Dmitri Ivanov, PhD

Associate Professor; CPRIT Scholar in Cancer Research; Director of NMR Core Faculty

Personal Statement:

In our lab we are trying to understand how physical interactions at protein interfaces determine biological outcomes. We are particularly interested in the macromolecular machinery of the innate antiviral immunity. We investigate how distinctive molecular patterns associated with infection are recognized by the innate immune system, and what defense mechanisms block viral replication within cells. Understanding how these defenses function and how viruses evade them may open novel avenues for treatment of viral infections, autoimmune diseases and cancer.

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Laboratory Website: https://ivanov-laboratory.org/

 


Education

B.Sc. Biophysics, St. Petersburg State University,
B.S. Physics, Northeastern University
Ph.D. Biophysics and Structural Biology, Brandeis University
Post Doctoral: Harvard Medical School

Research

Please, Visit our website for more information: https://ivanov-laboratory.org/

My laboratory is interested in 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 treating and possibly curing this deadly infection.

TRIM5alpha is an immune factor that protects rhesus macaques against HIV, but the virus evades the human variant of this restriction factor. 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.

We are also 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, high-throughput screening and many other experimental tools from the powerful arsenal of modern biochemistry and structural biology.

Publications

  • Wang Z, Bhattacharya A, White T, Buffone C, McCabe A, Nguyen LA, Shepard CN, Pardo S, Kim B, Weintraub ST, Demeler B, Diaz-Griffero F, Ivanov DN (2018) “Functionality of Redox-Active Cysteines Is Required for Restriction of Retroviral Replication by SAMHD1,” Cell Reports 24(4):815-823.

 

  • Wang Z, Bhattacharya A, Villacorta J, Diaz-Griffero F, Ivanov DN (2016) “Allosteric Activation of SAMHD1 Protein by Deoxynucleotide Triphosphate (dNTP)-dependent Tetramerization Requires dNTP Concentrations That Are Similar to dNTP Concentrations Observed in Cycling T Cells,” J Biol Chem. 291(41):21407-21413.

 

  • Bhattacharya A, Wang Z, White T, Buffone C, Nguyen LA, Shepard CN, Kim B, Demeler B, Diaz-Griffero F, Ivanov DN (2016) “Effects of T592 phosphomimetic mutations on tetramer stability and dNTPase activity of SAMHD1 can not explain the retroviral restriction defect,” Scientific Reports 6:31353.

 

  • Yudina Z, Roa A, Johnson R, Biris N, de Souza Aranha Vieira DA, Tsiperson V, Reszka N, Taylor AB, Hart PJ, Demeler B, Diaz-Griffero F, Ivanov DN (2015) “RING Dimerization Links Higher-Order Assembly of TRIM5a to Synthesis of K63-Linked Polyubiquitin,” Cell Reports 12(5):788-97.