Research
We are using various approaches to map the topography of schizophrenia-associated genes
(click on the image to play the movie).
(click on the image to play the movie).
The Cruz-Martin Lab at the University of Colorado focuses on several key research areas, primarily centered on neuroimmune modulation and its effects on brain development, function, and disease. Here are some of the main areas of research:
1. Neuroimmune Modulation of Synaptic Plasticity and Pathology in Neuropsychiatric Disorders
1. Neuroimmune Modulation of Synaptic Plasticity and Pathology in Neuropsychiatric Disorders
- Overview: The lab investigates how immune molecules, particularly those in the complement system, influence synaptic plasticity and contribute to neuropsychiatric disorders such as schizophrenia (SCZ) and Alzheimer's Disease (AD).
- Key Focus: Understanding the role of complement component 4 (C4) overexpression (C4-OE) in aberrant circuit wiring and synaptic pathology. The lab uses techniques like in vivo imaging, STED super-resolution microscopy, electrophysiology, and optogenetics to study these mechanisms.
- Goals: To uncover how C4 regulates synaptic protein recycling and synaptic plasticity and to discover novel pathways by which complement pathways influence brain development and neurodegeneration.
2. Cell-Type Specific Contributions to Neuropsychiatric Disorders and Anxiety
- Overview: This research explores how specific types of interneurons, such as Vasoactive Intestinal Peptide-expressing interneurons (VIP-INs) and Parvalbumin-expressing interneurons (PV-INs), contribute to the pathology of neuropsychiatric disorders and anxiety.
- Key Findings: The lab has identified distinct subpopulations of VIP-INs that respond to different stimuli, providing insights into cortical encoding of information related to anxiety and social behavior. They are also investigating the role of C4-OE in PV-INs and its effects on neural circuits and behavior.
- Techniques: Techniques include optogenetics, electrophysiology, in vivo Ca2+ imaging, genetic models, and machine learning approaches to dissect molecular mechanisms underlying complement pathology in interneuronal populations.
We use behavioral paradigms and imaging of calcium activity using miniscopes to study the neuronal circuits that underlie
social behaviors (click on the mage to play the movie).
social behaviors (click on the mage to play the movie).
3. Environmental Perturbations and Neuroimmune Mechanisms in Brain Disorders
- Overview: This research area explores how environmental risk factors—such as early-life stress, inflammation, or hypoxia—interact with genetic susceptibility to shape brain development and contribute to neuropsychiatric disorders. We focus on how these perturbations impact neuroimmune signaling and cortical circuit formation.
- Approach: We apply cutting-edge spatial transcriptomics technologies (e.g., Xenium) to map gene expression across the brain with single-cell and subcellular resolution. These datasets are analyzed using advanced computational frameworks, including FICTURE (Si et al., 2024), a segmentation-free spatial factorization method that enables scalable, transcriptome-wide analysis in complex tissues.
- Goals: Our aim is to uncover how immune-related pathways, stress responses, and cell-type-specific transcriptional programs are spatially reconfigured in response to environmental insults. These insights may reveal new mechanisms of vulnerability and resilience in neurodevelopmental and psychiatric disorders.
FICTURE (Si et al., 2024) is a segmentation-free algorithm that reveals fine-scale spatial gene expression patterns in complex tissues by analyzing transcriptome-wide data at subcellular resolution, with Sheyla Esther Carmen Sifuentes, Paige Caley, and Mingxia Huang.
