PHILADELPHIA — The Penn Center for Precision Medicine Accelerator Fund is providing close to $600,000 in funding to eight research teams from Penn Medicine to implement personalized medicine projects along a range of clinical specialties. It is the third annual round of funding for the program.
Precision medicine is personalized therapy based on a patient’s unique physical and genetic data. It recognizes that patients with the same diagnosis may need different treatments according to their individual circumstances. Advances in genomics, data analytics, biomarkers, and imaging are enabling more specific, targeted therapies, which can also reduce wasteful, ineffective treatments.
“Precision medicine is shifting the ground in patient care, generating bold new possibilities for improving health,” said David B. Roth, MD, PhD, director of the Penn Center for Precision Medicine and chair of the Department of Pathology and Laboratory Medicine. “As in our two previous rounds of funding, this was a highly competitive series of applications. The winning projects show great promise for translating emerging precision medicine techniques into the types of standard care that we deliver to our patients.”
The following projects were selected for the third round of accelerator funding:
Single cell genomic analysis of bone marrow tumor cells for breast cancer patients harboring minimal residual disease
Principal investigator: Lewis A. Chodosh, MD, PhD; co-investigators: Jonni Moore, PhD; Michael Feldman, MD, PhD; and Angela DeMichele, MD, MSCE
More than three million women in the United States have been diagnosed with breast cancer; most are at theoretical risk of the disease returning, with current tests having poor predictability. The danger of recurrence often stems from cells that break off from the original tumor and lie dormant in the bone marrow and other sites. Women who have detectable levels of these cells in their bone marrow show a significantly elevated risk of disease recurrence. To address this problem, the team will develop a new clinical test to detect and analyze these cells to identify women at risk for recurrence and monitoring response to treatment.
PERSPIRE: Preventing rehospitalization in lung transplant recipients using tailored rehabilitation prescriptions
Principal Investigator: Joshua Diamond, MD, MSCE; co-investigators: Andrew Courtwright, MD, PhD, Derek Zaleski, PT, DPT, Steve Hays, MD (UCSF), Jonathan Singer, MD, MS (UCSF), Jasleen Kukreja, MD, MPH (UCSF), Chris Garvey (UCSF), Allan Bruun (Aidcube)
Advances in medical therapies and changes in the US organ allocation system have prioritized lung transplant for sicker and older patients. Recent trends in recipients include increased disability, poorer health-related quality of life, and increased longer-term mortality. Additionally, lung transplant recipients have a high risk of unexpected readmission, with frailty at the time of discharge one of the leading factors. To address these problems, Diamond aims to improve individualized exercise training plans, each modified based on a patient’s progress and needs. The goal is to improve transplant recipients’ levels of physical fitness and independence and decrease the risk of hospital readmission.
Towards predicting the analgesic response to ibuprofen following third-molar extraction
Principal investigator: Tilo Grosser, MD; co-investigators: Katherine N. Theken, PharmD, PhD, Elliot V. Hersh, DMD, MS, PhD, John T. Farrar, MD, PhD, Gregory R. Grant, PhD
Prescription opioid pain medicines are considered a central gateway to opioid and heroin addiction. Significant efforts are underway to limit opioid exposure and identify alternative therapeutic options, including nonsteroidal anti-inflammatory drugs such as ibuprofen. Grosser aims to identify in advance who will likely obtain sufficient pain relief from ibuprofen – and therefore not need to be prescribed an opioid -- following dental surgery.
Implication of the Gleason score for precision medicine approaches for patients with localized prostate cancer
Principal investigator: Kara Maxwell MD PhD; co-investigators: Lauren Schwartz MD, and Vivek Narayan, MD
While the vast majority of prostate cancer patients have excellent outcomes, some men develop aggressive prostate cancer, with nearly 30,000 dying of the disease every year in the United States. Inherited mutations in certain genes involved in the repair of damaged DNA, such as BRCA2, are found more frequently in patients with aggressive metastatic prostate cancer. The team asks whether these and other inherited genetic factors are associated with aggressive forms of localized prostate cancer. They will do this by studying the relationship between DNA repair mutations and Gleason scores, as well as performing prostate tumor genomic sequencing in patients with DNA repair mutations to predict response to treatment and find molecular signatures that suggest how the tumors may have formed.
Looking beyond the visible: precision diagnostics for GBM coupling ultra-high field capabilities of 7-Tesla with machine learning
Principal investigator: Suyash Mohan, MD; co-investigators: Sanjeev Chawla, PhD, Robert Lustig, MD, Donald M. O’Rourke, MD, Christos Davatzikos, PhD, Ravinder Reddy, PhD, Sumei Wang, MD, MacLean Nasrallah, MD, PhD
Fewer than one percent of patients diagnosed with glioblastoma, the most aggressive form of brain cancer, are alive five years later, mostly because these tumors do not have a defined boundary and cannot be completely removed. This infiltrative pattern of tumor growth is not typically visible on conventional imaging. Mohan will work with the latest imaging techniques, coupled with artificial intelligence, to better detect “invisible” tumors and aid surgeons for treatment planning.
IL13Rα2-targeting chimeric antigen receptor T cell therapy in the canine patient as a proof-of-concept for human trials
Principal investigator: Donald O’Rourke, MD; co-investigators: Nicola J Mason, BVetMed, PhD, Zev A. Binder, MD, PhD, Yibo Yin, MD
CAR-T cells are modified immune cells that hunt down cancer cells, generating an immune response while avoiding side effects throughout the body. CAR T-cell therapy is registering significant success in certain blood cancers; however, there is much less success in solid tumors such as glioblastoma. O’Rourke will test the treatment of dogs with brain tumors by using CAR T cells to target a protein called IL13Rα2, which is found in glioblastoma cells. Examining the tumor- and immune system-response in canine patients will provide information on how humans might respond and help dogs with brain tumors.
Use of acylcarnitine signature for predicting heart failure and targeting intervention
Principal investigators: Ping Wang, PhD, J. Eduardo Rame, MD MPhil; co-investigators: Thomas Cappola, MD, Hongzhe Li, PhD
Wang will use a set of fatty acid metabolites called acylcarnitines as biomarkers to differentiate heart failure patients. The aim is to predict which patients may progress rapidly in their disease courses. This will allow clinicians to tailor decisions on the timing of advanced surgical therapies, such as left-ventricular-assisted-device placement or heart transplant. He also explores using acylcarnitines as biomarkers to predict patient response to novel heart failure medications targeting metabolic pathways.
Delivery of community resources for patients with chronic obstructive pulmonary disease through qualitative interviews and natural language processing
Principal investigator: Gary Weissman, MD, MSHP; co-investigators: Julia Szymczak, PhD; Shreya Kangovi, MD; Blanca Himes, PhD; Michael Sims, MD; Vivek Ahya, MD; Rebecca Hubbard, PhD; Lyle Ungar, PhD; Scott Halpern, MD, PhD
Millions of patients are readmitted to the hospital for chronic obstructive pulmonary disease (COPD) in the United States every year, costing billions of dollars annually. Current models for preventing these readmissions have largely failed to account for individualized risk factors, such as the lack of transportation to follow-up appointments, undertreated heart failure, and unrecognized depression, leading to increased tobacco use. To determine a person’s risk of and the underlying reasons for readmission, the team will conduct interviews with patients, clinicians, and caregivers. Using natural language processing techniques to identify patients with the risk factors identified through the interviews, they aim to match resources to individual circumstances to reduce 30-day hospital readmissions.