Team Stem Cell and Organoid models in health and disease: Nuclear receptor signaling mechanisms
We investigate how liver X receptors (LXRs) and estrogen receptor beta (ERβ) regulate immune responses, cholesterol metabolism, and cellular differentiation, with a particular focus on their roles in neurodegeneration. Using stem cell biology and 3D organoid technologies, we replicate human physiology to explore disease mechanisms in a human-relevant context. Our work also examines lipid metabolism and nuclear receptor signaling in the progression of cancer and inflammatory conditions.
Our research integrates nuclear receptor biology with cutting-edge stem cell technologies to uncover disease mechanisms and develop innovative therapeutic strategies. A central focus is the application of organoid and organ-on-chip systems derived from stem cells to study nuclear receptor signaling in neurodegenerative diseases, cancer, and other conditions. These animal-free, human-relevant models allow us to dissect complex interactions and uncover developmental mechanisms underlying genetic disorders. By leveraging advanced tools such as gene editing, high-throughput omics, and multi-modal imaging, we aim to identify novel therapeutic targets and validate effective interventions.
Current projects
- High-throughput production and AI-based screening of organoids for label-free drug development assay VINNOVA
- Influence of Estrogen on Brain Insulin Resistance in Alzheimer’s disease
- LXR-ER crosstalk in neurodevelopment, neuroinflammation and neurodegenerative disorders
- Decoding Cancer’s Lipid Secrets with Oxysterols, LXRs, and Patient-Derived Organoids
- Complex in vitro models of reproductive system
Main collaborators
LXR and ER in health and disease
Jan-Åke Gustafsson, Prof., Karolinska Institute, Sweden and University of Houston, USA
Margaret Warner, Prof., University of Houston, USA
Organoid models in fertility preservation for young cancer survivors
Kenny Rodriguez-Wallberg, Prof., Karolinska University Hospital and ONKPAT, Karolinska Institute, Sweden
Super resolution and label-free imaging of 3D in vitro models
Balpreet S Ahluwalia, Prof., Arctic University of Tromso (UiT), Norway and Karolinska Institute, Sweden
PET tracer characterization in AD/PD brain organoids
Amit Kumar, PhD, Karolinska Institute, Sweden
Neurotoxicity in brain development
Kristina Pilipovic, Prof., Faculty of Medicine, University of Rijeka, Croatia
Selected Publications
Proof-of-Concept for Long-Term Human Endometrial Epithelial Organoids in Modeling Menstrual Cycle Responses.
Jiang Y, Palomares AR, Munoz P, Nalvarte I, Acharya G, Inzunza J, Varshney M, Rodriguez-Wallberg KA
Cells 2024 Nov;13(21):
Mapping reactive astrogliosis in Parkinson's brain with astroglial tracers BU99008 and Deprenyl: New insights from a multi-marker postmortem study.
Rocha FM, Roy A, Varshney M, Kumar A
Alzheimers Dement 2025 Feb;21(2):e14488
Loss of ERβ in Aging LXRαβ Knockout Mice Leads to Colitis.
Song X, Wu W, Dai Y, Warner M, Nalvarte I, Antonson P, Varshney M, Gustafsson JÅ
Int J Mol Sci 2023 Aug;24(15):
Generation of nonviral integration-free human iPS cell line KISCOi001-A from normal human fibroblasts, under defined xeno-free and feeder-free conditions.
Inzunza J, Arias-Fuenzalida J, Segura-Aguilar J, Nalvarte I, Varshney M
Stem Cell Res 2021 Mar;51():102193
Motor Function Deficits in the Estrogen Receptor Beta Knockout Mouse: Role on Excitatory Neurotransmission and Myelination in the Motor Cortex.
Varshney MK, Yu NY, Katayama S, Li X, Liu T, Wu WF, Töhönen V, Krjutškov K, Kere J, Fan X, Inzunza J, Gustafsson JÅ, Nalvarte I
Neuroendocrinology 2021 ;111(1-2):27-44
Role of estrogen receptor beta in neural differentiation of mouse embryonic stem cells.
Varshney MK, Inzunza J, Lupu D, Ganapathy V, Antonson P, Rüegg J, Nalvarte I, Gustafsson JÅ
Proc Natl Acad Sci U S A 2017 Nov;114(48):E10428-E10437