LAM Treatment Alliance Fast Tracking Treatment Research

Dr. Chada is a Professor in the Department of Biochemistry at Robert Wood Johnson Medical School. Dr. Chada received his D.Phil. at Oxford University, England. He serves as Director of the Genomic Center of New Jersey. He is a recognized expert in mammalian genetics and a leader in the field of HMGA proteins. Dr. Chada has lectured extensively, published over 60 scientific articles, received several awards and is a member of review panels at the National Institutes of Health. In the last decade, Dr. Chada was awarded numerous research grants from the National Institutes of Health, the National Science Foundation, the March of Dimes and others. His research includes the identification of a gene responsible for a number of tumor cell types which include uterine fibroids and lipomas. In addition, a portion of his laboratory has identified a number of genes critical in obesity.

Augustine Choi is currently the Parker B. Francis Professor of Medicine at Harvard Medical School and Chief of Pulmonary and Critical Care Medicine at the Brigham and Womens Hospital. He received his doctorate degree from the University of Louisville School of Medicine, and completed training in internal medicine at Duke University and a subsequent fellowship in Pulmonary and Critcal Care Medicine at the Johns Hopkins University. He joined the faculty at Johns Hopkins prior to moving to Yale University in 1998. Dr. Choi was recruited to lead the Division of Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh in 2000. Dr. Choi joined the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital in 2007.

Dr. Choi's research interest has focused on the regulation and function of stress response genes in response to oxidative stress and inflammation. He has extensively examined the molecular regulation/signaling pathways and function of anti-oxidant enzymes, in particular heme oxygenase-1 and gaseous molecule carbon monoxide, in variety of in vitro and in vivo models of lung and vascular diseases. Dr. Choi also has interest in genomic approaches in identifying candidates genes important in the pathogenesis of lung diseases, in particular ARDS/sepsis and COPD.

Dr. Cutz is Professor of Pathology,Department of Laboratory Medicine and Pathobiology,University of Toronto, Senior Staff Pathologist,Division of Pathology,Department of Paediatric Laboratory Medicine, The Hospital for Sick Children and Senior Associate Scientist, Physiology & Experimental Medicine programe, The Research Institute, The Hospital for Sick Children. Dr. Cutz received his M.D. degree from Charles University Medical School, Prague, Czechoslovakia and completed his Post graduate training(research & clinical): Department of Histology & Embryology,Charles University,Prague; Centre Anticancereux,Toulouse, France; Dept.Pathology ,The Hospital for Sick Children; Toronto General Hospital, Princess Margaret & Wellesley Hospitals, Toronto, Ontario, Canada. Dr. Cutz received his FRCP(C) Speciality certification in Anatomical Pathology from Royal College of Physicians and Surgeons of Canada. Pulmonary Neuroendocrine Cell System in Health and Disease

Dr. D'Armiento is an Associate Professor in the Department of Medicine at Columbia University. She received both her MD and PhD in biochemistry and molecular biology from UMDNJ-Robert Wood Johnson Medical School, and then completed both her internship and residency in internal medicine at the Columbia University Medical Center. She next completed a fellowship in pulmonary medicine, also at the Columbia University Medical Center. She is board certified in both Pulmonary Medicine and Internal Medicine, and has a clinical specialty in lymphangioleiomyomatosis (LAM). She is the Director for the Center for LAM and Rare Lung Diseases at Columbia University. She is also the Chair of the Women’s Leadership Committee on the ATVB council of the American Heart Association and is serving as a member of the Grants Advisory Committee of the Alpha-1-Antitrypsin Foundation. In 2008, she completed a two-year appointment as the Associate Dean for Gender Equity and Faculty Development.

Her research interests are broad, spanning from COPD, to LAM, to asthma, to smoking injury, and her work extends from the laboratory to investigating the pulmonary status of women exposed to biomass in India and Bangladesh. One of the key aspects of her research has been the effect of matrix metalloproteinases on normal physiology and in human disease, and her laboratory integrates both in vitro and in vivo approaches to this study. Dr. D’Armiento has more than 45 publications and is supported by several grants, including an NIH RO1 through the year 2011, and an Established Investigator Award from the American Heart Association through the year 2012. Tsc2+/- mice develop tumors in multiple sites due to misexpression of developmental genes Hmga2 and Imp2 Identification of the benign mesenchymal tumor gene HMGA2 in lymphangiomyomatosis.

Jack A. Elias, MD is the Waldemar Von Zedtwitz Professor of Medicine. Dr. Elias is Professor of Immunobiology and Chair, Department of Internal Medicine, Yale University School of Medicine and Chief, Beeson Service at Yale New Haven Hospital. Dr. Elias earned his MD degree from the University of Pennsylvania School of Medicine. Dr. Elias' research interests include cellular and molecular pathogenesis of asthma and COPD; cellular and molecular mechanisms of lung injury, repair and remodeling; transgenic modeling of pulmonary diseases and disorders; effector mechanisms of IL-13, VEGF and TGF-beta type cytokines in the lung; and effector mechanisms of Th2 and Th1 cytokines in the lung.

Amy Farber, PhD, is the Founder and Chief Executive Officer of the LAM Treatment Alliance (LTA), a 501(c)(3) non-profit organization. After being diagnosed with LAM in April 2005, Dr. Farber founded the LTA with the goal of fast-tracking bench-to-bedside research to find a treatment for LAM in time for women now living with the disease. She is trained as a social scientist focused on the study of law, medicine and society and received her BA from UC Berkeley and PhD from Harvard University. She has completed a Fellowship in Medical Ethics at Harvard Medical School and is a member of the Harvard Medical School faculty and the Institutional Review Boards of Brigham and Women's Hospital and Massachusetts General Hospital in Boston. Dr. Farber lives in Cambridge, MA with her husband, Michael Nurok, and daughter, Charlotte.

Dr. Finlay obtained her medical degree from University College Dublin, Ireland in 1990. She received her Internal Medicine training in St Vincents University Hospital, Dublin, Ireland. She obtained her MD thesis examining the role of Matrix Metalloproteinases in pathogenesis of COPD and Emphysema from University College Dublin Ireland in 1996. She received her higher training in Pulmonary and Critical Care Medicine at Tufts-New England Medical Center, Boston, Massachusetts. She is currently an Associate Professor of Medicine at T-NEMC. As a Pulmonary and Critical Care physician, she has a strong clinical interest in Emphysema and lymphangioleiomyomatosis (LAM). She has been the recipient of the LAM Foundation Fellowship and Established Investigator awards. Dr Finlay's basic research interests focus on the mechanisms that control cell growth in tuberin null cells. In particular, her research has focused on the signaling mechanisms employed by growth factors and estrogen that lead to smooth muscle cell proliferation in tuberin null states such as lymphangioleiomyomatosis (LAM) and therapeutic modalities that could potentially inhibit growth in tuberin null states.

Dr. Gorio is professor of Pharmacology and Clinical Pharmacology at the University of Milano, Medical School . He is director of a research laboratory where several projects of basic and clinical pharmacology are under investigation. The main projects are Tuberous Sclerosis Complex and LAM, Early Intervention in Spinal Cord Injury, and Biology and Application of Stem Cells. He is director of the University Program on TSC and LAM that employs about 40 people among clinical and basic scientists. Patients are followed in all the disease aspects since they enter the study, without any charge. The clinical work is totally supported by Regional Health care Program. His laboratory has isolated and characterized "human TSC2 smoth muscle cells", likely responsible of LAM and angiomyolipoma development. The Methylation of the TSC2 Promoter Underlies the Abnormal Growth of TSC2 Angiomyolipoma-Derived Smooth Muscle Cells Anti-EGFR Antibody Efficiently and Specifically Inhibits Human TSC2-/- Smooth Muscle Cell Proliferation. Possible Treatment Options for TSC and LAM

Caroline Heckman is a senior researcher at the Biomedicum Helsinki working with Prof. Kari Alitalo in the Molecular/Cancer Biology Program of the University of Helsinki. Her training includes an undergraduate degree from the University of Chicago before moving on to the University of Texas MD Anderson Cancer Center where she earned her PhD in 1996. From there she went on to Stanford University as a postdoctoral fellow and later as a staff scientist working with Prof. Linda Boxer to elucidate the molecular mechanisms involved in the development of B cell lymphomas and identifying new targets for therapy. Her current research interests include translational studies investigating the efficacy of anti-angiogenic and anti-lymphangiogenic therapies in cancer and establishing preclinical models for therapeutic testing, while more recent research efforts have focused on lymphangioleiomyomatosis and its association with the lymphatic system. The Tyrosine Kinase Inhibitor Cediranib Blocks Ligand-Induced Vascular Endothelial Growth Factor Receptor-3 Activity and Lymphangiogenesis Molecular Regulation of Angiogenesis and Lymphangiogenesis

Elizabeth (Lisa) Petri Henske recently joined the faculty at the Brigham and Women's Hospital and Harvard Medical School, after spending 12 years at Fox Chase Cancer Center in Philadelphia, where she was a Senior Member. Her research focuses on lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC), a tumor suppressor gene disorder that leads to benign tumors in multiple organs, including the brain, heart, and kidney, as well as seizures, mental retardation, and autism. Her laboratory uses a broad range of approaches to study TSC, including genetic analyses of human tumor specimens, cell-based and biochemical assays, and mouse, Drosophila, and yeast models. Dr. Henske graduated summa cum laude from Yale University, attended Harvard Medical School, and was trained in Internal Medicine and Hematology-Oncology at the Massachusetts General Hospital, followed by postdoctoral training at the Brigham and Women's Hospital. She has received the Scientific Advancement Award from The LAM Foundation (2000), the Manuel Gomez Award from the Tuberous Sclerosis Alliance for "extraordinary scientific and humanitarian efforts to find a cure for Tuberous Sclerosis" (2005), and the Medtronic Prize from the Society for Women's Health Research (2007) for "an outstanding scientist whose work has led or will lead directly to the improvement of women's health." Dr. Henske is a member of the American Society for Clinical Investigation. She is Chairperson of an NIH study section (Cellular and Molecular Biology of the Kidney) and also Chairs the DOD Neurofibromatosis Research Program Integration Panel. She is an elected member of the Tuberous Sclerosis Alliance (TSA) Board of Directors, and Chair of the TSA Professional Advisory Board.

Dr. Hogg has been on the Staff of the University of British Columbia located at St. Paul's Hospital since 1977 and is Currently an Emeritus Professor of Pathology at UBC. He earned his medical degree from the University of Manitoba in1962 and a Ph.D. in Experimental Medicine from McGill University in Montreal in 1969 and completed residency training in Anatomic Pathology at the Massachusetts General Hospital and McGill University. He maintains an active Research program focused on the inflammatory process in the lung with particular reference to the structure and function of the lungs in COPD. He works in collaboration with Dr Peter Pare, Dr. Stephan Van Eeden and Dr Shizu Hayashi.

David Hwang is a pathologist at the University Health Network and an assistant professor at the University of Toronto. He completed MD and PhD degrees at the University of Toronto, followed by a residency in Anatomical Pathology and specialized training in pulmonary pathology. His primary research interests are in mechanisms of lung regeneration and repair, and in metagenomic characterization of the pulmonary microbiota in cystic fibrosis and other chronic lung diseases.

Lester Kobzik is a pulmonary pathologist at the Brigham & Women's Hospital and Professor of Pathology, Harvard Medical School and School of Public Health. His research interests center on innate lung defense mechanisms against inhaled pathogens and particles. He is a 'newbie' to the LAM community, and hopes to catch up, learn all he can, and eventually contribute to the research effort.

Po-Shun Lee, MD, is an instructor in medicine at Harvard Medical School and, a member of the Pulmonary & Critical Care Division and the medical director of Pulmonary Function Lab at the Brigham & Women's Hospital. His current research interest is rapamycin-insensitive pathways in LAM and TSC-related diseases, including the association of MMP and TSC-deficiency.

Graduated from the University of Pennsylvania School of Medicine in 1988, and performed his internship and residency at BWH. After training in the Harvard joint fellowship program in pulmonary and critical care medicine, he returned to BWH to be a chief medical resident in 1993. Since then, Dr. Levy has been a member of the Pulmonary and Critical Care Medicine Division at BWH where he sees patients in the Center for Chest Diseases, including patients with LAM, and performs basic research. He is appointed as an Associate Professor of Medicine at Harvard Medical School and serves as a teacher of medical students, residents and fellows. Dr. Levy is the Director of the Brigham and Women’s Hospital Medical Residency Program for Academics and Career Development. He has a long-standing interest in internal medicine and training the next generation of academic physicians.

His specific areas of research interest are in endogenous mechanisms for the resolution of acute lung inflammation and injury. His laboratory uses lipidomics to identify natural small molecule regulators of the severity and duration of innate and adaptive immune responses in the lung. During Dr. Levy’s post-doctoral training in biochemistry with Charles Serhan and with his current research team, he has laid the groundwork for polyisoprenyl phosphate remodeling to serve as a new counter-regulatory signal transduction pathway in leukocytes and lung parenchymal cells. In addition, his research is focused on the molecular signaling circuits for autacoids that promote resolution, such as lipoxins, protectins and resolvins from arachidonic acid and the omega-3 fatty acids docosahexaenoic and eicosapentaenoic acid, respectively. Moreover, he is linking these basic observations to the genesis of human illness to gain a molecular understanding of the pathobiology of inflammatory lung disease and to use these insights towards new therapeutic strategies for refractory lung diseases.

Joel Moss is Deputy Chief of the Translational Medicine Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland. He graduated from Brandeis University (1967), summa cum laude, and received M.D.- Ph.D. (Biochemistry) degrees from New York University School of Medicine (1972). Following internship and residency (medicine; Johns Hopkins), he completed post-doctoral and pulmonary fellowships (NHLBI). At the NHLBI since 1974, he has co-authored over 500 scientific papers, edited/co-authored several books, and is a co-inventor of biotechnology patents. Dr. Moss was a member of the NHLBI Institutional Review Board from 1988-2006, and Chair from 1995-2006. Subjects of his research include lymphangioleiomyomatosis (LAM), with emphasis on roles of the LAM cell and susceptibility/modifier genes on disease progression. Lymphangioleiomyomatosis (LAM) - A Review of Clinical and Morphological Features Prognostic Significance of Pulmonary Lymphangioleiomyomatosis Histologic Score

Dr. Nagy is currently a Senior Scientist at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Professor in the Department of Molecular Genetics at the University of Toronto, and Investigator at the McEwen Centre for Regenerative Medicine. He also holds a Tier I Canada Research Chair in Stem Cells and Regeneration. His research focuses on several areas of interest, which include 1) Functional studies of genes belonging to families with known roles in vessel formation; 2) Development of sophisticated genetic manipulation tools in the mouse model; 3) Applying genetics to cancer research; 4) Derivation, differentiation and genetic modification of both mouse and human Embryonic Stem cells; 5) Reprogramming of somatic cells to pluripotent stem cells. Dr. Nagy¬πs research is currently funded by the National Cancer Institute of Canada, Genome. piggyBac Transposition Reprograms Fibroblasts to Induced Pluripotent Stem Cells Virus-Free Induction of Pluripotency and Subsequent Excision of Reprogramming Factors

A long standing focus of her laboratory has been to investigate the cell biology of serine proteinases, matrix metalloproteinases (MMPs), and ADAMs (proteinases with a disintegrin and a metalloproteinase domain) in leukocytes and lung structural cells. In particular, we have been examining the mechanisms by which serine proteinases and MMPs circumvent their physiologic inhibitors, and thereby promote tissue destruction by degrading extracellular proteins during inflammatory responses. These mechanisms include: 1) binding of enzymes to the cell membranes of leukocytes in proteinase inhibitor resistant forms; 2) binding of enzymes to substrates; and 3) quantum proteolysis (evanescent bursts of obligate catalytic activity which occur following degranulation of leukocytes) which can temporarily overwhelm inhibitors in the pericellular environment of leukocytes. We are also investigating the mechanisms by which serine proteinases and MMPs bind to the cell membranes of inflammatory cells. In addition, we are studying the activities of MMPs and ADAM family members in lung biology and pathology by studying mice genetically deficient in MMPs and ADAMs murine models of acute lung injury, pulmonary fibrosis, pulmonary emphysema, and asthma. Leukocyte Cell Surface Proteinases: Regulation of Expression, Functions, and Mechanisms of Surface Localization Roles for Proteinases in the Pathogenesis of Chronic Obstructive Pulmonary Disease

Betsy Peters is the nurse coordinator for the Center for LAM Research and Clinical Care. She is the first point of contact for patients referred to the Center. Betsy helps guides patients through their initial orientation to the team, assists in patient travel arrangements, and coordinates patient care throughout each visit. She also coordinates LAM research for the Center. She received her BS in Bioscience and Technology at University of New Hampshire in 1997 and her BSN at Point Loma Nazarene University in San Diego 2003. She brings with her a nursing background in Critical Care and research experience in Clinical Trials.

Martin Post received his PhD from the University of Utrecht in Utrecht, The Netherlands in 1982. Following postdoctoral research training at Harvard Medical School, he was appointed as an Assistant Professor at Harvard in 1985. This was followed by a move to Sick Kids in 1986. Post is the head of the Lung Biology Research Program. Research in this program focuses on the study of the normal development of the lung and the consequences for the health of children when normal lung development fails to occur. In addition to his role as head of the Lung Biology Research Program, he is also the acting head of the Integrative Biology Research Program. Research in this program focuses on the study of complex, integrated systems. This includes analyses of the immune, endocrine, nervous, and cognitive systems. Dr. Post's research looks at the complex processes of lung development.

David Rodman's basic and clinical focus has been on genetic lung diseases, including cystic fibrosis, alpha-1 antitrypsin deficiency, lymphangeoleiomyomatosis and hereditary pulmonary artery hypertension. He received funding from the National Institutes of Health, American Heart Association, American Lung Association, Cystic Fibrosis Foundation, LAM Foundation and other public and private research agencies. His studies of the pathogenesis of pulmonary artery hypertension include establishing much of the methodology used for pulmonary vascular phenotyping in mice and the development of conditional-tissue specific BMPR2 transgenic mice that model the early events in the pathogenesis of hereditary PAH. In addition to his studies in Colorado, during his academic tenure David was a visiting scientist at the Hopkins Marine Biology Laboratories at Stanford, the laboratory of Dr. Elizabeth Nabel at the University of Michigan, the laboratory of Prof. Jeremy Ward at St. Thomas and Guys Hospital, London, and the INSERM unit at Hôpital Henri Mondor, Créteil, France, directed by Prof. Serge Adnot and maintained an affiliate appointment in the Gene Therapy Research Center at the University of Iowa. Role of Discoidin Domain Receptors 1 and 2 in Human Smooth Muscle Cell-Mediated Collagen Remodeling Activation of the Estrogen Receptor Contributes to the Progression of Pulmonary Lymphangioleiomyomatosis via Matrix Metalloproteinase-Induced Cell Invasiveness

Dr. William L. Stanford received his Bachelor’s degree in Chemistry from Duke University and his Doctorate in Immunology from the University of North Carolina in Chapel Hill. Following postdoctoral fellowships in Chapel Hill and the Samuel Lunenfeld Research Institute in Toronto, Bill established his laboratory at the University of Toronto in January 2002 where he is currently an Associate Professor and Associate Director of the Institute of Biomaterials and Biomedical Engineering. Bill is a Canada Research Chair in Stem Cell Bioengineering and Functional Genomics and a McLaughlin Centre for Molecular Medicine Scientist in Regenerative Medicine. Recent awards include the Premier’s Research Excellence Award by the Government of Ontario, the Institute of Musculoskeletal Health and Arthritis Quality of Life Top Research Award, and the Maud Menton Biomedical Research Award in Genetics. His laboratory is focused on basic and applied research in stem cell biology, tissue engineering and modeling human disease using mouse mutagenesis and patient-specific induced pluripotent stem (iPS) cells. As Director of the Centre for Modeling Human Disease (CMHD) gene trap mutagenesis program, Bill is generating a freely available resource of polyA trap gene trap insertional mutants in embryonic stem cells (http://www.cmhd.ca/genetrap/index.html). Bill is also co-Scientific Director of the Ontario Human iPS Cell Facility, which is generating a biobank of reprogrammed patient and disease specific iPS cells to model disease. Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors

Bela Suki was born in Hungary in 1958. He graduated as a physicist from the Jozsef Attila University in Szeged, Hungary. His thesis work was on the proton pump of purple membrane in bacteria. He then received a position at the same university in the Computer Center and worked under the guidance of Zoltan Hantos who also was the supervisor of his PhD work. The thesis of the PhD work was on the mechanical impedance of soft biological membranes. As a post-doctoral fellow, Dr. Suki spent a year at INSERM, UNITE 14 in Nancy, France working with Rene Peslin on the mechanical properties of human lungs at and below breathing frequencies. In 1990, he joined the laboratory of Jason Bates as a post-doctoral fellow and in 1991 he accepted a research associate position at Boston University. In 1995, he became assistant professor and in 2007 he became full professor at the Department of Biomedical Engineering at Boston University. In the same year he became a Fellow of the American Institute for Medical and Biological Engineering as well as Elected Biomedical Engineering Professor of the Year, at Boston University. He has given 77 invited talks at various international meetings, universities and hospitals and he has published 145 peer reviewed publications. His current research includes the progressive nature of pulmonary emphysema, mechanical ventilation of patients with acute lung injury and modeling various complex phenomena and processes in physiology and biology. Early Emphysema in the Tight Skin and Pallid Mice: Roles of Microfibril-Associated Glycoproteins, Collagen, and Mechanical Forces On the Progressive Nature of Emphysema: Roles of Proteases, Inflammation, and Mechanical Forces

Neil Sweezey graduated with a BSc from the University of Toronto and his MD from Queen's University at Kingston, Ontario. Following pediatric residency in Toronto and Halifax, Nova Scotia, he did a fellowship in pediatric pulmonology at The Children's Hospital, Boston. His research training in the cell and molecular biology of the developing lung was with John Torday in Boston and Martin Post in Toronto. His first faculty appointment was at McGill University. He is now an Associate Professor of Paediatrics and Physiology in the University of Toronto. His research addresses the modulation of lung development and of cystic fibrosis (CF) lung disease by steroid hormones and steroid responsive genes, with funding from the Canadian Institutes of Health Research and the Canadian CF Foundation.

Rubin Tuder is currently the Hart Family Professor of Medicine and Director, of the Program in Translational Lung Research at the University of Colorado Denver, School of Medicine. He received his M.D. in 1979 and completed his Pathology residency at S√£o Paulo University, School of Medicine. After completing a post-doctoral fellowship at Stanford University, he worked as both an Attending Pathologist and Medical Supervisor at University Hospital in S√£o Paulo, Brazil. He then moved to the University of Colorado Health Sciences Center where he worked as an Instructor, Assistant Professor, and Associate Professor. In 2001, he accepted a position as an Associate Professor of Medicine and Pathology, and Director of the Division of Cardiopulmonary Pathology at Johns Hopkins University. In 2003 he was promoted to the position of Professor of Pathology and Medicine and continued to lead the Department of Cardiopulmonary Pathology. In 2008, he returned to the University of Colorado Denver, School of Medicine (formerly University of Colorado Health Sciences Center) and his current appointment. Dr. Tuder serves on the Alpha-1 Foundation as Director of Program Evaluation and Director of the Tissue Bank Advisory Committee. He is a Founding Member and Senior Fellow of the Pulmonary Vascular Research Institute. He is currently on the Educational Board of the American Journal of Respiratory Cell Molecular Biology, the Journal of Cell Death, Respiratory Disorders Faculty of the Faculty of 1000 Medicine, and Translational Medicine. His research has included: focus on defining the mechanisms of COPD pathogenesis, exploring the molecular, cellular, and histopathological features of Pulmonary Hypertension, studies of the pathogenesis of cigarette smoke induced emphysema and its underlying mechanisms, including the role of RTP-801 and adipocytokine, as well as his investigation in the pathogenesis of schistosomiasis-related pulmonary hypertension. Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice Precursors and Stem Cells of the Pulmonary Neuroendocrine Cell System in the Developing Mammalian Lung

Dr. Charles Vacanti received a B.A. at Creighton University, and completed his medical training at the University of Nebraska College of Medicine in 1975. He joined the faculty at the Massachusetts General Hospital and Harvard Medical School as an Instructor in Anesthesiology in 1983. His research activities focus on the generation of new tissue, using a technology later termed Tissue Engineering. In 1990, he established the first laboratory for Tissue Engineering at the MGH. In 1994 he was appointed Professor and Chair of the Department of Anesthesiology at the University of Massachusetts. He is the founding president as well as first elected president of the international Tissue Engineering Society, which was also established in 1994. In addition, he is the founding editor of the international journal Tissue Engineering. In 2002, he was appointed Chair of the Department of Anesthesia, Perioperative and Pain Medicine at the Brigham and Women’s Hospital in Boston where he established the laboratories for Tissue Engineering and Regenerative Medicine.

The two major components of his research are (a) scaffolds specially configured to deliver cells in a manner that will result in the generation of functional tissue and (b) a source for optimal cell type to generate new tissues.

A. The use of biocompatible, biodegradable scaffolds to deliver cells for the purpose of generating new functional tissue: The concept is to maximize the delivery of cells, obtained by biopsy and expanded in vitro, into a recipient in a manner that will allow survival of the cells by diffusion of oxygen, and the generation of new tissue with the ingrowth of a vascular supply. The approach that we have used in our laboratories is to attach cells to synthetic or naturally occurring biocompatible, biodegradable polymer scaffoldings, and to transplant the cell polymer complex into an animal. Scaffold materials play a critical role in providing mechanical stability to constructs prior to synthesis of new extracellular matrix by the cells. In addition, we postulated that the polymer scaffolds might act as cell anchorage sites and give the transplanted complex intrinsic structure. The use of synthetic rather than naturally occurring polymers could allow exact engineering of matrix configuration so that the biophysical limitations of mass transfer would be satisfied. Synthetic matrices would also give one the flexibility to alter physical properties and potentially facilitates reproducibility and scale-up. The configuration of the synthetic matrix could also be manipulated to vary the surface area available for cell attachment as well as to optimize the exposure of the attached cells to nutrients. The chemical environment surrounding a synthetic polymer can be affected in a controlled fashion as the polymer is hydrolyzed. With synthetic polymers, one also has the potential of adding side chains to the polymer structure. Thus one might potentially deliver nutrients and hormones to the cells as the polymer breaks down. In contrast, the use of naturally occurring scaffolds could provide bioactive molecules to the new tissue as it is being generated. Bioactive matrices might encourage cell attachment to the scaffold through cell surface adhesion proteins.

B. The identification of an optimal source of cells, which will be useful in efforts to generate new tissue. Autologous adult stem/progenitor cells is a focus of his lab. It was one of the first to identify a population of adult stem cells. The potential for these cells to multiply in vitro and differentiate into the populations of cells desired, and their ability to generate new functional tissue when used in combination with the principles of tissue engineering is being optimized. These combined efforts resulted in the first reports concerning the generation of new cartilage in the shape of the seeded scaffold in Plastic and Reconstuctive Surgery in 1991. They progressed to the implantation of cartilage to correct a sternal defect associated with Poland’s syndrome, in a child followed by the generation of an intact bone in the shape of the distal phalanx of a thumb was reported, in the New England Journal of Medicine, by our lab in 2001. During the last 3-4 years, the research as expanded to generate more highly metabolic tissues such as brain, spinal cord, and lung. The studies have resulted in more than 20 pending/issued patents. One of the patents, entitled, “Guided development and support of hydrogel cell composites,” US patent number 6,171,610 B1, which issued on January 9, 2001, was cited by MIT’s Technology Review as one of the five most promising patents that issued in the United States in that year. Recent evidence suggests that the same stem cells responsible for normal repair of minor tissue injury, may be the same cells responsible for further damage when the cells multiply in an uncontrolled fashion. This may indeed represent a mechanism for the development of some cancers. It is believed that endeavors in tissue engineering and regenerative medicine, using engineered scaffolds and immature cells will lead to the effective therapy of previously “untreatable” diseases.

With a Medical Degree from Ottawa and surgical training in Toronto, Dr. Tom Waddell first came to the University of Toronto in 1987. Within five years he achieved his Masters under the supervision of Dr. Alec Patterson, a founder of lung transplantation, and went on to complete his Doctorate with Dr. Greg Downey, Director of U of T's Division of Respirology. A post-doctoral fellowship followed in England, studying the transfer of tissues from one species to another (xenotransplantation).

Dr. Waddell practices thoracic surgery at UHN and Mount Sinai Hospital and cardiothoracic surgery at the Hospital for Sick Children. A prolific researcher and reviewer, he has earned numerous awards grants and lectured worldwide. Dr. Waddell has led UHN in the strategic planning for our research platform in regenerative medicine, a unique and visionary approach to healing. Through regenerative medicine, scientists repair and grow new cell structures, tissues and organs. This exciting field will transform healthcare delivery in the next decade. Dr. Waddell current research projects will advance understanding of how epithelial cells, which comprise the interior lining of the lungs, may be engineered to defend themselves against infectious or immune attacks. Growing new epithelial cells in the lab opens the door to breakthrough, healing treatments for injured lungs. As an active clinical thoracic surgeon, Dr. Waddell has also developed clinical trials and translational science projects examining the role of the EGFR signalling pathway in early lung cancer.

Vicky Whittemore is Vice President and Chief Scientific Officer at the Tuberous Sclerosis Alliance in Silver Spring, MD. Her nephew was diagnosed with Tuberous Sclerosis Complex (TSC) in 1985. Vicky and her son were diagnosed with TSC in 1990. Vicky received a B.S. in Zoology from Iowa State University in 1977 and a Ph.D. in Anatomy from the University of Minnesota in 1982. She did postdoctoral fellowships at the University of California, Irvine and the Karolinska Institute in Stockholm, and was on the faculty of University of Miami School of Medicine from 1986-1993. She served on the Board of Directors of the TS Alliance from 1987-1993, and joined the staff of the Tuberous Sclerosis Alliance in 1994 where she has worked to build the interest and support of TSC research. She is the co-editor of the third edition of Tuberous Sclerosis Complex, and is currently co-editing the fourth edition with two of her colleagues. She has authored more than 30 scientific publications. She serves on the Review Committee for the Collaboration, Education, Translational Testing (CETT) Program for the Office of Rare Diseases at the National Institutes of Health, and serves as the Vice-Chair of the Board of Directors of the National Coalition for Health Care Professional Education in Genetics (NCHPEG), and as a member of the National Advisory Council of the National Institute of Neurological Disorders and Stroke, National Institute of Health.

Herman Yeger, PhD, is a Professor in the Department of Laboratory Medicine & Pathobiology, University of Toronto and Senior Scientist, Programme in Developmental and Stem Cell Biology, Research Institute, Hospital for Sick Children, Toronto. His research interests are in the differentiation programming of neuroblastoma, a neural crest derived cancer of the peripheral nervous system in children, with a view to development of therapeutic interventions based on differentiation therapy and transcriptional reprogramming. In parallel, he has worked on the pulmonary neuroendocrine cell system with a focus on their physiological function as airway chemosensors and modulators of lung development. In addition he has paid attention to identifying and characterizing the potential progenitors/stem cells of the neuroendocrine lineage. His laboratory has derived several cell line models to facilitate the cancer studies with in vitro systems to model tumor invasiveness and growth, and the lung studies with procedures for neuroendocrine cell culture and functional characterization. Hypoxia Enhances Tumor Stemness by Increasing the Invasive and Tumorigenic Side Population Fraction Precursors and Stem Cells of the Pulmonary Neuroendocrine Cell System in the Developing Mammalian Lung

Dr. Jane Yu is an Instructor of Medicine, Division of Pulmonary and Critical Care in the laboratory of Dr. Elizabeth Henske at Brigham and Women’s Hospital/Harvard Medical School, Boston, MA. She received her BS in Biology from the Peking University of China. In 1999 she received her PhD in Biochemistry from the Graduate School of the City University of New York. She joined Dr. Henske’s lab for her postdoctoral training in Fox Chase Cancer Center. Recently, she moved to Dr. Henske’s lab in Brigham and Women’s Hospital in Boston. She worked on the characterization of the primary cell cultures derived from angiomyolipoma and LAM, demonstrated that estrogen and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways, and uncovered that estrogen-induced activation of mTOR is mediated via tuberin and Rheb. She currently develops animal models of LAM, studies mechanisms through which tuberin and hamartin regulate estrogen-mediated metastatic phenotypes, and develops estrogen-focused targeted therapeutic strategies for LAM. Estrogen Promotes the Survival and Pulmonary Metastasis of Tuberin-Null Cells The Tuberous Sclerosis Complex

Sima Zacharek is a postdoctoral research fellow in the lab of Dr. Carla Kim, of Children's Hospital Boston. She is broadly interested in understanding the molecular mechanisms regulating stem cells in normal tissue homeostasis and in lung disease. She is currently focused on elucidating the cell-of-origin of LAM. She is testing the idea that LAM lesions may originate from the neural crest, which may contribute to the development of a much-needed mouse model of LAM. Her graduate work was completed at the University of North Carolina in the labs of Drs. Yue Xiong and Robert Duronio, where her interests centered on the link between the cell cycle machinery and the TSC/ mTOR growth signaling network in cancer development. Cell Lineage and Cell Migration in the Neural Crest Molecular Regulation of Bronchioalveolar Stem Cells in Normal Lung and Adenocarcinoma