Meet the Expert: Lindsey James

Dr. James’ lab is creating novel molecules to combat cancers and HIV

Story and photo by Kate Slate | Published June 6, 2023

Lindsey James sits at her desk

Many of the faculty of the UNC Eshelman School of Pharmacy are known as national or international experts in their field. Our Meet the Expert series introduces you to these extraordinary researchers, teachers, and leaders.

Lindsey James, PhD ‘10, is the Director of Chemical Biology at the Center for Integrative Chemical Biology and Drug Discovery at the UNC Eshelman School of Pharmacy, where she also serves as an Assistant Professor in the Division of Chemical Biology and Medicinal Chemistry. Lindsey studies chromatin reader proteins –  proteins responsible for the recognition of post-translational modifications on histones – by creating molecules that block their function. To her kids, she’s a scientist. To the pharmaceutical community, she’s an invaluable researcher whose work benefits multiple disciplines.

Reader proteins, Lindsey explains, regulate the expression of certain genes. When they are misregulated, they can lead to inappropriate gene expression and contribute to diseases such as cancer. Lindsey and students in her lab create molecules that block the interaction between reader proteins and their substrates. By conducting biochemical and cellular assays, her lab assesses their molecules in the context of various diseases and the biological consequences of introducing their compounds to a complex cellular mixture. “Are we preventing cell growth or encouraging proliferation?” is a question Lindsey and her lab continually explore.

While Lindsey focuses on creating well characterized, potent and selective molecules, once developed, they’re utilized in various capacities to help understand disease mechanisms and validate new targets for drug discovery. In the case of cancer, Lindsey explains, her molecules are often used as a therapeutic strategy to try to prevent the growth of cancer cells or tumors.

In 2020, Lindsey received funding from the Eshelman Institute for Innovation to develop molecules against a reader protein involved in multiple myeloma. Results have been successful to date and, given the high impact potential of this work, the Eshelman Institute granted Lindsey follow-on funding to continue development.

Cancer is not the only disease state Lindsey’s lab aims to probe. “We want to use our molecules in as many different biological applications as possible to better understand where targeting these proteins might be beneficial,” says Lindsey.

One realm where her molecules have been evaluated is at the HIV Cure Center. Here, they are interested in blocking the function of reader proteins that contribute to viral latency.

“The reason HIV is persistent for someone’s life is that there’s a population of virus that remains dormant and often undetectable, but it can turn on and start to replicate at any time,” Lindsey explains. “If you’re able to intentionally turn on the virus by inhibiting some of the proteins that contribute to latency and then eliminate it, you might be able to remove all of the virus.”

The eventual goal, Lindsey says, is to direct their preliminary findings toward the pharmaceutical industry. That way, the molecules she and her team have crafted and studied can be used to validate new drug targets and potentially translate into compounds of therapeutic value.

This vision of bringing impact to patients may begin in Lindsey’s lab, but she recognizes it will take a whole community to realize. “Drug discovery is very, very collaborative,” she notes. “and collaborative science is something I’ve tried to embrace, because I don’t think you can do things like this on your own.”