Laboratory for Neuroimmune Engineering
Email: mjorfi@mgh.harvard.edu
Call: 617-726-8307
Overview
The Laboratory for Neuroimmune Engineering (Jorfi Lab) takes a fundamentally new approach to brain disease. We view neurodegeneration as a disorder of neuroimmune circuits, not just neurons. We engineer human multicellular systems built from iPSC-derived neural and glial cells, brain barrier components, and patient-derived immune cells to recreate the key interfaces where the immune system talks to the brain. Using integrated omics, imaging, computational modeling, and functional perturbation, we map how peripheral immunity, brain barriers, and tissue-resident cells cooperate to drive or protect against neurodegeneration, with a central focus on Alzheimer’s disease and related disorders. Our goal is not only to mechanistically understand these pathways but also to reprogram neuroimmune circuits by blocking pathological ones and amplifying protective ones as a blueprint for future neuroimmune therapies.
Research Projects
Human neuroimmune circuit platforms
We build human neuroimmune platforms that reconstruct the key circuits between brain, barriers, and blood in Alzheimer’s disease and related disorders. These multicellular systems integrate iPSC-derived neurons and glia, vascular and barrier elements, and peripheral immune cells into living disease models that capture human neuroimmune biology far beyond what is possible in animals. These platforms are the foundation for all of our discovery and intervention work.
Neuroimmune circuits and mechanisms
We study the mechanisms by which neuroimmune circuits connect peripheral immunity to the brain. We investigate how peripheral immune cells sense brain pathology and how they gain access to the brain, building on the idea that “nipping Alzheimer’s in the blood” can change disease trajectory. Using our tissue chips and organoid–barrier models, we define when immune entry is harmful, when it is protective, and how to shift this balance by precisely modulating neuroimmune checkpoints at the blood–brain interface. This work informs therapeutic strategies that intervene in the periphery to protect synapses and circuits in the brain.
Neuroimmune biomarkers and disease staging
We use patient-derived blood and brain samples together with our human models to discover immune signatures that report on brain pathology and disease stage. Inspired by immune-based diagnostics that read brain amyloid from the blood, we profile neuroimmune states to identify markers that predict risk, progression, and response to neuroimmune therapies. These biomarkers guide both our mechanistic studies and the design of clinical strategies.
Reprogramming neuroimmune pathways
We design and repurpose interventions to reprogram neuroimmune pathways so they protect rather than damage the brain. Using antibodies, small molecules, and gene engineering in our human neuroimmune platforms, we test how targeted modulation of peripheral and brain-resident immune circuits can reduce pathology and restore function. By focusing on mechanisms that are shared across neurodegenerative diseases, this work aims to provide a general blueprint for immune-based therapies that could ultimately be applied beyond Alzheimer’s disease.
Research Team
Mehdi Jorfi, PhD
Assistant Professor of Neurology, Harvard Medical School and Massachusetts General Hospital
Dr. Mehdi Jorfi is an Assistant Professor of Neurology at Harvard Medical School and Massachusetts General Hospital. He directs the Laboratory for Neuroimmune Engineering in the Genetics and Aging Research Unit, where his group builds human neuroimmune platforms to study neurodegeneration as a disorder of immune–brain circuits rather than neurons alone. His team combines stem cell–derived neural and glial models, brain barrier systems, patient-derived immune cells and brain tissues, and systems-level profiling to define and reprogram neuroimmune pathways in Alzheimer’s disease and related disorders.
Yuyao Tian, PhD
Research Fellow
Dr. Yuyao Tian joined the Jorfi Lab in 2024 as a Research Fellow. Her work focuses on neuroimmune interactions in neurological conditions, including Alzheimer’s disease and multiple sclerosis, using organ-on-chip systems, stem cells, and patient-derived immune cells. She earned her Ph.D. in Biomedical Sciences from the Chinese University of Hong Kong, where she investigated developmental defects in Werner Syndrome. Outside the lab, she enjoys drawing, trying new food, and spending time with her cat, Lucky Tian. Email address: ytian12@mgh.harvard.edu
Sarah Verduci
Research Technician
Sarah Verduci is a Research Technician in the Jorfi Lab. Her research investigates neuroimmune interactions and translational targets of Alzheimer’s disease using patient-derived stem cell and immune cell models. She holds a B.S. in Neuroscience with High Honors from the University of Michigan and is particularly interested in using patient-derived models to develop personalized treatments of neurological disease. Outside the lab, she enjoys baking, sports, and exploring Boston. Email address: sverduci@mgh.harvard.edu
Katalin Czopf
Visiting Graduate Student
Katalin Czopf is a visiting researcher in the Jorfi Lab. She holds a B.S. in Biology from the Ludwig Maximilian University of Munich and is currently pursuing a Master´s in Biomedical Engineering and Medical Physics at the Technical University of Munich. Beyond research, she enjoys trying out new sports, reading and exploring the world. Email address: kczopf@mgh.harvard.edu
Yannis Chen
Undergraduate Student
Yannis Chen is an undergraduate neuroscience major at Boston University and a member of the Jorfi Lab. Her interests lie in understanding neurodegenerative diseases, with plans to attend medical school and specialize in neurology. Outside her academic work, she enjoys playing piano and exploring new cuisines. Email address: ychen172@mgh.harvard.edu
Max Lee
Undergraduate Student
Max Lee is an undergraduate intern in the Jorfi Lab. He is currently studying Neuroscience at Harvard College, with a focus on understanding and addressing neurodegenerative diseases. In the lab, Max is investigating the role of CD8+ T cells in Alzheimer’s disease using human stem cell–derived chip models to study their impact on neurodegeneration and brain inflammation. Outside the lab, he enjoys reading and exploring the best coffee shops around Boston. Email address: mlee129@mgh.harvard.edu
Rina Kubota
Research Intern
Rina Kubota is a visiting researcher in the Jorfi Lab, where she investigates the role of neuroinflammation in Alzheimer’s disease using stem cells and patient-derived immune cells. She holds a B.S. in Neuroscience with Distinction from Yale University and is currently pursuing her Master’s in Violin Performance at the New England Conservatory, studying with Donald Weilerstein with the support of the Dean’s Scholarship. Beyond the lab, Rina enjoys writing short stories, performing with her string quartet, playing jazz violin, and engaging in community outreach throughout Boston. Email address: rkubota@mgh.harvard.edu
Langtian (Sky) Zhang
Undergraduate Student
Sky Zhang is an undergraduate researcher in the Jorfi Lab studying biomedical engineering, focused on the intersection of artificial intelligence and neuroimmunology. His work integrates transcriptomic profiling and drug-perturbation analysis to inform therapeutic candidates for neurodegenerative diseases. Outside the lab, Sky is an avid 2D artist and animator. Email address: lzhang96@mgh.harvard.edu
Vaishnavi Moturi
Undergraduate Student
Vaishnavi Moturi is an undergrad at Harvard College planning on pursuing Neuroscience with a secondary in Global Health and Health Policy. She is interested in studying the neuroimmune axis of neurodegenerative diseases with a focus on stem-cell derived models. She aims to integrate computational modelling with experimental neuroscience to better identify potential therapeutic avenues. Outside the lab, she enjoys running, dancing, and experimenting with new recipes. Email address: vmoturi@mgh.harvard.edu
Publications
Selected Publications
- Lin C', Tian Y, Tanzi RE*, Jorfi M*. Approaches for studying neuroimmune interactions in Alzheimer's disease. Trends Immunol. 2024 Dec;45(12):971-986. doi: 10.1016/j.it.2024.10.002. Epub 2024 Nov 12. PubMed PMID: 39537528.
- Butovsky O, Rosenzweig N, Kleemann KL, Jorfi M, Kuchroo VK, Tanzi RE, Weiner HL. Immune dysfunction in Alzheimer disease. Nat Rev Neurosci. 2026 Mar;27(3):196-218. doi: 10.1038/s41583-025-00997-0. Epub 2025 Nov 28. PMID: 41315874.
- Hall CK, Barr OM, Delamare A, Burkholder A, Tsai A, Tian Y, Felix E Ellett, Li BM, Tanzi RE, Jorfi M. Profiling migration of human monocytes in response to chemotactic and barotactic guidance cues. Cell Rep Methods. 2024 Sep 16;4(9):100846. doi: 10.1016/j.crmeth.2024.100846. Epub 2024 Sep 5. PMID: 39241776.
- Pavlou G, Spitz S, Pramotton FM, Tsai A, Li BM, Wang X, Barr OM, Ko EC, Zhang S, Ashley SJ, Maaser-Hecker A, Choi SH, Jorfi M*, Tanzi RE*, Kamm RD*. Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction. Biomaterials. 2025 Mar;314:122864. doi: 10.1016/j.biomaterials.2024.122864. Epub 2024 Sep 28. PubMed PMID: 39357152.
- Jorfi M, Kim DY, Tanzi RE. T cell-microglia signaling exacerbates neuropathology in an Alzheimer's disease model. Nat Neurosci. 2023 Sep;26(9):1487-1488. doi: 10.1038/s41593-023-01417-1. PMID: 37620444.
- Jorfi M*, Park J, Hall CK, Lin CJ, Chen M, von Maydell D, Kruskop JM, Kang B, Choi Y, Prokopenko D, Irimia D, Kim DY*, Tanzi RE*. Infiltrating CD8+ T cells exacerbate Alzheimer's disease pathology in a 3D human neuroimmune axis model. Nat Neurosci. 2023 Sep;26(9):1489-1504. doi: 10.1038/s41593-023-01415-3. Epub 2023 Aug 24. PMID: 37620442.
- Jorfi M*, Maaser-Hecker A, Tanzi RE*. The neuroimmune axis of Alzheimer's disease. Genome Med. 2023 Jan 26;15(1):6. doi: 10.1186/s13073-023-01155-w. PMID: 36703235.
Open Positions
The Laboratory for Neuroimmune Engineering always welcomes inquiries from motivated postdoctoral fellows, graduate students, and research staff who are excited about neuroimmune engineering and neurodegeneration. Prospective PhD students interested in the lab should apply to the Harvard PhD Program in Biological and Biomedical Sciences (BBS) at https://bbsphd.hms.harvard.edu and can then discuss potential lab rotations after admission. Prospective postdocs and research staff are encouraged to email Dr. Jorfi with a CV and a brief statement of research interests describing how their background connects to the lab’s work. We also consider visiting graduate students and research interns on a case-by-case basis; interested candidates should briefly outline their proposed dates, funding source, and fit with ongoing projects in their initial email.