Publications by authors named "Nishith R Reddy"

Article Synopsis
  • - Scientists identified specific proteins and molecules in the central nervous system (CNS) that can be targeted to create engineered cells for therapy.
  • - They developed synthetic Notch receptors to program T cells to release certain treatments only in the brain, effectively clearing brain tumors without affecting cells in other areas.
  • - The research also found that T cells delivering interleukin-10, an immune-suppressing cytokine, helped reduce symptoms in a mouse model of neuroinflammation, showing potential for targeted treatment strategies.
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Chimeric antigen receptor (CAR) T cells are ineffective against solid tumors with immunosuppressive microenvironments. To overcome suppression, we engineered circuits in which tumor-specific synNotch receptors locally induce production of the cytokine IL-2. These circuits potently enhance CAR T cell infiltration and clearance of immune-excluded tumors, without systemic toxicity.

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Protein conformations are shaped by cellular environments, but how environmental changes alter the conformational landscapes of specific proteins remains largely uncharacterized, in part due to the challenge of probing protein structures in living cells. Here, we use deep mutational scanning to investigate how a toxic conformation of α-synuclein, a dynamic protein linked to Parkinson's disease, responds to perturbations of cellular proteostasis. In the context of a course for graduate students in the UCSF Integrative Program in Quantitative Biology, we screened a comprehensive library of α-synuclein missense mutants in yeast cells treated with a variety of small molecules that perturb cellular processes linked to α-synuclein biology and pathobiology.

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Many cellular responses for which timing is critical display temporal filtering-the ability to suppress response until stimulated for longer than a given minimal time. To identify biochemical circuits capable of kinetic filtering, we comprehensively searched the space of three-node enzymatic networks. We define a metric of "temporal ultrasensitivity," the steepness of activation as a function of stimulus duration.

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