Transcript: Shaping NF1 care: Johns Hopkins biorepository

- The Johns Hopkins NF1 Biospecimen Repository was born out of the concept that major scientific advances in the field of NF1 research was limited by access to primary human tissue, and in some cases adequate models that reflect the major NF1 disease manifestations. At the Johns Hopkins Comprehensive NF Center, we care for a very high volume of patients and those patients during the course of their care may need biopsies, for example, of a concerning lesion and in some cases surgeries to remove tumors that may range from benign to malignant. And so we knew that if we banked those tissues and corresponding blood samples from people with NF1, we could build a resource that would fuel research in many different domains. What's important to us and has been a key driver of the mission of NTAP funding is that the samples can support research not only at Johns Hopkins but worldwide. We know that there are fantastic research ideas led by diverse and really, really motivated scientists that simply in the past couldn't truly be realized because those scientists or those institutions didn't on their own have sufficient samples to analyze. So really what we've built allows any researcher with an important scientific question to reach out to us, and for the most part, we've been able to fulfill every request that comes our way. What we've also learned is that the clinical annotation of the samples is critical. So for instance, the researcher who we are supporting may have additional questions about patients after they've done their preliminary analysis.

So our corresponding clinical database can become more of an interactive experience with scientific exchange back and forth that truly advances the analysis and ultimately the discoveries that come out of this research. We've learned that when we truly understand as much as we can from every patient from whom these samples originated, the clinical implications of the discoveries is most impactful. And what's also important to note is that we do all of this in a way that respects the necessary protections for patient's privacy. What distinguishes this biorepository in terms of genomic characterization is that a large number of samples on the order of about 150 to 200 samples have undergone genomic sequencing using whole exome and subsequently whole genome as well as bulk RNA sequencing. These sequencing data are then stored in the NF data portal, and we published the bulk of them in a paper that came out in scientific data in 2025, so that other researchers can download and use that either alone or in combination with other data sets to interrogate their own scientific direction. In many cases, the same samples that have been sequenced are also stored either in the freezer or in paraffin blocks in our lab. So when investigators are receiving samples, it's very possible that the corresponding genomic data already exists. Every sample then has a unique identifier.

So the researcher knows that they can use these matched genomic data and see how the data support or add depth to the question that they're asking in their lab. We have already begun to see how the genomic insights that are derived from the NF1 biobank can advance understanding of tumor progression and in some cases malignant transformation. What's important to recognize is that the biobank itself is meant to be the resource, not the main discovery engine. So our goal has been to get the useful data out there to support as many scientists as possible. An example of this is a discovery made by Wade Claps lab, where they identify DLK1 as a marker that's up-regulated in malignant transformation, and then using Hopkins Biobank samples, they were able to validate this finding in an independent cohort, which is scientifically validating and also adds important rigor to the discovery. Based on this, the field is now looking forward to testing how drugs that target DLK1 may or may not be useful to treat people with malignant tumors. And what's important to recognize about the samples in the NF1 biobank and perhaps the limitation in some ways is that they aren't what we would call scientifically controlled. So they're not coming from patients who are on a trial or patients who are all treated in an identical way, for instance. Sometimes we have but not always a corresponding pre-malignant tumor that may have predated the malignancy by some timeframe, say a year or so. But we only would've bank that tumor if the clinician's taking care of that patient had a reason to do that surgery or biopsy. In other words, it was clinically indicated. So that means that sometimes what could be a very revealing tumor sample was not made available for research. Sometimes we might wish that we had specific pairs or sets of tumors that would be perfect for the research question.

But the bottom line is that we do our very best to collect every tissue that is made available, but those are only on the basis of clinically indicated procedures. Some of the practical considerations for clinicians, especially those practicing outside of specialized NF centers, is that we have so much to learn about the biology and risk factors that underlie the many manifestations related to the NF1 condition. We've found that our patients are living with a condition that in many cases may result in pain or disfiguring or cosmetically challenging tumors or symptoms related to nervous system or motor dysfunction. And they are just on the whole so incredibly motivated to support research on their own condition. Many of the families we care for have more than one affected family member, and in some cases, they may have watched a family member struggle, and this definitely adds to their desire to want to be part of something bigger that changes the field and treatments that can make it better for other people with NF1.

So we definitely want to encourage physicians outside large NF centers to consider what a referral to a specialized NF center may do not only for individual patients, but on the whole for the advancement of research in the field of NF1. What we're finding is that the biorepository in its current form, can drive the future of NF care. What we've seen, especially in the past five years, is a dramatic increase in the number of collaborations fueled by the biobank. And really, collaboration has such a strong presence in the NF1 research field. You often see multiple groups from institutions across the US and Europe and beyond bringing their discoveries and unpublished early findings to conferences and collaborative settings. And there's really just this feeling that being whole is better than the sum of its parts. It's been really rewarding to see how the biobank has been part of that growth. So the next steps, as you can imagine, are to ensure that we build upon the lab discoveries and make sure that we have the clinical infrastructure that allows the translational potential. These steps, such as clinical trial awards and cooperative group infrastructure require collaborative approach and willingness by all scientists to bring the best science forward and make sure that it gets to patients. The care of patients with NF1 requires specialty input from so many different teams.

Usually the primary care of a patient with NF1 involves a dedicated NF1 team, and these are often neurologists or in some cases geneticists or sometimes oncologists because of the risk of malignancy. But key input is also needed from surgeons, including neurosurgeons and orthopedic oncologists and radiologists who very often are doing their own research to build and develop tools to understand how they can spot malignant transformation and tell us which areas on a scan needs to be watched or biopsy. Our patients also have input from so many other teams, including dermatologists, ophthalmologists, spine surgeons, plastic surgeons, just to name a few. And the more eyes to have on the patient, the better, because each team can bring a unique expertise that ensures that the patients are really well taken care of.