Interview on RNA in PPMI with Dr. Van Keuren-Jensen

Today, we will be asking Dr. Van-Keuren Jensen a few questions about RNA and hearing her insight as to why this vital element is something, we are focusing on in the Parkinson’s Progression Markers Initiative (PPMI). Dr. Van Keuren-Jensen received her Ph.D. from Cold Spring Harbor Laboratory in New York, where she studied the role of activity-regulated genes in synaptic transmission and neuronal morphology. Following her Ph.D., she was a postdoctoral fellow at Harvard Medical School before going to TGen (Translational Genomics Research Institute in Phoenix, Arizona). She currently serves as the co-director for the Center for Noninvasive Diagnostics at TGen and co-director of the RNASeq working group of the National Institutes of Health (NIH) program on Extracellular RNA Communication.

1. Why do you feel that the study of RNA is so valuable when studying neurological diseases? What can RNA samples tell us that DNA samples cannot?

RNA is an incredibly dynamic biomolecule that is a working copy of one’s DNA, responding to the cellular environment by changing composition and expression. As such, RNA is an ideal marker to provide clues about cellular injuries that occur in neurological diseases. Coupled with the ability to detect RNA alterations in circulation (even when the injury occurs in the brain), we felt this could produce valuable markers of disease progression in neurological pathologies. Neurological diseases, unlike cancer, for example, are not usually governed by thousands of mutations at the DNA level and thus we must employ other biomolecules that may provide markers of disease progression. Also, the dynamic nature of RNA complements the study of DNA in these studies, by associating changes in RNA levels to known genetic subtypes of these diseases.     

2. Why is PPMI specifically looking at RNA samples and have you discovered anything noteworthy so far? What will be done with the data collected from PPMI participants?

PPMI is looking at changes in the circulating levels of RNA in participants with Parkinson’s disease (PD) or people with known risk factors for developing PD compared with people who do not have the disease. We believe that the changes at the RNA level will be reflective of cellular injuries associated with PD, and can be used as biomarkers in the arenas of diagnostics, prognostics, and therapeutics. We are currently analyzing the RNA data from this incredible cohort, generating the largest transcriptomic dataset for a single disease that we are aware of. This dataset is publicly-available, to be mined and analyzed by any researcher.

3. What is the additive in the blood collection tube that is used for RNA and why is it important? Building off that question, why are two tubes of RNA required instead of just one?

What we can say is that the RNA we received for this analysis was collected in PaxGene tubes. The additives and preservatives in these tubes typically serve to prevent coagulation of the blood, break up cell walls to release nucleic acids (such as DNA and RNA) and then protect the RNA to preserve molecule quality during shipping and storage.

4. Have you found any similarities in the RNA from participants with PD with other neurological diseases such as Alzheimer’s or Dementia?

We are currently analyzing the initial RNA data from the PD participants in the PPMI study. Once analyses are completed, we will absolutely be looking for similarities and differences to other studies of PD, as well as other neurological diseases like Alzheimer’s or dementia. We should point out that there are no studies in these other neurological diseases that have systematically looked at the blood transcriptome at this scale, and we hope that this PPMI study will unequivocally show the value of this type of endeavor.