V O L U M E 3 I S S U E 1 J U N E 1 9 9 8
|W A Y N E S T A T E U N I V E R S I T Y S C H O O L O F M E D I C I N E|
I N S I D E
|1 Message from the Director||7 Human Genome Project|
|2 Developmental Biology Program||8 WSU Genetics Program|
|3 Meet Mark Hughes, M.D., Ph.D.||9 Faculty & Student News|
|4 Technology Transfer||10 Diabetes Symposium|
|5 CMMG Virtual Library||11 Bumpers for Babies|
|6 CMMG Scientific Retreat|
Message From the Director
Center Advances the Field of Molecular Medicine and Genetics
George Grunberger, M.D.,
Director, Center for Molecular Medicine and Genetics
I am pleased to present to you Advances, the redesigned newsletter of the Center for Molecular Medicine and Genetics. With this updated publication, we also introduce the Centers new logo.
These important changes signify the substantial growth and development taking place within the Center over the past several months. We have been focusing our efforts on bringing the resources we need--outstanding faculty, interdisciplinary collaborations, state-of-the-art facilities, new sources of funding--to fulfill our mission of excellence and discovery.
Making scientific Advances is really what the Center is all about. Our goal is to be a premiere site where fundamental discoveries are made in molecular medicine and genetics so that we may profoundly impact the diagnosis, treatment, and prevention of human disease. And were already making a difference. Every day our basic scientists and clinician-investigators are uncovering the mysteries of the mammalian genome and evolving their findings into translational research and technology transfer. Every day they are pushing the boundaries of knowledge.
As the number of people affiliated with the Center has grown, it has become increasingly important to find ways to communicate with each other and build a sense of cohesion. We already have some methods in place--from regular meetings to informal gatherings. In the months ahead, we will be looking at other ways as well and welcome your input into this process.
In the meantime, this publication continues to be an important tool for providing valuable news and information about the Centers people, research, programs and activities. In addition to a new look for the newsletter, we have added some new columns that we hope you will find useful. On page 7, for example, you will find a new section for faculty, student and alumni news. We hope you will let us know of any important accomplishments and recognitions for future issues.
This issue of Advances features a wide range of activities and efforts at the Center. On page 3, youll meet Mark Hughes, M.D., Ph.D., and learn how his revolutionary research in single cell biology and early human development is helping families around the world. On page 1, youll read about the Centers involvement in the creation of a comprehensive developmental biology program at Wayne State University, Karmanos Cancer Institute, and Detroit Medical Center. On page 5, youll get an interesting overview of the Human Genome Project. On page 4, youll discover how the Centers new Biotechnology/Technology Transfer Program can help increase your grant approval success rate.
I am excited about the positive momentum of change and development at the Center and welcome your continued input and involvement as we move forward. I look forward to your feedback and comments about Advances.
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F O C U S
Developmental Biology Program
Brings Researchers Together
Linking discoveries from animal research quickly and directly to the understanding and curing of human disease is the goal of Wayne State Universitys new Developmental Biology Program.
The program brings together researchers from throughout the Wayne State University and Detroit Medical Center campuses for the purpose of studying the underlying mechanisms of embryonic development, with a focus on gene discovery, analysis of gene function in mammalian systems and translation of these findings into clinical practice.
The intent is to foster interactive and interdisciplinary investigations among basic science and clinical researchers of the fruit fly, mouse, and human who have common and complementary interests and skills.
"We're setting the stage so that people...can interact closely and collaboratively."
-- Jack Lilien, Ph.D.
"Were setting the stage so that people who work in the development of fruit flies, mouse models, and human disease can interact closely and collaboratively," says Jack Lilien, Ph.D., professor and chair of the Department of Biological Sciences. "We will try to centralize researchers so they can share their ideas, techniques and skill sets. We also plan to recruit additional faculty members."
The Center for Molecular Medicine and Genetics is one of the partners in the newly formed consortium at Wayne State University, which also includes the Childrens Hospital of Michigan, Department of Anatomy and Cell Biology, Department of Biological Sciences, Department of Obstetrics and Gynecology, Department of Pharmacology, Karmanos Cancer Institute, Kresge Eye Institute, and the School of Medicine.
While Wayne State has had nationally recognized researchers in the area of developmental biology for a long time, this new effort marks a broader commitment of resources and talent to creating a comprehensive, innovative program that rapidly transfers new knowledge to the understanding of human disease.
"This is an exciting time in the field of genetics, especially as the Genome Project identifies genes and links between organisms as diverse as the fruit fly, mouse, and the human," says Mark Hughes, M.D., Ph.D., director of basic research for the Center for Molecular Medicine and Genetics.
"The Human Genome Project is producing the rosetta stone of biological information that will allow the ultimate translation of the genetic story," he says. "Still, it will require the next century of study to truly understand this message and how the thousands of genes function in concert to produce the normal story of life, or how they malfunction to cause diseases such as cancer and birth defects. What is clear already is that the genes of a fruit fly, a mouse, and a human are incredibly similar and that knowledge about one of these systems enhances greatly our understanding about the other two.
"Wayne State University is already strong in many areas of developmental biology, and we want to enhance our position by building an across-the-campus program that focuses onto this common theme the attention of scientists at the laboratory bench and clinicians at the bedside," says Hughes.
To this end, Wayne State already has excellent fruit fly developmental geneticists as well as mouse and human geneticists. Now it is in the process of recruiting several new faculty members, including four vertebrate developmental biologists with expertise in mammalian mouse systems. Wayne State is also planning a new high quality transgenic facility, which will make mouse models of human disease.
The Developmental Biology Program plans to focus initially on three main areas: the development of the nervous system; cancer genetics; and the understanding of developmentally important pathways, which help explain how genes interact to give each of us a unique set of features as humans and individuals.
For more information about the Developmental Biology Program, please visit the World Wide Web at URL: http://sun2.science.wayne.edu/~devbio
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P R O F I L E
Meet Mark Hughes, M.D., Ph.D.
Mark R. Hughes, M.D, Ph.D., was drawn to Wayne State University and the Center for Molecular Medicine and Genetics because of their forward-thinking attitude and openness to new ideas.
"Theres a can-do attitude here," says Hughes, who joined Wayne State in Fall 1997, and is director of basic research at the Center as well as director of the division of translational research in the department of Obstetrics and Gynecology, director of the Cancer Genetics Laboratories in the Karmanos Cancer Institute, and director of the Diagnostic Genetics Laboratories in the Department of Pathology.
"The infrastructure is in place to do great things. I believe in what the Center stands for. The Center is committed to bridging basic research and clinical practice and integrates across the campus, from the School of Medicine to the Karmanos Cancer Institute to the College of Science, to name just a few. I have been impressed by the willingness of people throughout the university to work together. There is a synergy here that is very healthy," he says.
"There's a can-do attitude here. The infrastructure is in place to great things."
-- Mark Hughes, M.D., Ph.D.
Before joining the Center for Molecular Medicine and Genetics, Hughes was the chief of the Section on Reproductive and Prenatal Genetics in the Diagnostic Development Branch of the National Center for Human Genome Research at the National Institutes of Health and professor of medicine, pediatrics and OB/GYN at Georgetown University Medical Center.
He received his medical degree at Baylor College of Medicine in Houston, Texas. He completed his residency in internal medicine at Duke University Medical Center in Durham, North Carolina, and his fellowship in medical genetics at Baylor. He received his Ph.D. in biochemistry from the University of Arizona College of Medicine and completed a postdoctoral fellowship in cell biology at Baylor.
In the short time hes been at Wayne State, Hughes not only is continuing to pursue his internationally recognized research in single cell biology and early human development, hes also harnessing the enthusiasm and support hes found to develop several new programs and facilities.
Families from all over the United States and world have benefited from Hughess groundbreaking research and technology development in single cell genetic analysis. He has developed rapid and reliable DNA testing of individually isolated single cells and applied this technology to the preimplantation diagnosis of genetic disease. As a result, couples at high genetic risk now have an alternative to conventional prenatal testing during the first and second trimesters
Preimplantation genetics involves the biopsy of a single cell from the eight cell embryo. DNA or cytogenetic analysis of that individually isolated cell is completed and then an unaffected embryo is transferred to the mothers uterus so that she begins her pregnancy with the knowledge that the embryo will not possess the disease. This method has been developed for a number of disorders, including cystic fibrosis, Duchenne muscular dystrophy, factor VIII deficiency, Tay Sachs disease, myotonic dystrophy, Huntington disease and Lesch Nyhan syndrome.
The basic science objective of Hughess research has been to develop and then use single-cell biology to investigate fundamental genetic questions, such as: When in human development do triple-repeats become unstable and expand? When does X-inactivation occur? What regulates genetic imprinting in human development? He is developing technologies that are expected to be useful both in clinical diagnostic applications as well as in basic developmental biology and cancer genetics.
In addition to his research, Hughes is in the process of developing the following new programs and facilities at Wayne State:
Diagnostic Development Technology Center. This state-of-the-art facility will be equipped with the latest genome technology and expertise to provide high throughput DNA and chromosome analysis. To promote translational research, an interdisciplinary group of researchers will identify basic science discoveries, learn about them and develop ways to apply them in other areas, such as in clinical service labs, preliminary data for research grants or technology transfer.
Developmental Biology Program. See the story about this program on page 1.
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P R O G R A M S
New Biotechnology/Technology Transfer
Program Helps WSU Faculty Seek Grants
A chemistry professor is preparing a grant application but needs help writing an important section on molecular biology. He also needs some preliminary data to establish the feasibility of his proposed experiments, but isn't sure of the molecular techniques to use and is short on time to learn before the application is due.
A principal investigator in anatomy has a research project that is ideally suited to technology transfer, but needs help finding an industry partner and seed funding.
These are just two examples of the kind of help Wayne State University faculty members are receiving through the Center for Molecular Medicine and Genetics' new Division of Biotechnology/Technology Transfer directed by Wayne D. Lancaster, Ph.D.
Since the program was created last fall, Dr. Lancaster and Joan Dunbar, Ph.D., have been assisting dozens of researchers to either improve the competitiveness of their traditional grants or helping them seek new sources of funding, including National Institutes of Health grants from its Small Business Technology Transfer (STTR) program and Small Business Innovative Research (SBIR) program.
"The long-term goal is to increase the amount of funding coming to WSU School of Medicine faculty members," says Dr. Dunbar. "The charter of the Center states that part of its mission is devoted to technology transfer, and one way to approach that is to provide services designed to help other departments. That is what we're trying to do. Grant dollars have become harder to get in recent years. Molecular biology has been developing over the past 15-20 years and has become increasingly integral to many grant applications. What we hope to do is use our expertise and experience in molecular biology to help researchers prepare their grants in a short period of time and get them funded."
"The long-term goal is to increase the amount of funding coming to WSU School of
Medicine faculty members."
-- Joan Dunbar, Ph.D.
Specifically, the Division of Biotechnology/Technology Transfer helps faculty members improve the quality and effectiveness of their grant applications by assisting them with the sections related to molecular techniques, including devising strategies, reviewing/editing, writing, getting started on experiments and even conducting some research - for example, getting the preliminary data.
In the area of technology transfer, Drs. Dunbar and Lancaster help faculty members prepare applications for STTR and SBIR grants. They are available not only to help prepare the applications, but also to seek biotechnology and pharmaceutical industry partners, which are needed to receive this type of NIH funding. The Division also acts as a liaison with the WSU Office of Technology Transfer.
For more information about the services provided by the Center's Biotechnology/Technology Transfer Program, please contact Joan Dunbar, Ph.D., at 313-577-5542, firstname.lastname@example.org , or Wayne D. Lancaster, Ph.D., at 313-577-0028, email@example.com.
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CMMG Virtual Library
Please visit the new online CMMG Virtual Library, developed in partnership with the Shiffman Medical Library. The CMMG Virtual Library is a new endeavor in which scientific journals are made available online to Wayne State University scientists. Accessible through the World Wide Web at URL: http://www.lib.wayne.edu/shiffman/cmmg/virtual_library.html, the CMMG Virtual Library is pioneering the presentation of journals online here at WSU. All comments and suggestions concerning the CMMG Virtual Library are welcome, and may be forwarded to Dr. Stephen Krawetz of the CMMG, at 313-577-6770, firstname.lastname@example.org , or Keir Reavie of the Shiffman Library, email@example.com .
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CMMG Scientific Retreat
The CMMG Scientific Retreat will be held the weekend of October 2-3, 1998. The anticipated location is Bay Valley, Michigan, with participants departing from the Detroit area on Friday morning by bus. The planned activities will start with a scientific poster session, followed by lectures and an invited speaker. Mark Hughes, M.D., Ph.D., (313-993-1353, firstname.lastname@example.org ) invites any comments, suggestions and volunteers.
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F E A T U R E
Human Genome Project:
Impact on Clinical Medicine
The Human Genome Project (HGP) began in 1990 with the goal of discovering all of the 60,000 to 80,000 human genes (the human genome) and determining the complete sequence of the three billion DNA base pairs. Since then, research has progressed much more rapidly than expected. Related research is being done on model organisms, such as the mouse, to help develop technology and interpret human gene function. Other efforts include technology development and transfer, database management, analysis and distribution, and research training.
The HGP is an international effort coordinated by the National Institutes of Health and the U.S. Department of Energy. Its ultimate goal is to develop better treatments and cures for human disease. Determining the DNA sequence differences among people can reveal who is healthy and who has, or is predisposed to, specific diseases. Researchers can also identify the cause and genetic component of human disease and develop diagnostic genetic tests.
|Research generated by the HGP has already had a profound impact on clinical medicine.|
In fact, research generated by the HGP has already had a profound impact on clinical medicine. Genes associated with numerous genetic conditions such as Huntingtons disease, cystic fibrosis, fragile X syndrome, inherited colon cancer, Alzheimers disease and inherited breast cancer are among the 7,000 human genes identified so far.
The ability to identify a gene responsible for a specific disease allows researchers to better understand its pathophysiology and makes gene therapy a possible avenue for treatment. In the current practice of medicine, genetic testing gives clinicians better diagnostic and prognostic tools. It allows patients and their families to better understand the implications of their genetic disorder and allows for genetic testing.
For example, the gene for cystic fibrosis was mapped to chromosome 7 and then cloned in 1989. The gene product, cystic fibrosis transmembrane conductance (CFTR), was shortly identified and found to function as a cell membrane chloride channel. This has greatly increased our understanding of the disease process in patients with cystic fibrosis and has given clinicians predictive information about patients based on their specific gene mutations. The options of carrier testing, prenatal diagnosis, and preimplantation diagnosis are now available to family members, and several gene therapy clinical trials are underway.
In addition to genes for relatively rare disorders, the HGP has also helped to identify genes for more common conditions. In 1994, the first gene to be associated with an inherited form of breast cancer, BRCA1, was identified on chromosome 19. This is an example of a disease where genetic testing can reveal that patients have a very high likelihood of developing breast or ovarian cancer long before they have any symptoms.
There is great potential for aggressive surveillance and prophylactic treatment to reduce the morbidity and mortality associated with this disease in specific families. However, with this information comes a threat to an individuals personal privacy and the possibility of genetic discrimination. It also reveals information about the rest of the family who may or may not want this knowledge.
The ability to obtain genetic information about individuals, families, and even populations clearly raises questions about who will have access to this information and how it will be used. Since the beginning of the HGP, it was recognized that questions about the societal implications of genetic information would need to be anticipated and addressed prior to its clinical application. Consequently, a portion of the HGP budget is being spent to develop programs and policies to address the ethical, legal, and social issues (ELSI) related to the rapid progress in understanding human genetics. This effort represents the largest research investment ever in ethics.
The practice of medicine will be dramatically changed when clinical applications based on DNA diagnostics emerge as a result of the HGP. Emphasis will shift from treatment of the sick to primary prevention of disease. Clinicians will be able to identify individuals predisposed to certain diseases and will develop novel therapeutic approaches based on new classes of drugs, immunotherapy techniques, avoidance of environmental conditions that trigger disease, and possible replacement of defective genes through gene therapy.
For more information about the Human Genome Project, explore this Web site: http://www.ornl.gov/hgmis/home.html .
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P R O G R A M S
WSU Human Genetics Program
Receives "Targets of Opportunity" Funding
Every aspect of human experience is influenced by genetics. Most human health problems, including cardiovascular disease, cancer, neurological and neuromuscular disorders, have recognized genetic components. And although lifestyle and other environmental factors play a role in disease development and progression, research has linked them with genetic susceptibility.
The ever-growing importance of genetics, along with Wayne States recognition in genetics-related research, have led to the creation of a new Program on Human Genetics, which recently received a five-year $1 million grant through the universitys "Targets of Opportunity" initiative.
Under the direction of Mark Evans, M.D., professor of obstetrics and gynecology and a member of the Center for Molecular Medicine and Genetics in the School of Medicine, the Genetics Program is the result of an effort that began four years ago to establish a campus-wide, comprehensive research program that addresses the most current issues in the field. The Genetics Program originally sought funding under WSUs Centers for Excellence initiative (which later became the Targets" program). Evans and colleagues expect the Genetics Program will develop faster now that the grant has been received.
WSU already has national prominence in fetal therapy, bone marrow transplantation, immune diseases, cancer, and molecular toxicology, which are areas closely aligned with genetic factors of disease, prevention, and potential gene therapy for diseases. The Genetics Program proposes to expand these prominent research areas through an interdisciplinary enhancement of human genetics research.
|The Genetics Program is the result of an effort that began four years ago to establish a campus-wide, comprehensive research program that addresses the most current issues in the field.|
The Genetics Program will tie together several separate foci of genetics activity on campus, and represents a collaborative effort among multiple departments in the School of Medicine, the Center for Molecular Medicine and Genetics, the Karmanos Cancer Institute, the Institute of Chemical Toxicology, the Environmental Health Sciences Center in Molecular and Cellular Toxicology, the College of Pharmacy and Allied Health Professions, and the College of Science.
The six key areas to be addressed by the Genetics Program include: developmental genetics and fetal therapy; genetic screening; biostatistical studies and community-based research (e.g. susceptibility genes and biomarkers); neuroimmune diseases; vascular diseases; and social science implications of genetic technologies.
According to Evans, focusing on those areas will allow the program to have a significant practical impact on fetal therapy and cancer biology, helping to better determine the epidemiology of genetic diseases making it easier to spot them and treat them.
|The Genetics Program will tie together several separate foci of genetics activity on campus.|
Evans and his colleagues are also interested in early embryo development and looking at ways to improve conception rates in in vitro situations. They hope to become better able to diagnose and treat diseases early on in pregnancy.
Initially it was expected that the Genetics Program would create new programs and recruit personnel, and some of that has already been accomplished with existing funds. Now, with the Targets of Opportunity money, Evans and his colleagues are trying to increase the sophistication and scope of the program into what could become the premiere program in the United States.
Source: Wayne State University Campus News, May 28, 1998.
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F A C U L T Y &
S T U D E N T N E W S
Center Welcomes New Faculty
Michael A. Tainsky, Ph.D., joins the Center faculty July 1, 1998, as professor (also with pathology, biological sciences, and Karmanos Cancer Institute). He most recently served as professor in the Department of Tumor Biology at the University of Texas M.D. Anderson Cancer Center in Houston, where he was also professor in the Graduate School of Biomedical Sciences. Dr. Tainsky will serve Wayne State as program leader, Cancer Genetics and Molecular Therapy, where he will be responsible for the overall direction, development, and coordination of that program.
|Dr. Tainsky will server Wayne State as Program Leader, Cancer Genetics and Molecular Therapy.|
In addition to our new primary faculty member, the Center welcomes the following new associate and adjunct faculty members: Allen W. Nicholson (biological sciences), Fazlul H. Sarkar (pathology), Vasily M. Studitsky (biochemistry and molecular biology), Martin Tobi (internal medicine), and Ming-Hai Wang (internal medicine).
Mark Evans, M.D., was a member of the organizing committee for the Nobel Symposium on Fetal Medicine, which was held in Stockholm, Sweden, in May. Dr. Evans, as well as Mark P. Johnson, M.D., were featured speakers at the symposium.
Congratulations to Mark P. Johnson, M.D., who was elected into the Alpha Omega Alpha Medical Honor Society by the student body. Each year, the society selects one faculty member who is distinguished in his or her professional career and made significant teaching contributions.
Saied Jaradat has two new publications in press. They are:
Jaradat, S.A., Ko, M.S.H. and Grossman, L.I. (1998). Tissue specific expression and mapping of the COX7AH gene in mouse. Genomics 49, in press.
Grossman, L.I., Seelan, R.S., Jaradat, S.A. (1998). Transcriptional regulation of mammalian cytochrome c oxidase genes. Electrophoresis, in press.
Michail Kolonin attended the 39th Annual Drosophilia Research Conference in March in Washington, DC. His trip was made possible in part by the financial award he received as the runner-up in the poster competition at the Rownd Symposium last fall.
David OHagan and Center faculty member Dr. Gerardus Tromp are collaborating with a biotechnology company, Genomic Solutions, to develop the use of micro array technology for the purpose of "expression profiling."
Sompong Vongpunsawad and Xioaju Wang presented posters at the Fifth Joint Clinical Genetics Meeting on February 27-March 1 in Los Angeles, Calif. Vongspunsawad received a Travel Award to attend.
Sungpil Yoon received a scholarship to attend the workshop, "Population Genetics Data Analysis" at the 1998 Summer Institute in Statistical Genetics at North Carolina State University. He also received an award from the American Foundation for Aging Research.
Dominique Broccoli (Ph.D. 92) has accepted a position as associate member at the Fox Chase Cancer Center in Philadelphia, Pennsylvania.
Chi-hua Chiu (Ph.D. 97) has been awarded an NSF/Sloan Foundation postdoctoral fellowship to support her study of molecular evolution at Yale University.
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International Motor City
The International Motor City Diabetes Symposium will be held in Detroit on October 16-17, 1998. The Symposium will feature presentations by local (WSU), national and international faculty on the latest scientific developments in the fields of insulin signal transduction and diabetic complications. Abstracts for scientific presentations at the Symposium are due August 15, 1998. Questions concerning the science of the Symposium should be forwarded to Dr. Anders A. F. Sima (departments of Pathology and Neurology) at 313-577-1150, email@example.com . Questions about the Symposium itself should be forwarded to the WSU department of Continuing Medical Education, 313-577-1180, firstname.lastname@example.org. Additional information about the symposium is available on the Web at: http://www.med.wayne.edu/diabetes/symposium98
|The Symposium will feature presentations on the latest scientific developments in the fields of insulin signal transduction and diabetic complications.|
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Mark Your Calendars for the Third Annual
Bumpers for Babies Classic Car Show
More than 100 Concours-level cars will highlight the Third Annual Bumpers for Babies Classic Car Show on Sunday, September 20, 1998, at the Alger Estate on the grounds of the Grosse Pointe War Memorial.
Last year, the car show raised $50,000 to help expectant parents travel to Detroit for the services of the internationally known Center for Fetal Diagnosis and Therapy. The center consists of a multidisciplinary team of experts, including several members of the Center for Molecular Medicine and Genetics faculty, dedicated to treating birth defects and genetic conditions in fetuses before birth. The overwhelming success of the previous car shows has enabled nearly two dozen families to receive this highly specialized fetal medical evaluation and treatment.
Bumpers for Babies has become one of the premiere auto shows of the entire year thanks in large part to the creativity and hard work of faculty member, Mark P. Johnson, M.D.
This years show will feature the Grand Saloons of the Great Gatsby Era, including Dusenbergs, Bugattis, and Pierce-Arrows and a special tribute to the Designs of Donald Healey and other classic sports designs. For the first time, Bumpers for Babies will also include a black tie social event the Friday before the show at the Alger Mansion.
If you are interested in contributing to this program or volunteering to help with this years show, please contact the WSU School of Medicine Development Office at 313-577-1495.
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Advances is published by the Center for Molecular Medicine & Genetics.
This newsletter is edited by
Anne E. Greb, M.S.
David D. Womble, Ph.D.
Wayne State University School of Medicine
Enhancing Research and Training in Molecular Medicine and Genetics
Wayne State University is an equal opportunity/affirmative action employer.
Wayne State University School of Medicine
3216 Scott Hall
540 East Canfield
Detroit, MI 48201