Kierra Franklin, a fifth-year Ph.D. student at the Wallace H. Coulter Department of Biomedical Engineering, was recently awarded the 2024 Gina M. Finzi Memorial Student Summer Fellowship. This fellowship supports her research into Systemic Lupus Erythematosus (SLE), an autoimmune disease that disproportionately affects women, and particularly impacts minorities.

Franklin’s journey into this research is both scientific and personal. Since completing her undergraduate degree in chemical engineering at Stanford University, her passion lay in drug development, with a focus on diseases that are understudied or have few treatment options. In Asst. Prof. Karmella Haynes' lab, Franklin’s early work centered on engineering epigenetic proteins and their interactions. 

But it wasn’t until her third year of graduate school, when her mother experienced a lupus flare-up, that Franklin considered making lupus a focus of her research.

"It’s a slight deviation from my current work that I’ve been working on in grad school," Franklin said. "But it’s a disease that’s impacted a lot of people in my life, including my mom. So, I’m super passionate about this work."

The Finzi Fellowship, awarded by the Lupus Foundation of America, supports young researchers like Franklin who are dedicated to advancing a better understanding of lupus. Over the course of 10 weeks, Franklin will probe the genetic function of a disease that remains misunderstood in many ways.

Systemic lupus disproportionately affects women, with 90% of diagnosed cases occurring in women. Among them, minority women face an even greater burden from the disease. Yet, until recently, no drugs had been specifically developed for lupus patients. Instead, existing treatments are pulled from therapies designed for other conditions.

“Seeing the impact it can have on the people around me, that’s what inspired me to start learning more about this disease, to see if there’s anything I could study that’s in my wheelhouse and could be effective or useful," said Franklin.

To be selected for the fellowship, Franklin’s research proposal had to undergo a review–first from a panel of experts in the lupus field and then from lupus patients as well. For Franklin, this recognition was deeply meaningful, and not just because it validated her ideas as a scientist.

“As a Black woman in science, I’ve sometimes struggled with imposter syndrome, questioning whether my ideas are worth pursuing,” said Franklin. “To have experts in the lupus field say that my work, my questions, matter—that this is something that needs to be studied—it meant everything to me.”

Lupus patients often show abnormalities in DNA methylation, an epigenetic process that typically silences certain genes in the body. In her research, Franklin zeroes in on two key proteins involved in the DNA methylation process, DNA methyltransferase 1 (DNMT1) and Methyl-CpG Binding Protein 2 (MeCP2).

Disruptions in the function of these two proteins are often linked to irregularities in methylation patterns. Historically, the effects of these two DNA methylation regulators, DNMT1 and MeCP2, have been studied in isolation. But Franklin’s research takes a different approach.

"While studies have shown that these components interact, scientists have not yet fully investigated how this interaction might influence their function in the context of lupus," said Franklin.

Franklin is not just asking whether there’s an interaction effect between these two DNA methylation regulators—she’s uncovering the precise ways these proteins influence one another.

Think of baking a cookie: too much flour makes it dense and hard, too much sugar and it becomes crumbly. In the same way, each protein plays a crucial role in how DNA methylation functions—or, in the case of lupus, how it fails to function properly. Franklin’s research aims to study these two proteins together to reveal new insights into their combined role in lupus.
"It's like asking whether having too much MeCP2 or not enough DNMT1 creates the same conditions seen in lupus. Do those imbalances result in the same phenotypic traits [as lupus]?" Franklin explained.

By using an orthogonal CRISPR system—an advanced gene-targeting tool—Franklin can simultaneously modulate two different proteins. With this, she can observe how varying ratios of these proteins affect the methylation process and gene expression.
Franklin’s experience in Haynes' lab leveraging synthetic biology also equips her to find new ways to investigate protein interactions and epigenetic changes that are difficult to study with traditional methods. Rather than relying solely on gene knockouts or drug inhibition, she uses fusion proteins to get clearer insights into the interaction effect of these proteins.
Her ultimate goal is to use the CRISPR technology to engineer a cell line that models lupus, creating a system to better understand the disease.

"Right now, there’s no true in vitro model for lupus—most studies rely on animal models, and we’re missing something vital," Franklin says. "As far as a cure, if I can do anything that brings us closer to understanding the pathology of lupus, that would make my life."
In addition to the Finzi Fellowship, Franklin was also awarded the Achievement Rewards for College Scientists (ARCS) fellowship—a prestigious scholarship providing financial awards to students advancing research in science, engineering, and medical fields.