My laboratory has broad research interest in areas of complement system and its impact in the induction of immune inflammation in rare genetic, lysosomal storage, cancer and neurodegenerative diseases. Using multiple mouse models and human specimens, my laboratory is discovering the exact mechanism by which complement activation fuels innate and adaptive immune inflammation and spark tissue destruction in Gaucher, Hunter, Fabry, Sandhoff, Tay-Sachs, Niemann-Pick, cancer and Parkinson's diseases.
I have a proven record of innovative and productive research projects which are patented (e.g., 1) Methods and compositions for treatment of Gaucher disease via modulation of C5a receptor; WO 2017/048495; PCT/US2016/049237, 2) Methods and compositions for treatment of Parkinson's disease; Patent Serial No. 62/857,972, 3) Methods and compositions for treatment of Hunter's syndrome; Patent Serial No 62/618,185) and published in high-impact, peer-reviewed journals including the Journal of Clinical Investigation (2006), the Journal of Experimental Medicine (2007), Cellular Microbiology (2010), Nature Medicine (2012), Nature (2017), Seminars in Immunology (2018), and the Journal of Immunology (2019).
I am the first researcher to discover the immune complexes of glucosylceramide (GC) specific IgG2a/c autoantibodies in experimental and clinical Gaucher's disease, which induced massive complement activation and C5a generation. I found that C5a-mediated activation of its cognate C5aR1 alters the balance between GC formation and degradation, thereby accumulating excess GC leading to inflammation in visceral tissues in experimental and clinical Gaucher's disease (Nature 2017). Before this study, the molecular process that connects GC accumulation to inflammation was unknown, as was the role of inflammation in disease development. We are testing the C5a-C5aR blocking reagents in multiple mouse models and human lysosomal storage diseases. We are researching these compounds as a novel adjunctive therapeutic approach in humans with Gaucher disease and as a possible therapy for other lysosomal storage and neurodegenerative diseases.
I am honored to have participated in many research studies and to have received several awards and honors, including:
PhD: Sanjay Gandhi Post Graduate Institute of Medical Sciences, India, 2003.
Post Doc: Molecular Medicine Program, Mayo Clinic, Rochester, MN; Division of Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2004-2008.
Clinical immunology (e.g. complement, cytokines, chemokines, innate and adaptive immunity); genetics; lysosomal storage diseases, (e.g. Gaucher, Fabry, Tay-Sachs, Sandhoff, Niemann-Pick, Farbar, Krabbe, metachromatic leukodystrophy, Wolmen, mucopolysaccharidoses); neurodegenerative disorders (e.g. Parkinson's and Alzheimer's diseases)
Lipid arbitrated autoantibodies, complement activation products, and cytokines comebacks in several lysosomal storage and rare genetic diseases.
Human Genetics
Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms. International Journal of Molecular Sciences. 2024; 25:12252.
Immunological harmony: the dynamic influence of cellular and humoral immunity on pregnancy success. 2024; 1:2.
Targeting the Complement-Sphingolipid System in COVID-19 and Gaucher Diseases: Evidence for a New Treatment Strategy. International Journal of Molecular Sciences. 2022; 23:14340.
C-X-C Motif Chemokine Ligand 9 and Its CXCR3 Receptor Are the Salt and Pepper for T Cells Trafficking in a Mouse Model of Gaucher Disease. International Journal of Molecular Sciences. 2021; 22:12712.
Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease. Frontiers in Neurology. 2021; 12:636139.
Hypoxia-induced Pulmonary Hypertension in Different Mouse Strains: Relation to Transcriptome. American Journal of Respiratory Cell and Molecular Biology. 2019; 60:106-116.
Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease. Nature. 2017; 543:108-112.
Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of FcγRIIB and dectin-1. Nature Medicine. 2012; 18:1401-1406.
An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD). Human Molecular Genetics. 2010; 19:4694-4704.
Staphylococcal complement evasion by various convertase-blocking molecules. The Journal of Experimental Medicine. 2007; 204:2461-2471.
Manoj K. Pandey, PhD6/29/2019