The Kannan lab is focused on understanding the role of neuroinflammation in injury and repair in the juvenile brain and in developing targeted nanotherapies to enable normal brain development. Our translational lab focuses on bench to bedside development of novel dendrimer nanotherapies to modulate glial cells and injured neurons to attenuate injury and enable repair.
In collaboration with the Center for Nanomedicine, JHU Drug Discovery and Kennedy Krieger Institute we are developing novel nanotherapies that target glutamate, NAAG and kynurenine pathways in immune cells and glia in the brain for treatment of disorders such as cerebral palsy, autism, Rett syndrome and traumatic brain injury. Some of the therapies developed in our labs are now in clinical trials.
Our group has shown that maternal inflammation/infection leads to neuroinflammation in the neonatal brain leading to cerebral palsy as seen in children. We have also shown that targeting and modulating glial cells using dendrimer nanotherapies can attenuate the brain injury and lead to improvement in neurologic deficits in pre-clinical models of cerebral palsy and Rett syndrome.
Current projects include (1) Studying the role of NAAG and microglial activation in cerebellar development and cerebellar learning and targeting glutamate carboxypeptidase to attenuate cerebellar injury in cerebral palsy; (2) Dendrimer targeted therapies for Rett Syndrome with a focus on targeting glutaminase enzyme in glial cells and (3) Understanding the role of immune dysregulation and developing targeted therapies in traumatic brain injury, autism, cardiac arrest and mental health disorders.
Gusdon AM, Faraday N, Aita JS, Kumar S, Mehta I, Choi HA, Cleland JL, Robinson K, McCullough LD, Ng DK, Kannan RM, Kannan S. Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial. Sci Transl Med. 2022 Jul 20;14(654):eabo2652. doi: 10.1126/scitranslmed.abo2652. Epub 2022 Jul 20. PMID: 35857827. https://www.science.org/doi/10.1126/scitranslmed.abo2652?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Zhang Z, Lin YA, Kim SY, Su L, Liu J, Kannan RM, Kannan S. Systemic dendrimer-drug nanomedicines for long-term treatment of mild-moderate cerebral palsy in a rabbit model. J Neuroinflammation. 2020 Oct 25;17(1):319. doi: 10.1186/s12974-020-01984-1. PMID: 33100217; PMCID: PMC7586697.
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-020-01984-1
Nemeth CL , Tomlinson SN , Sharma R , Sharma A , Kannan S , Kannan RM , Fatemi A . Glial restricted precursor delivery of dendrimer N-acetylcysteine promotes migration and differentiation following transplant in mouse white matter injury model. Nanoscale. 2020 Aug 14;12(30):16063-16068. doi: 10.1039/c9nr10804a. Epub 2020 Jul 29. PMID: 32724988; PMCID: PMC7448752.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448752/
Zhang Z, Ishrat S, O'Bryan M, Klein B, Saraswati M, Robertson C, Kannan S. Pediatric Traumatic Brain Injury Causes Long-Term Deficits in Adult Hippocampal Neurogenesis and Cognition. J Neurotrauma. 2020 Jul 15;37(14):1656-1667. doi: 10.1089/neu.2019.6894. Epub 2020 Apr 17. PMID: 32079496.
Khoury ES, Sharma A, Ramireddy RR, Thomas AG, Alt J, Fowler A, Rais R, Tsukamoto T, Blue ME, Slusher B, Kannan S, Kannan RM. Dendrimer-conjugated glutaminase inhibitor selectively targets microglial glutaminase in a mouse model of Rett syndrome. Theranostics. 2020 Apr 27;10(13):5736-5748. doi: 10.7150/thno.41714. PMID: 32483415; PMCID: PMC7254984.
https://www.thno.org/v10p5736.htm
More publications at:
https://pubmed.ncbi.nlm.nih.gov/?term=Sujatha+Kannan&sort=pubdate
Sujatha Kannan, MD
Professor, Anesthesiology and Critical Care Medicine & Pediatrics
Vice Chair for Research, Anesthesiology and Critical Care Medicine
Richard Traystman Endowed Chair
Johns Hopkins University School of Medicine
Email: [email protected]