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Integrative Structural Biology Lab

Structural biology is used to determine the shape of molecules at atomic resolution. This allows us to understand exactly how disease mutations affect proteins and how we can correct them. An important goal in the lab is to understand the structure of Calpain-5 (CAPN5), a calcium-activated regulatory cysteine protease that is expressed throughout the central nervous system and retina. Mutations in the catalytic core of CAPN5 make it hyperactive and cause Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV; OMIM#193235), a severe, blinding eye disease. Structural studies of CAPN5 ADNIV disease mutants will inform how these mutations alter CAPN5 structure and function. Our laboratory is using x-ray crystallography and other biophysical techniques (small angle x-ray scattering, dynamic light scattering, cryo-EM, and fluorescence assays) to study the structural mechanisms of CAPN5 activation.

The lab also uses molecular modeling to study disease-causing mutations. With the rapidly-reducing costs of whole genome and exome sequencing, clinical genomic testing is being increasingly applied in the identification of pathogenic disease variants in patients. New sequence variants are often identified, but many are classified as variants of uncertain significance (VUS) due to the lack of functional assays to study their effects. Molecular modeling of protein structures can provide information at the atomic level and help to predict the pathogenicity of novel mutations by placing variants of uncertain significance in the context of the patient’s disease, pathophysiology, and protein function. Our team collaborates with clinicians and researchers around the world to model novel disease variants and better understand their patients’ disease. Please contact us for a consultation or collaboration. 


Small-angle x-ray scattering (SAXS) is a powerful, alternative tool to x-ray crystallography and can be used to obtain structural information on proteins in the absence of a crystal structure.
Structure-based drug design for inherited eye diseases.
Predicting the effects of disease mutations using structural bioinformatics.

We are using x-ray crystallography to understand the structure of Calpain-5 (CAPN5), a calcium-activated regulatory cysteine protease that is expressed throughout the central nervous system a

Oue research team purifies proteins for crystallography and enzymatic assays at the Macromolecular Structure Knowledge Center (MSKC).


Nov 4 2022 | Posted In: 20/20 Blog
Sep 27 2022 | Posted In: 20/20 Blog
San Francisco, CA —Mahajan lab postdoctoral fellows Young Joo Sun Ph.D. and David Dennis Ph.D. attended the inaugural Chemical Biology Symposium hosted by UCSF’s Quantitative Biosciences Institute, which had been delayed by COVID.
Sep 30 2021 | Posted In: 20/20 Blog
Apr 4 2021 | Posted In: 20/20 Blog, Awards
Palo Alto, CA —Young Joo Sun Ph.D., postdoctoral fellow in the Mahajan Lab, received a grant from the Brightfocus Foundation to study a key protein involved in macular degeneration.


Expanding the phenotype of TTLL5-associated retinal dystrophy: a case series., Oh, Jin Kyun, Del Valle José G. Vargas, de Carvalho Jose Ronaldo Li, Sun Young Joo, Levi Sarah R., Ryu Joseph, Yang Jing, Nagasaki Takayuki, Emanuelli Andres, Rasool Nailyn, et al. , Orphanet J Rare Dis, 2022 04 01, Volume 17, Issue 1, p.146, (2022)
Calpains as mechanistic drivers and therapeutic targets for ocular disease., Vu, Jennifer T., Wang Elena, Wu Jolan, Sun Young Joo, Velez Gabriel, Bassuk Alexander G., Lee Soo Hyeon, and Mahajan Vinit B. , Trends Mol Med, 2022 08, Volume 28, Issue 8, p.644-661, (2022)
Structure-based phylogeny identifies Avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice., Sun, Young Joo, Velez Gabriel, Parsons Dylan E., Li Kun, Ortiz Miguel E., Sharma Shaunik, McCray Paul B., Bassuk Alexander G., and Mahajan Vinit B. , J Clin Invest, 2021 Apr 12, (2021)
Peptidomimetics Therapeutics for Retinal Disease., Parsons, Dylan E., Lee Soo Hyeon, Sun Young Joo, Velez Gabriel, Bassuk Alexander G., Smith Mark, and Mahajan Vinit B. , Biomolecules, 2021 Feb 24, Volume 11, Issue 3, (2021)
Structural Insights into the Unique Activation Mechanisms of a Non-classical Calpain and Its Disease-Causing Variants., Velez, Gabriel, Sun Young Joo, Khan Saif, Yang Jing, Herrmann Jonathan, Chemudupati Teja, MacLaren Robert E., Gakhar Lokesh, Wakatsuki Soichi, Bassuk Alexander G., et al. , Cell Rep, 2020 Jan 21, Volume 30, Issue 3, p.881-892.e5, (2020)
Novel REEP6 gene mutation associated with autosomal recessive retinitis pigmentosa., Y., Lin, C.L. Xu, G. Velez, J. Yang, A.J. Tanaka, M.P. Breazzano, V.B. Mahajan, J.R. Sparrow, and S.H. Tsang , Doc Ophthalmol. 2020 Feb;140(1):67-75. doi: 10.1007/s10633-019-09719-1. Epub 2019 Sep 19., (2020)