Collaborators ::

Dr. Kuhn is a physicist by background, he leads large scale research collaborations and interdisciplinary research teams at the interface of physics, life sciences and biomedical sciences for the past decade. He has, jointly with Dr. Bethel, developed the concepts of the fluid biopsy and the third microenvironment and has demonstrated the morphologic coherence between primary, metastatic and fluid biopsies in cancer.

The first step toward the development of a model of cancer in the metastatic phase is the establishment of the fundamental physical parameters of cancer cells in the circulation. Surprisingly little quantitative information is currently known about the size, shape and feel of cancer during transit in the vasculature. Dr. McCarty’s goal is to answer questions that are fundamental to the development of a model of cancer metastasis: how big are circulating epithelial tumor cells (CTC)? Are these properties comparable to or distinct from the physical properties of primary tumor cells? or of blood cells? Do the physical parameters of CTCs change over time? Is the biophysical signature of CTCs heterogeneous for a single patient at a single time? The goal of Dr. McCarty’s team is to characterize the size, mechanical, and ultrastructural properties of individual cancer cells across time, space, and disease stages.

Dr. Newton specializes in using tools and concepts from nonlinear dynamical systems theory applied to fluid dynamics and other problems in mechanics.
His concept of 'embedded dynamical systems' will be used in the modeling and simulation of individual and swarms of metastasizing cancer cells as they circulate through the human vascular system. He is leading the 4DB effort in physical and predictive modeling with his group of graduate students and postdoctoral researchers based at the Viterbi School of Engineering.

Dr. Shork is Professor, Molecular and Experimental Medicine at TSRI and Director of Bioinformatics and Biostatistics for the Scripps Translational Science Institute, an NIH Clinical Translational Science Award Center devoted to translational research. Over 250 publications have come out of Dr. Schork’s laboratory focusing on the development and implementation of data analysis methods that can be used for understanding the genetic determinants of complex human traits and diseases such as cancer, neuropsychiatric disease, and cardiovascular disease. Methodologies that Dr. Schork has developed, or is working currently, focus on both the design of studies making use of contemporary high-throughput, high-dimensional genomic technologies such as DNA sequencing technologies, multilocus genotyping technologies, and DNA microarrays, as well the interpretation of the results obtained from studies making use of these technologies. Recently, Dr. Schork and his laboratory have focused on the characterization of the effect of DNA sequence alterations contributing to tumorigenesis using computational and modeling strategies in addition to developing methods to accommodate a large number of variables collected on relatively few individuals. Dr. Schork has a long history of collaborative research in which he has contributed data analysis methodology and data analysis expertise. Dr. Schork has trained 19 graduate students and 11 post doctoral students.

Dr. Griffin has been advising the PI and senior co-investigator on the study of the third microenvironment and the design of experiments as they relate to the overarching framework of the 4DB. Dr. Griffin received a B.S. in Physics from Santa Clara University and then a Ph.D. in Biophysics from the University of California, Davis, in 1969. Following four years of post-doctoral training in spectroscopic studies of protein structure and function with Dr. Elkan R. Blout at Harvard Medical School and with Dr. Christian B. Anfinsen at the NIH in Bethesda, he continued NMR studies of peptide and protein structure at the French Atomic Energy Commission Laboratory (C.E.A.) in Saclay, France. In 1974, he was appointed Assistant Professor in the Department of Experimental Pathology at The Scripps Research Institute where he currently is Professor of Molecular and Experimental Medicine. He also is an Adjunct Professor of Medicine at the University of California at San Diego.

Over the past 30 years at Scripps, Dr. Griffin’s research interests with an emphasis on blood components and blood proteins have evolved in the hematology arena and have included a wide range of problems. Translational research in his lab spans from bench to bedside and includes basic structure-function studies of proteins, lipids and lipoproteins, blood cells, animal injury model studies, and clinical investigations of blood-borne biomarkers and genetic risk factors for thrombosis. Based on his clinical research efforts, he was among the first Ph.D. researchers to be awarded honorary membership in the American Society of Clinical Investigation. He currently chairs the Hemostasis and Thrombosis Study Section that is part of the Hematology IRG of CSR at NIH.

Dr. Levy is the Director of Human Genomics at JCVI where he co-leads the Human Genomic Medicine group with Dr Robert Strausberg. Dr Levy has extensive experience in genomics, genetics and computational biology and currently leads a Re-sequencing and Genotyping Center contract from the National Heart, Lung and Blood Institute, providing targeted DNA sequencing of the human clinical samples for multiple investigators. Since its inception in October 2004, NHLBI Resequencing Center at JCVI has collaborated with over 14 distinct research teams working on over 2,700 human samples representing diverse human disease phenotypes. The re-sequencing team led by Dr Levy has produced over 300mb of “finished” human sequence, detecting variant genotypes within targeted gene regions, providing over three million genotype calls inclusive of SNP and insertion/deletion polymorphisms. Dr Levy has also spearheaded efforts to employ second generation sequencing technologies (454, Illumina and SOLiD) for targeted sequencing in human samples and has conducted extensive studies aimed at understanding their strengths and limitations. Dr Levy co-directed a multidisciplinary team that recently identified novel gene fusions in breast cancer cell lines. Dr Levy brings extensive hands-on experience in genomics and computational biology to the current proposal as well as his tested abilities in large-scale project management. Dr. Levy will direct the efforts of Research Project 3, coordinating the amplification efforts of Dr Lasken’s group, directing the targeted gene and RNA sequencing and data analysis in coordination with Dr Nicholas Schork’s group at Scripps Genomic Medicine.

Dr. Jacques received his Ph.D. degree in biophysics and medical physics from the University of California-Berkeley in 1984, where he used dielectric microwave measurements to explore the in vivo distribution of water in the stratum corneum of human skin. His postdoctoral work was at Massachusetts General Hospital, rising to the position of Lecturer in Dermatology/Bioengineering, Harvard Medical School. His work was on laser effects in skin, both experimental and theoretical. He developed the use of Monte Carlo computer simulations to study optical transport in biological tissues, which is now widely used in the field of biophotonics. In 1988, he joined the University of Texas M. D. Anderson Cancer as an Assistant Professor of Urology/Biophysics and established a laboratory developing novel laser and optical methods for medicine, later achieving a tenured position as Associate Professor. He developed a hand-held spectrometer and the analysis software to noninvasively measure hyperbilirubinemia in newborns. This device was patented, licensed, and FDA approved to replace heel stick tests, and is now becoming accepted practice in neonatal care. In 1996, he moved to Oregon, and joined the Oregon Health and Science University, where he now serves as Professor of Dermatology and Biomedical Engineering. His work continues on developing novel uses of optical technologies for both therapy and diagnosis. Currently, he has developed a hand-held polarized light camera to visualize skin cancer margins and guide surgical excision, now in clinical trials. He has developed in vivo sub-nm measurements of vibration of the cochlear membrane of the inner ear in animal models. He is developing novel microscopes sensitive to the ultrastructure of cells and tissues. Dr. Jacques has authored over 96 papers.

Dr. Bethel, a member of the Scripps Clinic Medical Group and the Dept of Pathology at Scripps Green Hospital, also holds academic appointments as an Adjunct Professor of Cell Biology at The Scripps Research Institute and Voluntary Assistant Clinical Professor at UCSD School of Medicine.

She is the Program Director of the Scripps Clinic/Scripps Green Hematopathology Fellowship and the Medical Director of the Scripps Clinic Medical Laboratory Blood Bank. As an active staff hematopathologist, she supervises the diagnostic hematopathology service at Scripps Clinic/Scripps Green Hospital, including interpretation of complex flow cytometry cases, serving patients at the Scripps Cancer Center and Stem Cell Transplant Program. She also provides medical directorship services to several clinical laboratory sections of the Scripps Clinic Medical Laboratory at Green Hospital. As well, she serves on multiple hospital and medical group committees, including credentialing, blood transfusion utilization review (chairperson), cancer committee, and tissue committee. In the last few years, Dr. Bethel has been published in multiple co-authored research papers on subjects ranging from hairy cell leukemia to extramedullary and choroidal hematopoiesis, as well as circulating tumor cells. She is currently the PI for a pilot research project on circulating tumor cells in colon cancer, funded by a competitive institutional grant awarded in 2008. She has extensive experience at the translational research interface having collaborated with the physical sciences research team of Dr. Kuhn for the past six years and having supervised numerous fellows and trainees in translational research. Through her ongoing experience in administrative roles at Scripps Clinic/Scripps Green Hospital, as well as extensive leadership roles in her earlier career as an active duty Navy physician, Dr. Bethel is well versed in the management of large enterprises. She will dedicate 100% of her research effort to the research program of the 4DB Center. She will also provide the oversight and team leadership to the entire medical oncology team from Scripps Clinic, the UCSD Cancer Center and Billings Clinic. As a pathologist, a hematopathologist, and a flow cytometrist, she will address the problems of detecting small numbers of malignant cells in the circulation and guide the development of optimal fluorescent staining approaches. She will also take primary responsibility for the study designs with regards to the patient selection strategies, will have oversight responsibility for the lung tissue sampling, and will carry out the tissue sampling of all colon cancer specimens.

Dr. Kosty is the Director of Graduate Medical Education and Scripps Cancer Center at Scripps Clinic/Scripps Green Hospital. He is also the program director of the Scripps Clinic hematology/oncology fellow training program where he performs clinical research in thoracic and genitourinary malignancies. He is board certified in internal medicine, medical oncology and hematology and has received numerous honors and awards. Dr. Kosty is a member of the American Society of Hematology and the American Society of Clinical Oncology, where he has served as chairman of the genitourinary program committee, and is currently a member of the ASCO Workforce Initiative Group. He has worked as an investigator on many research projects, publishing dozens of papers and abstracts and has served on multiple cancer-related committees at Scripps and for ASCO. Dr. Kosty graduated with honors from the University of California at Berkeley with a BS and with an MA in biophysics. He received an MD from George Washington University School of Medicine and Health Sciences. He also served as an intern, resident and fellow at Naval Hospital, San Diego and was a visiting fellow at the Dana-Farber Cancer Institute, Harvard Medical School and Scripps Clinic.

Dr. Nieva is a graduate of the University of California, Irvine College of Medicine. He trained in Internal Medicine at the University of California, San Diego and completed his fellowship in Hematology and Oncology at the Scripps Clinic (La Jolla, CA). He is presently a clinical hematologist and oncologist at the Billings Clinic (Billings, MT) where he serves as Program Leader for the thoracic oncology program. Billings Clinic is one of ten U.S. sites for the National Cancer Institute’s National Community Cancer Centers Pilot Program (NCCCP). In 2008, he led all physicians within the Montana CCOP in accrual to cancer clinical trials. Dr. Nieva maintains an active clinical trial program in thoracic oncology and specifically in the field of circulating tumor cells. Prior to his current position, Dr. Nieva was the Director of Translational Research at the Scripps Cancer Center from 2003 to 2007 and recipient of a Skaggs Clinical Science Award for his work on innate immunity and protein-metabolite interactions. Dr. Nieva received an Outstanding Teacher Award from the Scripps Clinic Graduate Medical Education.

Dr. Bazhenova is an Assistant Clinical Professor at the UCSD Moores Cancer Center where she concentrates on lung cancer patients, particularly as this relates to females and non-smokers. She actively participates in cooperative group trials, designing and implementing clinical investigations at Moores Cancer Center, including phase II studies and correlative science projects with several UCSD investigators. Dr. Bazhenova completed her medical education at Nizhny Nogorod Medical Academy in Russia and then finished her residency and internship in Internal Medicine at West Los Angeles Healthcare Center/UCLA. She completed her fellowship in Hematology/Oncology at Scripps Clinic before joining the Moores UCSD Cancer Center.

Dr. Reid received his MD from Stanford University, where he also received a Ph.D. in biochemistry. His doctoral thesis focused on the use of interferon to treat cancer and identified pathways involved in the anticancer effects of interferon. He joined the University of California, San Diego, as an Associate Professor of Clinical Medicine in 2004. He also served as a Staff Physician in the Department of Oncology at the Palo Alto Veterans Affairs Health Care System/Stanford University Medical Center. Dr. Reid was the lead investigator on the original trials using Onyx-015 to treat colorectal cancer and has pioneered the use of adenoviral and vaccinia vectors to the treatment of cancer. Dr. Reid has received national recognition for his work including the awards from the Interferon Society, the International Society of Gene Therapy and the Society for Interventional Radiology. He also serves on the review board of numerous journals including Nature Cancer Gene Therapy, Gene Therapy and Clinical Cancer Research.

Dr. Lin is an Assistant Clinical Professor in the Department of Pathology at the University of California, San Diego Medical Center. She is a member of the Division of Anatomic Pathology and has a special interest in pulmonary pathology. She has collaborative research projects with investigators at the Moores Cancer Center and in the Pulmonary and Critical Care Division at UCSD Medical Center. Dr. Lin completed her medical and graduate school training in the Medical Scientist Training Program at the Northwestern University Feinberg School of Medicine in Chicago, IL. At Northwestern University, she was a graduate student in the laboratory of Dr. Robert A. Lamb where she studied the paramyxovirus simian virus 5 (SV5). She then went on to a residency in a combined Anatomic and Clinical Pathology program, followed by a Surgical Pathology fellowship and Placental Pathology fellowship, which were all at the UCSD Medical Center. Dr. Lin then joined the faculty in the Department of Pathology at UCSD Medical Center.

Dr. Strausberg will oversee the integration of the 4DB Education and Training program with the JCVI, which has an established Education Group led by Dr. Lisa McDonald. This program offers opportunities in the areas of Professional Development as well as an Internship program for young scientists and science professionals. In the area of Professional Development the JCVI has a tradition of offering educational opportunities for science professionals and educators as well as non-science professionals. This year the Institute is offering training courses and workshops in the following areas: Prokaryotic Genome Annotation & Analysis Course; Eukaryotic Genome Annotation & Analysis Course; Introduction to Microarray Technology; Introduction to Microarray Data Analysis; Advanced Microarray Data Analysis; DiscoverGenomics! Workshop; Genomics Course for Educators. Together with Scripps Genomic Medicine, the JCVI offers a course on the Future of Genomic Medicine in San Diego. Dr. Strausberg serves as co-Director of that course together with Dr. Eric Topol of Scripps Health and The Scripps Research Institute.

Dr. Lasken directs a robust program in genomics and whole genome amplification technologies. Previously, he was a Professor at the Center for Genomic Sciences at Allegheny General Hospital in Pittsburgh. He is an experienced molecular biologist with 24 years of work in the fields of DNA replication and amplification. As the first employee of Molecular Staging Inc., he built a genomics department of 20 scientists and developed MDA amplification which is licensed under the brand names TempliPhi and GenomiPhi (GE Healthcare) and REPLI-g (Qiagen). He is the lead inventor on a patent enabling these products. His laboratory was the first to sequence genomic DNA from a single. He is currently funded by the NHGRI to develop methods for single cell sequencing of uncultured nicrobes from the human microbiome. Dr. Lasken is guiding the JCVI’s work to expand its state-of-art single cell sorting capabilities into a high-throughput production pipeline. His lab infrastructure includes a Becton Dickenson Aria flow cytometer that is available for the proposed cell sorting activities.

Dr. Marrinucci is the 4DB Project Manager. She is also the Clinical Studies Manager of the Kuhn lab at TSRI and will take primary responsibility for the initiation and maintenance of clinical studies involved with the 4DB Center.  She has more than 5 years of experience in collaborative research projects involving the detection and characterization of circulating tumor cells from patients with epithelial cancers.  Her doctoral thesis completed at The Scripps Research Institute focused on the clinical significance of circulating tumor cells.  Dr. Marrinucci is also actively involved in high school and college student mentorship and scientific training.

Dr. Nelson is the 4DB Program Manager.  Dr. Nelson has extensive expertise in cell based assays, fluorescent detection technologies, and oncology.  He has served as the Principal Investigator for an SBIR Phase II grant and has served on NCI Grant Review Committees.  He has been working with Dr. Kuhn for the last 18 months on CTC detection and is currently a Scientific Associate at The Scripps Research Institute in the Department of Cell Biology.