QB3 was built to unite scientists, initiate new research directions, and promote collaboration across its three campuses: UC Berkeley, UC Santa Cruz and UCSF. Each campus has strengths, be they life sciences, computation, engineering, or medicine.

The QB3 collaborative unit, spearheaded by grants coordinator Lise Barbé, leverages these strengths and resources to build a deeper understanding of complex biological systems and to stimulate the discovery of solutions to societal problems in human health. Our current focus areas are autoimmune diseases and neural organoids for human disease research and drug screening.

We continuously work with investigators at all QB3 campuses, other UCs and academic institutions, and industry including startups. If you are interested in joining QB3’s Collaborative Research program, please reach out through this website’s contact form.

Focus area: Autoimmune Disease

Following our March 2025 symposium on autoimmune disease (AID), we held brainstorming sessions for this theme, including an in-person workshop. Key areas of interest include the restoration of immune tolerance, targeting microbiome-host pathways to treat AID, unraveling of antigen-antibody binding mechanisms, and mapping heterogeneity in autoimmune conditions.

Restoration of self tolerance

Restoring immune tolerance, the immune system’s ability to avoid attacking the body’s own tissues, is a major goal in autoimmune disease research and therapy. Multiple strategies are being explored across immunology, cell therapy, and bioengineering, among which antigen-specific tolerance therapies, tolerogenic cell therapies, immune modulating biologics and CRISPR to suppress autoreactive BCRs and TCRs. We will explore strategies to restore self-tolerance in a range of autoimmune conditions. 

Cell membrane crowding: antigen-antibody binding mechanisms

The cell membrane is not a flat, free plane but rather a packed and dynamic mosaic. The question remains what affects, and how we can modulate, antigen presentation and crowding to alter antigen-antibody binding. Steric hindrance, antigen/antibody mobility, conformational constraints, antigen organization and antigen burying could all directly or indirectly change the effectiveness of antibody binding. For example, cancer cells are known to overexpress bulky mucins or glycosylated proteins, physically shielding target antigens from antibodies. We will explore strategies to do the inverse: to modulate cell membrane proteins and antigen presentation to inhibit auto-antibodies from binding to self-antigens.

Heterogeneity in autoimmune conditions

Autoimmune diseases show a large range of heterogeneity concerning severity, genetics, environmental triggers, and gender. We will apply multi-omics approaches, including genomics, proteomics, sequencing of long non-coding RNAs and AI, to build a classification system of autoimmune profiles across autoimmune conditions with a goal to identify subgroups, commonalities, biomarkers and potential treatment paradigms most relevant per patient and subgroup. 

Target microbiome-host pathways to treat AID

Disruptions in the gut microbiome are linked to autoimmune diseases (type 1 diabetes, MS, RA, IBD, lupus) and certain diets are thought to restore microbial balance and improve autoimmune symptoms. Can we learn which pathways microbiomes and diets are targeting? Knowing the pathways and individual players could lead to additional and potentially more effective traditional therapeutics (small molecules, etc) that are not microbiome or diet-based.

Focus area: Neural Organoids

Organoids are 3D structures that self-assemble into developmentally relevant cellular models. The promise of neuronal organoids lies in their ability to more accurately model brain development, study neurodevelopmental and neurodegenerative diseases and utilize organoids as a 3D human model in drug screening. However, several roadblocks currently hinder the widespread use of organoids in these applications. Through collaborative research, QB3 aims to address some of these challenges and propel organoids to be more relevant in disease modeling and drug screening. We currently have grant initiatives in autism, Alzheimer’s, stroke, traumatic brain injury, and a platform technology for vascularized brain organoids.

Neural organoids as a model for autism and other psychiatric disorders

Autism and other psychiatric disorders are predominantly polygenic, and animal models often fail to replicate the diverse human disease phenotypes observed in autism and psychiatric disorders. To comprehend how different genetic causes can yield similar disease patterns, it is imperative to uncover the functions of these mutated genes. CIRM recently awarded QB3 a CIRM ReMIND-L grant, led by Alex Pollen, an associate professor of neurology at UCSF, to identify and target autism disease pathways. Additionally, we secured funding from UCOP through a MRPI grant, led by Helen Bateup, an associate professor of molecular and cell biology at UC Berkeley. Across these two projects, will use neural organoids, patient imaging and clinical data, human brain samples, CRISPR, machine learning and gene therapy to identify and test new potential disease treatments for autism.

Neural organoids as a model for neurodegenerative diseases

Current FDA-approved Alzheimer’s disease drugs have only shown minimal effectiveness for symptom relief and have been unsuccessful to halt neurodegeneration. Alterations in microglia function have been identified in Alzheimer’s disease; however, the exact role they play in pathology remains elusive. With this effort, we aim to understand the complex interplay between microglia, pathological protein accumulation and neurotoxicity. We will use multicellular systems and neural organoids to understand the role of immune cells in Alzheimer’s disease pathology and to identify new potential therapeutic targets and biomarkers for Alzheimer’s.

Neural organoids for brain replacement

Stroke and other sudden brain insults will leave a part of the brain nonfunctional, and scar tissue will replace the affected areas. The lost brain function can result in many different consequences including (partial) loss of physical, emotional, cognitive and communicative abilities and typically results in extensive rehabilitation programs. With this project, we aim to pre-assemble functional brain cells in vitro and then transplant them to the patient’s brain with minimally invasive surgery. Successful integration of the transplanted cells will result in regaining lost cells and cell-to-cell interactions, resulting in a rescue of the lost brain function.

Vascularized brain organoids to model neuroinflammation, the blood-brain barrier, and perform drug screening

Brain organoids face limitations in size and cell maturation due to their primarily composition of neurons. The incorporation of vascular and immune cells alongside neuronal cells can generate open lumens and vascular channels throughout the organoids that increase neuronal maturation. In this project, we aim to create perfused vascularized brain organoids with flow of nutrients and oxygen throughout the vascular structures similar to the in vivo human brain. The outcomes of this research are expected to significantly advance the utility of neural organoids in modeling the blood-brain barrier and neuroinflammation and will be validated using human clinical data. Additionally, we will increase throughput of the system to enable drug screening for Alzheimer’s disease, traumatic brain injury and other neurological disorders, especially those with a vascular-immune component.