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Activities Overview Brochure A Partnership in Precision Medicine INSTITUTE FOR PRECISION MEDICINE The Institute for Precision Medicine (IPM) is a collaboration between the University of Pittsburgh and UPMC that facilitates movement of biomedical research into personalized clinical care. The overarching goal is to help researchers and clinicians discover and capitalize on clinically actionable information concerning the risk of disease, disease course, and optimal treatment/response. Founded in 1787, the University of Pittsburgh (commonly referred to as Pitt) is consistently ranked among the top 10 recipients of National Institutes of Health research funding. With 16 schools and thriving multidisciplinary centers, Pitt has demonstrated leadership in the specialty areas of aging, biochemistry, bioengineering, computer modeling, drug discovery, neuroscience, organ transplantation, and translational medicine, among others. Pitt researchers commonly collaborate with colleagues from more than 80 other universities—including nearby Carnegie Mellon University—and corporate partners near Pitt’s urban campus. UPMC is a $20 billion world-renowned health enterprise operating centers of excellence in cancer, geriatrics, neurosurgery, pediatrics, psychiatry, rehabilitation, transplantation, and women’s health. The integrated health care system is composed of 40 academic, community, and specialty hospitals; a network of rehabilitation and long-term care facilities; 700 doctors’ offices and outpatient sites; a 3.5 million-member insurance division; and numerous commercial ventures across the globe. UPMC’s leadership role in technology has resulted in productive partnerships with Microsoft, GE Healthcare, and other innovators. THE PROMISE OF PRECISION MEDICINE The massive life-saving potential of precision medicine is undisputed. Enormous consumer and clinician demand continue to propel the precision medicine industry forward at blistering speed, with the global market predicted to exceed $99 billion by 2025. Responding to the need for As a leader and central hub a more exacting model for for precision medicine, we the treatment of disease, the believe we have a responsibility University of Pittsburgh and to foster collaborative research UPMC created a multidisciplinary and entrepreneurial innovation; collaboration – the Institute raise understanding of precision for Precision Medicine (IPM) – medicine through multifaceted to accelerate the clinical education and training; and implementation of biomedical move research to personalized research. With colleagues around well-being and clinical care. the globe, our researchers Here, we offer highlights of and clinicians are embracing some of the IPM’s ongoing efforts a still-new transformative to advance precision medicine approach to medicine … an within a large academic health approach that looks beyond the care system. “average person” and considers individual differences in patients’ genetic makeup, medical history, environments, and lifestyle. While precision medicine already has delivered powerful discoveries and dramatically improved patient strategies and outcomes, we know there are untold possibilities for further advancement. ADVANCING NEXT-GENERATION BIOBANKING At the nucleus of precision medicine is the development and sharing of large-scale biological databases and analytical tools. The IPM is in the unique position of Enterprise housing an institutionalized biobank – the Pitt Biospecimen Bioinformatics Training Core (PBC) – with more than 800,000 biological At the Institute for Precision samples. Our proven, decades-strong system enables Medicine, we make resources a multidisciplinary network of researchers to gain access widely available through our Molecular Biology Information Service to human tissue, without having to overcome the (MBIS) of the Health Sciences Library System. Through the library, we common barriers associated with sample collection. identify, procure, and implement commercially licensed bioinformatics As one of the largest submitters CTSI also runs the Pitt+Me software; teach hands-on workshops of tissue to the NIH/NCI Cancer Discovery biorepository, which using bioinformatics tools to answer Genome Atlas (TCGA) program is enabling the implementation research questions; provide in-person the PBC is relentless in its of pharmacogenomics for and email consultations on software/ pursuit and industry-wide patient care. databases; and maintain a web sharing of new approaches, In addition, the PBC provides portal providing overall guidance such as biobanking of live support to major research on the access and use of tissue and blood specimens initiatives such as the Pittsburgh bioinformatics resources and that can later be used for Lung Screening Study (PLuSS), MBIS-created webtools. single-cell sequencing and Early Detection Research human explant drug screening. Network (EDRN), the National Pushing still further, the IPM Mesothelioma Virtual Bank is now developing three- (NMVB), the Lung Tissue dimensional culture models, Research Consortium (LTRC), such as patient-derived and the Magee-Womens organoids, and establishing Gynecologic Cancer Program, a living biobank for multiple among other research projects, disease types. large and small. An integral partner, the To ensure research integrity, University of Pittsburgh Clinical the PBC maintains a full-service, and Translational Science IRB-approved Honest Broker Institute (CTSI), is leading the System, HB015, which All of Us Pennsylvania research is considered the gold program and runs the Pitt+Me standard model. registry, which has more than 200,000 adult and pediatric patients being considered for inclusion in research studies and clinical trials. WORLD-CLASS GENOMIC TESTING AND BIG DATA ANALYTICS: BUILDING ON A ROBUST INFRASTRUCTURE A central component of precision medicine is the use of molecular features to better understand disease and predict risk and response to therapy. Through genomics (DNA sequencing), we are developing personalized disease models and enabling personalized patient care for a full range of conditions. The IPM supports investigators Hospital of Pittsburgh and Further, in collaboration with who are conducting important UPMC Magee-Womens Hospital. the Department of Biomedical biomedical computing work with Rapid genome sequencing Informatics, we are developing increasingly larger patient cohorts allows quick diagnosis of genetic infrastructure that enables – giving them access to analytical defects, leading to decreases in researchers to gain access to software, human resources, and infant mortality and NICU stay clinical data. As an example, genomics education and training. length and positive long-term we developed a tool that allows health and economic outcomes. for visualization of UPMC The UPMC Genome Center The grant also is supporting Network Cancer Registry data, is one of the world’s largest educational efforts, like our giving researchers access to clinical-grade, industrial-scale Test2Learn program, and pilot approximately 300,000 genomics infrastructures. In programs focused on abstracted unique cases. large part due to a $2.8 million commercializing genomics. grant from the Richard King Mellon Foundation, the center Another essential ingredient is currently supporting whole to precision medicine is access genome sequencing of critically to big data. At UPMC and the ill infants receiving care at the University of Pittsburgh, we share neonatal intensive care units large-scale genomic and health (NICUs) of UPMC Children’s record data through the Pittsburgh Genome Resource Repository (PGRR). The system holds 1.2PB of data at the Pittsburgh Supercomputing Center and the Center for Research Computing and has more than 50 registered principal investigators. STUDYING GENOMICS IN CANCER AND BEYOND We are pleased to sponsor a full range of genomic studies spanning the disease spectrum. Cancer projects are in collaboration with UPMC Hillman Cancer Center. Examples of the breadth of projects are shown below. • Comprehensive characterization of the mutational and transcriptional landscape of pleomorphic lobular invasive breast cancer • Personalizing chemotherapy for pediatric liver cancer • Whole-genome sequencing to explore variability in treprostinil response in patients with pulmonary arterial hypertension • Unanticipated heterogeneity in PAH-deficient phenylketonuria: Defining the neuro-refractory PKU phenotype • Whole-genome sequencing for treatment-resistant multiple sclerosis • Whole-genome sequencing to identify inborn errors of immunity in neurologic injury following viral infection • Somatic mutation burden in hypertrophic cardiomyopathy • Elucidating the multi-omics and genome-phenome architecture of pulmonary hypertension • Quantifying genetic variation in postpartum women for pain and depression Detecting Cancer with Liquid Biopsies • Clinical, radiologic, and molecular characteristics Liquid biopsy permits our of anaplastic pleomorphic xanthoastrocytomas clinicians to track cancer relatively noninvasively. Once (WHO grade III) blood is drawn, we can isolate the DNA and sequence it to identify cancer mutations. Because it is less invasive than traditional biopsy, we can take blood every month and see how DNA changes over time. Liquid biopsies also are valuable when there are significant challenges or risks associated with obtaining tumor tissue. 1,975 LEARNERS TRAINED IN 54 PROGRAMS 600 25 500 Each Year Taught 20 # of Programs 400 15 300 10 200 Taught Each Year Taught # of New Learners # of New 5 100
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