Cleared brain sample imaged for large-volume neural projection mapping

Future independent research program

Ochoa Lab

We aim to understand why some neural circuits fail early in neurodegenerative disease while others remain resilient by linking projection-resolved 3D anatomy, glial states, and spatial molecular programs across scales.

Explore Research About Lorenzo

Circuit vulnerability why specific projections fail early or remain resilient

Spatial neurobiology glial states and molecular programs in anatomical context

Quantitative 3D imaging tissue transformation, microscopy, and computation

Research

Connecting selective circuit failure to the tissue environments where it begins.

The planned research program combines projection-resolved anatomy, spatial molecular profiling, and computational analysis to study early mechanisms of neurodegeneration in intact tissue systems.

Tract-selective vulnerability in neurodegeneration

We will investigate why particular neuromodulatory projections, including locus coeruleus pathways, show early dysfunction while neighboring circuits remain comparatively resilient.

Glial states in spatial context

We aim to connect axonal injury and connectivity loss with local microglial, astrocytic, and tissue-state programs using spatial profiling and multimodal integration.

Scalable tissue transformation and computation

Tissue clearing, large-volume microscopy, registration, segmentation, and machine learning make circuit-scale pathology measurable while preserving anatomical context.

Dense orange neural labeling across a cleared tissue volume — Projection-rich tissue volumes reveal anatomy that is easy to miss in thin sections.

Red and cyan whole-brain microscopy image showing large-scale anatomical structure — Whole-brain and large-tissue imaging can connect regional pathology to system-level structure.

Dynamic Imaging

Watching vascular and immune responses unfold in living tissue.

Intravital two-photon microscopy through thinned-skull cranial windows captures blood vessels and microglia as dynamic events, making cellular responses visible in the tissue environment where disease processes emerge.

Data status Dynamic imaging shown below appeared in the doctoral thesis and has not yet been published in a peer-reviewed scientific article.

Preliminary data · Not yet peer-reviewed

Microglial process dynamics

Blood vessels are labeled red and microglia green during intravital imaging after noxious intranasal exposure.

Preliminary data · Not yet peer-reviewed

Vascular response

Time-lapse microscopy reveals how vascular and immune-cell behavior can shift across minutes in a living cortical field.

Preliminary data · Not yet peer-reviewed

Transient response event

Dynamic imaging captures brief events that are difficult to infer from fixed tissue alone.

Optically cleared mouse lung held for imaging — Optically cleared mouse lung prepared for organ-scale imaging.

Large-volume methods across biological systems

The lab's methodological foundation extends beyond thin-section imaging to intact organs, living tissue dynamics, and cleared specimens that preserve spatial relationships across scales.

Two-photon mouse brain image from a cerebral malaria model with vessels in green and astrocytes in red — **Cerebral malaria model** Two-photon imaging of mouse brain with vessels in green and astrocytes in red.

Two-photon image of a cleared mosquito prepared as a vector-borne pathogen proof of concept — **Cleared vector specimen** Preservation, delipidation, and optical clearing applied to a mosquito as a proof of concept for vector-borne pathogen studies.

Approach

Methods built for spatial context.

The lab's scientific questions depend on methods that preserve anatomical context while enabling rigorous comparison across scales, samples, and disease states.

Tissue clearing and thick-tissue labeling
Light-sheet, confocal, and multiphoton microscopy
Whole-organ and large-tissue sample preparation
Projection-resolved quantitative image analysis
Spatial biology and multimodal integration
Machine learning for volumetric data interpretation

Principal Investigator In Development

Lorenzo Francisco Ochoa

Lorenzo is a neuroscientist and bioengineer developing an independent research program at the intersection of circuit vulnerability, tissue transformation, spatial biology, and computational 3D pathology.

He is a Postdoctoral Fellow at MIT's Picower Institute for Learning and Memory in the Chung Lab, where he investigates systems-level mechanisms of neurodegenerative disease and the role of locus coeruleus circuitry in Alzheimer's pathology.

His multidisciplinary training spans neuroscience, biochemistry, biomedical engineering, optical clearing, whole-organ imaging, light-sheet and multiphoton microscopy, quantitative computation, infectious disease, and neuroinflammation.

Picower Postdoctoral Fellow
NIH Outstanding Scholars in Neuroscience awardee
2025 Koch Institute Image Award recipient

Google ScholarCitations and research record PubMedPeer-reviewed publications LinkedInProfessional profile NIH BiosketchCurrent PDF

Selected Publications

Work spanning tissue clearing, neuroinflammation, imaging, and quantitative analysis.

Selected peer-reviewed work is shown below. Complete and current records are available through PubMed and Google Scholar.

View all publications on PubMed View Google Scholar

Dynamic intravital imaging reveals reactive vessel-associated microglia play a protective role in cerebral malaria coagulopathy. Solomon O. D., Villarreal P. P., Domingo N. D., Ochoa L. F., et al. Scientific Reports, 2023.
Semi-automated micro-computed tomography lung segmentation and analysis in mouse models. Luisi J. D., Lin J. L., Ochoa L. F., et al. MethodsX, 2023.
Powassan Virus Induces Structural Changes in Human Neuronal Cells in vitro and Murine Neurons in vivo. Nelson J., Ochoa L., Villarreal P., et al. Pathogens, 2022.
Light-Sheet Microscopy of the Optic Nerve Reveals Axonal Degeneration and Microglia Activation in NMDA-Induced Retinal Injury. Ha Y.*, Ochoa L. F.*, et al. EC Ophthalmology, 2021.
Imaging of Murine Whole Lung Fibrosis by Large Scale 3D Microscopy aided by Tissue Optical Clearing. Ochoa L. F., Kholodnykh A., Villarreal P., et al. Scientific Reports, 2018.
Elimination of intravascular thrombi prevents early mortality and reduces gliosis in hyper-inflammatory experimental cerebral malaria. Wilson K. D., Villarreal P. P., Ochoa L. F., et al. Journal of Neuroinflammation, 2018.

Mentoring And Culture

Ambitious science with care, clarity, and respect.

Science is strongest when people feel intellectually challenged, professionally supported, and respected as whole individuals. The Ochoa Lab will aim to build a culture where rigorous research, technical creativity, openness, and care for one another are inseparable parts of the scientific process.

Individualized mentoring

Regular one-on-one meetings, constructive feedback, project planning, and support for short-term milestones and long-term career goals.

Transparent expectations

Clear conversations about project goals, authorship, training needs, conference plans, fellowship applications, and progress.

Sustainable excellence

High standards paired with documentation, reproducibility, clear communication, mutual respect, and lives outside the lab.

Contact

Start a conversation about science, collaboration, or the future lab.

The lab is in development. Prospective trainees, research staff, computational collaborators, and scientific partners interested in neurodegeneration, neuroinflammation, volumetric imaging, tissue transformation, computational pathology, or spatial biology are welcome to reach out.

Formal positions and institutional details will be added once available.