The Scientist - USA (2022 - Spring)

SPRING 2022 | THE SCIENTIST 61

SCIENTIST TO WATCH

THOMAS LOZITO, KECK SCHOOL OF MEDICINE

T

homas Lozito began investigating amph-

ibians and reptiles when he was just

five years old. He says he was fasci-

nated by the rescued turtles his father, a real

estate agent, would bring him from work in

New Jersey, and by the time Lozito was in kin-

dergarten, he had even joined the local her-

petological society. Once a month, he’d find

himself “in the back of a public library with a

bunch of middle-aged men talking about tur-

tle breeding,” he laughs. Lozito remained a

member until leaving for college, and has kept

various reptiles, especially lizards, ever since.

After completing his undergraduate degree

in biomedical engineering at Johns Hopkins

University, Lozito enrolled at the University of

Cambridge, where he studied stem cell biol-

ogy. During his doctoral work researching the

environmental signals that regulate adult stem

cell differentiation and homeostasis, he began

working with Rocky Tuan, a bioengineer at the

National Institutes of Health (NIH), as part of

a joint program between the two institutions.

Lozito earned his PhD in 2009 and moved to

Tuan’s new lab at the University of Pittsburgh

for a postdoc. Together, the two did seminal

work uncovering how endothelial cells talk to

stem cells using cell-derived vesicles.

“All along, he [was] a lizard lover,” Tuan

says of Lozito, who introduced Tuan to his

many pets, which included mourning geckos

(Lepidodactylus lugubris), a species that would

later prove critical to Lozito’s research. Through

their discussions, Tuan realized that herpe-

tology was highly relevant to his research

interests in stem cells, musculoskeletal bio-

medicine, and regenerative medicine. Under-

standing how lizards regrow their cartilaginous

tails, the two speculated, could one day lead

to treatments for human conditions such as

osteoarthritis. In 2015, Lozito was promoted to

assistant professor at the University of Pitts-

burgh, and the pair turned their sights toward

the secrets of limb regeneration in lizards.

With so little known, they had to start

by answering basic questions, such as why

regenerated lizard tails remain almost entirely

cartilaginous, with only the most terminal

remaining vertebra generating new bone fol-

lowing amputation. In the course of tail regen-

eration, a cartilaginous tube encapsulates the

regenerated spinal nerves and is covered by

muscle and skin. Lozito and Tuan found that

differentiation at both ends of this tube is

partly regulated by variability in the signaling

protein Indian hedgehog (Ihh), a protein homo-

log involved in the Hedgehog signaling path-

way that promotes the growth of bone and

cartilage. Lozito also studied which cells con-

tribute to the regenerated appendage, find-

ing that existing cartilage cells in the mourn-

ing gecko’s tail contribute not just to cartilage

repair, but also to muscle regeneration, and

muscle cells similarly contribute to the regen-

eration of both tissues.

In 2019, Lozito joined the faculty of the

University of Southern California (USC) and

started his own lab. Today, he and his team are

investigating the imperfections of lizard tail

regeneration, specifically the fact that regrown

tails lack dorsal-ventral patterning. But after

taking embryonic neural stem cells from a

mourning gecko, using CRISPR-Cas9 to ren-

der them unresponsive to Hedgehog signal-

ing, and reimplanting them into an adult with

an amputated tail, Lozito was able to induce

the patterning in the regenerated appendage.

If the goal is human regeneration, Lozito’s

success with reptiles may sound like incre-

mental progress, he says, but he adds

that his work has been defined by con-

stant small steps interspersed with the

occasional leap forward. “Our five- to

ten-year goal is to make a mouse

regenerate its tail like a lizard,” Lozito

says. “So every time we meet in the

lab, we keep that goal in the back of

our minds.”

Studying lizards to one day treat people

is certainly a novel approach, says Lozito’s col-

league Denis Evseenko, the director of skel-

etal regeneration at USC. The two men are

working together on a novel drug to regen-

erate human joint and skin tissues that will

soon enter clinical trials. During their early

research, which has not yet been pub-

lished, they tested it on non-regenerating

lizard species, and to Evseenko’s surprise,

it worked, he says. When they applied the

compound to the tail stumps of these non-

regenerating lizards, the tails started growing

back. Evseenko calls the findings “remark-

able,” adding that working with Lozito has

made him “a little bit more open and enthu-

siastic to this [lizard] model, because it helps

us know what questions to ask.” g

Assistant Professor, Orthopaedic Surgery, Stem Cell Biology,

and Regenerative Medicine, University of Southern California

BY CONNOR LYNCH

Thomas Lozito: Probing Lizard Regeneration

THOMAS LOZITO, KECK SCHOOL OF MEDICINE