Dmitri Ivanov, Ph.D.
In our research, we are trying to understand how interactions between biological molecules enable their function. Our primary focus is on innate antiviral immunity and the proteins that protect us against retroviral infections. Understanding how our antiviral defenses work, and how HIV-1 is able to penetrate them, may open novel avenues for treatment and possible cures for this deadly infection.
For example, TRIM5alpha is an immune factor that protects rhesus macaques against HIV infection, but the virus evades the human variant of TRIM5alpha. We investigate how TRIM5alpha proteins block retroviral replication, why the human version is not active against HIV and whether anything could potentially be done about it.
SAMHD1 forms another line of antiretroviral defenses, and its activity determines which non-cycling immune cells become infected by HIV-1. We want to understand the mechanism of SAMHD1 immune function and how it may contribute to HIV latency, one of the key remaining challenges in our search for the cure.
Drug discovery is another theme of our research. We are interested in identifying and optimizing small molecules with immunomodulatory or anti-cancer activities. Our cancer-related targets include DNA repair nucleases XPF/ERCC1 and TREX2, and for modulation of immune responses we target TREX1 and SAMHD1.
To gain mechanistic insight we use NMR, X-ray crystallography, mass spectrometry, fluorescence-based assays, and many other experimental tools from the powerful arsenal of modern biochemistry and structural biology.
Related Diseases: HIV/AIDS and Cancer
Techniques: NMR, X-ray crystallography, mass spectrometry, fluorescence-based assays, etc.
Laboratory Website: https://ivanov-laboratory.org/
Structural Biology and Biophysics -
Brandeis University Waltham , MA
St. Petersburg State University St. Petersburg , Russia
Northeastern University Boston , MA
Postdoctoral Training -
Structural Biology -
Children's Hospital Boston Boston , MA
Postdoctoral Training -
Biophysics and Structural Biology -
Harvard Medical School Boston , MA
Wang Z, Bhattacharya A, Ivanov DN. Identification of Small-Molecule Inhibitors of the HuR/RNA Interaction Using a Fluorescence Polarization Screening Assay Followed by NMR Validation PLoS One 2015 Sep;10(9):0138780-0138780.
Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, Demeler B, Pornillos O, Ganser-Pornillos BK, Diaz-Griffero F, Ivanov DN, Yeager M. Structural basis of HIV-1 capsid recognition by PF74 and CPSF6 Proc Natl Acad Sci U S A 2014 Dec;111(52):18625-18630.
Kovalskyy DB, Ivanov DN. Recognition of the HIV capsid by the TRIM5a restriction factor is mediated by a subset of pre-existing conformations of the TRIM5a SPRY domain Biochemistry 2014 Mar;53(9):1466-1476.