A photo of Manoj Pandey.

Manoj K. Pandey, PhD


  • Member, Division of Human Genetics
  • Assistant Professor, UC Department of Pediatrics

About

Biography

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:

  • 2013 Research work entitled "C5a mediated increases of CD40 and CD40L molecules on dendritic and T cells are critical to Th1-Th17 mediated inflammation in Gaucher disease model," selected for platform presentations for the 9th annual World Symposiums on Lysosomal Storage Diseases at Orlando, FL
  • 2014 Research work entitled "Gaucher disease: Glucosylceramide - mediated TLR4 - MyD88 induction cause enhanced CXCL13 secretion and increased B cell trafficking in a mouse model," selected for platform presentations for the 10th annual World Symposiums on Lysosomal Storage Diseases organized by World Symposia Ltd, at San Diego, CA
  • 2015 Research work entitled "Glucosylceramide induced complement activation triggers inflammation in Gaucher disease," selected for poster presentations for Immunology 2015 at New Orleans, LA
  • 2015 Selected for Early Career Faculty Travel Grant awards by the American Association of Immunologists, Rockville, MD
  • 2015 Rare Disease Innovation Funding Award by Alexion Pharmaceuticals (Boston, MA, USA)
  • 2016 Research work entitled "Immune cells attack and neurodegeneration in Gaucher disease" and "Immune cells encounter with α- synuclein fuels neurodegeneration in Parkinson's disease," selected for platform presentations for the 12th annual World Symposiums on Lysosomal Storage Diseases organized by World Symposia Ltd, at San Diego, CA
  • 2016 Research work entitled "Immune cells encounter with α- synuclein fuels neurodegeneration in 'Parkinson's disease," selected for poster presentations for IMMUNOLOGY 2016 at Seattle, WA
  • 2016 Selected for Early Career Faculty Travel Grant awards by the American Association of Immunologists, Rockville, MD
  • 2016 Research work entitled "α-synuclein collaboration with immunological villains.” Selected for platform presentations for Annual Immunology Retreat at Columbus, OH
  • 2016 Research work entitled "C5a drives glucosylceramide accumulation and tissue inflammation in Gaucher disease," selected for Platform presentation for XXVI International Complement Workshop at Kanazawa, Japan
  • 2017 Research work entitled "Glucosylceramide partnership with immunological villain in Gaucher disease" and "Complement drives neurodegeneration in Gaucher disease," selected for platform presentations for the 13th annual World Symposiums on Lysosomal Storage Diseases organized by World Symposia Ltd, at San Diego, CA
  • 2017 Rare Disease Innovation Funding Award by Alexion Pharmaceuticals (Boston, MA, U.S.)
  • 2017 Research work entitled "Complement drives neurodegeneration in Gaucher disease," selected for poster presentations for Immunology 2017 at Washington, DC
  • 2017 Selected for Early Career Faculty Travel Grant awards by the American Association of Immunologists, Rockville, MD
  • 2018 Just in Time Core Usage Funding Award by the Center for Clinical and Translational Science, University of Cincinnati (Cincinnati, OH, U.S.)
  • 2018 Research work entitled "Complement 5a galvanizes immune inflammation in Hunter syndrome," selected for poster presentations for Immunology 2018 at Washington, DC
  • 2018 Selected for Early Career Faculty Travel Grant awards in 2018 by the American Association of Immunologists, Rockville, MD
  • 2018 Alexion Discovery Partnerships Funding Award by Alexion Pharmaceuticals (Boston, MA, USA)
  • 2018 Research work entitled "Dendritic cells, CD4+ T cells, and a synuclein triangle fuels neuroinflammation in Parkinson's disease," selected for poster presentation for the 70th American Academy of Neurology Annual Meeting organized by the American Academy of Neurology (AAN) at Los Angeles, CA
  • 2019 Research work entitled "Complement activation causes oncogene expression in Gaucher disease," selected for poster presentations for Immunology 2019 at San Diego, CA
  • 2019 Selected for Early Career Faculty Travel Grant awards in 2019 by the American Association of Immunologists, Rockville MD
  • 2019 Parkinson Research Funding Award by Michael J. Fox Foundation (New York, NY, US)
  • 2019 Research Innovation/Pilot Funding Award by Cincinnati Children's Research Foundation (Cincinnati, OH, US)
  • 2020 Selected for Early Career Faculty Travel Grant awards in 2020 by the American Association of Immunologists, Rockville MD
  • 2021 Selected for Early Career Faculty Travel Grant awards in 2021 by the American Association of Immunologists, Rockville MD
  • 2021 Million Dollar Bike Ride Research Program Award by Orphan Disease Center, University of Pennsylvania (Philadelphia, PA)

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.

Interests

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)

Interests

Lipid arbitrated autoantibodies, complement activation products, and cytokines comebacks in several lysosomal storage and rare genetic diseases.

Research Areas

Human Genetics

Publications

Selected

Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms. Magnusen, AF; Pandey, MK. International Journal of Molecular Sciences. 2024; 25:12252.

Selected

Immunological harmony: the dynamic influence of cellular and humoral immunity on pregnancy success. Pandey, MK. 2024; 1:2.

Selected

Targeting the Complement-Sphingolipid System in COVID-19 and Gaucher Diseases: Evidence for a New Treatment Strategy. Trivedi, VS; Magnusen, AF; Rani, R; Marsili, L; Slavotinek, AM; Prows, DR; Hopkin, RJ; McKay, MA; Pandey, MK. International Journal of Molecular Sciences. 2022; 23:14340.

Selected

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. Magnusen, AF; Rani, R; McKay, MA; Hatton, SL; Nyamajenjere, TC; Magnusen, DN A; Köhl, J; Grabowski, GA; Pandey, MK. International Journal of Molecular Sciences. 2021; 22:12712.

Selected

Genetic Defects and Pro-inflammatory Cytokines in Parkinson's Disease. Magnusen, AF; Hatton, SL; Rani, R; Pandey, MK. Frontiers in Neurology. 2021; 12:636139.

Selected

Hypoxia-induced Pulmonary Hypertension in Different Mouse Strains: Relation to Transcriptome. Ikeda, KT; Hale, PT; Pauciulo, MW; Dasgupta, N; Pastura, PA; Le Cras, TD; Pandey, MK; Nichols, WC. American Journal of Respiratory Cell and Molecular Biology. 2019; 60:106-116.

Selected

Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease. Pandey, MK; Burrow, TA; Rani, R; Martin, LJ; Witte, D; Setchell, KD; Mckay, MA; Magnusen, AF; Zhang, W; Liou, B; Koehl, J; Grabowski, GA. Nature. 2017; 543:108-112.

Selected

Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of FcγRIIB and dectin-1. Karsten, CM; Pandey, MK; Figge, J; Kilchenstein, R; Taylor, PR; Rosas, M; McDonald, JU; Orr, SJ; Berger, M; Petzold, D; Finkelman, FD; Brown, GD; Ehlers, M; Koehl, J. Nature Medicine. 2012; 18:1401-1406.

Selected

An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD). Fritsche, LG; Lauer, N; Hartmann, A; Stippa, S; Keilhauer, CN; Oppermann, M; Pandey, MK; Koehl, J; Zipfel, PF; Weber, BH F; Skerka, C. Human Molecular Genetics. 2010; 19:4694-4704.

Selected

Staphylococcal complement evasion by various convertase-blocking molecules. Jongerius, I; Kohl, J; Pandey, MK; Ruyken, M; van Kessel, KP M; van Strijp, JA G; Rooijakkers, SH M. The Journal of Experimental Medicine. 2007; 204:2461-2471.

From the Blog

Targeting C5ar1 Shows Early Promise as New Therapy for Gaucher Disease
Genomics and Development

Targeting C5ar1 Shows Early Promise as New Therapy for Gaucher Disease

Manoj K. Pandey, PhD6/29/2019