Penn Center for Precision Medicine awards $565,000 in second Accelerator grants

PHILADELPHIA – The Penn Center for Precision Medicine (PCPM) Accelerator Fund awarded eight research teams from Penn Medicine in their second round of funding for the implementation of personalized medicine projects across a range of clinical specialties, from dermatology and psychiatry to radiology and cardiology.

"This again was a competitive round of applications, and I am very pleased that the winning finalists are all part of a diverse mix between emerging clinical trials and applications of new technologies that promise to be scalable and reach patients very soon," said David B. Roth, MD, PhD, director of the Penn Center for Precision Medicine and chair of the department of Pathology and Laboratory Medicine.

"Our two cohorts of recipients to date make it clear that there are significant emerging themes, such as integration of pharmacogenomics into daily patient care and informatics to redefine the patient phenotype, which are taking shape in the area of precision medicine," said Abigail Berman, MD, an assistant professor of Radiation Oncology who directs clinical affairs within PCPM. See here for video summaries on the first eight projects.

PCPM, founded in January 2016, funds and implements precision medicine-based research related to patient care at Penn Medicine. The center brings together an interdisciplinary clinical team with experts in data analysis, biomedical informatics, biostatistics, and health economics to measure both biological and economic outcomes.

The following eight projects, which include 14 investigators from nine Penn departments and divisions, were selected for this second round of accelerator funding from a total of 26 applications:

Translating a precision medicine approach for treating idiopathic multicentric Castleman disease into a clinical trial

David Fajgenbaum, MD, MBA, MSc, Translational Medicine & Human Genetics

Investigation of new treatments for idiopathic multicentric Castleman disease (CD), a deadly and poorly understood immunologic disorder. CD is part of a hyperactivated protein pathway among immune cells, which may be a target for patients who do not improve on siltuximab.

Clinical decision making for AML patients using algorithms

Robert Faryabi, PhD, MSc, Cancer Biology, Pathology and Laboratory Medicine
Michael Feldman, MD, PhD, Pathology and Laboratory Medicine

Development of an algorithm to improve the accuracy of detection and characterization of the ITD mutation and apply it to AML patients. Currently, several small-molecule FLT3 inhibitors are in clinical trials for targeted therapy of FLT3-ITD-positive AML. However, response to these therapies are variable, suggesting that the mere presence of FLT3-ITD in a patient might not guarantee effective clinical response to targeted inhibition of FLT3.

Chemical-genomic screening to enable functional precision medicine in hepatocellular carcinoma

Terence Gade, MD, PhD, Radiology, Cancer Biology
Junwei Shi, PhD, Cancer Biology
Sara Cherry, PhD, Microbiology

Addressing the limited therapeutic options for hepatocellular carcinoma (HCC) patients by integrating precision-medicine approaches into care models that are currently employed for the diagnosis and treatment of HCC patients. The project will apply advances in small-molecule-inhibitor screening to repurpose existing FDA-approved therapeutics on a patient-by-patient basis.

Systematic, automated screening to improve the diagnosis and management of primary aldosteronism

Daniel Herman, MD, PhD, Pathology and Laboratory Medicine

Development and implementation of a systematic approach to screen all Penn Medicine patients for primary aldosteronism, a cause of high blood pressure that can be treated or cured by targeted medications or surgery. The aim is to dramatically increase the number of patients diagnosed and, for identified patients, directly translate into improved blood pressure levels and decreased risk of cardiovascular disease.

Molecular genetic prediction of opioid analgesic dosage requirements in African-American orthopedic surgery patients

Henry Kranzler, MD, Psychiatry
Martin Cheatle, PhD, Psychiatry

Prediction of dosage requirements of patients receiving methadone maintenance, using genetic variation, to treat opioid use disorders or opioid pain medications following surgery. The study will recruit 300 African-American patients following hip or knee replacement at Penn Presbyterian Medical Center.

Advancing diagnostic precision in patients with non-ischemic cardiomyopathy

Kenneth Margulies, MD, Cardiology
Francis Marchlinski, MD, Cardiology

Identification of the cause of cardiomyopathy in a higher proportion of cases — in 75 percent of cases the underlying cause is not known. This study will use a combination of better-targeted biopsies, more extensive heart-tissue analysis, and genetic testing to characterize cases and identify better treatments.

Translating targeted cellular immunotherapies for autoimmune disease to clinical practice

Aimee S. Payne, MD, PhD. Dermatology
Mike Milone, MD, PhD, Pathology and Laboratory Medicine

Completion of preclinical experiments to open a phase I trial of chimeric autoantibody receptor T cells (CAAR-Ts) to treat pemphigus vulgaris, a potentially fatal autoimmune blistering disease caused by autoantibodies against a skin protein. Because of the potential for CAAR-Ts to persist indefinitely to prevent disease recurrence, they have the potential to transform autoimmune-related therapy in general from a strategy of chronic immune suppression to a one-time treatment, possibly leading to a cure.

PARPVAX: A two arm, open label phase Ib/II trial of maintenance niraparib plus either nivolumab or ipilimumab in patients with advanced pancreatic cancer who have achieved durable stability on platinum-based chemotherapy

Kim Reiss Binder, MD, Hematology/Oncology

Development of a clinical trial for patients with pancreatic adenocarcinoma who have demonstrated continued disease control on platinum-based therapies for at least four months. These patients may have tumors that do not effectively fix DNA damage and are therefore hypersensitive to therapy that breaks DNA strands. This project will identify less toxic, more sustainable therapies to use after chemotherapy toxicities sets in for these patients.

Progress reports by the first PCPM accelerator funds cohort were presented at a symposium last month. Project Requests for Application for the third round of Accelerator Fund projects, due on February 1, 2018, will be announced on the PCPM website later this year.

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

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