brain

Season 3, Episode 4: Listening to Neurons with Sumner Norman

First Author: Sumner Norman

Episode Summary: Brain machine interfaces untangle the complex web of neurons firing in our brains and relay the underlying meaning to a computer. These devices are being adapted to help patients regain motor control, monitor our mental well being, and may one day even make us more empathetic. State of the art methods to do this have massive trade-offs, either being high resolution yet requiring devices to be embedded in our heads, or low resolution but non-invasive. Finding a key middle ground, Sumner uses advances in ultrasound to monitor the brain activity of monkeys performing specific tasks. With this data, he can not only record the brain activity associated with performing the task itself but also the intention of doing it before the subject even has a chance to move.

About the Author

  • Sumner started his career in mechanical and aerospace engineering, performing research on haptics and mechatronics.

  • This developed in him the love for how humans and computers interact, leading him to earn a PhD developing exoskeleton robots for motor learning and control.

  • Through this, he realized that to translate these technologies, we need better methods to get information out of the brain.

Key Takeaways

  • Ultrasound technologies are leveraged to monitor brain activity.

  • The signal that is generated when these methods “listen” to the brain is extremely complex and entangled, akin to trying to make out a sentence from across a loud stadium.

  • Sumner taught monkeys how to perform a task, reading the brain with ultrasound and using machine learning to decode the message.

  • With it, they were able to read which way the monkey intended to move, when the movement would occur, which way the monkey actually moved, and whether it would move its hands or eyes.

Translation

  • This technology has massive potential to help those suffering from motor impairment and could one day connect us all on a deeper level.

  • To get there, the device will need to be optimized to find the best way to maximize signal-to-noise but minimize invasiveness.

  • Additionally, advances in miniaturization, wireless connections, lowered cost of goods, and finding the right balance between AI and BMI control are needed to get this extremely new technology into the hands of everyone.

Paper: Single-trial decoding of movement intentions using functional ultrasound neuroimaging

Season 2, Episode 4: Why CAR T Therapies are Such a Headache with Kevin Parker

First Author: Kevin Parker

Episode Summary: Engineered T cells that hunt and kill blood cancers have recently obtained three landmark FDA approvals, forever changing the way we treat this disease. Even with its massive clinical success, these cells come with life-threatening neurotoxicities. But is neurotoxicity a set feature of using T cell therapies or is our engineering accidentally targeting the brain? Utilizing advances in bioinformatics and the huge sequencing datasets available to science, Kevin uncovers similarities between a cell type in our brain and the cancer we target with engineered cells. Finding this needle in a haystack, Kevin creates a link between how we engineer these cells and the neurotoxicities we see, discovering a potential root cause of the problem and generating a rule for how to engineer around it.

About the Author

  • Kevin recently received his PhD from Stanford University in the labs of Professor Howard Chang and Professor Ansuman Satpathy. These labs specialize in uncovering the molecular mechanisms of disease using advanced sequencing modalities.

  • Bridging both biology and computer science, Kevin’s background and expertise made him uniquely suited to hunt down the culprit of CAR T cell neurotoxicity.

Key Takeaways

  • CAR T cells are excellent at killing blood cancers but are not without side-effects -- they can cause severe neurotoxicities.

  • The receptor engineered into CAR T cells was thought to be specific to these blood cancers, ensuring the therapies don't attack healthy tissue.

  • Kevin looked at publically available single cell sequencing data to find a small subset of brain cells hiding in plain sight that the CAR T cells could attack. 

  • In mice, engineered “blood cancer specific” T cells attack the brain, demonstrating that neurotoxicity is an off-target effect of the therapy, not a byproduct.

Translation

  • The finding points to the potential need for different engineered receptors to be used to target these blood cancers.

  • As CAR T cells expand to other cancers and malignancies, this process can be run to ensure we engineer cells that minimize the opportunity for damage to healthy tissue.

Paper: Single-Cell Analyses Identify Brain Mural Cells Expressing CD19 as Potential Off-Tumor Targets for CAR-T Immunotherapies