects of noninvasive neuromodulatory tools on the treatment of neuropsychiatric disorders. Some of these highly cited studies investigated the impact of neuromodulation on motor function, mood and cognition; others assessed brain activity changes using neuroimaging (SPECT). While pushing the boundaries of neuromodulation, Dr. Fregni has kept his focus on addressing issues of chronic pain, being the first to publish a trial investigating the impact of transcranial direct current stimulation for chronic pain in spinal cord injury. The focus of his research has largely been centered upon developing methods of neuromodulation as potential treatment tools as well as investigating their mechanisms and impact on brain plasticity. The ultimate goal of his research is to develop novel methods of neuromodulation for the treatment of neuropsychiatric disorders.
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Opportunities in the Lab The Laboratory of Neuromodulation is a cutting‐edge Harvard Medical School Laboratory located at Spaulding Rehabilitation Hospital (http://www.neuromodulationlab.org/) in Boston, that investigates the clinical effects and mechanisms of noninvasive brain stimulation techniques. The team’s primary focus is the study of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) for treatment of several neuropsychiatric disorders in human subjects, such as: Stroke, Parkinsonʹs disease, Chronic Pain, Spinal Cord Injury, and Traumatic Brain Injury, among others. Throughout this comprehensive one‐year program, the student will have the opportunity to learn in‐depth concepts in this dynamic field, involving clinical research methodology as well as non‐invasive brain stimulation (TMS and tDCS). During this time, the student will be expected to be an active and integrated part of research process in the lab and participate in fundamental research activities, including: writing research protocols, subject recruitment and scheduling, collecting and analyzing data, and writing manuscripts for publication. In addition, Dr. Fregni provides his students with an opportunity to enroll in Principles and Practice of Clinical Research (PPCR), a 6‐month distance‐learning course offered through Harvard Medical School (http://www.clinicalresearchlearning.org/). This intensive, multi‐center course is directed by him and covers all aspects of conducting clinical research, including topics such as: how to formulate a research question, how to select study population, statistical methods, data collection and reporting, and study designs. The team’s mission is to offer theoretical and practical preparation for leadership in distinguished clinical or research careers. Through a collaborative environment, students should leave with a well‐rounded knowledge of non‐invasive brain stimulation and clinical research methodology.
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Hiep Nguyen
Hiep Nguyen is Associate Professor of Surgery in the Department of Urology at Harvard Medical School (HMS), as well as Director of Robotic Surgery Research and Training at Children’s Hospital in Boston. He also serves as co‐director of the Center for Robotic Surgery at Children’s. His specialties include pediatric urology and robotic surgery, and his research activities deal with obstructive uropathy, vesicoureteral reflux, and molecular imaging, among other areas. Dr. Nguyen works extensively with the da Vinci Surgical System, also known as “the robot,” to perform more difficult surgeries than traditional minimally invasive technologies have allowed. In Urology alone, such procedures include complete and partial kidney removal, uretral reconstruction, and correction of undescended testes. The robot directly transcribes the surgeon’s wrist movements, rotating as much as 270 degrees and allowing for the precise movement of miniature surgical instruments introduced into the body through incisions as small as 5 millimeters. Dr. Nguyen’s hope is to continue increasing the efficacy of new technology in medicine. For more information on his work, please see: http://specialists.childrenshospital.org/directory/profile.asp?dbase=main&setsize=5&pict_id=105 5945
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Opportunities in the Lab The Robotic Surgery, Research and Training Center at Children’s Hospital in Boston, under the direction and supervision of Dr. Hiep Nguyen, has several areas of research interest, providing numerous opportunities for hands‐on learning and investigation. Dr. Nguyenʹs research is focused on innovation and maximizing the utility of technology in medicine. Current projects include clinical pediatric urological research (e.g. research in vesicoureteral reflux, prenatal hydronephrosis, and predictive treatment and diagnostic nomograms for urological diseases), new technology research (e.g. surgical training and learning using robotic systems, the development of robotic replacement organs, drug‐delivery devices for the urinary system, and home care robotic systems), and molecular imaging (e.g. cancer, infection and obstructive processes). The laboratory includes a da Vinci surgical robotic system that is dedicated solely to research purposes and a full‐staffed animal research facility. Each Brazilian student in the lab will spend one year conducting research under the supervision of Dr. Nguyen, and be active in 5‐7 projects at any given time. Publications are numerous, and the lab has traditionally had a strong presence at regional and national meetings. In addition to research activities, laboratory assistants are encouraged to attend the conferences and teaching activities of the Department of Urology at the Childrenʹs Hospital, Boston.
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John Godleski
John Godleski is Associate Professor in the Department of Environmental Health at the Harvard School of Public Health (HSPH) and Senior Pulmonary Pathologist at Brigham and Women’s Hospital in Boston. Dr. Godleski’s research focuses on the pulmonary and systemic responses to inhaled ambient air particles. His studies use cardiac and pulmonary mechanical measurements as well as cell and molecular biological approaches with inhalation exposure to concentrated ambient air particles. The overall hypothesis being tested in his laboratory is the following: Ambient urban air particles are complex mixtures with intrinsic toxicity; particulate exposure results in stimulation of lung receptors, release of reactive oxygen species, and induction of pro‐inflammatory mediators that lead to local and systemic effects especially on the cardiovascular system, which ultimately account for epidemiologic associations between adverse health effects and particulate air pollution.
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Opportunities in the Lab Students who spend a year in Dr. Godleski’s laboratory at the Harvard School of Public Health participate in a research program studying the health effects of ambient air pollution. Research projects include analysis of lung inflammatory responses, cardiovascular responses, and central nervous system responses to concentrated ambient particles in animal models of social stress and pre‐existing cardiovascular disease. Research on sources of air pollution using a mobile laboratory study the effects of primary (direct from a source) and secondary (resulting from atmospheric chemical reactions) particulate air pollution on health effects using animal models. New areas of research in his laboratory include the role of epigenetic effects in cardiovascular responses to air pollution, and the health effects caused by inhalation of nanoparticles. The students work directly with Dr. Godleski as well as with senior research staff who teach the necessary skills in basic laboratory research needed for their projects. After initial training, the students are encouraged to take on primary responsibility for a specific experimental task or question. Examples of specific skills include small animal surgery to implant devices for collection of data, broncho‐alveolar lavage in small animals, morphometric analyses, in vivo chemiluminescence, analyses of blood pressure, heart rate and other cardiovascular parameters from telemetric data, and pulmonary function analyses. In addition, the students are expected to present their progress during laboratory meetings, and in a final department‐level seminar at the end of the research experience. The goal is for the students to gain a direct hands‐on laboratory experience with state‐of‐ the‐art methods in biomedical science, to contribute to progress in the specific project areas, to work in a focused team atmosphere, and to be better prepared for a life‐long career that has its basis in understanding the advances of research. Students researching at Godleski’s lab in 2011: João Paulo Vaz Tostes Ribeiro de Oliveira and Rodrigo Sato.
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Joseph Brain
Joseph Brain is Cecil K. and Philip Drinker Professor of Environmental Physiology in the Department of Environmental Health at the Harvard School of Public Health (HSPH). His studies extend from the deposition of inhaled particles in the respiratory tract to their clearance by respiratory defense mechanisms. Of particular interest is the role of lung macrophages and the pathogenesis and prevention of environmental lung diseases and respiratory infection. His research has utilized magnetic particles in macrophages as a non‐invasive tool for measuring cell motility and the response of macrophages to various mediators and toxins. Other experiments deal with the use of lung lavage to obtain and characterize macrophages. Another area of study is drug delivery to and through the lungs. A rodent bioassay utilizing lung lavage has been developed; the assay has been used to estimate the relative toxicity of new and complex mixtures such as molds, urban dusts, welding fume, nanomaterials, as well as drugs and excipients administered by inhalation. For more details on Professor Brainʹs work, please see: http://www.hsph.harvard.edu/faculty/joseph‐brain/
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Opportunities in the Lab During 2012, research opportunities for Brazilian students include studies of metals, especially zinc and manganese, which are essential micronutrients as well as potential toxins. Nanotoxicology, which deals with novel and poorly characterized metal oxides and carbon nanotubes, is another research option. Students may also research various applications of metabolomics to biological responses, or the characterization of the gut microbiome and resulting consequences for cardiopulmonary status. There are also opportunities to study the effects of obesity and starvation on the uptake of micronutrients and toxic metals from the lungs and GI tract. Medical students will join graduate students, postdocs, and research staff to study environmental causes of cardiopulmonary disease. Dr. Brain works primarily with animal models, especially rats and mice, to explore gene‐environment interactions, exposure‐dose relationships, and mechanisms of injury, inflammation, and disease. His team emphasizes dosimetry since “dose makes the poison” and because toxins and nutrients entering the body through the GI tract or lungs have varying distributions throughout the body. Students working in his lab will learn to work with radioactive materials and to use them as a valuable tool. They will learn animal anesthesia procedures, such as a variety of dosing and surgical procedures, as well as multiple analyses techniques. Lung lavage and analyses of bronchoalveolar lavage fluid is a common assay. In addition to a typical suite of cell and protein analyses, they will also learn multiplex assays, epigenetics and metabolomics. Students will be guided by Dr. Brain, as well as the senior research staff, who will teach essential skills in laboratory research. Each student will have a particular project and will take responsibility for a specific question. The goal is not only to develop laboratory skills, but also to acquire experience in designing and interpreting experiments. A main goal is to develop a data set, which can be communicated through presentations and in a manuscript, which may be published. His team seeks to provide experiences which will help create independent physician‐scientists who will pursue clinical or basic research throughout their careers. Student researching at Brain’s lab during 2011: Lucas Nobrega.
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Lester Kobzik
Lester Kobzik is a Professor in the Department of Environmental Health at the Harvard School of Public Health (HSPH) and Professor of Pathology at the Harvard Medical School (HMS). His main research interest is how the lung interacts with inhaled particles—be they environmental particulates, pathogens or allergens. One focus of his work is the role of the lung macrophage in lung defense mechanisms and pulmonary inflammation, especially in relationship to environmental lung disease. A fascinating aspect of lung macrophages is their selective interaction with inhaled particles‐ they respond with simple ingestion and clearance to some particles (the harmless, ʹinertʹ dusts). In contrast, encounters of lung macrophages with pathogenic particles result in release of mediators that initiate inflammation and injury. These mysteriously regulated responses are central to the public health problems caused by air pollution in urban areas, by dusts in certain occupations, and by certain inhaled pathogenic organisms. For more details on Professor Kobzikʹs work, please see: http://www.hsph.harvard.edu/faculty/lester‐kobzik/
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Opportunities in the Lab Students who spend a year in Dr. Kobzik’s basic research laboratory at the Harvard School of Public Health have the opportunity to participate in a research program centered on lung host defense. His research projects include analyses of innate immunity and resistance to viral and bacterial pneumonias, and the role of epigenetic effects on responses to inhaled allergens, i.e. asthma. Brazilian students are partnered with the senior research doctorate staff who work with them to teach the required skills in basic laboratory research needed for the particular project to which they are assigned. The students also meet with Dr. Kobzik regularly to discuss the scientific basis for the project in general and progress in their specific experiments. After initial training, the students are encouraged to take on primary responsibility for a specific experimental task or question. Examples of specific skills include cell culture, performance of in vitro assays, immunologic analysis using flow cytometry, PCR and ELISA assays, as well as use of mouse in vivo models of disease if needed. In addition, the students are expected to present their progress during their turn in weekly laboratory meetings, and in a final department‐level seminar at the end of the research experience. The goal is for students to gain a direct hands‐on appreciation of current research approaches and methods in biomedical science. They also contribute constructively to progress in the specific project areas. In addition, this experience will prepare those who are interested for further involvement in clinical or basic research later in their careers. Students researching at Kobzik’s lab in 2011: Beatriz Borba Casella and Fernando Barros Ezquerro.
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Richard Verrier
Richard Verrier is Associate Professor in the Department of Environmental Health at the Harvard School of Public Health, Associate Professor of Medicine at the Harvard Medical School (HMS), and a member of the Cardiovascular Division of the Beth Israel Deaconess Medical Center. His research is focused on neural, behavioral, and environmental triggers of sudden cardiac death and arrhythmias. The laboratory specializes in computerized analysis of electrocardiographic markers, especially T‐wave alternans, which are a beat‐to‐beat fluctuation in the area and form of the T‐wave of the ECG. His team demonstrated that T‐wave alternans provide an index of vulnerability to life‐threatening cardiac arrhythmias as well as a means of identifying individuals at risk and measuring the efficacy of pharmacologic therapy. Current investigations include neural triggers of sudden death during ischemia, anger, REM sleep, and exposure to environmental air particles. His research has led to a novel technique for selective delivery of angiogenic and myogenic factors to the heart via the pericardial sac. This technology provides a natural interface between molecular and integrative biology.
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Opportunities in the Lab Students who spend a year in Dr. Verrier’s basic research laboratory at Beth Israel Deaconess Medical Center have the opportunity to participate in all aspects of his team’s investigations of electrophysiologic effects of cardioactive pharmacological agents. The students provide hands‐on assistance in acute research projects in large animals, including monitoring, storing, and analyzing physiological data on sophisticated equipment, as well as performing interventions under Dr. Verrier’s immediate oversight. They have the opportunity to develop and exercise surgical skills, as they may participate in thoracotomy and coronary artery dissection. They perform percutaneous access of femoral arteries and veins to position introducer sheaths and observe cardiac catheterization, cardiac pacing, and programmed cardiac electrical stimulation. Through discussion and observation, they gain a working understanding of cardiovascular physiology and interpretation of the electrocardiogram. In several cases, students’ contributions to the research projects were of sufficient merit to be included in authorship of research publications. Students researching at Verrier’s lab in 2011: Alexandre Fligelman Kanas, Marcel Faraco Sobrado and Vitor Penteado Figueiredo Pagotto.
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Stephanie Shore
Stephanie Shore is a Senior Lecturer in the Department of Environmental Health at the Harvard School of Public Health (HSPH). She studies the impact of obesity on the lungs. Her particular interest is the mechanistic basis for the relationship between obesity and asthma. Within the last decade, as obesity rates have soared, it has become apparent that asthma is more prevalent in the obese. Dr. Shore’s lab uses animal models to address the role of adipose derived hormones such as adiponectin and leptin, and aspects of the low grade systemic inflammation of obesity in promoting asthma. The focus is on establishing alternative treatment modalities for this population, since traditional forms of asthma therapy have reduced efficacy in the obese asthmatic. Other interests include the impact of obesity on responses to air pollution, particularly ozone, and the role of IL‐17 expressing macrophages in these events. Dr. Shore uses a variety of techniques in her research, including measurements of pulmonary mechanics in rodents, ELISA assays, real time PCR, and microarray analysis. For more details on Dr. Shore’s work, please see: http://www.hsph.harvard.edu/faculty/stephanie‐shore/
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Opportunities in the Lab Students who spend a year in Dr. Shore’s laboratory at the Harvard School of Public Health will participate in a research program studying the impact of obesity on the lung. Research projects include analysis of changes in pulmonary mechanics and airway responsiveness, pulmonary inflammation, and mRNA expression, in obese and lean mice exposed to ozone. Both wildtype mice and mice deficient in specific genes or mice in which certain genes have been blocked using antibodies will be employed. Areas of emphasis include the role of adiponectin, and the involvement of IL‐17 expressing macrophages in obesity‐ related responses. Students will work directly with Dr. Shore, as well as with senior research fellows and research associates, who will provide hands‐on training in the various laboratory techniques that the students will need to master in order to complete their project. After initial training, the students will be encouraged to take on primary responsibility either for a specific experimental technique or a specific component of the project. Examples of specific techniques include bronchoalveolar lavage, measurement of pulmonary mechanics, RNA extraction and real time PCR, or flow cytometry. An additional essential component of the training is the development of skills in experimental design, data analysis, and data interpretation. To that end, the students are expected to meet with Dr. Shore on a regular basis to discuss their progress, to present their results during weekly laboratory meetings, and in a final department‐ level seminar at the end of the research experience. The goal is for students to have a laboratory experience in a cutting‐ edge area of research, to develop an appreciation for the importance of teamwork in the advancement of science, and to prepare themselves for careers that include life‐long learning through research. Students researching at Shore’s lab in 2011: Leandro Augusto Pinto Benedito and Lucas Chen.
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