11/13/2024
This lab advances biomarker testing by collaborating with clinicians on tricky conditions
A standard visit to the doctor includes a familiar cadence of steps —stepping on the scale, blood pressure measurements, and occasionally blood draws. While these tests may seem routine, you're providing your physician with the information they need to take a proactive approach to your healthcare, called biomarkers.
The biomarkers we can look for depend on scientific understanding of a disease or condition. That’s where researchers like Daniel Rotroff, PhD, come in. Dr. Rotroff founded his Quantitative Health Sciences lab in 2018 to better understand complicated, multi-system diseases including obesity, diabetes and multiple types of cancer. His research program has expanded to include over 40 projects and clinical collaborations across the Cleveland Clinic, including the Center for Quantitative Metabolic Research, which he directs.
With multi-million dollars in federal funding, Dr. Rotroff studies factors that can help diagnose diseases, identify proper treatment plans and even develop new therapeutics.
“The best part about biomarker discovery is that it advances the clinical and research fields,” Dr. Rotroff says. “On one hand, you have the potential to find a way to predict a condition that could advance clinical decision making. On the other hand, once you find the measurement that works, you can use that biomarker to unravel the thread and work backwards to uncover the processes driving human health and disease and maybe even develop new treatments.”
The Rotroff Lab works closely with clinicians on collaborative projects to address complex health problems directly affecting patients and the community. Together, the teams analyze existing patient data and establish disease-specific patient registries and biobanks to collect more information on conditions like diabetes, obesity and bariatric surgery.
Just a few of their ongoing projects include biomarker discovery to identify at-risk patients such as:
- Individuals who are likely to experience relief from chronic eye pain after cataract surgery, by using autologous serum tears.
- Women who are more likely to develop long-lasting nerve damage as a side effect of breast cancer treatments, or patients more likely to experience nausea due to chemotherapy in general.
- People who have inherited genetic variants that influence how they metabolize alcohol and how alcohol-associated liver diseases can progress.
- Individuals with diabetes whose conditions are not easily fixed by bariatric surgery, or whose conditions are not responsive to standard-of-care blood sugar management.
- Improved tools to understand the driving mechanisms of pain in patients with lipedema compared to their peers.
- Individuals with preexisting conditions like COPD and obesity who may be more likely to experience benefits from weight loss with GLP-1 agonists like Ozempic, and individuals who may be more likely to experience potential adverse effects such as muscle weakness.
What are biomarkers?
Biomarkers can help researchers and clinicians predict the development of a disease or how patients will react to medication. Some are now standards for detection and care, like blood sugar for diabetes. The connections between biomarkers like blood pressure or hormone levels to specific outcomes can support a doctor’s treatment plan.
"People being treated with the same medication for the same disease can have wildly different responses. This doesn’t just happen by chance,” says Dr. Rotroff. “These responses are driven by specific biological processes working behind the scenes. If we can identify and measure these processes, we can figure out how to better diagnose and treat patients on an individual level.”
In addition to being a guide for personalized care, biomarkers can be used to diagnose diseases that are difficult to detect. Changes to biomarkers can signal significant changes to how the body is working, like whether an organ is not functioning as it should. The Rotroff Lab is working diligently to discover diagnostic biomarkers that can identify whether someone has a disease earlier and more accurately than current diagnostic tests. And they’re succeeding.
Click through some of the lab's recently-published and ongoing projects below.
Daniel Rotroff, PhD (left) discusses data with Noah Daniels, PhD (right), a postdoctoral fellow in his lab who is leading a project to understand why some individuals with lipedema experience high levels of pain. Dr. Daniels was the first author on a recently published paper detailing biomarker discovery in the plasma and saliva of individuals with liver diseases. The paper can be found below.
Courtney Hershberger, PhD (foreground), analyzes genetic samples from individuals with breast cancer to identify biomarkers associated with severe treatment side effects. She is the first author on a recently published paper identifying a subset of patients with Type 2 Diabetes who may respond favorably to a medication that negatively affected the general population in clinical trials. The paper can be found below.
Dr. Rotroff (left) discusses data with Noah Daniels, PhD (right), a postdoctoral fellow in his lab who is leading a project to understand why some individuals with lipedema experience high levels of pain. Dr. Daniels was the first author on a recently published paper detailing biomarker discovery in the plasma and saliva of individuals with liver diseases. The paper can be found below.
Hamed Javidi, PhD (center) recently received PhD in Engineering for work in the Rotroff Lab designing artificial intelligence networks that uses genomic and health record data to flag at-risk patients by predicting their risk for developing a complex disease. He is the first author on a recently published paper detailing an AI algorithm to identify younger individuals at-risk for developing pediatric metabolic syndrome. The paper can be found below.
Vai Pathak (right) is a data scientist and part time PhD student in the Rotroff Lab. He is heavily involved in a collaboration with Laura Nagy, PhD, where he is conducting biomarker studies to investigate how an individual’s genetics can change the way their liver reacts to and breaks down alcohol.
Dr. Daniels’s paper, discussed in caption #1, can be found here. Dr. Hershberger’s paper, discussed in caption #2, can be found here. Dr. Sharma’s paper, discussed in caption #3, can be found here. Dr. Javidi’s paper, discussed in caption #4, can be found here.
Discovering biomarkers for liver cancer
Hepatocellular carcinoma (HCC), the most common form of liver cancer, can often be treated effectively in its early stages. However, only 21% of patients survive five years after their initial diagnosis. This discrepancy, says Dr. Rotroff, happens because HCC is so difficult to detect that it is often detected at late stages when treatment options are much more limited.
“The biomedical field currently diagnoses HCC by looking for biomarkers in the bloodstream or with ultrasound, but biomarkers may not be present in as many as 40-60% of HCC cases, resulting in many false negative findings,” he says. “Improved biomarker testing that more accurately detects cancer, and catches the cancer earlier, will be one of the best ways to improve overall survival for these individuals.”
After analyzing patient blood and saliva, the team identified small circulating pieces of RNA (micro-RNA, or miRNA) in our mouths that seem to better detect liver cancer than the protein we currently look for in our patients’ blood, called alphafetoprotein.
The saliva test they developed in response appears much better at detecting HCC in pilot studies than the current standard of care.
The team also found that individuals living with liver cancer appeared to have higher levels of metabolites related to citric acid metabolism in their blood and saliva. Researchers now know that this process is important in cancer progression and can do follow up studies to determine whether new drugs related to this mechanism can help slow or halt the disease.
Dr. Rotroff and his team have recently expanded the scope of their biomarker test to find blood-based biomarkers based on cells in the blood that express specific changes in their RNA, called alternative splicing. They are finding highly promising markers to detect HCC, and opening new lines of drug development not previously explored for HCC.
“As biomarker discovery improves the field’s knowledge of health and disease, biomarker testing can become more readily available,” Dr. Rotroff says. “We can empower patients and physicians with the information they need to develop proactive, personalized healthcare regimens for each individual patient.”
