Dighe, Abhijit S.
Primary Appointment
Assistant Professor, Genome Sciences
Contact Information
Telephone: 4342432598
Email: asd2n@virginia.edu
Research Interests
Genome Sciences
Research Description
My research interest in last 15 years has been the biology of skeletal stem cells - identification of stem cells using surface receptors, signaling pathways governing differentiation of stem cells, role of host immune response in stem cells mediated bone formation and stem cells therapy for treatment of bone diseases as well as for bone regeneration applications. I also have keen interest in genetics. In my post-doctoral studies, I used QTL mapping and generation of congenic mice to show that the host genetic background, particularly the MHC genes, control the resistance mechanisms against virus infection which involves innate immune response. Transfer of H-2k locus alone from the chromosome 17 of a resistant mouse strain to a susceptible mouse strain having H-2b MHC haplotype was sufficient to confer resistance in the congenic mouse model. We found that this involves activation of NK cell into CD3-NK1.1+IFN-γ+ phenotype. I started working on adult stem cells in 2008. We showed that stem cells are not immunoprivileged and balance between Th1 and Th2 immune response governs their bone forming ability. We have also worked extensively on stem cells signaling pathways and have shown that co-activation of VEGF signaling pathway is necessary for stem cells to respond optimally to BMP-stimulus, through mechanism involving p38 mediated phosphorylation of osterix. In recent years, I am intrigued to find that stem cells possess distinct sub-populations displaying varying degrees of expression of surface receptors and BMP-responsiveness and am curious to find if this is genetically controlled and how this relates to bone phenotypes. Currently we are investigating role of genetic background in the context of differentiation of human bone marrow derived mesenchymal stem cells (MSCs) using RNAseq and scRNAseq. Our goal is to collect ~400 human bone marrow aspirates, isolate MSCs from individual donors, perform genotyping of MSCs, study differentiation of MSCs into osteogenic lineage under different stimuli to understand role of 1300 SNPs known to regulate bone mineral density (BMD) in humans. The eQTLs identified in MSCs will elucidate how genetic variation at SNPs controls functions of MSCs thereby regulating bone phenotypes in humans. Current funding available: NIH R01 AR086161 Farber/Dighe (MPI) 08/15/2025 – 07/31/2030 Leveraging Context-Specific eQTL to Inform BMD GWAS