LAM Animal Summit Participants

Steve Niemi is Director of the Center for Comparative Medicine at Massachusetts General Hospital and an Instructor in Pathology at Harvard Medical School. With over 33 years experience in biomedical research and commercial biotechnology as both a scientist and executive, he has held senior management positions in drug and device development, gene therapy, genomics, and laboratory animal care.

Dr. Niemi is a Diplomate and past Director of the American College of Laboratory Animal Medicine. He has also served on the boards of the Biotechnology Industry Organization's Food and Agriculture Governing Body, Illinois Biotechnology Industry Organization, National Association for Biomedical Research, Massachusetts Biotechnology Council, Massachusetts Society for Medical Research, Public Responsibility in Research & Medicine, and Scientists Center for Animal Welfare. He has been invited to participate on numerous national task forces addressing medical product development and lab animal welfare. Dr. Niemi earned an AB in biology from Harvard College, a DVM from Washington State University, and then received a US Public Health Service National Research Service Award while a Postdoctoral Fellow at the Massachusetts Institute of Technology. He later completed the Program for Management Development at the Harvard Business School.

His current research interests include developing new animal models of human diseases, and detecting and alleviating distress in lab animals.

Michael Nurok, MD, PhD is a founding member of the LAM Treatment Alliance. He lives in Cambridge, Massachusetts with his wife, LAM Treatment Alliance Executive Director Amy Farber, and daughter Charlotte. Dr. Nurok is a practicing Critical Care physician and Cardio-thoracic anesthesiologist at Brigham and Women's Hospital, Harvard Medical School in Boston.

Pier Paolo Pandolfi received his M.D. in 1989 and his Ph.D. in 1996 from the University of Perugia, Italy, after having studied Philosophy at the University of Rome, Italy. He received post-graduate training at the National Institute for Medical Research and the University of London in the UK. He became an Assistant Member of the Molecular Biology Program and the Department of Human Genetics at Memorial-Sloan-Kettering Cancer Center in 1994. Dr. Pandolfi grew to through the ranks to become Member in the Cancer Biology and Genetics Program at the Sloan Kettering Institute; Professor of Molecular Biology and Human Genetics at the Weill Graduate School of Medical Sciences at Cornell University; Professor, Molecular Biology in Pathology and Laboratory Medicine, Weill Medical College at Cornell University; and Head of the Molecular and Developmental Biology Laboratories at MSKCC. Dr. Pandolfi was also the incumbent of the Albert C. Foster Endowed Chair for Cancer Research at Memorial Sloan-Kettering Cancer Center.

The research carried out in Dr. Pandolfi's laboratory has been seminal at elucidating the molecular mechanisms and the genetics underlying the pathogenesis of leukemias, lymphomas and solid tumors as well as in modeling these cancers in the mouse. Dr. Pandolfi and colleagues have characterized the function of the fusion oncoproteins and the genes involved in the chromosomal translocations of acute promyelocytic leukemia (APL), as well as of major tumor suppressors such PTEN and p53 and novel proto-oncogenes such POKEMON. The elucidation of the molecular basis underlying APL pathogenesis has led to the development of novel and effective therapeutic strategies. As a result of these efforts, APL is now considered a curable disease. Novel therapeutic concepts have emerged from this work that are currently been tested in clinical trials.

Dr. Pandolfi has received numerous awards in recognition of these achievements including the LLSA Scholar Award in 1997, the Irma T. Hirschl Trust Award, the Alexandra J. Kefalides Prize for Leukemia Research in 1999, the Hamdan Award for Medical Research Excellence 2000, the Lombroso Prize for Cancer Research of the Weizmann Institute of Science in 2001, the LLSA Stohlman Scholar Award, in 2004, the William and Linda Steere Foundation Award and in 2005 the prize for Scientific Excellence in Medicine from the AICF. He also has recently been awarded the NIH MERIT Award for superior competence and outstanding productivity in research. In 2006 Dr. Pandolfi was elected as a member of the American Society for Clinical Investigation and the American Association of Physicians, and in 2007, he was elected as an Associate Member of the European Molecular Biology Organization.

Dr. Pandolfi is presently Professor of Medicine and Pathology, Harvard Medical School; Associate Director, Beth Israel Deaconess Cancer Center; Director, Cancer Genetics Program; and Chief, Division of Genetics in the Department of Medicine, Beth Israel Deaconess Medical Center, and Member, Department of Pathology, Beth Israel Deaconess Medical Center.

Craig Douglas Peacock is currently a Research Associate at the Kimmel Cancer Center at Johns Hopkins University. He holds a BSc in Microbiology/Biochemistry and a PhD in Viral Immunology from the University of Western Australia. He has completed two post-doctoral fellowships, his first in 2003 from the University of Massachusetts in Viral Immunology and his second in 2006 from Johns Hopkins University in Oncology. He has been a member of the American Society of Hematology since 2005 and the Association of Cancer since 2006.

Relevant Publications:

Peacock CD., Wang Q., Gesell GS., Corcoran-Schwartz IM., Jones E., Kim J., Devereux DL., Rhodes JT., Huff CA., Beachy PA., Watkins DN. and Matsui W. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. PNAS. 2007; 104(10): 4048-4053.

Watkins DN. and Peacock CD. Small cell lung cancer: Carcinoma or primitive neural tumor? ASCO Educational Book. 2007.

Peacock CD. and Watkins DN. Cancer stem cells and the ontogeny of lung cancer. In Press. Journal of Clinical Oncology. 2007.

Rudin CM., Hann CL., Peacock CD. and Watkins DN. Novel therapeutic approaches to small cell lung cancer. In Press. Journal of the National Comprehensive Cancer Network. 2007.

Matsui M., Wang Q., Barber JP., Smith BD., Borrello I., McNiece I., Lin L., Ambinder RF., Peacock CD., Watkins DN., Huff CA. and Jones RJ. Clonogenic multiple myeloma progenitors, stem cell properties and drug resistance. Cancer Research. 2008; 68(1): 190-197.

David Sabatini is an Associate Member of the Whitehead Institute for Biomedical Research, Broad Institute, and MIT Center for Cancer Research as well as an Assistant Professor of Biology at the Massachusetts Institute of Technology. David is also a founding member of The RNAi Consortium of labs in the Boston area that is developing and using a genome-scale RNA interference (RNAi) library targeting human and mouse genes.

David and his lab, located at the Whitehead Institute, study the basic mechanisms that regulate cell growth, the process whereby cells and organisms accumulate mass and increase in size. The pathways that regulate growth are often deranged in human diseases, such as diabetes and cancer. His current focus is on a cellular system called the Target of Rapamycin (TOR) pathway, a major regulator of growth in many eukaryotic species. In addition to his work on growth control, David is developing and applying new technologies that facilitate the analysis of gene function in mammalian cells. He has developed ‘cell-based microarrays' that allow us to look at the cellular effects of perturbing the activity of thousands of genes in parallel. His long-term goals are to identify and characterize these mechanisms and to understand their roles in the normal and diseased physiology of mammals.

David received his B.S. from Brown University magna cum laude and his M.D./ Ph.D. from Johns Hopkins University in 1997. Later this same year, David was appointed a Fellow at the Whitehead Institute for Biomedical Research. This was followed in 2002 by a dual appointment to Associate Member at the Whitehead and Assistant Professor of Biology at the Massachusetts Institute of Technology.

Awarded the prestigious W. M. Keck Foundation Distinguished Young Scholar in Medical Research Fellowship in 2005, David has been the recipient of many awards and honors. He was named one of the "Worlds Top 100 Innovators in 2003" by Technology Review and his patented cell microarray process and identification of the component parts of cell growth protein implicated in diseases such as cancer have resulted in numerous publications in refereed journals. David was named both a Ross and Pew Scholar in 2003 and awarded a Rita Allen Fellowship in 2004.

Instructor, Harvard Medical School and Research Associate, Department of Surgery and Vascular Biology Program, Children's Hospital Boston

I received my undergraduate degree in Chemistry from the University of California, Santa Cruz and my doctorate degree in Pharmacology from the University of North Carolina at Chapel Hill (Advisor: Dr. Rudy Juliano). My research focused on understanding collaborative signaling pathways between integrin receptors and G-protein coupled receptors in endothelial cells. In 2000, I began my postdoctoral training (Dr. Bruce Zetter, Children's Hospital Boston). My research focused on the mechanism of thrombospondin's inhibitory effect on migration in endothelial cells. Thrombospondin 1 (TSP1) is an endogenous antiangiogenic protein, and some of its effects are mediated by binding of the type-1 repeat (TSR) domains to the cell surface receptor CD36. However, I showed that TSP1 and a TSR-containing peptide inhibited VEGF-induced migration of HUVEC, cells which do not express CD36. My studies led to the finding that Β1 integrins are a critical receptor in TSR-mediated inhibition of HUVEC migration. Thus, inhibition of migration by TSP1 appears to involve both CD36 and Β1 integrins and can be mediated solely by Β1 integrins in cells lacking CD36.

In 2006 I joined Dr. Folkman's laboratory as an Instructor of Surgery at Harvard Medical School and an investigator in the Vascular Biology Program at Children's Hospital. My major area of research has been in understanding the mechanism of several angiogenesis inhibitors in endothelial cell migration in different vascular beds. More recently, my research interests have included the study of LAM, a rare but progressive cystic lung disease characterized by abnormal and potentially metastatic growth of atypical smooth muscle-like LAM cells within lungs and axial lymphatics. I am focused on the isolation, characterization, expansion and functional studies of both the smooth muscle-like LAM cells and the LAM-associated lymphatic endothelial cells, and in investigating the role of angiogenic regulators in LAM disease.

Relevant Publications:

Short, S. M., J. L. Boyer, and R. L. Juliano. (2000) Integrins regulate the linkage between upstream events in G protein-compled receptor signaling to mitogen-activated protein kinase. J. Biol Chem. 275 (17):12970-7

Short, S. M., A. Derrien, R.P. Narsimhan, J. Lawler, D.E. Ingber, and B.R. Zetter. (2005) Inhibition of endothelial cell migration by thrombospondin-1 type-1 repeats is mediated by Beta-1 integrins. J. Cell Biol. 168(4):643-653.

Italiano, J. E. Jr., J. L. Richardson, S. Patel-Hett, E. Battinelli, A. Zaslavsky, S. Short, S. Ryeom, J. Folkman, and G. L. Klement. (2008) Angiogenesis is regulated by a novel mechanism: pro- and ant-angiogenic proteins are organized into separate platelet alpha-granules and differentially released. Blood. 111(3):1227-33

Dr. Cheryl Lyn Walker is the Ruth and Walter Sterling Professor of Carcinogenesis in the Department of Carcinogenesis, UT MD Anderson Cancer Center. She holds joint academic appointments in the College of Pharmacy at the University of Texas at Austin and in the College of Veterinary Medicine at Texas A&M University. She is also Director of the Genetics and Epigenetics of Early Life Exposures Focus Area for the National Institute for Environmental Health Sciences Center for Research on Environmental Disease.

Dr. Walker is currently Vice-President, Elect for the Society of Toxicology and is a member of the International Scientific Advisory Board for the Tuberous Sclerosis Alliance and the Scientific Advisory Board for the LAM Foundation. Previously, Dr. Walker has held appointments from the Department of Health and Human Services to the Board of Scientific Councilors of the National Toxicology Program and is a former Chair of the Environmental Genomics and Carcinogenesis Panel for the Congressionally mandated US-Japan Cooperative Medical Exchange Program. She is also a former member of the Board of Scientific Councilors of the National Cancer Institute and the National Academy of Sciences Committee on Emerging Issues and Data on Environmental Contaminants.

Dr. Walker's research is focused on the role of tumor suppressor genes in cancer and proliferative smooth muscle diseases including uterine leiomyoma and LAM. Her laboratory is actively investigating how signal transduction pathways, such as the PI3K pathway, become perturbed as a result of loss of function of tumor suppressor genes involved in kidney and uterine cancer including TSC-2 and PTEN. She has developed several unique animal models for studying the molecular defects that cause cancer, which are widely used for preclinical studies to identify new therapeutic interventions for several diseases, including LAM. Dr. Walker also has research interests in the area of mechanisms by which endogenous hormones and xenoestrogens in the environment promote disease.

Relevant Publications:

Vicky Holets Whittemore, Ph.D., 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.

Kwok-Kin Wong, MD, PhD, develops mouse models of lung cancer to gain a better understanding of the disease's origins. In addition, these models help validate mutated genes found in human lung cancers, thereby illuminating new genetic relationships and potentially "druggable" targets. The models are also extremely useful in fine-tuning new treatments, which can then be translated back to patients in clinical trials. Dr. Wong's team has generated a mouse lung cancer model to uncover the molecular processes that govern cancer metastasis, the principal cause of death in patients with solid tumors. This unique mouse cancer model will enable Dr. Wong ‘s team to study the genes and pathways that are utilized in the various stages of metastasis – tumor cell invasion, migration, circulation, scattering to distant tissues, migration out of blood vessels, and colonization of distant organs. A better understanding of the genetic events involved in metastatic growth will help guide the development of novel therapeutics to interfere with this deadly process.

Dr. Sima Zacharek is a postdoctoral research fellow in the lab of Dr. Carla Kim, of Children's Hospital Boston. Her current focus is on the study of bronchio-alveolar stem cells (BASCs) in normal lung homeostasis and lung disease. She is working toward the development of novel knock-in alleles to study BASC function in vivo. 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.

Relevant Publications:

Hu J, Zacharek S, He YJ, Lee H, Shumway S, Duronio RJ, Xiong Y. WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase. Genes Dev. 2008; Apr 1;22(7):866-71.

Zacharek SJ, Xiong Y, Shumway SD. Negative regulation of TSC1-TSC2 by mammalian D-type cyclins. Cancer Res. 2005; 65(24): 11354-60.