Hassane Mchaourab
Last active: 4/3/2018

Profile

Research in the Mchaourab Laboratory is focused on understanding the structural and dynamic basis of protein function with focus on proteins that are involved in diseases. Using spectroscopic approaches, our laboratory studies the molecular aspect of: protein aggregation diseases such as cataract, the widespread phenomenon of multidrug resistance in cancer and infectious diseases and more recently neurotransmitter transport across the synaptic cleft in collaboration with Aurelio Galli’s Laboratory. Lens aging, protein folding and Cataract: Small heat-shock proteins, including the major protein component in the lens alpha-crystallin, are molecular chaperones that help other proteins avoid aggregation. Protein aggregation is associated with many pathogenic conditions including alzheimer's diseases, mad cow disease and cataract. Our laboratory has pioneered novel assay to understand the mechanisms of both inherited and age-related cataract. We investigate small heat-shock proteins from various organisms and across the evolutionary spectrum. Multidrug resistance in Cancer: Active drug extrusion by multidrug transporters is one of four general mechanisms associated with the multidrug resistance phenomenon, a key problem in the treatment of bacterial and fungal infections and cancers. The overexpression of adenosine triphosphate binding cassette (ABC) transporters is the most frequent cause of resistance to cytotoxic agents. In addition, mutations in the genes encoding the 48 human ABC transporters are associated with diseases such as cystic fibrosis, Tangier disease and adrenoleukodystrophy. Our laboratory is investigating how these transporters work, a key step in the design of therapeutic strategies. Neurotransmitter transport: Chemical synapses are junctions at which electrical signals are relayed from one neuron to another via release of neurotransmitters such as dopamine, serotonin and norepinephrine. The process of clearing these molecules controls the magnitude and duration of synaptic signaling. Neurotransmitter transporters are integral membrane proteins that move neurotransmitter back into the neuronal terminal thus terminating signaling. In collaboration with the Galli laboratory at Vanderbilt, we are investigating the process of transport as well as its modulation by kinases. A future goal is to determine the structural basis of antidepressants, amphetamine and cocaine effects on the properties of these transporters.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Conformational cycle and ion-coupling mechanism of the Na+/hydantoin transporter Mhp1. Kazmier K, Sharma S, Islam SM, Roux B, Mchaourab HS (2014) Proc Natl Acad Sci U S A 111(41): 14752-7
    › Primary publication · 25267652 (PubMed) · PMC4205665 (PubMed Central)
  2. Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states. Dürr KL, Chen L, Stein RA, De Zorzi R, Folea IM, Walz T, Mchaourab HS, Gouaux E (2014) Cell 158(4): 778-792
    › Primary publication · 25109876 (PubMed) · PMC4263325 (PubMed Central)
  3. Conformational dynamics of the nucleotide binding domains and the power stroke of a heterodimeric ABC transporter. Mishra S, Verhalen B, Stein RA, Wen PC, Tajkhorshid E, Mchaourab HS (2014) Elife : e02740
    › Primary publication · 24837547 (PubMed) · PMC4046567 (PubMed Central)
  4. Conformational dynamics of ligand-dependent alternating access in LeuT. Kazmier K, Sharma S, Quick M, Islam SM, Roux B, Weinstein H, Javitch JA, McHaourab HS (2014) Nat Struct Mol Biol 21(5): 472-9
    › Primary publication · 24747939 (PubMed) · PMC4050370 (PubMed Central)
  5. Protonation drives the conformational switch in the multidrug transporter LmrP. Masureel M, Martens C, Stein RA, Mishra S, Ruysschaert JM, Mchaourab HS, Govaerts C (2014) Nat Chem Biol 10(2): 149-55
    › Primary publication · 24316739 (PubMed) · PMC4749020 (PubMed Central)
  6. Drosophila melanogaster: a novel animal model for the behavioral characterization of autism-associated mutations in the dopamine transporter gene. Hamilton PJ, Campbell NG, Sharma S, Erreger K, Hansen FH, Saunders C, Belovich AN, Sahai MA, Cook EH, Gether U, McHaourab HS, Matthies HJ, Sutcliffe JS, Galli A (2013) Mol Psychiatry 18(12): 1235
    › Primary publication · 24253181 (PubMed)
  7. De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder. Hamilton PJ, Campbell NG, Sharma S, Erreger K, Herborg Hansen F, Saunders C, Belovich AN, NIH ARRA Autism Sequencing Consortium, Sahai MA, Cook EH, Gether U, McHaourab HS, Matthies HJ, Sutcliffe JS, Galli A (2013) Mol Psychiatry 18(12): 1315-23
    › Primary publication · 23979605 (PubMed) · PMC4046646 (PubMed Central)
  8. Na⁺-substrate coupling in the multidrug antiporter norm probed with a spin-labeled substrate. Steed PR, Stein RA, Mishra S, Goodman MC, McHaourab HS (2013) Biochemistry 52(34): 5790-9
    › Primary publication · 23902581 (PubMed) · PMC3842230 (PubMed Central)
  9. On the origin of large flexibility of P-glycoprotein in the inward-facing state. Wen PC, Verhalen B, Wilkens S, Mchaourab HS, Tajkhorshid E (2013) J Biol Chem 288(26): 19211-20
    › Primary publication · 23658020 (PubMed) · PMC3696692 (PubMed Central)
  10. Structural refinement from restrained-ensemble simulations based on EPR/DEER data: application to T4 lysozyme. Islam SM, Stein RA, McHaourab HS, Roux B (2013) J Phys Chem B 117(17): 4740-54
    › Primary publication · 23510103 (PubMed) · PMC3684008 (PubMed Central)