NEW YORK (GenomeWeb) – Cedars-Sinai plans this fall to open a research and clinical laboratory focused on validating and implementing disease biomarkers.
Called the Cedars-Sinai Precision Biomarker Lab, the facility will be mass spectrometry-focused and will comprise both a research service contract lab for building and validating protein biomarker tests as well as a CAP-accredited, CLIA-certified lab for offering protein biomarker tests clinically, said Jennifer Van Eyk, codirector of the hospital's Precision Medicine Initiative.
By offering expertise in building targeted mass spec assays, the lab is "trying to shorten that really challenging time from discovery through to true use in the clinic," Van Eyk said.
"The idea of the service contract lab is to be able to increase the efficiency around getting data on clinical utility [of potential biomarkers]… in a way that is rigorous and transparent so that they are ready to move forward or be ruled out as a biomarker," she said. "And then it can move to the CAP/CLIA lab where we will have an R&D lab that can do small clinical trials."
The CAP/CLIA lab will be integrated with Cedars-Sinai's Epic EMR system, allowing doctors to order tests and view results generated by the lab, Van Eyk said. She added that she and her colleagues have several proteomic assays addressing areas like cardiovascular health, chronic kidney disease, and neurological disease that they hope to launch through the facility shortly after it opens.
Cedars-Sinai may in some cases work through its biobank to help collect samples needed for biomarker validation, but "for the most part," researchers will need to come with "the clinically phenotyped cohorts that go with the question you are asking," she said.
Van Eyk noted that it has historically been very difficult moving proteomic tests from the discovery phase through validation and into clinical implementation.
"All of the aspects of that are just very challenging," she said. "I know because I have tried every possible way of getting biomarkers through [to the clinic]. Some successful and some less so."
She said that Cedars-Sinai has hired Cory Bystrom, formerly executive director of the Cleveland HeartLab and associate scientific director at Quest Diagnostics, to oversee the service contract lab.
The lab will feature a range of instruments and assays for protein analysis but will be roughly 90 percent mass spec-focused, Van Eyk said, adding that the facility will launch with around 20 mass spec instruments from a variety of vendors and will have capacity for around 30 or 40 instruments.
She said that she and her colleagues have collaborated with Beckman Coulter to implement a "completely hands-free automation" system for sample preparation and is now expanding the system to also cover upfront sample enrichment processes as well as desalting prior to mass spec analysis.
She said the lab can run just under 600 samples per day, though that number will vary depending on the exact nature of the assay.
The lab's mass spec focus is driven in large part by the need for high levels of multiplexing and a desire to measure not just protein expression but also protein variants and modifications, Van Eyk said.
"We recognize that disease is complicated, with multiple mechanisms… and you can have the same phenotype but many different mechanisms, with each person having a different mechanism that drives that phenotype," she said. "You are going to need to have markers that recognize and can quantify the different mechanisms that go into the disease process. So we want to be able to multiplex [proteins] and that currently, I would say, is easiest by mass spectrometry."
"We also believe [it will be important] to use mass spectrometry to look at not just total protein quantitation but also disease-induced modifications — phosphorylation or citrullination or the processing of hormone — to get biological insight from monitoring different aspects of a protein," she added.
Another factor driving the emphasis on mass spec is the lab's plan to explore remote sampling using dried blood spots and related technologies, which have drawn attention from researchers and industry due to their potential to enable easier patient sampling and significantly lower costs. Van Eyk noted that mass spec has proved more effective than immunoassays for analyzing proteins captured by these sampling techniques.
At the Mass Spectrometry Applications to the Clinical Laboratory (MSACL) annual meeting in March, Kelly Mouapi, a postdoc in Van Eyk's lab, presented data from a study exploring the use of remote sampling combined with targeted mass spec to monitor patients at risk of cardiac events.
In the study, the researchers analyzed fingerprick samples collected by 200 patients with stable ischemic heart disease using Neoteryx's Mitra microsampling device. Patients collected samples at baseline, one month, two months, and three months, collecting the one-month and two-months samples from home and mailing them to Cedars-Sinai for analysis. Van Eyk and her colleagues used multiple-reaction mass spec to analyze an 11-protein panel consisting primarily of apolipoproteins.
The MSACL presentation dealt primarily with questions of patient compliance with sampling along with the consistency of the Mitra device and the stability and reproducibility of the protein measurements made on those samples. Van Eyk said she and her colleagues are currently analyzing the study data to look at how the protein panel measurements correlate with patient outcomes and established cardiac markers.
The researchers are also using remote sampling devices for several other studies, including one monitoring irritable bowel syndrome patients to identify responders and non-responders to therapy and another to identify the optimal timing of chemotherapy treatments in patients with head and neck cancer.
They have also established a patient registry for the cardiac condition Takotsubo syndrome and plan to collect blood samples via remote sampling for proteomic profiling.
The remote sample work "is still in the pilot, academic stage," Van Eyk said, "but we are driving it so that it will be in the clinic within a few years."