Katya Vinogradova

Organic chemists do not typically reach for a half liter of warm human blood when they start an experiment. But Katya Vinogradova is not a typical chemist. She is using organic chemistry know-how to tackle big questions in biology. To do that, Vinogradova has taken an unusual path. She honed her organic chemistry skill set as a PhD student in Stephen L. Buchwald’s lab at the Massachusetts Institute of Technology. After doing some bioconjugation chemistry as a graduate student, Vinogradova was inspired to delve into chemical biology. For her postdoc, she decided to map the reactive cysteines in all the proteins in human T cells. This is where her story gets gory: to get those proteins, Vinogradova had to isolate T cells from 500 mL of human blood.

The sanguine science paid off. She and her colleagues found that more than 3,400 cysteines in roughly 2,200 T-cell proteins can be tagged by small-molecule electrophiles. Tacking small molecules onto these cysteines could suppress aberrant T cells that cause autoimmune disorders or could activate T cells to attack cancers. The cysteines could also serve as anchors for an emerging class of drugs called protein degraders, which tag misbehaving proteins for destruction.

“Katya is a rare talent with expertise that spans mechanistic organic chemistry, chemical proteomics, and human immunology,” says Vinogradova’s postdoc mentor, Benjamin F. Cravatt of Scripps Research in California. “Add into the mix her fearless approach to research and highly collaborative spirit, and you have an exceptional young scientist poised to make a major impact in her independent career.”

Vinogradova got an early start on her career in chemistry. Thanks to a nudge from her mother (who is not a scientist but loves chemistry), Vinogradova attended the Moscow Chemical Lyceum, a specialized chemistry high school in Russia. At just 14 years old, Vinogradova started doing hands-on research in glycoconjugate chemistry.

But Vinogradova says her passion for chemistry really emerged during her undergraduate studies at the Higher Chemical College of the Russian Academy of Sciences. That’s when she fell in love with organometallic chemistry. “I liked how you could use rational design to come up with novel methods to create bonds that you couldn’t before,” she says. As an undergraduate, Vinogradova spent summers doing research at labs around the world, including the University of California, Santa Barbara; the California Institute of Technology; MIT; the University of Burgundy; and the Swiss Federal Institute of Technology (ETH), Zurich.

Research at a glance

Vinogradova uses electrophilic probe molecules to map amino acids, such as cysteine, in proteins in immune cells. The connection of a reactive cysteine and the electrophile is shown in red. These amino acids’ ability to react with the probes can change depending on whether the proteins are in a healthy or diseased state. Mapping those changes can suggest targets for new drugs.

Credit: Yang H. Ku/C&EN

In December 2020, Vinogradova opened her own lab, which is devoted to chemical proteomics and immunology, at Rockefeller University. She still uses small molecules to interrogate cysteines in proteins, but she’s hoping to map other amino acid residues too, including lysine and tyrosine. Because cysteine has been the main target for this type of mapping chemistry, using other residues to make these maps could open up new avenues in proteomics. Vinogradova also plans to study other types of cells, like macrophages, which are part of the immune system, and neuroglia, which are cells found in the brain and spinal cord. Her goal is to make discoveries that illuminate immunology and that might also lead to new therapies. “I like the basic side of science,” she says, “but I always like when there’s a path towards translational applications.”