AOA Research Conference-2009:

The Translation of Genomic Science into
Osteopathic Clinical Practice and Research

November 1-3, 2009
Ernest N. Morial Convention Center
Rooms 226-227

The Osteopathic Research Center and Steven Berley, DO, a family physician from Lindenhurst, NY, are teaming up to co-host the 2009 AOA Research Conference November 1-3 in New Orleans. Join us for this dynamic program featuring a number of leading experts in the field of clinical and research genomics.

John C. Licciardone, DO, MS, MBA, the executive director of the ORC and the Osteopathic Heritage Clinical Research Chair, submitted the application to the AOA last fall to lead a conference focused on genomics in osteopathic clinical practice and research.

Martha Felini, PhD, MPH, assistant professor of epidemiology in the School of Public Health at the University of North Texas Health Science Center in Fort Worth, has also been instrumental in helping plan this conference.

In addition to Drs. Berley, Licciardone and Felini, this conference will include many national level speakers such as:

• W. Gregory Feero, MD, PhD, the special advisor to the director of genomic healthcare at the National Human Genome Research Institute at the National Institutes of Health. Dr. Feero will deliver the keynote address for the Research Conference;

• Raoul Tibes, MD, PhD, director of the hematological malignancies program at the Translational Genomics Research Institute in Scottsdale, Ariz.;

• David Dooling, PhD, assistant director of the Genome Center, oversees the Information Systems and Medical Genomics groups at the Washington University School of Medicine;

• Judith Benkendorf, MS, CGC, special assistant to the director of the American College of Medical Genetics;

• Jim Chinitz, BS, chief executive officer of Population Diagnostics, Inc.;

• Michael Christman, PhD, president and CEO of the Coriell Institute for Medical Research;

• Brandon Colby, MD, MBA, founder and CEO of Existence Genetics;

• George Grills, PhD, director of operations and core facilities and director of advanced
technology assessment for the life sciences core laboratory facilities at Cornell University;

• Stuart Scott, PhD, assistant professor in the pharmacogenetics program at Mount Sinai School of Medicine;

• Roy Martin, DMin, assistant professor of clinical ethics, Texas College of Osteopathic Medicine, University of North Texas Health Science Center;

• Shannon Kiernan, MS, CGC, genetic counselor, Navigenics;

• David Tegay, DO, FACMG, associate professor of medicine and medical genetics at the New York College of Osteopathic Medicine; and

• Michael Terzella, DO, assistant professor of osteopathic manipulative medicine at the New York College of Osteopathic Medicine.

“This conference will contain significant material on genomics for the practicing osteopathic physician and osteopathic clinical researcher,” said Dr. Berley. “Because this conference is designed to impart foundational knowledge in this area that is frequently not addressed at this level in the medical school curriculum, it is appropriate for physicians, medical students, educators and basic scientists.”

2009 AOA Research Conference
The Translation of Genomic Science into
Osteopathic Clinical Practice and Research

Sunday, November 1
The Science Behind Genomics

8:00 a.m. -
8:15 a.m.

Introductory remarks
Steven Berley, DO
Doctors’ Care

John C. Licciardone, DO, MS, MBA
The Osteopathic Research Center

berley

licciardone

8:15 a.m. -
9:00 a.m.
Research Conference Keynote Address:
From genetics to genomics
W. Gregory Feero, MD, PhD
National Human Genome Research Institute
feero
9:00 a.m. -
9:45 a.m.

The current state of next generation DNA sequencing technologies
George Grills, PhD
Cornell University

New DNA sequencing technologies, often called next generation sequencing technologies, are having a fundamental impact on life sciences research and an increasing crucial role in advancing knowledge and understanding in a wide variety of health-related areas of research. They are disruptive technologies in the positive sense, providing qualitatively new alternatives to previously established paradigms of research. New sequencing technologies present an exceptional opportunity for creative applications with potential for breakthrough discoveries. This is a rapidly developing field. These technologies have a wide and growing range of applications, including whole genome assembly, amplicon resequencing, mutation detection, SNP genotyping, small RNA profiling, and genome-wide measurements of protein-nucleic interactions. The Cornell University Life Sciences Core Laboratories Center has implemented various next generation sequencing platforms as academic core facility shared research resources. We have established sample handling methods and informatics tools to build robust processing pipelines in support of these new technologies. Implementation of next generation sequencing platforms as shared resources with multi-disciplinary core facility support enables cost effective access and broad based use of these emerging technologies.

grills
9:45 a.m. - 10:00 a.m.
Q & A
10:00 a.m. - 10:15 a.m.
Break
10:15 a.m. - 11:00 a.m.
Osteopathic principles applied in the genomic era
Michael Terzella, DO
New York College of Osteopathic Medicine

The emerging field of genomics in medicine provides osteopathic physicians with an opportunity to improve the health care provided to millions of people as they discover they have a genetic predisposition to one or more of the myriad diseases that burden our society. The implications of genomics are broad. Many ethical and clinical decisions will eventually be made based on a patient’s genetic fingerprint. How will the osteopathic community prepare itself to move forward given the new information afforded it by genomics?

While the osteopathic and non-osteopathic communities will provide preventative medical services to patients with genetic predispositions to a disease state, the osteopathic physician is in a unique position to be able to perform yearly screening tests and preventative treatments with their hands.

Knowing where viscerosomatic reflexes and Chapman’s points may occur can help the osteopathic physician to manually screen for organ-related disease. This knowledge would be valuable when performing a yearly physical on a patient with a known genetic propensity for certain diseases.

By decreasing stress levels, helping to maintain homeostasis and incorporating osteopathic teachings into a general medical plan, the osteopathic physician is uniquely qualified to treat and screen patients with genetic predispositions for certain disease states that genomic evaluations may uncover.

terzella
11:00 a.m. - 11:45 a.m.
From data to metadata: bioinformatics in the age of genomics
David Dooling, PhD
Washington University School of Medicine

Massively parallel DNA sequencing technologies have revolutionized genomic research. No longer are years spent sequencing a single human genome; this can now be accomplished in about one week. Along with a commensurate drop in cost, this has allowed sequencing to be applied across a wide spectrum of biological and medical research. Such capabilities do not come without their challenges. Generating massive amounts of sequence data requires significant amounts of disk storage and computational capacity. Analyzing the sequence data and extracting biologically relevant results requires yet more disk storage and computational capacity. However, identifying genomic variations that correlate with specific phenotypes requires much more than large information technology infrastructures. Sequencing several genomes per week and performing comparisons between genomic sequences of dozens of patients requires detailed tracking of clinical information, sample information, laboratory processes, and analysis pipelines.

The Genome Center at Washington University in St. Louis has developed an information management system that provides this detailed tracking while also allowing extreme flexibility and adaptability as new laboratory processes and analysis tools become available. This talk will detail how this system has been used to sequence DNA from tumor and normal tissues of several dozen cancer patients.

dooling
11:45 a.m. - 12:00 p.m.
Q & A

12:00 p.m.-
1:00 p.m.

AOA Research Conference Lunch
Monday, November 2
Translational Genomics

8:00 a.m. - 10:00 a.m.
Convention-wide Keynote Address
10:15 a.m. - 10:55 a.m.
The Coriell personalized medicine collaborative: examining the utility of genome-informed medicine
Michael Christman, PhD
Coriell Institute for Medical Research

The Coriell Personalized Medicine Collaborative (CPMC) is a research study that employs an evidence-based approach to determine the utility of using personal genome information in health management and clinical decision-making1. The CPMC also aims to build a cohort with rich genotypic and phenotypic data with which to discover genetic variants that affect drug toxicity and efficacy, as well as to discover presently unknown gene variants that elevate a person’s risk of cancer and other complex diseases. This forward-looking, collaborative effort involves physicians at several hospital partners, scientists, ethicists, genetic counselors, volunteer study participants, and information technology experts. Its goal is to better understand the impact of personalized or genome-informed, medicine and guide its ethical, legal, and responsible implementation2. The study will enroll 10,000 individuals by the end of 2009 with an ultimate goal of 100,000 participants. As of April 2009, there were ~4,000 participants enrolled in the study. There is no charge to study participants.

1“Personalized Health Care: Pioneers, Partnerships, Progress” A report prepared by the Initiative on Personalized Health Care under Federal HHS Secretary Michael O. Leavitt. Found at: http://www.hhs.gov/myhealthcare/news/presonalized-healthcare-2008.html
2Prainsack, P., Reardon, J., Hindmarsh, R., Gottweis, H., Naue, U., Lunshof, J.E. (2008) “Commentary on Personal Genome Tests”, Nature 456, 34-35.


christman
10:55 a.m. - 11:35 a.m.

Copy number variation (CNV) analysis and causative mutations
Jim Chinitz, BS
Population Diagnostics, Inc.


Historically, patients having a common complex disease have been lumped together and considered homogeneous according to phenotype. Research efforts and the design of mutation discovery tools to date have focused primarily on the premise that common genetic variants will be associated with common disease. However, a paradigm shift is underway where appreciation is gaining for the heterogeneity of common disease, which is likely caused by highly penetrant rare variants, which are multi-genic and independently capable of generating the common phenotype. Ultimately, it is necessary to dissect phenotypes into genotypic differences to understand common disease and to personalize medicine. Beyond SNPs, there is a surprising abundance of structural variation in the genome called Copy Number Variants (CNVs), including insertions, deletions and duplications, much of it occurring de novo rather than being inherited. The task relating CNVs to disease etiology or to drug efficacy & safety for predictive testing and patient stratification for targeted drugs has only just begun. Recent studies have revealed rare CNV associations in autism, schizophrenia and ALS. In these models, the metrics that define the level of clinical relevance (i.e. odds ratios) of the rare variants is unprecedented, making them ideal candidates as biomarkers. In fact, these biomarkers can be classified as having “causative” associations and establish a new standard (versus “risk” or “predisposition”) for diagnostic, personalized medicine and drug discovery applications.

Jim Chinitz
11:35 a.m. - 12:15 p.m.
Translating genomic information into personalized medical care
Brandon Colby, MD, MBA
Existence Genetics

Translating Genomic Information into Personalized Medical Care will focus on the new field of Predictive Medicine and how you, the physician, can integrate comprehensive genetic screening into your own practice. In the past, utilizing a patient’s genetic information in the prevention and treatment of disease has been hindered by three significant issues: first, lack of access to the patient’s genetic code, second, inexperience analyzing the meaning behind genetic information, and third, questions surrounding the actionability of the results. With the emerging specialty of Predictive Medicine and the advent of next-generation genetic analysis technologies, however, these issues are now being solved.

The primary goal of Predictive Medicine is to facilitate the adoption of genetic information by both the healthcare provider and the patient. In this regard, Predictive Medicine acts like any other medical specialty by enabling any physician to efficiently integrate a complex field of medicine into their daily practice. The talk will cover cutting edge technologies that will empower you, the physician, to choose the most appropriate genetic screening for your patients and, most importantly, easily understand all of the results and how each one is clinically actionable. After this presentation, you’ll have a better understanding not only of the immense benefits of next-generation genetic analysis technologies but also how you will be able to integrate the genetic revolution into your own daily practice of medicine.

12:15 p.m. - 12:55 p.m.
Direct-to-consumer genomic medical services
Shannon Kieran, MS, CGC
Navigenics

Less than a decade since the completion of the Human Genome and HAPMAP projects, the combination of genomic advances with the accessibility of the internet has set the stage for an unprecedented new development in medicine: open access to genomic testing for all. Consumers can now choose to purchase genetic testing directly from a laboratory or business, often with little or no oversight from their health care provider. While this growing market has reduced geographical barriers to genetic testing services and increased public awareness of genomics, it has also placed the burden of deciphering reliable tests from those with less scientific rigor on the consumer.

Health care providers are on the front line of this new industry, often faced with interpreting genomic results and assisting patients with follow-up steps. Organizations such as the American College of Medical Genetics and the National Society of Genetic Counselors have begun to provide guidelines and recommendations to aid consumers in choosing genomic test providers, and companies like Navigenics and DeCode are making efforts to establish an ethically responsible market and lead regulatory discussions. However, until a formal regulation system has been defined, consumers will continue to depend on their health care provider for guidance. By understanding the direct-to-consumer landscape, as well as the potential benefits and pitfalls of these services, providers will be better prepared for patient questions, and better equipped to help guide testing decisions.


kieran
1:15 p.m. -
2:30 p.m.
COM Alumni Luncheons
Tuesday, November 3
Clinical Genomics
8:00 a.m. -
8:30 a.m.
An osteopathic primary care model for integrating genomic medicine into clinical practice
Steven Berley, DO
Doctors’ Care

While the genomic era in clinical medicine is just beginning to gain traction in every day clinical medicine, current trends in research suggest that in the next couple of years a rapidly expanding number of genomic laboratory tests and therapeutic options will be available to the clinician with demonstrable clinical validity and utility. I will present an overview of several different categories within medicine where genomic research is transitioning into daily practice.

I. Currently an accurate and thorough family history has been well demonstrated to be an essential component in accessing relative health risks for our patients. Using family history information in clinical scenarios it will be demonstrated how genomic based medical decisions are obtained in a cost effective manner. The need for physicians to have a family history format that is properly systematized, streamlined and readily incorporated into a patient's medical record will be reviewed and useful sources for accomplishing this will be provided.

II. Pharmacogenomics is the area of study currently providing the most clinical utility for everyday practice. Most likely this will remain true over the next several years. Several examples will be reviewed including Wafarin, Plavix, SSRIs, and a number of chemotherapeutic agents.

III. Patients presenting genomic sequencing data to their physicians will occur with increasing frequency as the cost factor for these tests drops exponentially. Currently the most likely source for this information is third-party commercial companies such as Navigenics and 23andMe. We are just beginning to see the advent of private and public sector organizations providing services to directly interpret this data. Physicians will need to be familiar with this data format and appreciate benefits and pitfalls in reviewing results with patients.

IV. With the anticipated conversion of most clinical practices to EMRS within the next five years the opportunity will exist to network genetic information between separate practices on a large scale. This opportunity to interface genomic data on a real-time basis will allow ongoing clinical research to be implemented within a physicians office setting.

berley
8:30 a.m. -
9:00 a.m.
Genomic factors as predictors of response to osteopathic manipulative treatment in patients with chronic low back pain
John C. Licciardone, DO, MS, MBA
The Osteopathic Research Center

A re-analysis of data originally collected in the North Texas Clinical Trial of OMT for chronic low back pain was performed to study the “OMT responder.” These data suggest that one-half or more of patients receiving OMT may be successful responders.

The OSTEOPATHIC Health outcomes In Chronic low back pain (OSTEOPATHIC) Trial is an ongoing phase III clinical trial using a randomized, double-blind, placebo-controlled, 2x2 factorial design to study the efficacy of OMT. Ultrasound physical therapy is the other factor studied in this trial which aims to randomize 488 subjects (122 subjects in each of the four treatment dyads). The OSTEOPATHIC Trial affords an opportunity to assess multiple factors associated with successful response to OMT.

Buccal swabs were routinely collected from subjects enrolled in the OSTEOPATHIC Trial beginning in 2009 and sent for laboratory analyses by the Center for Human Identification at the University of North Texas Health Science Center. The initial results of this study to assess the relationship between genomic factors, including those involving high priority candidate genes for human pain, and response to OMT will be unveiled at this conference.

licciardone
9:00 a.m. -
9:40 a.m.
Oncogenomics in clinical practice
Raoul Tibes, MD, PhD
The Translational Genomics Research Institute
tibes
9:40 a.m. - 10:20 a.m.

Pharmacogenomics and the promise of personalized medicine
Stuart Scott, PhD
Mount Sinai School of Medicine

Pharmacogenetics is the study of how an individual's genetic inheritance affects the body's response to drugs. Environment, diet, age, lifestyle, and state of health all can influence a person's response to medicines, but understanding an individual's genetic makeup is thought to be the key to creating personalized drugs with greater efficacy and safety. Some of the anticipated benefits of pharmacogenomics include the development of more accurate and safer medicines, improved ability to determine appropriate drug dosage and assistance to advance screening for disease. Decreasing the number of adverse drug reactions, improving the efficiency of drug trials and approval, the minimizing length of time and the number of medications patients must take to find an effective therapy, and improving early detection of common diseases will lead to reducing the cost of health care and promote a healthier population.

The Pharmacogenetics Program at the Mount Sinai School of Medicine Department of Genetics and Genomic Sciences has efforts that range from education, through basic research, to the development and promotion of NYS CLEP-approved pharmacogenetic tests. A survey of the field of pharmacogenetics and some of the specific activities occurring at Mount Sinai will be described.

Stuart Scott
10:20 a.m. - 10:30 a.m.
Break
10:30 a.m. - 11:10 a.m.

Clinical neurogenetics
David Tegay, DO, FACMG
New York College of Osteopathic Medicine

Neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are chronic, progressive, and, to a great extent, heritable and incompletely understood. In families with these and other neurodegenerative disorders, traditional genetic approaches including linkage analysis, positional cloning, and searches for mutations in candidate genes have been productive in discovering a number of causative genetic loci and have revealed that the causes of neurodegenerative diseases are varied and complex. Newer molecular methods have uncovered an even greater degree of genetic heterogeneity at the root of many of these disorders. This presentation will review the state of knowledge of the genetic basis of common neurodegenerative disorders and explore some implications for clinical practice, prevention, diagnosis, and treatment.

11:10 a.m. - 11:40 a.m.
The role of the genetic counselor
Judith Benkendorf, MS, CGC
American College of Medical Genetics

Genetic counseling is both a profession and an activity; like osteopathic clinical practice, it is underpinned by art and science. Genetics counselors, who earn graduate degrees and are trained in the science of medical genetics and the art of counseling, will become increasingly important partners with the osteopathic practice team as gene-based discoveries are translated into healthcare. At the same time, osteopathic physicians will need to learn how to view their patients through a genetic lens and both acquire and apply new knowledge and skills to 1) identify patients with genetic risk factors and 2) help these patients and their families understand and adapt to the medical, psychological and familial implications of genetic contributions to disease.

As a result of this presentation, attendees will have crossed the chasm from asking, “What’s in the genomic revolution for me?” to stating, “I am ready to deliver healthcare in the genomic era.” Topics presented will include: 1) assessing family and medical histories to identify genetic risk factors; 2) strategies for presenting risk information, promoting informed choices, and facilitating appropriate follow-up; 3) ways in which genetic information differs from other types of medical information; 4) working with genetic counselors; and 5) recent developments in the genetics of common diseases and pharmacogenomic medicine.

benkendorf
11:40 a.m. - 12:10 p.m.
Public health issues in genomic medicine
Martha Felini, PhD, MPH
University of North Texas Health Science Center

Public health efforts are focused on determining how the population’s health can benefit from the plethora of genetic discoveries garnered through GWAS. The most immediate response is often within its promise of identifying susceptible individuals at high risk of disease, allowing healthcare professionals to intercede earlier in disease and facilitating the targeting of treatment to the specific problem rather than the secondary event. Some have argued this ‘high risk’ approach to prevention will not provide the most ‘bang for our buck’ in improving population health. The fact that not all ‘high risk’ individuals end up with disease supports this position. Rather, we will likely have more success pursuing smaller reductions of risk within the total population. Such a strategy will require greater understanding of how specific genetic variants interact with environmental determinants to influence risk or the clinical characteristics of disease.

This presentation will highlight perceptions of risk as it relates to human genetic variation and the challenges of interpreting this risk as we move toward individualized medicine.

felini
12:10 p.m. - 12:50 p.m.
Social and ethical issues pertaining to genomic medicine
Roy Martin, DMin
University of North Texas Health Science Center

The rapid development in genomics research has changed the landscape of clinical medicine. Once more, scientific imagination and the findings of medical research—with apparently immense translational possibilities—have raised persistent and socially framed ethical questions related to the actual treatment of patients. Kurt Vonnegut’s reply to a reporter’s questions: “What do you think modern medicine means to most Americans,” was “Magic that works!” It has a special resonance in relation to stem cell research. Many social/ethical issues present themselves in this context; today I want you to look with me at a few of them that relate to basic ethical principles that belong to medical practice: What are the promises of genomic research for patient treatment? What are the present realities that require ethical considerations? What are the moral dilemmas that this research and its promise of treatment bring to our notions of autonomy, justice, and authenticity? What can osteopathic practitioners, given our view of patients as “subjects”, rant than “objects” of care—bring to the prospects of these exciting research possibilities? I hope we will contribute vigorous critical thinking to the ethical regulation of such promising research and thoughtful guidance to policies affecting its available employment in patient care.
martin
12:50 p.m. - 1:00 p.m.
Wrap-up