Versiti - Joshua Muia, PhD | Versiti Blood Research Institute
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Joshua

Muia, PhD

Associate Investigator

Thrombosis and Hemostasis

Associate Investigator

Assistant Professor
Department of Biochemistry, Medical College of Wisconsin

Education and Training

Postdoctoral Training
Postdoctoral Research Associate, Washington University School of Medicine

Doctoral Training
Doctor of Philosophy, Western Michigan University

Contact
Email jmuia@Versiti.org
Social LinkedIn
Links MyNCBI
  MCW
  ResearchGate

Research Interests

My research interests include Metalloproteases (mainly the ADAMTS family) that are involved in the pathogenesis of cardiovascular disease, ADAMTS13 testing in Thrombotic Thrombocytopenia Purpura (TTP), and the role of von Willebrand factor (VWF) in thrombotic/bleeding disorders. I am also interested in developing and optimizing fluorogenic substrates for enzymes of clinical significance.

Major Projects Being Pursued

  1. Structural and Functional Studies of ADAMTS13
  2. Vascular Biology and Pathophysiology of von Willebrand factor
  3. Role of Proatherogenic Metalloprotease ADAMTS7 in Coronary Artery Disease.
  4. Clinical trials: TTP, Sepsis, and Von Willebrand disease

Techniques and Approaches in the Lab

  • Recombinant DNA Technology
  • Synthetic Biology
  • FRET-Based Assays
  • Protein substrate identification techniques: Yeast two-hybrid, proximity labeling, proteomics
  • Protein-protein interactions (Biolayer interferometry, Surface Plasmon Resonance, Co-IP)
  • Animal models

Grant Support

NIGMS  1R35 GM142926 - Maximizing Investigators' Research Award (MIRA) (R35)- Investigating the regulation and substrate processing of ADAMTS13 and ADAMTS7 metalloproteases. Role: PI (2021-2026)

Lab Team

Constance Kwas
Senior Research Technologist

Jeremy Mattson
Senior Research Technologist

Thomas Momanyi
Graduate student

Selected Publications

  1. Barton, C., Anderson, A., Miranda., J., Terrell, D., Hovinga, J., Vesely, S., George, J., and Muia, J. Cattle-FRETS71, a Novel Fluorogenic Substrate with Broad Applicability in Characterizing ADAMTS13 Properties and Function. J Thromb Haemost. 2023; 21: 3393- 3401. doi 10.1016/j.jtha.2023.08.016
  2. Mackie, I., Mancini, I., Muia, J., Kremer Hovinga, J., Nair, S., Machin, S., and Baker, R. (2020). International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of ADAMTS13. Int J Lab Hematol. 2020:685-696.. doi: 10.1111/ijlh.13295.
  3. Zwicker, J., Muia, J., Dolatshahi, L., Westfield, L., Nieters, P., Rodrigues, A., Antun, G., Metjian, A., and Sadler, J. E. Adjuvant low-dose rituximab and plasma exchange for acquired TTP, Blood 2019, in the press, https://doi.org/10.1182/blood-2018-99-113677.
  4. Zhu, J., Muia, J., Deforche, L., Vanhoorelbeke, K. and Tolia, N.H., Sadler, J. E. The Hunt for the "Minimal" Structure of a Functional ADAMTS13: Study of Deletion Mutations of ADAMTS13 By Small-Angle X-Ray Scattering, Blood 2019; 133:1909-1918. PMCID: PMC6484386
  5. Muia, J., Zhu, J., Garima, G., Westfield, L. A., Greco, S., Deforche, L., Vanhoorelbeke, K., and Sadler, J. E. Phylogenetic Analysis Identifies a Subset of ADAMTS13 Domains That Are Highly Conserved and Essential for Allosteric Regulation, Blood 2019; 133:1899-1908. PMCID: PMC6484387
  6. Muia, J., and Catarina Casari. Reflections on scientific collaboration between basic researchers and clinicians. J Thromb Haemost 2016; 14:1905–7. (See the editorial commentary “The transcendental scientist.”)
  7. Muia, J.*, Zhu, J.*, Gupta, G., Haberichter, S.L., Friedman, K.D., Feys, H., Vanhoorelbeke, K., Westfield, L.A., Roth, R., Tolia, N.H., Heuser, J.E., and J. Evan Sadler. Allosteric Activation of ADAMTS13 by Von Willebrand Factor. Proc Natl Acad Sci U S A. 2014; 111(52):18584-18589. PMCID: PMC4284596
  8. Muia, J., Gao, W., Haberichter, S. L., Dolatshahi, L., Zhu, J., Westfield, L. A., Covill, S. C., Friedman, K. D., and Sadler, J. E. An Optimized Fluorogenic ADAMTS13 Assay with Increased Sensitivity for the Investigation of Patients with Thrombotic Thrombocytopenic Purpura, J Thromb Haemost, 2013; 11:1511-8. PMCID: PMC3807872