Dr. Peter Vekilov

Bioactive materials

We focus on how bioactive materials form and how we can control and direct their growth. Our long-term goal is to advance the fundamental understanding of complex aggregation and crystallization pathways as a platform to design materials beneficial to humankind or suppress the growth of pathogenic structures

We dedicate our efforts to five major themes:

Molecular mechanisms of fibrillization and toxicity of amyloid b

Bioactive materials

We focus on how bioactive materials form and how we can control and direct their growth. Our long-term goal is to advance the fundamental understanding of complex aggregation and crystallization pathways as a platform to design materials beneficial to humankind or suppress the growth of pathogenic structures

We dedicate our efforts to five major themes:

Molecular mechanisms of fibrillization and toxicity of amyloid β

Amyloid fibrillization is a key step in Alzheimer’s disease pathogenesis. We test whether blocking fibril growth may be a pathway to suppressing the formation of amyloid aggregates that are toxic to the neurons in the brain. We combine thermodynamic, kinetic, and structural experiments at the single fibril level, all uniquely focused on events at the fibril tip. Besides their fundamental significance for mechanistic understanding of AD and other condensation diseases, the results of this novel approach may empower new strategies to search for potential AD drugs.

Nucleation of pharmaceutical crystals

Crystalline drugs offer the advantage of steady medication release rates. The recent discovery of nonclassical nucleation and growth pathways, in which our groups was a major player, has addressed a huge knowledge gap in understanding crystallization. These pathways involve two-step and multi-step nucleation hosted and assisted by clusters, dense liquids, and amorphous precursors. We systematically investigate nonclassical crystallization pathways. We establish new methodologies to control nucleation of organic and biological pharmaceutical compounds.

Polymorph control

A ubiquitous challenge for controlling crystallization stems from the multiple crystal structures that a compound can adopt. Polymorph transformations severely impact the design and manufacture of advanced crystalline materials. We experimentally test and validate methods  to control polymorph transitions. Using machine learning, we develop an innovative methodology to predict a priori crystal structures (polymorphs and solvates) and to control intercrystalline transformations.

Control organic crystal nucleation and growth

We integrate advanced experimental and theoretical approaches to close knowledge gaps on how foreign compounds impact the nucleation growth of organic semiconductor crystals. We develop a novel mechanism to control crystal nucleation that exploits the precursors embodying the nonclassical nucleation modes; nucleation that follows a classical pathway can only be coarsely promoted. We design a strategy to irreversibly inhibit crystal growth even after the inhibitor is removed from the growth medium by manipulating the interactions of inhibitors with crystal growth precursors and with step bunches on the crystal surface. We explore interactions between pairs of inhibitors mediated by the step structures and dynamics that lead to antagonistic, additive, or synergistic cooperativities.

Hematin crystallization and malaria parasites.

During their intraerythrocytic lifecycle, malaria parasites catabolize hemoglobin and hematin, which is extremely toxic to the parasite in its free state. The main mechanism of detoxification implemented by the parasite is hematin sequestration as non-toxic, crystalline hemozoin. Hematin crystallization has been identified as the target of several antimalarial drugs, which are hypothesized to increase the concentration of free hematin within the parasite to toxic levels. The current first line of antimalarial defense are artemisinin–based combination therapies, but resistance to them is emerging. To combat the parasites’ ART resistance we put forth a covalent heme-artemisinin adduct and explore the mechanisms by which this adduct suppresses hematin crystallization and kill the malaria parasites.