The Weill Neurohub leads breakthroughs in neuroscience by strengthening collaborative relationships among world-class researchers and clinicians.

Program Areas:

The Weill Neurohub Pillars Program

This program unites researchers around four major pillars to support the creation and application of next generation tools to speed innovation: neuroimaging, neuroengineering, neurogenomics, neuromolecular therapeutics, and neurocomputation/data analytics.

The projects awarded in the Pillars Program are:

CRISPR-based therapeutics

This project is aimed at achieving a knock-down of tau expression that is clinically effective. The team will collaborate to test MAPT epigenic silencing strategies in animal models. In addition, based on data from respective DNA cutting approaches, multiple delivery methods, and the epigenetic silencing strategy, we will collaborate on advancing the most promising preclinical strategy.

Project leaders: Andrea Gomez, PhD (UCB); Fyodor Urnov, PhD (UCB); Claire Clelland, MD, PhD (UCSF)

Strategies to promote tau clearance

This project aims to identify new strategies to reverse the age-associated decline in tau clearance by turbocharging the efficiency of existing clearance pathways. Additionally, this project will determine how tau aggregates impair stress response silencing and dissect the “degrons” or degradation motifs in tau that lead to proteasomal clearance. Critically, this combination of approaches—boosting lysosomal-based clearance of tau and mitigating the cell-stressing effects of tau degradation—lay the groundwork for a potential combination therapy that could represent a robust approach to combating tau toxicity.

Project leaders: Michael Rapé, PhD (UCB); Aimee Kao, MD, PhD (UCSF); Martin Kampmann, PhD (UCSF)

Targeted tau degradation by de novo-designed proteins

This project aims to apply cutting-edge computational protein design to the challenge of clearing aggregated Tau in neurodegenerative disease. Two major routes will be explored for intracellular tau clearance - the autophagy-lysosome and proteasome systems, as well as clearance of extracellular tau to reduce spreading using our EndoTag technology. The designs most effective in clearing tau will be tested in animal models of neurofibrillary degeneration seen in Alzheimer’s Disease and related tauopathy disorders.

Project leaders: David Baker, PhD (UW); Brian Kraemer, PhD (UW)

Engineering non-invasive therapeutic technologies for stroke and addiction

This program aims to develop next-generation, non-invasive brain therapies targeting two major neurological challenges: substance use disorder and stroke-related motor disability. The goal is to create innovative, non-invasive therapies that directly target the brain’s misfiring circuits-without the need for surgery. By studying brain activity in both patients and laboratory models, we aim to identify key brain signals that indicate dysfunction. From there, we will develop new technologies that can safely and effectively adjust brain activity externally, mimicking the benefits of invasive treatments.

Project leaders: Ricky Muller, PhD (UCB); Karunesh Ganguly, MD, PhD (UCSF); Khaled Moussawi, MD, PhD (UCSF); Azadeh Yazdan-Shahmorad, PhD (UW)

Engineering and application of “NextGen 7T” MRI scanner

The NextGen 7T project aims to create the world’s most powerful magnetic resonance imaging (MRI) scanner. It will allow investigators to see brain structures as small as 200 to 300 microns – one-quarter of the size of a grain of sand – which is about 60 times sharper than a standard hospital MRI. This ultra-high resolution will enable the discovery of previously unknown brain circuits and functions, providing investigators with new insights into brain diseases and how to treat them. Weill Neurohub funding will complete the construction of the scanner and the facility to operate it and support research to evaluate the first use cases.

Project leaders: David Feinberg, MD, PhD (UCB); Thomas Grabowski, MD (UW); Chunlei Liu, PhD (UCB); Pratik Mukherjee, MD, PhD (UCSF)

DeepNeuro: synthetic and augmented MRI for a shared neuroimaging infrastructure across Neurohub

This project aims to develop shared processes for neuroimaging acquisition and interpretation that will allow the Weill Neurohub to collect, combine and compare advanced neuroimaging data for patients with brain disorders across conditions, across silos, and across institutions. These neuroimaging measures represent one of the foundations of the DeepNeuro Initiative – our ambitious endeavor to phenotype over 10,000 patients at UCSF and the University of Washington and collect harmonized datasets that include common patient-reported, clinical, biosample and MRI data elements. These rich data will enable fertile collaborations and new lines of enquiry throughout the Weill Neurohub.

Project leaders: Riley Bove, MD MMSc (UCSF); Thomas Grabowski, MD (UW); Reza Abbasi Asl, PhD (UCSF); David Feinberg, PhD (UCB); Roland Henry, PhD (UCSF); Andrew Josephson, MD (UCSF); Peder Larson, PhD (UCSF); Thabele Leslie-Mazwi, MD (UW); Chunlei Liu, PhD (UCB); Pratik Mukherjee, MD PhD (UCSF); Swati Rane, PhD (UW); Annette Wundes, MD (UW)

Identification of novel treatments for Alzheimer’s and related disorders

This project aims to speed progress toward safe and effective therapies for Alzheimer’s disease and related disorders (ADRD). Historically, progress has been limited by two barriers: an incomplete understanding of the cellular processes that lead to ADRD and a lack of robust cellular models for identifying and evaluating new therapeutic targets. Weill Neurohub support will fund the development of cross-disciplinary strategies and tools to overcome these barriers, including biobanks for collecting brain tissue and cells and platforms for investigating new therapies.

Project leaders: Jennifer Doudna, PhD (UCB); Lea Grinberg, MD, PhD (UCSF); Suman Jayadev, MD (UW); C. Dirk Keene, MD, PhD (UW); Michael Rape, PhD (UCB); William Seeley, MD (UCSF); Jessica Young, PhD (UW)

Advancement of electrical stimulation for treating neurological and psychiatric illness

Electrical stimulation of the brain is a promising technique for treating a wide range of neuropsychiatric disorders, including stroke; chronic pain; and severe, intractable depression and anxiety. This project aims to improve the efficacy of next-generation neurostimulation devices, which could decode a patient’s brain activity and use that information to provide personalized, targeted stimulation for relieving symptoms. Weill Neurohub funding will support research and engineering to improve and test the effectiveness of these devices.

Project leaders: Edward F. Chang, MD (UCSF); Karunesh Ganguly, MD, PhD (UCSF); Michel Maharbiz, PhD (UCB); Chet Moritz, PhD (UW); Rikky Muller, PhD (UCB); Jeffrey G. Ojemann, MD (UW); Amy Orsborn, PhD (UW); Azadeh Yazdan-Shahmorad, PhD (UW)

Construction of next-generation microscopes for live brain imaging

This project aims to build three state-of-the-art microscopes that will allow investigators to observe brain cells in unprecedented detail. Weill Neurohub funding will support the design and engineering of the microscopes’ hardware as well as the computational infrastructure for data analysis and sharing. The completed microscopes will be available to all Weill Neurohub investigators, thereby expanding research opportunities and collaborations.

Project leaders: Graeme Davis, PhD (UCSF), Adrienne Fairhall, PhD (UW), Na Ji, PhD (UCB), Saul Kato, PhD (UCSF), Laura Waller, PhD (UCB)

Creation of a Weill Neurohub collaborative platform for data and analytics

This project will provide a platform for data-science innovation and training at the Weill Neurohub. In launching the platform, Weill Neurohub funding will support the development of new algorithms, software, and shared infrastructure for processing the vast amounts of data currently being generated in neuroscience. The funding will also support outreach and training in advanced computational science for students, fellows, and faculty members from diverse disciplines across the Weill Neurohub community.

Project leaders: Kristofer Bouchard, PhD (UCB, LBNL); Bing Brunton, PhD (UW); Thomas Grabowski, MD (UW); Roland Henry, PhD (UCSF); Geoffrey Manley, MD, PhD (UCSF); Shankar Sundaram, PhD (LLNL); Bin Yu, PhD (UCB)

The Weill Neurohub Investigators Program

This program has two main goals:

• Foster new cross-campus, interdisciplinary teams of roughly five to eight researchers who will explore, create, and test bold new concepts and technologies. Modeled on the success of the Chan Zuckerberg Biohub, funding for top faculty supports their participation in new multi-year explorations of novel projects with transformational potential.

• Help recruit talented faculty by supporting start-up costs for laboratories and other needs for top talent acquisition across campuses.

The current projects awarded in the Investigators Program are:

Chemogenetic neuromodulation of human brain circuits for the treatment of neuropsychiatric disorders

This project aims to lay the groundwork for advancing neuromodulation techniques in humans for the treatment of neuropsychiatric disorders by employing chemogenetics, thus allowing for cell-type-specific neuromodulation and titratable treatment plans.

Project leaders: David Schaffer, PhD (UCB); Khaled Moussawi, MD, PhD (UCSF); Tomasz Nowakowski, PhD (UCSF); Azadeh Yazdan-Shahmorad, PhD (UW)

Mapping the developmental logic of midbrain dopamine circuits in autism models

This project aims to characterize the development of midbrain dopamine circuits, creating a spatiotemporal molecular atlas, and interrogate the impact of Syngap1 deletion on dopamine circuitry development and reward-related behaviors to further our understanding of dysfunctional dopamine in autism spectrum disorder.

Project leaders: Helen Bateup, PhD (UCB); Corey Harwell, PhD (UCSF); Garret Stuber, PhD (UW)

The protein code of brain aging: from molecules to mechanisms

This project aims to map proteomic changes at the single-cell level across brain regions during healthy aging and disease, integrated with transcriptomics to identify differential protein regulation, with the goal to identify vulnerable/resilient cell populations and mechanisms of aging.

Project leaders: Amy Herr, PhD (UCB); Cindy van Velthoven, PhD (Allen); Danielle Swaney, PhD (UCSF)

Development of an AI-driven, all-optical brain machine interface

This project aims to advance brain machine interfaces by leveraging optical approaches to access single cell resolution over large neural populations - developing the first optical brain machine interface for non-human primates.

Project leaders: Doris Tsao, PhD (UCB); Hillel Adesnik, PhD (UCB); Christoph Kirst, PhD (UCSF); Edward Chang, MD (UCSF); Adrienne Fairhall, PhD (UW)

Molecular, microstructural and mesoscale imaging of white matter myelin and axonal integrity in TBI

This project will leverage ultra-high-field magnetic resonance imaging in combination with positron emission tomography and ex vivo validation of in vivo findings to interrogate white matter pathology in traumatic brain injury.

Project leaders: Suzanne Baker, PhD (UCB); Pratik Mukherjee, MD, PhD (UCSF); Amber Nolan, MD, PhD (UW); C. Dirk Keene, MD, PhD (UW); Christine MacDonald, PhD (UW)

NexGen 7T sub-millimeter resolution mapping of the temporal lobes in healthy aging

This project aims to improve detection of frontotemporal dementia through developing both functional and anatomical maps of the temporal lobes in healthy aging brains.

Project leaders: Jack Gallant, PhD (UCB); Katherine P. Rankin, PhD (UCSF); Maria Luisa Gorno Tempini, MD, PhD (UCSF); An Vu, PhD (UCSF); Ariel Rokem, PhD (UW)

Imaging glioblastoma infiltration to aid surgical resection and prognosis

This project aims to decrease glioblastoma recurrence through developing a novel MRI-based technique that can identify tumor infiltration of tissue surrounding the contrast-enhancing region of the glioblastoma to support improved surgical resection parameters.

Project leaders: Chunlei Liu, PhD (UCB); Ed Lein, PhD (Allen); Mitchel Berger, MD (UCSF); Shawn Hervey-Jumper, MD (UCSF); Jacob Young, MD (UCSF); Javier Villanueva-Meyer, MD (UCSF); Melike Pekmezci, MD (UCSF); C. Dirk Keene, MD, PhD (UW)

High throughput lipid nanoparticle-enabled CRISPR-based epigenetic editing of neurological diseases

This project aims to advance the treatment of neurological diseases through the development of epigenetic editors targeting specific neurological diseases (glioblastoma and Alzheimer’s Disease) and an effective brain tissue delivery system.

Project leaders: Niren Murthy, PhD (UCB); S. John Liu, MD, PhD (UCSF); Jessica Young, PhD (UW)

Revealing disease-specific tau conformers in neurons and glia: towards next generation molecular diagnostics for ADRD tauopathies

This project aims to characterize cell-type-specific tau conformational strains in Alzheimer’s disease and related dementias utilizing human brain samples and stem cell models.

Project leaders: Ke Xu, PhD (UCB); Carlo Condello, PhD (UCSF); Jason Gestwicki, PhD (UCSF); Martin Kampmann, PhD (UCSF); William Seeley, MD (UCSF); Daniel Southworth, PhD (UCSF); Danielle Swaney, PhD (UCSF); C. Dirk Keene, MD, PhD (UW)

A novel pipeline for rapid identification and targeting of Alzheimer’s disease-related endo-lysosomal dys-function in aging and disease models

This project aims to develop a novel CRISPR-based screening pipeline focused on endolysosomal network targets for Alzheimer’s Disease therapeutics.

Project leaders: Kyle Travaglini, PhD (Allen); Courtney Lane-Donovan, MD, PhD (UCSF); Jessica Young, PhD (UW)

Dynamic layer-specific brain connectivity: a new frontier in functional imaging and understanding brain microcircuit dysfunction

This project aims to develop a novel method for non-invasive imaging of neuronal activity across layers of the brain utilizing the NextGen 7T scanner and an innovative Graph Diffusion Autoregressive model.

Project leaders: David Feinberg, MD, PhD (UCB); Alexander Beckett, PhD (UCB); An Vu, PhD (UCSF); Hesamoddin Jahanian, PhD (UW)

The Weill Neurohub Next Great Ideas Program

This program calls for research proposals from interdisciplinary teams of two or more researchers representing inter-campus partnerships. The awards rapidly fund high-risk, high-reward research projects. In so doing, the program inspires creative, collaborative thinking and accelerate discovery.

The current proposals awarded in the Next Great Ideas Program are:

Molecular and therapeutic dissection of cholesterol-mTORC1 signaling in Niemann-Pick type C pathogenesis

This project interrogates the mechanistic action of mTORC1 in Niemann-Pick type C and the therapeutic potential of targeting mTORC1 signaling prenatally to disrupt disease pathology.

Project leaders: Roberto Zoncu, PhD (UCB); Tippi MacKenzie, MD (UCSF)

Continuous mental state decoding with wearable biosensors: an AI approach to psychiatric care

This project aims to develop a novel digital psychiatry platform that detects changes in mood state through AI-powered wearable biosensors to then appropriately deliver digital therapeutics in real time.

Project leaders: Adrian Aguilera, PhD (UCB); Peter Washington, PhD (UCSF)

Deep-brain stimulation and real-time cortisol-sensing for closed-loop electroceuticals of depression

This project aims to advance towards personalized, closed-loop deep brain stimulation for depression through developing technology to continuously monitor cortisol levels as a proxy for mood state and investigating the temporal dynamics between deep brain stimulation and cortisol.

Project leaders: Jun-Chau Chien, PhD (UCB); Andrew Krystal, MD (UCSF)

Visual cues and retinal mechanisms encoding image defocus and implications for human health

This project investigates the mechanism underlying aberrant eye growth driving myopia through examining and comparing the response to visual cues measured via multi-electrode array recordings of non-human primate retina and accommodation reflex in humans using adaptive optics scanning laser ophthalmoscopy.

Project leaders: William Tuten, OD, PhD (UCB); Fred Rieke, PhD (UW); Ramkumar Sabesan, PhD (UW)

Brain-computer interfaces to uncover consciousness in acute traumatic brain injury

This project aims to identify biomarkers predictive of consciousness recovery after traumatic brain injury and develop a brain-computer interface framework applied to diseases of consciousness in order to advance towards future therapeutic strategies.

Project leaders: Frederic Theunissen, PhD (UCB); Edilberto Amorim, MD (UCSF)

Data-driven design of an under-sensorized, movement-monitoring hand wearable

This project aims to enhance the speed and effectiveness of treatment for movement disorders involving hand function by developing an accessible motion tracking hand wearable.

Project leaders: Preeya Khanna, PhD (UCB); Chet Moritz, PhD (UW)

Dynamic and energy-minimizing intelligent brain-machine interfaces: co-adaptive machine learning algorithms to enable real-world deployment

This project aims to overcome technical barriers to effective, long-term brain-machine interface use through the development of a closed-loop brain machine interface system that utilizes adaptive machine learning algorithms and reconfigurable neural recording hardware.

Project leaders: Rikky Muller, PhD (UCB); Amy Orsborn, PhD (UW)

Integrating Allen Brain Bank data with the SPOKE knowledge graph via cell ontology mapping

This project aims to develop a powerful resource tool for neuroscience and biomedical researchers, providing a detailed survey of brain cell type involvement in diseases and treatments.

Project leaders: Mariano Gabitto, PhD (Allen); Sergio E. Baranzini, PhD (UCSF)

Designing a protein binder to block the alpha-synuclein translocation in Parkinson’s disease

This project aims to characterize a mechanism through which alpha-synuclein spreads between neurons and then design a protein binder to inhibit this process in order to slow Parkinson’s Disease progression.

Project leaders: Shenjie Wu, PhD (UCB); Holger Mueller, PhD (UCB); David Baker, PhD (UW)

FACED-CT: imaging cleared tissue with minimal infrastructure for high-throughput mapping of large samples at cellular resolution

This project aims to combat inaccessibility issues in imaging cleared tissue for individual laboratories by developing a new microscope technology that reduces computational demand from both the software and user without hindering data quality.

Project leaders: Na Ji, PhD (UCB); Christoph Kirst, PhD (UCSF)

Linking the molecular, synaptic and circuit effects of psilocybin to engineer a new generation of psychedelic-inspired therapies

This project interrogates the therapeutic mechanism of psychedelics focusing on the effect on prefrontal parvalbumin interneurons and their role in cognitive flexibility.

Project leaders: Andrea Gomez, PhD (UCB); Vikaas Sohal, MD, PhD (UCSF)

Understanding inter-area interactions in the Scn2A heterozygous rat

This project aims to characterize the circuit-level phenotype of autism spectrum disorder through the development of a novel interaction subspace identification algorithm.

Project leaders: Kristofer Bouchard, PhD (UCB); Loren Frank, PhD (UCSF)

The Weill Neurohub Fellows Program

This program trains the next generation of innovators and help launch their careers as independent researchers by supporting graduate students, post-docs, and post-residency MDs aspiring to be clinician-scientists. This funding provides opportunities for Weill Neurohub Fellows to spend time on multiple campuses. See more details on our current fellows here.