Juan Pablo Maianti

Vitals

Current Affiliation: stealth biotech (it’s still top secret)

Age: 33

Ph.D. alma mater: Harvard University

Role model: “Researchers who seamlessly navigate the interface of chemistry and multiple other fields with unbound scientific curiosity.” Maianti couldn’t pick one particular person but points to influential meetings and lectures with chemical biology superstars Christopher Walsh, Stuart Schreiber, and Peter Schultz.

Advice for young scientists: “It’s OK to be human: love, eat, sleep, exercise. In principle, we all started doing science because it made us happy; that seems like a good principle to uphold.”

Codename: Disease Decipherer

Whether you’ve eaten a chunk of bread, a spoonful of honey, or a bite of steak, your endocrine system magically adapts to the various levels of sugar flooding your bloodstream. Except, of course, when the magic fails. Type 2 diabetes occurs when our bodies stop being able to properly use insulin, the peptide tasked with lowering blood sugar after meals.

Juan Pablo Maianti hopes to restore that balance. He’s devoted the past several years to exploring the biology and chemistry of insulin-degrading enzyme (IDE), which, since its discovery in 1949, has been bandied about as a potentially important diabetes drug target.

While a graduate student in David Liu’s lab at Harvard University, Maianti developed the first true IDE inhibitor and then led mouse studies of the compound that upended 60 years of conventional wisdom about IDE. As hoped, the animal studies showed his IDE inhibitor slowed insulin breakdown, thereby lowering blood sugar; however, the studies also revealed that IDE acts on two other hormones, amylin and glucagon.

Because glucagon raises glucose levels while insulin lowers them, Maianti was faced with a daunting new task: With just three months until his thesis defense, he needed to come up with substrate-selective IDE inhibitors—that is, compounds that would slow insulin degradation while allowing glucagon breakdown to proceed as usual. He did it.

Designing complex compounds is an impressive feat. But what has made Maianti “arguably the most talented student I’ve had,” Liu says, is his ability to also orchestrate all of the other aspects of a drug discovery campaign—from chemical synthesis through animal studies.

Maianti is now trying to turn his substrate-selective inhibitors into drugs. Together with Liu and former Harvard colleague Alan Saghatelian, he’s founded a stealth biotech firm that is raising money while Maianti works to tweak and test compounds.

“I didn’t really think I would end up creating a new company,” Maianti says. “But once this opportunity was in front of me, I realized that even if I lived 30 different alternative lives, this wouldn’t come up again.”

Research at a glance

Maianti and his collaborators not only designed the first compounds that block insulin-degrading enzyme, a prized diabetes target, they also made those inhibitors selective: The compounds slow the breakdown of insulin in mice but don’t interfere with the enzyme’s breakdown of another important hormone, glucagon. Juan Pablo Maianti/C&EN

Maianti and his collaborators not only designed the first compounds that block insulin-degrading enzyme, a prized diabetes target, they also made those inhibitors selective: The compounds slow the breakdown of insulin in mice but don’t interfere with the enzyme’s breakdown of another important hormone, glucagon. Credit: Juan Pablo Maianti/C&EN

Three key papers:

“Anti-diabetic Activity of Insulin-Degrading Enzyme Inhibitors Mediated by Multiple Hormones” (Nature 2014, DOI: 10.1038/nature13297)

“Toxicity Modulation, Resistance Enzyme Evasion, and A-site X-ray Structure of Broad-Spectrum Antibacterial Neomycin Analogs” (ACS Chem. Biol. 2014, DOI: 10.1021/cb5003416)

“Structural and Kinetic Study of Self-Assembling Macrocyclic Dimer Natural Product Aminoglycoside 66-40C and Unnatural Variants” (Chem. Sci. 2012, DOI: 10.1039/C1SC00538C)

 

Career paths:

They might be young scientists, but our Talented 12 have already traveled far and wide.

juan_pablo_map

Story in C&EN about Maianti’s work:

Diabetes-Related Enzyme Modulates Insulin, Amylin, and Glucagon

 


Watch Maianti talk about his research during a special Aug. 22 Talented 12 symposium held at the American Chemical Society national meeting in Philadelphia.

 

Lili He 
Bill Morandi
Leave a Reply

Your email address will not be published. Required fields are marked *

*

*