Cedars-Sinai Precision Health Awards $700,000

Cedars-Sinai Precision Health, a partnership among scientists, clinicians and industry, has announced its 2019 awards totaling more than $700,000 for eight projects to advance personalized medicine.

The partnership aims to drive the development of the newest technology and best research, coupled with the finest clinical practice, to rapidly deliver precise and personalized healthcare solutions. Since its launch in 2016, the partnership has awarded more than $2.2 million to research projects and developed collaborations with more than a dozen companies.

"This was a very competitive year. Our program's committee reviewed 31 grant applications, which we narrowed down to 14 finalists before choosing the eight awardees," said Dermot McGovern, MD, PhD, FRCP(LON), who co-directs Cedars-Sinai Precision Health with Jennifer Van Eyk, PhD. "It was a difficult decision because these were really outstanding projects." McGovern is director of translational medicine in the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute.

"We are especially pleased this year because nearly half the key investigators on the winning projects are women," said Van Eyk, director of basic science research in the Barbra Streisand Women's Heart Center and director of the Advanced Clinical Biosystems Institute.

The projects of the 2019 award recipients span an array of diseases and disciplines, including ovarian and prostate cancer, multiple sclerosis, Crohn's disease, cardiology, orthopaedics and undiagnosed diseases. Here they are with the lead investigators, awards and topics:

Simon Gayther, PhD; Michelle Jones, PhD; Dennis Hazelett, PhD ($120,000)

"Precision development and clinical application of epidemiological and polygenic risk scores for ovarian cancer."

The goal is to model individualized risk scores for ovarian cancer that incorporate genetics, lifestyle and epidemiological factors. The team would develop a genetic test that could be used to identify women with the greatest risk of ovarian cancer who might benefit from preventive surgery or drugs. External collaborations: Paul Pharoah, MD PhD, of University of Cambridge (clinical cancer epidemiologist); Fulgent Genetics (next generation sequencing).

Talin Haritunians, PhD; Jonathan Braun, MD, PhD ($90,000)

"Biomarking IBD patient-specific disease features using the epithelial antigenic peptidome."

The goal is to examine how the immune system's antibodies target cells of the intestinal epithelium (lining), which are injured in inflammatory bowel disease. The team will utilize recent advances that define protein-coding RNA molecules in these cells, along with a proven method that displays these molecules, to uncover targets of the antibody response. External collaborations: Ren Sun, PhD, of UCLA (expert in high-dimensional expression library analysis); Twist Bioscience (builder of virus display library).

Marwa Kaisey, MD; Nancy Sicotte, MD ($60,000)

"Accurate diagnosis and personalized care in multiple sclerosis."

The goal, given that patients without multiple sclerosis are commonly misdiagnosed with the disease, is to take a clinically relevant approach to evaluating two promising diagnostic tools by studying them in the populations that are most likely to be misdiagnosed. These same biomarkers potentially could serve as tools for accurately monitoring disease activity over time and effectively delivering more personalized treatment, replacing the current trial-and-error process.

Simon Knott, PhD; Stephen Freedland, MD; Adriana Vidal, PhD ($90,000)

"A genomics approach to identify race-specific immune susceptibilities in prostate cancer."

The goal is to use genomic profiling to predict the responsiveness of prostate cancer in African-Americans to immune checkpoint blockade treatments, creating a precision health approach to prostate cancer. To achieve this goal, the team will compare the tumor microenvironments in European-American and African-American men and identify the DNA mutations that distinguish these environments.

Sarah Parker, PhD; Daniel Berman, MD; Prediman K. Shah, MD ($83,790)

"A pilot study of the utility of circulating biomarker panels to improve selection of candidates for non-invasive coronary artery calcium imaging."

The goal is to quantify the informativeness of a panel of circulating protein biomarkers to identify individuals with measurable coronary artery calcification involvement, which can lead to heart disease. The study intends to establish the sensitivity and specificity of this panel to separate truly low-risk individuals from those inappropriately deemed low risk by existing standard-of-care assessments.

Brennan Spiegel, MD; Mark Vrahas, MD ($60,000)

"The development of a bioinformatic algorithm using biosensor, EHR and patient-reported outcome data to predict outcomes and patient satisfaction after total knee arthroplasty."

The goal is to compare the accuracy of two systems to predict outcomes and patient satisfaction after total knee replacement surgery: (1) a combination of biosensor remote monitoring data, ambulatory patient-reported outcomes assessments and electronic health records, and (2) a status quo assessment using standard clinical predictors such as age, gender, body mass index and preoperative functional status. The team also will estimate the cost-effectiveness and budget impact of a bioinformatics algorithm to reduce inappropriate utilization of the surgery and improve patient satisfaction. External collaborations: Fitbit; AliveCor (smartphone-based EKG); Fitabase (biosensor data transmission)

Clive Svendsen, PhD; Nur Yucer, PhD ($90,000)

"Personalized iPSC modeling of early stage ovarian cancer to identify screening markers for early stage disease detection and targets of chemoprevention."

The goal is to use novel modeling strategies to identify individualized clinical biomarkers for early detection and/or targeted chemoprevention in patients at high risk of high grade serous ovarian cancer. The team will create patient-specific organoid models of the fallopian tubes, where ovarian cancer originates, that are derived from induced pluripotent stem cells of patients with a family history of high-grade serous ovarian cancer. The study will examine differences in biomarkers between BRCA1/BRCA2 mutation carriers and those without the mutations.

Jennifer Van Eyk, PhD; Leon Fine, MD; Michael Lewis, MD; Lawrence Maldonado, MD; Tyler Pierson, MD, PhD; Jennifer Elad, NP ($110,000)

"Undiagnosed patients as a unique precision-health research resource."

The goal is to develop a research arm of the new Center for the Undiagnosed Patient at Cedars-Sinai, in which expanded specialty tests, including genetics, proteomics, metabolomics and microbiome analysis, are carried out initially on adult patients. Because undiagnosed patients represent complex and often extreme cases, the study could provide, over time, new patterns of disease that will not be easily determined in the general population. External collaborations: Thermo Fisher Scientific and Sciex (discovery proteomics); Agilent (metabolomic standard and support on automation of sample preparation).