Battling Disease at the Molecular Level

Kelley Shortsleeves ’09
Major: Chemistry
Associate scientist at Ensemble Therapeutics, Cambridge, Mass.

It’s no coincidence that when she describes her profession, Kelley Shortsleeves’ phrases are peppered with the vocabulary of conflict. She speaks of “antagonists” and “targets,” and about locating the weakness in an enemy that has proven impervious to traditional methods of attack.

Shortsleeves is a chemist. But the front line in the war against disease is populated by soldiers like her who are uniformed in white lab coats and do battle at the molecular level.

And yes, they do have victories.

Ensemble Therapeutics, the Cambridge, Mass.-based biotechnology company where Shortsleeves works as an associate scientist, recently announced that it has identified a series of small molecule antagonists of Interleukin-17 (IL-17), a cytokine — a type of protein molecule implicated in multiple inflammatory and autoimmune diseases such as psoriasis, rheumatoid arthritis, Crohn’s and intestinal bowel disease. The company is working to develop an oral inhibitor to IL-17 by the end of 2012.

“It’s still in the very early stages,” says Shortsleeves. “I’ve been fortunate to work on this project almost since its inception at Ensemble and have contributed a large amount of work to the med-chem and development of this lead series.”

At Ensemble Discovery, Shortsleeves helps build large libraries of macrocyclic molecules and screen them against drug-resistant protein-to-protein interactions that are common in oncology and inflammation-related diseases. “As a chemist, my job is to take the hits from these library screens, synthesize them on a larger scale, and supply compounds for in vitro testing,” she says.

A high school teacher inspired a love of chemistry in Shortsleeves, who pursued her passion at Clark. The summer after her junior year she interned at Abbott Labs in Worcester in the Organic Synthesis Department, and she later established a project working with Abbott in their labs to complete her master’s degree.

“While writing my thesis, I started applying to small biotech companies in and around Boston,” she recalls. “I got one interview with Ensemble. It was the only interview I went on, and they offered me the job a day later.”

Ensemble Therapeutics has created a new class of synthetic macrocyles called EnsemblinsTM using its proprietary chemistry platforms. These macrocycles are uniquely suited to address many protein targets that cannot be modulated effectively by traditional small-molecule pharmaceuticals. As Ensemble develops this novel class of therapeutics, it’s leveraging its findings to establish high-value partnerships with major pharmaceutical companies like Bristol-Myers Squibb and Pfizer.

Can Shortsleeves shed any light on other Ensemble initiatives in the pipeline?

She laughs. “Not without breaking confidentiality.”