- Chem Sci 402B
- Associate Professor, Chemistry
- Director, Graduate Programs
- PhD, Jawaharlal Nehru University, New Delhi, India
Dr. Tiwari is a broadly trained protein chemist and cell biologist. His research is in the area of ‘protein aggregation diseases’ with special emphasis on age related neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), prion diseases, and Huntington’s disease (HD). In these diseases, misfolded proteins are observed as intracellular or extracellular aggregates at the end stage of the disease. However, the underlying mechanism(s) by which these aggregated proteins impair cellular function(s) and cause toxicity is not clear and is a subject of intense debate. Tiwari laboratory is applying unique biochemical and biophysical approaches (including novel fluorescent molecules) to characterize the inherent vulnerability and instability of proteins associated with different neurodegenerative diseases. The long-term research goal of Tiwari lab is to understand consequences of protein misfolding and aggregation in vitro and how it relates to misfolding and aggregation in vivo, and its implication for neurodegenerative diseases.
Links of Interest
- Identify experimental conditions that can generate diverse aggregated protein structures from the same proteins.
- Develop novel tools and techniques to differentiate amongst the varied aggregated species of proteins.
- Understand the relationship between aggregated protein species and its associated cellular toxicity.
- Zhang J, Li C, Dutta C, Fang M, Zhang S, Tiwari A*, Werner T, Luo F-T, Liu H. A novel near-infrared fluorescent probe for sensitive detection of β-galactosidase in living cells. Analytica Chimica Acta (2017) 968:97-104.
- Zhang J, Yang M, Mazi W, Adhikari K, Fang M, Xie F, Valenzano L, Tiwari A*, Luo F-T, and Liu H. Unusual Fluorescent Responses of Morpholine-functionalized Fluorescent Probes to pH via Manipulation of BODIPY’s HOMO and LUMO Energy Orbitals for Intracellular pH Detection. ACS Sensors (2016) 1(2):158-165.
- Dorh N, Zhu S, Dhungana KB, Pati R, Luo FT, Liu H, Tiwari A*. BODIPY-Based Fluorescent Probes for Sensing Protein Surface-Hydrophobicity. Sci Rep. (2015) 5:18337.
- Dutta C, Yang M, Long F, Shahbazian-Yassar R, and Tiwari A*. Preformed Seeds Modulate Native Insulin Aggregation Kinetics. J. Phys. Chem. B (2015) 119(49): 15089-15099.
- Yang M, Dutta C, and Tiwari A*. Disulfide-Bond Scrambling Promotes Amorphous Aggregates in Lysozyme and Bovine Serum Albumin. J. Phys. Chem. B (2015) 119(10): 3969-3981.
- Zhang J, Yang M, Li C, Dorh N, Xie F, Luo F-T, Tiwari A*, and Liu H. Near-infrared fluorescent probes based on piperazine-functionalized BODIPY dyes for sensitive detection of lysosomal pH. J Mater. Chem. B (2015) 3(10): 2173-2184
- Vegesna G, Janjanam J, Bi J, Luo F-T, Zhang J, Olds C, Tiwari A*, and Liu H. pH-activatable near-infrared fluorescent probes for detection of lysosomal pH inside living cells. J Mater. Chem. B (2014) 2(28): 4500-4508.
- Zhu S, Zhang J, Janjanam J, Bi J, Vegesna G, Tiwari A, Luo F-T, Wei J, and Liu H. Highly water-soluble, near-infrared emissive BODIPY polymeric dye bearing RGD peptide residues for cancer imaging. Analytica Chimica Acta. (2013) 758: 138-144.
- Tiwari A , Liba A, Sohn SH, Seetharaman SV, Bilsel O, Matthews CR, Hart PJ, Valentine JS, and Hayward LJ. Metal deficiency increases aberrant hydrophobicity of mutant superoxide dismutases that cause amyotrophic lateral sclerosis. J Biol Chem. (2009) 284(40):27746-27758.
- Tiwari A, Xu Z, and Hayward LJ. Aberrantly increased hydrophobicity shared by mutants of Cu/Zn superoxide dismutase in familial amyotrophic lateral sclerosis. J Biol Chem. (2005) 280(33): 29771-29779.
- Tiwari A and Hayward LJ. Familial ALS Mutants of Cu/Zn Superoxide Dismutase are Susceptible to Disulfide Reduction. J Biol Chem. (2003) 278(8): 5984-5992.
- 03/17/2017: “Protein instability, aggregation, and toxicity: Disulfide-bond integrity holds the key.” in Biological Sciences at Michigan Technological University, Houghton, MI.
- 03/15/2017: “Understanding the role of protein misfolding in neurodegenerative diseases.” “Tech Talks 2017” at Michigan Technological University, Houghton, MI.
- 01/14/2016: “Scrambling of Disulfide Bonds Promotes Insulin Aggregation and Toxicity”. 15th Annual Convention of the ISVPT on “Nutritional Pharmacology and Toxicology beyond Calories”. January 14-16, 2016. NDRI, Karnal, Haryana, INDIA.
- 03/10/2015: “Disulfide-Bond Scrambling Promotes Amorphous Aggregates in Proteins at Physiological pH”. Computational Science Campaign Meeting. March 10-11, 2015. Army Research Lab, Aberdeen Proving Ground, MD.
- 10/23/2014: “Amorphous Protein Aggregates at Physiological pH: Disulfide Bond Scrambling Holds the Key”. BRC Research Forum. October 22-23, 2014. The Biotechnology Research Center, MTU, Houghton, MI.
- 10/23/2012: “Protein Aggregation at Physiological pH: Is Disulfide Bond Integrity Key to Protein Stability?” Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL.
- 03/05/2012: “Novel fluorescent probes for mapping hydrophobic surface of proteins.” Tenth International Consortium on Superoxide Dismutase and Amyotrophic Lateral Sclerosis, March 4-5, 2012. University of Liverpool, Liverpool, UK.